Toronto Notes 2023 9781998874019

Table of contents :
Front Page TN 2023
Table of Contents
Common Acronyms and Abbreviatins
Common Unit Conversations
Commonly Measured Lab Values
ELOM- Ethical, Legal and Org Medicine
The Canadian Healthcare system
Ethical and Legal Issues in Canadian Medicine
Legal Foundation
History of Canadian Healthcare System
Healthcare Expenditure and Delivery in Canada
Physician Licensure and Certification
Role of Professional Associations
Confidentiality
Consent and Capicity
Negligence
Truth-Telling
Ethical Issues in Health Care
Reproductive Technologies
End-of-Life Care
physician Competence and Professional Conduct
Research Ethics
Physician- Industry Relations
Resource Allocation
Conscientious Objection
Clinical Informatics and Ethical Considerations
Overview of Digital Health Technologies
Indigenous Health
Overview of the History and Impact of Colonialism
Movement Towards Reconciliation
Indigenous Disproportionate
Indigenous Health Coverage and Juridictions
Resources in Indigenous Health
Anesthesia
Preoperative Assessment
Preoperative Optimization
Monitoring
Airway Management
Intraoperative Management
Induction
Maintenance
Extubation
Complications of Extubation
Regional Anesthesia
Local Anesthesia
postoperative Care
Pain Management
Obstetrical Anesthesia
Paediatric anesthesia
Uncommon Complications
Appendices
Cardiology and Cardiac Surgery
Coronary Circulation
Differential Diagnoses of Common Presentations
Cardiac Diagnostic Tests
Approach to ECGs
Cardiac Disease- Arrhythmias
Ischemic Heart Disease
Heart Failure
Myocardial Disease
Cardiac Transplantation
Cardiac Tumours
valvular Heart Disease
Pericardial Disease
Extracorporeal Circulation
Common Medications
Clinical Pharmacology
General principles
Pharmacokinetics
Pharmacodynamics
Therapeutic Drug Monitoring
Adverse drug Reactions
Autonomic Pharmacology
Common Drug Endings
Dermatology
Introduction to Skin
Morphology
Differential Diagnoses for Common Presentations
Common Skin Lesions
Acneiform Eruptions
Dermatitis (Eczema)
Papulosquamous Diseases
Vesiculobullous Diseases
Drug Eruptions
Heritable Disorders
Infections
Pre-Malignant Skin Conditions
Malignant Skin Tumours
Diseases of Hair Density
Nails and Disorders of the Nail Apparatus
Adnexal Disorders
Oral Diseases
Skin Manifestations of Systemic Disease
Miscellaneous Lesions
Traumatic and Mechanical Disorders
Landmark Dermatology Trials
References
Emergency Medicine
Ptatient Assessment/Management
Traumatology
Approach to Common ED Presentations
Medical Emergencies
Otolaryngological Presentations and Emergencies
Gynaecologic/Urologic Emergencies
Opthalmologic Emergencies
Dermatologic Emergencies
Enverionmental Injuries
Toxicology
Psychiatric Emergencies
Common Pediatric ED Presentations
Common Medications
Endocrinology
Basic Anatomy Rivew
Dyslipidemias
Disorder of Glucose Metabolism
Obesity, Pituitary Gland
Thyroid
Adrenal Cortex
Adrenal Medulla
Disorders of Multiple Endocrine Glands
Calcium Homeostasis
Metabolic Bone Disease
Male Reproductive Endocrinology
Female Reproductive Endocrinology
Paraneoplastic Syndrome
Common Medications
Family Medicine
Four Principles of FM
Periodic Health Examination
Health Promotion and Councilling
Common Presentig Problems
Palliative Care
Complementary and Integrative Medicine
Antimicrobial Quic Reference
Gastroenterology
New Bookmark
Anatomy Review
Differential Diagnosis of Common Complaints
Esophagus
Stomach and Duodenum
Small and Large Bowel
Liver
Liver Transplantation
Biliary Tract
Pancreas
Clinical Neutrition
Common Medications
General and Thoracic Surgery
Basic Anatomy Review
Differential Diagnosis of Common presentations
preoperative Presentations
Surgical Complications
Thoracic and Foregut Surgery
Stomach and Duodenum
Small Intestine
Small Bowel Obstruction
Abdominal Hernia
Appendix
Inflammatory Bowel Disease
Large Intestine
Large Bowel Obstruction
Diverticular Disease
Colorectal Neoplasms
Other Conditions of the Large intestine
Anorectum
Liver
Biliary Tract
Pancreas
Spleen
Breast
Surgical Endocrinology
Paediatric Surgery
Skin Lesions
Common Medications
Geriatric Medicine
Physiology and Pathology of Aging
Framework for the Approach to the older Adult
Presentations in Older Adults
Driving Competency
Hazards of Hospitalization
Healthcare Institutions
Geriaric Pharmacology
Common Medications
Gynaecology
Basic Anatomy Review
Mensturation
Common Investigation and Procedures
Disorders of Mensturation
Endometriosis
Adenomyosis
Fibroids
Contraception
Termination of Pregnancy
Pregnancy- Related Complications
Ectopic Pregnancy
Infertility
Polycystic Overian Syndrome
Gynaecological Infections
Sexual Abuse
Sexuality and Sexual Dysfunction
Menopause
Urogynaecology
Gynaecological Oncology
Common Medications
Hematology
Basics of Hematology
Common Presenting Problems
Approach to Lymphadenopathy
Approach to Splenomegaly
Microcytic Anaemia
Normocytic Anaemia
Hemolytic Anaemia
Macrocytic Anaemia
Hemostasis
Disorders of Primary Hemostasis
Disorders of Secondary Hemostasis
Hypercoagulable Disorders
Venous Thrombolism
Hematologic Malignancies and Related Disorders
Myeloid Malignancies
Myeloproliferative Neoplasms
Lymphoid Malignancies
Lymphomas
Malignant Clonal Proliferations of Mature B-Cells
Complications of Hematologic malignancies
Blood products and Transfusions
Common Medications
Infectious Disease
Principles of Microbiology
Nosocomial Infections
Skin and Soft tissue Infections
Gastrointestinal Infections
Traveller's diarrhea
Chronic Diarrhoea
Peptic Ulcer Disease H.Pylori
Bone and Joint Infections
Cardiac Infections
CNS Infections
Systemic Infections
Tuberculosis
HIV and AIDS
Fungal Infections
Skin and Subcutaneous Infections
Endemic Mycoses
Opportunistic Fungi
Parasitic Infections
Protozoa - intestinal/ Genitourinary Infections
Blood and Tissue Infections
Helmenths
Ectoparasites
Travel Medicine
Fever of Unknown Origin
Infections in the Immunocomromised Host
A Simplified Look at Antibiotics
Antimicrobials
Antivirals
Antifungals
Antiparasitics
Common Infections and Their Antibiotic Management
Medical Genetics
Introduction to Genetics
Differences in Morphology
Genetic Conditions
Medical Imaging
Imaging Modalities
Chest Imaging
Abdominal Imaging
Genitourinary System and Adrenal
Neuroradiology
Musculoskeletal System
Nuclear Medicine
Interventional Radiology
Breast Imaging
Nephrology
Basic Anatomy Review
Assesment of Renal Function
Electrolyte Disorders
Acid- Base Disorders
Acute Kidney Injury
Parenchymal Kidney Diseases
Systemic Disease with Renal manifestation
Chronic Kidney Disease
Hypertention
Cystic Diseases of the Kidney
End Stage Renal Disease
Renal Replacement Therapy
Renal Transplantation
Common Medications
Neurology
Approach to the Neurological Complaint
The Neurological Exam
Approach to Common Presentations
Cranial nerve Deficits
Neuro Opthalmology
Abnormalities of Visual Field
Abnormalities of Eye Movements
Neutritional Deficiencies and Toxic Injuries
Seizure Disorders and Epilepsy
Behavioural Neurology
Mild Traumatic Brain Injury
Neuro Oncology
Movement Disorders
Wilson's Disease
Dystonia
Tic Disorders
Tourette's Syndrome
Cerebellar Disorders
Vertigo
Motor Neuron Disease
Perepheral Neuropathies
Neuromuscular Junction Diseases
Myopathies
Myotonic Dystrophy Type 1
Pain Syndromes
Headache
Sleep Disorders
CNS Infections
Spinal Cord Syndromes
Stroke
Neurocutaneous Syndromes
Multiple Sclerosis
Common medications
Neurosurgery
Basic Anatomy Review
Differential Diagnoses of Common Presentations
Intracranial Pathology
Intracranial Pressure Dynamics
Herniation Syndromes
Idiopathic Intracranial hypertention (Pseudotumer Cerebri)
Hydrocephalus
Spontaneous Intracranial Hypertention
CNS Tumours
Cerebral Abscess
Blood
Cerebrovascular Disease
Vascular Malformations
Cerebrospinal Fluid Fistulas
Extracranial Pathology
Approach to Limb/Back Pain
Extradural Lesions
Degenerative Cervical Myelopathy
Intradural Intramedullary Lesions
Spinal Cord Syndromes
Peripheral Nerves
Speciality Topics
Neurotrauma
Paediatric Neurosurgery
Functional Neurosurgery
Surgical Management of Epilepsy
Surgical Management for Trigeminal Neuralgia
Obstetrics
Basic Anatomy Review
Pregnancy
Maternal Physiologic Adaptations to Pregnancy
Antepartum Care
Counselling of the Pregnant Patient
antepartum Hemorrhage
Obstetrical Complications
Multi-Fetal Gestation and malpresentation
Hypertensive Disorders of Pregnancy
Medical Complications of Pregnancy
Normal Labour and Delivery
Induction and Augmentation of Labour
Abnormalities and Complications of Labour and Delivery
Operative Obstetrics
Postpartum Period Complications
Postpartum Care
Common Medications
Ophthalmology
Basic Anatomy Review
Differential Diagnoses of Common Presentations
Ocular Emergencies
The Ocular Examination
Optics
The Orbit
Lacrimal Apparatus
Lids and Lashes
Conjunctiva
Sclera
Cornea
The Uveal Tract
Lens
Viterous
Retina
Glaucoma
pupils
Malignancies
Ocular Manifestations of Systemic Disease
Paediatric Opthalmology
Ocular Trauma
Ocular Drug Toxicity
Common Medications
Orthopaedic Surgery
Basic Anatomy Review
Fractures- General Principles
Articular Cartilage
Orthopaedic X-Ray Imaging
Orthopedic Emergencies
Shoulder
Humerus
Elbow
Forearm
Wrist
Hand
Spine
Pelvis
Hip
Femur
Knee
Patella
Tibia
Ankle
Foot
Paediatric Orthopedics
Bone Tumours
Common Medications
Otolaryngology
Basic Anatomy Review
Differential Diagnoses of Common Presentation
Hearing
Vertigo
Tinnitus
Diseases of External Ear
Diseases of the Middle Ear
Diseases of the Inner Ear
Facial Nerve (CN VII) Paralysis
Rhinitis
Rhinosinusitis
Epistaxis
Hoarseness
Salivary Glands
Neck Masses
Congenital Neck Masses
Neoplasms of the Head and Neck
Paediatric Otolaryngology
Common Medications
Paediatrics
Paediatric quick Reference Values
Primary care
Common Complaints
Adolescent Medicine
Child Abuse and Neglect
Cardiology
Development
Endocrinology
Fluids and Electrolytes
Gastroenterology
Genetics, Dysmorphism, and Metabolism
Hematology
Oncology
Infectious Diseases
Neonatology
Nephrology
Neurology
Respirology
Rheumatology
Common Medications
Palliative Medicine
Palliative Approach to Care
Pain and Symptom Management
Care of the Dying Patient
Psychosocial and Spiritual Needs
End -of-Life Decision Making
Communication
Collaboration
Suffering
Self-Care
Paediatric Palliative Care
Assessment Tools
Plastic Surgery
Basic Anatomy Review
Skin Lesions and Masses
Basic Surgical Techniques
Wounds
Soft Tissue Infections
Ulcers
Burns
Hand
Brachial Plexus
Craniofacial Injuries
Breast
Aesthetic Surgery
Gender- Affirming Surgery (Transition- Related Surgery)
Paediatric Plastic Surgery
Psychiatry
Psychiatric Assessment
Assessment and Plan
Suicide
Psychotic Disorders
Mood Disorders
Anxiety Disorders
Obsessive- Compulsive and Related Disorders
Trauma and Stressor-Related Disorders
Bereavement
Neurocognitive Disorders
Somatic Symptom and Related Disorders
Dissociative Disorders
Sleep Disorders
Sexulity and Gender
Eating Disorders
Personality Disorders
Child Psychiatry
Neurodevelopmental Disorders
Disruptive, Impulsive Control, and Conduct Disorder
Psychotherapy
Pharmacotherapy
Somatic Therapies
Canadian Legal Issues
Public Health and Preventive Medicine
Public Health Context
Determinants of Health
Measurements of Health and Disease in a Population
Epidemiology
types of Study Design
Mehods of Analysis
Health System Planning and Quality
Economic Evaluation
Managing Disease Outbreaks
Environmental Health
Occupational Health
Occupational Hazards
Appendix- Mandatory Reporting
Respirology
Approach to the Respiratory Patient
Airway Disease
Interstitial Lung Disease
Pulmonary Vascular Disease
Pulmonary Embolism
Diseases of the Mediastinum and Pleura
Respiratory Failure
Neoplasms
Sleep-Related Breathing Disorders
Introduction to Intensive Care
Common Medications
Rheumatology
Anatomy and Joint Pathology
basics of Immunology
Differential Diagnosis of Common Presentations
Synovial Fluid Analysis
Septic Arthritis
Degenerative Arthritis: Osteoarthritis
Seropositive Rheumatic Disease
Connective Tissue Disorders
Vasculitides
Seronegative Rheumatic Disease
Crystal-Induced Arthropathies
Non-Articular Rheumatism
Common Medications
Urology
Basic Anatomy Review
Urologic History
Hematuria
Lower Urinary Tract Dysfunction
Lower Urinary Tract Symptoms
Overactive Bladder
Infectious and Inflamatory Diseases
Stone Disease
Urological Neoplasms
Scrotal Masses
Penile Complaints
Trauma
Infertility and Andrology
Testosterone Deficiency
Paediatric Urology
Wilms' Tumour (Nephroblastoma)
Selected Urological Procedures
Common Medications
Vascular Surgery
Arterial Disease
Aortic Disease
Carotid Stenosis
Venous Disease
Lymphedema

Citation preview

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TORONTO NOTES

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COMPREHENSIVE MEDICAL REFERENCE AND A REVIEW FOR MCCQE Editors-in-Chief

• Anders Erickson & Jennifer Parker

Associate Editors, Primary •Dorrin Zarrin Khat & Ming Li Associate Editors, Medicine • Karolina Gaebe & Alyssa Li Associate Editors, Surgery • Vrati Mehra & Chunyi Christie Tan

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TORONTO NOTES 2023 Comprehensive Medical Reference and a Review for the Medical Council of Canada Qualifying Exam

(MCCQE)

39th Edition Editors-in -Chief: Anders W. Erickson & Jennifer Parker

Toronto Notes for Medical Students, Inc. Toronto, Ontario, Canada

AL GRAWANY

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2 Editorial

Toronto Xotcs 2023

Thirty-ninth Edition Copyright © 2023 - Toronto Notes for Medical Students, Inc. Toronto, Ontario, Canada Typeset and production by Type & Graphics Inc. ISBN 978-1-998874-01-9 ( 39th ed.)

All rights reserved. Printed in Toronto, Ontario, Canada. Toronto Notes 2023 is provided for the sole use of the purchaser. It is made available on the condition that the information contained herein will not be sold or photocopied. No part of this publication may be used or reproduced in any form or by any means without prior written permission from the publisher. Ever)r effort has been made to obtain permission for all copyrighted material contained herein. Previous editions copyright © 1985 to 2023. Cover illustration: Jennifer Xin Ran Shao and Aimy Meng Yu Wang Illustrations: Biomedical Communications, University of Toronto

Notice:

THIS PUBLICATION HAS NOT BEEN AUTHORED, REVIEWED, OR OTHERWISE SUPPORTED BY THE MEDICAL COUNCIL OF CANADA NOR DOES IT RECEIVE ENDORSEMENT BY THE MEDICAL COUNCIL AS REVIEW MATERIAL FOR THE MCCQE PART I. THIS PUBLICATION HAS NOT BEEN AUTHORED, REVIEWED, OR OTHERWISE SUPPORTED BY THE NATIONAL BOARD OF MEDICAL EXAMINERS U.S.A. NOR DOES IT RECEIVE ENDORSEMENT BY THE NATIONAL BOARD AS REVIEW MATERIAL FOR THE USMLE.

The editors of this edition have taken every effort to ensure that the information contained herein is accurate and conforms to the standards accepted at the time of publication. However, due to the constantly changing nature of the medical sciences and the possibility of human error, the reader is encouraged to exercise individual clinical judgement and consult with other sources of information that may become available with continuing research. The authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this textbook, atlas, or software and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. In particular, the reader is advised to check the manufacturers insert of all pharmacologic products before administration.

FEEDBACK AND ERRATA

We arc constantly ttying to improve the Toronto Notes and welcome your feedback. If you have found an error in this edition please do not hesitate to contact us. As well, we look forward to receiving any comments regarding any component of the Toronto Notes package and website. Please send your feedback to: [email protected]

The Toronto Notes for Medical Students Inc. Editors-in -Chief, c/o The Medical Society 1 King’s College Circle, Room 2260 Toronto, Ontario MSS 1A8, Canada email: [email protected] Alternatively, send mail to:

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Library of Congress Cataloging-in-Publication Data is available upon request

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Toronto Notes 2023

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Dedicated to all the many contributors and supporters of Toronto Notes,

both past and present , who have shaped the 2023 edition!

The Toronto Notes for Medical Students is dedicated to helping fund many charitable endeavours and medical student initiatives at the University of Toronto’s Faculty of Medicine and beyond. Programs that have received Toronto Notes for Medical Students funding include:

Community Affairs Programs Adventures in Science (.VIS) Adventures in Science ( AIS) MAM Allies Live I lore Altitude Mentoring Altitude Mentoring MAM Blood Drive Exercise is Medicine Growing Up Healthy Growing Up Healthy MAM Healing Tonics Imagine Immigrant and Refugee Equitable Access to I Iealth Care ( iREACH) Kids2IIear Kids2See Kindlcr Arts Noteworthy Music Program Parkdale/Central Toronto Academy Mentorship Program Saturday Program Saturday Program MAM Scadding Court Mentorship Program Seniors Outreach

Smiling Over Sickness Student-Senior Isolation Prevention Partnership ( SSIPP ) Sun and Skin Awareness Swimming With A Mission ( SWAM ) Varsity Docs Woodgreen Tutoring Program Annual Showcase Events Dafiydil, in support of the Canadian Cancer Society Earth Tones Benefit Concert

Scholarships and Bursaries Memorial Funds CaRMS bursary Other Sponsorships Community of Support Indigenous Sutdent Mentorship Fund Black Health Alliance Ontario Medical Students Weekend Medical Student Research Day Class formats and graduations

NOTE:

Many of you have wondered about the Toronto Notes logo, which is based on the rod of Asclepius, the Greek god of medicine. The rod of Asclepius consists of a single serpent entwined around a staff. This icon symbolizes both rebirth, by way of a snake shedding its skin, and also authority, by way of the staff. In ancient Greek mythology, Asclepius was the son of Apollo and a skilled practitioner of medicine who learned the medical arts from the centaur Chiron. Asclepius’ healing abilities were so great that he was said to be able to bring back people from the dead. These powers displeased the gods, who punished Asclepius by placing him in the sky as the constellation Orphiudius. The rod of Asclepius is at times confused with the caduceus, or wand, of Hermes, a staff entwined with two serpents and often depicted with wings. The caduceus is often used as a symbol of medicine or medical professionals, but there is little historical basis for this symbolism. As you may have guessed, our logo uses the rod of Asclepius that is modified to also resemble the CN Tower - our way of recognizing the university and community in which we have been privileged to learn the art and science of medicine. Thomas O’Brien, MD Class of 2009, M.D. Program, University of Toronto

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Toronto Notes 2023

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Preface - From the Editors .

Dear reader

We are grateful to present Toronto Notes 2023 to you. This edition is the product of an exceptional effort from the

hundreds of editors and contributors who worked tirelessly with us as we navigated through the year. Together, we have created the thirty- ninth edition of Toronto Notes, thus continuing our organization's rich tradition of providing an up to- date, comprehensive, and concisely written medical resource to our readers.

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Thirty nine years ago, Toronto Notes began as a humble initiative, with medical students from the University of Toronto collecting and circulating their notes. Nearly four decades later - with annual editions and an ever-expanding vision - Toronto Notes has become one of the most trusted medical review texts; it is a resource that is cherished by trainees and physicians throughout Canada and around the world.

and the Climate Crisis are also fully addressed. In addition to content updates, the Toronto Notes 2023 Clinical Handbook has been restructured to prioritize high - yield content to guide your learning during clerkship rotations. Toronto Notes prioritizes cultural sensitivity, health equity, and strives for accurate representation of our vibrant and diverse communities. To enhance our team’s editorial lens on these concepts while editing the chapters, training was provided by the Anti - Racism and Cultural Diversity Office and Office of Inclusion & Diversity at the University of Toronto. We sincerely thank each of our 170 student editors and 103 faculty editors, whose meticulous revisions and shared dedication to the bettering of this text has helped make Toronto Notes 2023 possible. We have learned so much from leading this

team , and are especially grateful to everyone for contributions to Toronto Notes with challenging time commitments and demands. We thank our incredible Associate Editors - Ming Li, Dorrin Zarrin Khat, Christie Ian, Yrati Mehra, Alyssa Li,

The Toronto Notes for Medical Students Inc. is a nonprofit corporation whose mission is to proride a trusted medical resource in order to give back to our community. Keeping in line with our values and community needs, all proceeds from Toronto Notes sales are directly donated to support both global and local initiatives. Among other initiatives, we have supported U ofT Medicine class activities, student scholarships and bursaries ( such as the Mohammad and Zevnab Asadi Lari award ), our Daffy annual musical fundraiser for the Canadian Cancer Society, and the entirety of our (over twenty-five ) student-led outreach programs that seek to enrich lives in the

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community.

and Karolina Gaebe - for their tireless leadership, exceptional organization, and wonderful teamwork. We, and the success of this edition, lean on their shoulders. We also thank our Clinical Handbook Editors - Justin Lu, lanice Chan, and Rayoun for their exceptional editorial leadership and Ramendra spearheading the work on this resource. We owe a great deal of gratitude to the Editors-in-Chief of the 2022 edition - Yuliya Lytvyn and Maleeha Qazi - for their continued guidance over the past two years. We would also like to thank the wonderful BMC illustration team for their work and especially the cover designs, with inspiration from the medical illustrations of Barry T. O'Neil. Lastly, we thank our longtime partners at Type & Graphics Inc especially our backbone, Enrica Aguilera for their years of support and excellent and Maria Garcia work producing Toronto Notes 2023. Finally, we thank you for supporting our initiative by purchasing and reading our product We hope that you will find Toronto Notes 2023 to be a useful companion on your medical journey, both now and for years to come.

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This is why we, and all the members of our U of T team, gladly dedicated so many hours toward this immensely involved project. As our valued reader, we thank you for your honest and vital financial contribution through your purchase of our textbook. Each book sold makes an important difference. The 2023 edition features substantial content revisions to the text, figures, and graphics of all 32 chapters, following a comprehensive review by our student and faculty editorial team . Up- to-date, evidence - based medicine studies are also summarized in highlighted boxes throughout the text. In particular, the Ethical Legal, and Organizational Medicine chapter has been thoroughly revised and expanded, and all chapters reflect the most- updated COV1D-19 guidelines. The new MCCQE objectives on Clinical Informatics and Health

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Sincerely, rn

Anders W. Erickson, MD/ PhD student Jennifer Parker, MD/ PhD student Editors in Chief, Toronto Sotes 2023

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Toronto Notes 2023

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Acknowledgements We would like to acknowledge the exceptional work of all previous Toronto Notes ( formerly MCCQE Notes) Editors in-Chief and their editorial teams, lhe 39th edition of this text was made possible with their contributions.

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2022 ( 38th ed.): Yuliya Lytvyn and Maleeha A. Qazi 2021 ( 37 th ed.) : Megan Urupals and Matthacus Ware 2020 ( 36th ed.): Sara Mirali and Ayesh Seneviratne 2019 ( 35th ed.): Taraneh (Tara ) Tofighi and Mark Shafarenko

2018 ( 34 th ed.): Tina Binesh Marvasti and Sydney McQueen

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2017 ( 33rd ed ): Jieun Kim and Ilya Mukovozov 2016 (32 nd ed.): Zamir Merali and Justin D. Woodfine 2015 (31th ed.): Justin Hall and Azra Premji

2014 (30th ed.): Miliana Vojvodic and Ann Young

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2013 (29th ed ): Curtis Woodford and Christopher Yao 2012 (28 th ed.): Jesse M. Klostranec and David L. Kolin 2011 (27th ed.): Yingming Amy Chen and Christopher Tran 2010 (26th ed.): Simon Baxter and Gordon McSheffrey

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2009 ( 25th ed ): Sagar Dugani and Danica Lam

2008 ( 24th ed.): Rebecca Colrnan and Ron Somogyi

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2007 ( 23rd ed ): Marilyn Heng and Joseph Ari Greenwald

2006 ( 22 nd ed.): Carolyn

Jane Shiau and Andrew Jonathan Ibren

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2005 ( 21st ed ): Blair John Normand Leonard and Jonathan Chi Wai Yeung

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2004 ( 20 th ed ): Andrea Molckovsky and KashifS. Pirzada 2003 ( 19th ed.): Prateek Lala and Andrea Waddell 2002 ( 18th ed.): Neety Paint and Sunny Wong 2001 ( 17th ed.): Jason Yue and Gagan Ahuja

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2000 ( 16th ed ): Marcus Law and Brian Kotcnberg

. 1998 ( 14 th ed.): Marilyn Abraham and M Appleby

1999 ( 15th ed ): Sofia Ahmed and Matthew Cheung

1997 (13th ed.): William Harris and Paul Kurdyak 1996 (12th ed.): Michael B. Chang and Laura J. Macnow

1995 (11th ed.): Ann L. Mai and Brian

J. Murray

1994 (10th ed.): Kenneth Pace and Peter Ferguson

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1993 ( 9th ed.): Joan Cheng and Russell Goldman 1992 (8th ed.): Gideon Cohen - Nehemia and Shanthi Vasudevan

All former Chief Editors from 1991 ( 7th ed.) to 1985 ( 1st ed.)

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Toronto Notes 2023

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Student Contributors Editors- in -Chief Anders Erickson Jennifer Parker

Clinical Handbook Editors Justin Lu Rayoun Ramendra

BMC Production Editors Jennifer Xin Ran Shao Aimy Meng Yu Wang

Online Content Managers Jeffrey Lam Shin Cheung Sandra Lee Amanda Mac Muhammad Shahid

Copyright Managers Mercy Danquah Marta Karpinski

BMC ILLUSTRATORS Viktoriva Khymych

Viola Yu

Amy Ke Er Zhang

PRIMARY Associate Editors

EBM Editor

Ming Li Dorrin Zarrin Khat

Yijithan Sugumar

CHAPTER EDITORS Ethical, Legal, and Organizational Medicine Kenya Costa-Dookhan Zuhal Mohmand

Dermatology Natalie Kozlowski Yuliya Lytvyn Sara Mirali

Family Medicine Neda Pirouzmand Bree Sharma

Maryam Thrava

Evan Tang Kathak Vachhani

Emergency Medicine V'inyas 1 Iarish Danny Ma

Medical Genetics Andrew Mazzanti

Clinical Pharmacology

Kwasi Nkansah Tsz Ying So

Medical Imaging Grace Grafham Jeffrey Lam Shin Cheung

Anestlicsia

Max Solish

Paediatrics Onyinyechukwu Esenwa Anna Jiang Raima Rasouli Mary Xie Tinting Yang Palliative Medicine Manu Sharma Christine Wu

Psychiatry Tania Da Silva Rawaan Elsawi

Rachel Goud Public Health and

Preventive Medicine Jenny Cho Muhammad Maaz

COPY EDITORS Ethical, Legal, and Organizational Medicine Noroh Dakim Alex German

Dermatology'

Family Medicine

Paediatrics

Chidalu Edechi Jaycie Dalson

Jaskaran Gill

Anesthesia Max Solish Janet Tang

Emergency Medicine Graham Colby Sanch Gupta Lara Murphy Daniel Shane

Tania Da Silva Priscilla Kim Ajantha Xadarajah Yasmeen Razvi

Clinical Pharmacology Fatimah Roble

Shiyu Sunny Zheng Medical Genetics Ryan Karim i Medical Imaging

Victoria Anthes Hayley McKee

Palliative Medicine Samuel Wier

Psychiatry' David Kim Public Health and Preventive Medicine

Caitlin Monaghan HunsterYang rT c. J

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Toronto Notes 2023

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Student Contributors MEDICINE Associate Editors Karolina Gaebe Alyssa Li

EBM Editors Wei Fang Dai Camilla Giovino

CHAPTER EDITORS Cardiology and Cardiac Surgery I lardil Bhatt

Akachukwu Nwakoby Jeremy Roslt Emily Tam

Gastroenterology

Sahibjot Grewal Anna Lee Andrew Rogalsky Geriatric Medicine

Imnan Khcrani Endocrinology Maria Samy Claire Sethuram

Saba Manzoor

Hematology Reid Gallant Syed Sluhan I laider Nathan Kuelmc Infectious Diseases Christopher Knox Erika Nakajima Rachel Tran

Nephrology David Buchan I Juaqi Li

Neurology Thomas Milazzo Maleeha Qazi

Respirology Brian Bursic Emma Price Rajiv Tanwani Rheumatology

Rachel Goldlarh Eden Meisels

COPY EDITORS Cardiology and Cardiac Surgery Shamara Nadarajah Julianah Oguntala Calurn Slapnicar Vivian Tam

Endocrinology Winston Li Kathryn Wiens Gastroenterology Oliver Chow Parker McNabb

Hematology Pedro Boasquevisque Daniel Lindsay Brandon Tse

Nephrology Anders Erickson Jennifer Parker

Respirology Andrew Rogalsky Raza Syed

Neurology

Infectious Diseases Nicholas Chiang

Lauren Kanee

Rheumatology Serena Dienes Tsz Ying So

Kristiana Xhima

TediIloxha Geriatric Medicine Pooja Sankar

SURGERY Associate Editors Vrati Mehra Chunyi Christie Tan

EBM Editor Arjan Dhoot

CHAPTER EDITORS General and Thoracic

Surgery Ryan Daniel Jacqueline Lim

Neurosurgery Dan Budiansky Jack Su Raza Syed

Ophthalmology Michael Balas

Otolaryngology Alyssa Li

Josh I Ierman Michelle Lim

Sheila Yu

Obstetrics I Iarsukh Benipal Emma Sparks Jane Zhu

Orthopaedic Surgery

Jessica Trac

Smruthi Ramesh

Gynaecology Eliot Winkler Sarah Zachariah Rehona Zamani

Urology Adree Khondker Shamir Malik

Vascular Surgery

John - Petcr Bonello Kalter 1 Iali Robert Koucheki Marc Manzo

Plastic Surgery Shaishav Datta Tiffany Ni

George Elzawy Raumil Patel

COPY EDITORS General and Hioracic

Surgery Tasnim Abdalla Audrey Jong Lisa Vi Gynaecology

Laura Diamond Katherine Kim

Neurosurgery Bhadra Pandya Jacob Peller

Ophthalmology Kevin Chen Matthew Veitch

Otolaryngology Ryan Daniel Siddhartha Sood

Urology Kellie Kim Gabriela Leon

Obstetrics Julia Avolio I layley Good Erin Pucrsten

Orthopaedic Surgery 1 lannah Drkulec Anders Erickson

Plastic Surgery

Thomas Milazzo Jenn Parker

Vascular Surgery Serena I lope

I Iolsa Zia

AL GRAWANY

rT LJ

+

Toronto Notes 2023

S Editorial

Faculty Contributors, University of Toronto All of the following contributors have been appointed at the University of Toronto.

PRIMARY ETHICAL, LEGAL. AND ORGANIZATIONAL MEDICINE Andria Bianchi, PhD Bioethicist, University Health Network Assistant Professor, Delia Lana School of Public Health, University of Toronto Affiliate Scientist, KITE Research Institute,

Toronto Rehab Education Investigator 2, TIER ( The Institute for Education Research ) Nadia Incardona, MD, MHSc. BSc, CCFP ( EM )

Assistant Professor Department of Family and Community Medicine Michael Garron Hospital

Chase Everett McMurren , BA, BEd, MD, CCFP

Department of Family and Community Medicine University of Toronto

ANESTHESIA Ahtsham Niazi, MBBS, FCARCSI, FRCPC Department of Anesthesia and

Pain Management, University Health Network

CLINICAL PHARMACOLOGY Das id Juurlink, BPhm, MD, PhD, FRCPC

Division of Clinical Pharmacology and Toxicology, Departments of Medicine and Paediatrics, Sunnybrook Health Sciences Centre

Cindy Woodland, PhD Associate Professor, Teaching Stream

. .

Director, Collaborative Speci tli 7 uion in Biomedical Toxicology Director, Applied Clinical Pharmacology Program DERMATOLOGY Patrick Fleming, Sc ( Nutrition !. MSc (Community Health ), MD, FRCPC, FCDA Assistant Professor of Medicine, Department of Medicine, University of Toronto Dermatologist, York Dermatology & Research Centre Consultant Dermatologist, University Health Network

Marissa Joseph , MD, MScCH. FRCPC, FRCPC Division of Dermatology, Department of Medicine Women's College Hospital and The Hospital for Sick

Children

Jensen Yeung, MD, FRCPC

Division of Dermaiology, Department of Medicine Women's College Hospital EMERGENCY MEDICINE

Mark Freedman , BSc, MD, FRCPC Department of Emergency Medicine Sunnybrook Health Sciences Centre

Laura Hans, MD, CCFP ( EM ) Department of Emergency Medicine SL Michael's Hospital Adam Kaufman, MD CCFPiEM ) Emergency Physician, Michael Garron Hospital, Toronto East Health Network .Assistant Professor, Department of Family and Community Medicine, University of Toronto

Jo Jo Leung, MD, CCFPIEM ), MScCH( HPTE)

Emergence Physician , University Health Network and Trillium Health Partners Assistant Professor, Department of Family and Community Medicine, University of Toronto

.

Kaif Pardhan, BSc MD MMEd FRCPC Emergency Physician

Tyler Groves, MSc MBBS, FRCPC Department of Paediatrics, Michael Garron Hospital

Children’s Hospital

Giuseppe ( Joey ) Latino MD, FRCPC Department ot Paediatrics Division of Genetics, Department of Medicine North York General Hospital

Sunnybrook Health Sciences Centre & McMaster FAMILY MEDICINE Ruby Alvi, MD, CCFP, MHSc FCFP

Department of Family and Community Medicine University of Toronto Chung Kit ( Jacks ) Lai. MD, CCFP Department of Family and Community Medicine Royal Victoria Regional Health Centre University' of Toronto Chase Everett McMurren, BA, BEd, MD, CCFP Department of Family and Community Medicine

University of Toronto Rachel Walsh , MD, MSc, CCFP Department of Family and Community Medicine Sunnybrook Health Sciences Centre University' of Toronto MEDICAL GENETICS Vanda McNiven, MD, MSc, FRCPC

Division of Clinical Genetics and Metabolics & Division of Hematology and Oncology Departments of Paediatrics and Medicine The Hospital for Sick Children, The University Health Network, and Mount Sinai Hospital Graeme AM Nimmo, MBBS, MSc, FRCPC, FCCMG The Fred A Litwin Family Centre in Genetic Medicine, Department of Medicine Mount Sinai Hospital and University Health Network MEDICAL IMAGING Andrew Brown, MD, MBA, FRCPC Assistant Professor Vascular and Interventional Radiology Department of Medical Imaging Unity Health Toronto - SL Michaels Hospital

.

Beniamin Fine, SM MD, FRCPC Clinician Scientist, Medical Imaging Trillium Health Partners, University of Toronto Kieran Murphy, MB, FRCPC, FSIR

Interventional Neuroradiology, Professor of Medical Imaging

Ciara O’Brien , MB BCh BAO (MD ), FFR RCSI Staff Radiologist, Abdominal Division Joint Department of Medical Imaging University I Iealth Network, Ml Sinai 1 Iospital, Womens College Hospital Assistant Professor, Department of Medical Imaging, ' " University' of Toronto ‘

Anastasia Oikonomou, MD, PhD, FRCPC Associate Professor, University of Toronto Division of Cardiothoradc Imaging, Department of Medical Imaging, ~

Sunnybrook Health Sciences Centre

PAEDIATRICS Tanvi Agarwal, MD, FRCPC MScCH (c) Division of Paediatric Medicine

Department of Paediatrics The Hospital for Sick Children

Jillian Baker, MD, MSc, FRCPC Assistant Professor of Pediatrics, University of Toronto Divisions of Pediatrics and Hematology/Oncologv Department of Pediatrics, Unity Health Toronto (St Michaels Hospital ) & The Hospital for Sick Children

.

.

Laila Premji, MD FRCPC Division ol Paediatric Medicine, Department of Paediatrics The Hospital for Sick Children Shazeen Suleman MSc, MD, MPH ( FRCPC ! Women and Childrens Health SL Michael s HospitaL Unity Health Toronto

Janaki Vallipuram, MD. FRCPC

Division of Paediatric Medicine, Department of Paediatrics The Hospital for Sick Children, Markham Stouffville Hospital

PALLIATIVE MEDICINE Risa Bordman, MD, CCFP( PC ), FCFP Associate Professor Faculty Development Program Lead,

Office of Education Scholarship Department of Family & Community Medicine Adam Rapoport, MD, FRCPC, MHSc Departments of Paediatrics and Family & Community Medicine, University of Toronto Paediatric Advanced Care Team, SickKids Emily’s House Childrens Hospice

Donna Spaner, MD, CCFP( PC), FCFP, MScCH Division of Palliative Care, Department of Family and Community Medicine Toronto Grace Health Centre PSYCHIATRY

Saulo Castel, MD, PhD, FRCPC Director, Inpatient Services Sunnybrook Health Sciences Centre

Assisiant Professor Department of Psychiatry

Tamara Milovic, MD, MBA, FRCPC Psychiatrist, Centre for Addiction and Mental Health Lecturer, Department ot Psychiatry, University ot Toronto '

Jerome Perera, MD, FRCPC Psychiatrist, North York General I Iospital Clinician Teacher Department of Psychiatry,

.

University of Toronto

liana Shawn, MD FRCPC Department of Psychiatry, Sc Michael's 1Iospital Assistant Professor Department of Psychiatry PUBLIC HEALTH AND PREVENTIVE MEDICINE

Jason J Pennington. MD, MSc, FRCSC Division of General Surgery, Department of Surgery, Scarborough Health Network Assistant Professor, Department of Surgery', University' of Toronto

rT LJ

Andrew Pinto, BSc, MD, CCFP, FRCPC, MSc

Department of Family and Community Medicine, SL Michaels Hospital

Department of Family and Community Medicine University of Toronto Dalla Lana School of Public 1 Iealth , University'of Toronto

+

Toronto Notes 2023

9 Editorial

Faculty Contributors, University of Toronto MEDICINE CARDIOLOGY AND CARDIAC SURGERY Paul Dorian, MD, MSc, FRCPC

Division of Cardiology St. Michael 's Hospital

Thiru Yogaparan, MD, FRCP Division of Geriatric Medicine, Department of Medicine, Baycrest I lealth Sciences HEMATOLOGY

Douglas 1. Ing, MD, FRCPC, FACC Division of Cardiology Toronto General Hospital Bobby Yanagawa, MD, PhD, FRCSC Division of Cardiac Surgery St Michael 's Hospital ENDOCRINOLOGY

Angela Assal, MD, MHSc, FRCPC Division of Endocrinology and Metabolism, Department of Medicine Sunnybrook Health Sciences Centre University of Toronto

Jeremy Gilbert, MD, FRCPC Division of Endocrinology and Metabolism Sunnybrook Health Sciences Centre Adrian Lau, MD, MScCH, FRCPC Division of Endocrinology and Metabolism Department of Medicine Women’s College Hospital University of Toronto

Alireza Zahirieh, MD, FRCPC Division of Nephrology, Department of Medicine Sunnybrook I lealth Sciences Centre NEUROLOGY

.

Matthew Cheung, MD FRCPC Division of Medical Oncology and 1lematology Department of Medicine Sunnybrook Health Sciences Centre

.

Lisa Chodirker, MD, FRCPC Division of Medical Oncology and Hematology, Department of Medicine Sunnybrook Health Sciences Centre

Charles D. Kassardjian, MD, MSc, FRCPC Division of Neurology, Department of Medicine St. Michael's Hospital

Alexandra MucciUi, MD, MEd, FRCPC Division of Neurology, Department of Medicine SL Michaels Hospital Liza Pulcine, MD, MSc, FRCPC Assistant Prolessor, Fellowship Director

Helena Dhamko. MD, FRCPC MScCH Division of Hematology. E>epartment of Medicine University Health Network

Children's Stroke Program Division of Neurology, Department of Paediatrics, The Hospital for Sick Children

Zachary Liederman, MD, FRCPC MScCH Division of Hematology, Department of Medicine Universitv Health Network

RESPIROLOGY

Samir Gupta, MD, FRCPC Division ofRespirology Department of Medicine

Unity Health Toronto Michael Scott, MD, FRCPC Clinical Hematologist; Adjunct Lecturer, Division of Medical Oncology and HematologyDepartment of Medicine, Unity Health Toronto, SL Michael's Hospital

Ambrose Lau, MD, MEd, FRCPC Division ofRespirology, Department of Medicine University Health Network and Unity Health Toronto Assistant Professor, University of Toronto

Martina Trinkaus, MD, FRCPC

Maria Wolfs, MD MHSc FRCPC Division of Endocrinology and Metabolism St. Michael 's Hospital GASTROENTEROLOGY Maria Cino, BSc( Hon ), Hon BSc, MSc, MD,

FRCPC CAGF Division of Gastroenterology, Department of Medicine University Health Network - Toronto Western Site Associate Professor, University of Toronto Flavio Habal, MD,PhD,FRCP,FAGA Division of Gastroenterology University Health Network, Toronto Western Division Associate Professor, University of Toronto Piero Tartaro, MD, MScCl I , FRCPC Division of Gastroenterology, Department of Medicine Sunnybrook Health Sciences Centre

Division of Hematology, E>epartment of Medicine SL Michael's Hospital INFECTIOUS DISEASES Andrea K. Boggild, BSc, MSc, MD, DTMH,

FRCPC Tropical Disease Unit, Toronto General Hospital Division of Infectious Diseases, University Health Network Department of Medicine, University of Toronto Institute of Medical Science, University of Toronto

-

.

.

Paul L Bunce, BSc MA. MD FRCPC Division of Infectious Diseases Department of Medicine University Health Network

Susan M. Poutancn, MD. MPH, FRCPC

Department of Microbiology, University Health Network & Sinai Health Division of Infectious Diseases, Department of Medicine University Health Network & Mount Sinai Hospital

GERIATRIC MEDICINE

Jillian .Alston, MD, FRCPC, MScCH Division of Geriatrics Department of Medicine St. Michael's Hospital

Vicky Chau, MD, MScCH, FRCPC Division of Geriatric Medicine, Department of Medicine Sinai Health System & University Health Network

NEPHROLOGY Damien Noone MB BCh BAO, MSc

.

Christopher Li, MD, FRCPC, DABSM Division ofRespirology; Department of Medicine Unity Health Toronto - SL Michael’s RHEUMATOLOGY Ahmed Omar, MBBCh, MRCP, MSc Assistant Professor, University of Toronto

Division of Rheumatology, Department of Medicine Mount Sinai Hospital, University Health Network Arthur Bookman, MD, FRCPC Division of Rheumatology, Department of Medicine University 1 lealth Network

.

SahilKoppikar MD FRCPC Assistant Professor, Division of Rheumatology Department of Medicine, Women's College I lospital

Dharini Mahendira, MD, FRCPC, MScCH Assistant Professor, Division of Rheumatology Department of Medicine, St. Michael 's Hospital

-

Medha L. Soowamber, MD, MSc, FRCPC Division of Rheumatology, Department of Medicine Mount Sinai Hospital

ri

Division of Paediatric Nephrology, Department of Paediatrics The Hospital tor Sick Children

LJ

Gemini Tanna, MD, FRCPC Division of Nephrology, Department of Medicine Sunnybrook Health Sciences Centre

+

AL GRAWANY

Toronto Notes 2023

10 Editorial

Faculty Contributors, University of Toronto SURGERY GENERAL AND THORACIC SURGERY Abdollah Behzadi, MD, MBA, ERCSC FACS Division of Thoracic Surgery, Department of Surgery

Trillium Health Partners, University of Toronto Sayf Gazala, MD. MSc, FRCSC Assistant Professor, Thoracic Surgery Department of Surgery; Michael Garron Hospital

Jesse Pasternak, MD, MPH, FRCSC Section of Endocrine SurgeryDivision of General Surgery, Department of Surgery University Health Network

Fayez Quereshy, MD, MBA, FRCSC Department of General Surgery University Health Network Toronto Western Hospital

Melissa Walker, MD, MSc, ERCSC Staff Obstetrician Gynecologist, Department of Obstetrics & Gynecology, Mount Sinai Hospital Assistant Professor, Department of Obstetrics & Gynecology; University of Toronto OPHTHALMOLOGY

Asiin Ali, MD, FRCSC Professor of Ophthalmology, University of Toronto Ophthalmologist-in-Chief, The Hospital for Sick Children

Siba Haykal, MD, PhD, FRCSC, FACS Division of Plastic and Reconstructive Surgery,

Department of Surgery University' Health Network Monica Farcas, BEng, MEng, MD, FRCSC Assistant Professor, Division of Urology Department of Surgery, Unity I Iealth Toronto Yonah Krakowsky, MD, FRCSC Division of Urology Womens College & Mount Sinai Hospital

Jonathan Micicli, MD, FRCSC

GYNAECOLOGY Michael Chaikof MD, FRCSC, MS-HPEd Division of Urogynecology

Department of Ophthalmology and Vision Sciences; Division of Neurology; Department of Medicine; Kensington Vision and Research Centre, St. Michaels Hospital, University of Toronto

Department of OBGYN Sunnybrook Health Sciences Centre

ORTHOPAEDIC SURGERY

.

Department of Surgery The Hospital for Sick Children

UROLOGY

Wai-Ching Lam, MD, FRCSC Department of Ophthalmology and Vision Science University Health Network,

Toronto Western Hospital The Hospital for Sick Children

.

PLASTIC SURGERY Joel Fish, MD, MSC, FRCS Professor, Plastic and Reconstructive Surgery

.

Jason Lee, MD MHPE, FRCSC Division of Urology; Department of Surgery University Health Network Toronto General Hospital

.

Jeremy Hall, MD, FRCSC Division of Orthopaedic Surgery, Department of Surgery; St. Michaels Hospital

Michael Ordon, MD, MSc, FRCSC Division of Urology; Department of Surgery SL Michael’s Hospital VASCULAR SURGERY

NEUROSURGERY

Paul Kuzyk, MD, MASc, FRCSC Assistant Professor Lower Extremity' Reconstruction Surgery Division of Orthopaedic Surgery

Sunit Das, MD, PhD Division of Neurosurgery

Jesse Wolfstadt, MD, MSc, FRCSC

Sari Kives, MD, FRCSC Associate Professor Division of Obstetrics and Gynecology Department of Obstetrics and Gynecology

-

St Michaels hospital

-

St. Michaels Hospital

.

Michael G. Fehlings, MD PhD, FRCSC, FACS Professor of Neurosurgery; Department of Surgery; University ofToronto Vice Chair Research, Department of Surgery; University of Toronto Senior Scientist, Krembil Brain Institute, University Health Network Staff Neurosurgeon, University Health Network Co-Director, University of Toronto Spine Program

-

Eric M. Massicotte MIX MSc, MBA, FRCSC Associate Professor University of Toronto

Staff Neurosurgeon, University Health Network Medical Director, Back & Neck Program Altum Health OBSTETRICS

.

Granovsky Gluskin Division of Orthopaedic Surgery, Department of Surgery, Sinai 1 Iealth Sy stem

Elisa Greco, BSc, MEd, MD, RPYI, FRCSC Vascular Surgeon, St Michaels Hospital

George Oreopoulos, MD, MSc, FRCSC Division of Vascular Surgery, Department of Surgery University Health Network

OTOLARYNGOLOGY Yvonne Chan , MD, MSc, FRCSC Otolaryngologist in chief, St. Michael’s Hospital, Unity Health Associate Professor and Continuing Professional Development Director

--

Department of Otolaryngology Head & Neck Surgery Antoine Eskandcr, MD, ScM, FRCSC Assistant Professor

Department of Otolaryngology I lead & Neck Surgery Sunnybrook Health Sciences Centre, Odette Cancer Centre Michael Garron Hospital

Richard Pittini, MD, MEd FRCSC, FAC.OG

Department of Obstetrics and Gynecology; University of Toronto Sunnybrook I Iealth Sciences Centre Mara Sobel, MD, MSc. FRCSC Department of Obstetrics and Gynecology; University- of Toronto Mount Sinai Hospital University Health Network, Toronto General Hospital, Womens College Hospital

Jonathan Irish, MD, MSc, FRCSC Department of Otolaryngology, l lead and Neck Surgery, University Health Network

+

Toronto Notes 2023

11 Editorial

Table of Contents Index Abbreviations

Common Acronyms and Abbreviations Used in Medicine Common Unit Conversions Commonly Measured Laboratory Values

Ethical, Legal, and Organizational Medicine

ELOM

Anesthesia

A

Cardiology and Cardiac Surgery

.

C

Clinical Pharmacology

CP

Dermatology

D

Emergency Medicine

ER

Endocrinology

E

Family Medicine

FM

Gastroenterology

G

General and Thoracic Surgery

..

GS

Geriatric Medicine

GM

Gynaecology

GY

Hematology

H

Infectious Diseases

ID

Medical Genetics

MG

Medical Imaging

Ml

Nephrology

NP

Neurology

N

Neurosurgery

...

NS

Obstetrics

OB

Ophthalmology

OP

Orthopaedic Surgery

OR

Otolaryngology

OT

Paediatrics

P

Palliative Medicine

PM

Plastic Surgery

PL

Psychiatry

PS

Public Health and Preventive Medicine

PH

Respirology

R

Rheumatology .

.

RH

Urology

U

Vascular Surgery

VS

AL GRAWANY

ri LJ

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Toronto Notes 2023

12 Editorial

How To Use This Book This book has been designed to remain as one book or to be taken apart into smaller booklets. Identify the beginning and end of a particular section, then carefully bend the pages along the perforated line next to the spine of the book. Then tear the pages out along the perforation.

The layout of Toronto Notes allows easy identification of important information. These items are indicated by icons interspersed throughout the text: Icon

Icon Name

Significance

Key Objectives

This icon is found next to headings in the text. It identities key objectives and conditions as determined by the Medical Council of Canada or the National Board of Medical Examiners in the USA. If it appears beside a dark title bar, all subsequent subheadings should be considered key topics.

Clinical Pearl

This icon is found in sidebars of the text. It identifies concise, important information which will aid in the diagnosis or management of conditions discussed in the accompanying text.

S

Memory Aid

(§)

Wi

EH S

This icon is found in sidebars of the text. It identifies helpful mnemonic devices and other memory aids.

Clinical Flag

This icon is found in sidebars of the text. It indicates information or findings that require urgent management or specialist referral.

Evidence Based Medicine

This icon is found in sidebars of the text. It identifies key research studies for evidencebased clinical decision making related to topics discussed in the accompanying text.

Colour Photo Atlas

This icon is found next to headings in the text. It indicates topics that correspond with images found in the Colour Photo Atlas available online (www.torontonotes.ca).

Radiology Atlas

This icon is found next to headings in the text. It indicates topics that correspond to images found in the Radiology Atlas available online ( www.torontonotes.ca).

Online Resources

This icon is found next to headings in the text. It indicates topics that correspond with electronic resources such as Functional Neuroanatomy or ECGs Made Simple, available online ( www.torontonotes.ca).

Chapter Divisions To aid in studying and finding relevant material quickly, many chapters incorporate the following general framework: Basic Anatomy/ Physiology Review • features the high - yield , salient background information students are often assumed to have remembered from their early medical school

education

Common Differential Diagnoses • aims to outline a clinically useful framework to tackle the common presentations and problems faced in the area of expertise

Diagnoses

• the bulk of the book •

etiology, epidemiology, pathophysiology, clinical features , investigations , management, complications, and prognosis

r “i

LJ

Common Medications

• a quick reference section for review of medications commonly prescribed

+

Toronto Notes 2023

13 Editorial

Common Acronyms and Abbreviations Used in

Medicine The following are common medical acronyms/abbreviations that may be used without definition throughout the Toronto Notes text. These are typically not included in the acronym list at the beginning of each chapter. Please refer back to this list for definitions.

concentration

ECC,

p - hCG

beta human chorionic gonadotropin

ABx

antibiotics

ACE ACTH AIDS ALP ALT AR ASA AST aSx

angiotensin -converting enzyme Adrenocorticotropic hormone acquired immune deficiency syndrome alkaline phosphatase alanine aminotransferase absolute risk acetylsalicylic acid aspartate transaminase asymptomatic

ED EEC EMC ENT

AXR

abdominal x - ray

BID BMI BP BPM/ bpm

twice a day ( bis in die ) body mass index blood pressure beats per minute

C/I C&S CAD CBC CC CHF COPD CPR Cr CRH CSF CT CXR

contraindication culture and sensitivity coronary artery disease complete blood count

D&C dBP DDx DM DNR Dx

dilatation and curettage diastolic blood pressure differential diagnosis diabetes mcllitus do not resuscitate diagnosis

U

chief complaint congestive heart failure chronic obstructive pulmonary disease cardiopulmonary resuscitation creatinine corticotropin - releasing hormone

cerebrospinal fluid computed tomography chest x- ray

.

ESR EtOH

FMHx FSH

electrocardiogram emergency department electroencephalography electromyography cars, nose, and throat erythrocyte sedimentation rate cthanol/alcohol

family medical history follicle stimulating hormone

G 6PD GG T GH GHB GI GU

glucosc -6- phosphate dehydrogenase gamma - glutamyl transferase growth hormone gamma hydroxybutyrate gastrointestinal genitourinary

Hb HIV HR HTN Hx

hemoglobin human immunodeficiency disease heart rate hypertension history

I& D

incision and drainage intracranial pressure intensive care unit intramuscular

.

ICP ICU IM IV

intravenous

JVP

jugular venous pressure

LDH

lactate dehydrogenase liver function test luteinizing hormone likelihood ratio

LFT LH LR

r

+

AL GRAWANY

Toronto Notes 2023

H Editorial

Common Acronyms and Abbreviations Used in

Medicine MAO MAOI MDI MI MRI MSK

monoamine oxidase monoamine oxidase inhibitor

N/ V

nausea/vomiting nasogastric N - Mcthyl - D -aspartate

NG NMDA NPO NSAID

metered -dose inhaler myocardial infarction magnetic resonance imaging musculoskeletal

nothing by mouth ( nil per os ) non -steroidal anti - inflammatory drug

sBP SC SL SLE SOB STAT STI Sx

systolic blood pressure subcutaneous sublingual systemic lupus erythematosus shortness of breath urgent or immediately ( statum ) sexually transmitted infection

TlDM T2 DM

type 1 diabetes mellitus type 2 diabetes mellitus

TB TID

OR OTC

operating room over-die-counter

TNM TRH TSH

PCR PE PMHx

polymerase chain reaction pulmonary embolism past medical history oral administration ( per os ) point -of -care ultrasound proton pump inhibitor as needed ( pro re nata )

Tx

PO POCUS PPI

PRN QID

four times a day (quatcr in die)

RBC RCT

red blood cell randomized controlled trial review of symptoms medical prescription

ROS Rx

symptom (s)

tuberculosis three times a day ( ter in die) tumour, nodes, and metastases thyroid releasing hormone thyroid stimulating hormone treatment

urinalysis

U/A U/S UTI UTox

urinary tract infection urine toxicology screen

VDRL

Venereal Disease Research Laboratory test

WBC

white blood cell

wt

weight

ultrasound

pi

+

Toronto Notes 2023

15 Editorial

Common Unit Conversions To convert from the conventional unit to the SI unit, multiply by conversion factor To convert from the SI unit to the conventional unit, divide by conversion factor

Conventional Unit

Conversion Factor

SI Unit

ACTH

pg/mL

0.22

pmol/L

Albumin

g/dL

10

g/L

Bilirubin

mg /dL

17.1

pmol/ L

Calcium

mg /dL

0.25

mmol/L

Cholesterol

mg/dL

0.0259

mmol/L

Cortisol

pg /dL

27.59

nmol/L

Creatinine

mg /dL

88.4

pmol/ L

Creatinine clearance

mL/min

0.0167

mL/s

Ethanol

mg/dL

0.217

mmol/L

Ferritin

ng/mL

2.247

pmol/L

Glucose

mg /dL

0.0555

mmol/L

HbA1c

%

0.01

proportion of 1.0

Hemaglobin

g/dL

10

g /L

HDL cholesterol

mg/dL

0.0259

mmol/L

Iron, total

pg /dL

0.179

pmol/L

Lactate (lactic acid)

mg /dL

0.111

mmol/L

LDL cholesterol

mg/dL

0.0259

mmol/L

Leukocytes

x lO ells/mm

1

x 109cells/L

Magnesium

mg /dL

0.411

mmol/L

MCV

pm3

1

fL

Platelets

x lO ells/mm

1

x 109cells/L

Reticulocytes

% of RBCs

0.01

proportion of 1.0

Salicylate

mg /L

0.00724

mmol/L

Testosterone

ng /dL

0.0347

nmol/ L

Thyroxine (T 4)

ng/dL

12.87

pmol/L

Total Iron Binding Capacity

pg /dL

0.179

pmol/L

Triiodothyronine (T3)

pg/dL

0.0154

pmol/L

Triglycerides

mg /dL

0.0113

mmol/L

Urea nitrogen

mg/dL

0.357

mmol/L

Uric acid

mg/dL

59.48

pmol/L

Celsius •* Fahrenheit

F = (C x 1.8) + 32

r

Fahrenheit

C = (F - 32) x 0.5555

LJ

^ ^

Celsius

Kilograms •* Pounds

Pounds

Ounces

3

3

1 kg = 2.2 lbs

1 lb = 16 oz

Ounces •* Grams

1 oz = 28.3 g

Inches •* Centimetres

1 in = 2.54 cm

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Toronto Notes 2023

16 Editorial

Commonly Measured Laboratory Values Test

Conventional Units

SI Units

7.35 -7.45 35 -45 mmHg 80-105 mmHg

7.35 -7.45 4.7 6.0 kPa 10.6 -14 kPa

Arterial Blood Gases pH PC02 PO 2

-

Serum Electrolytes

-

95 -106 mmol/ L

22 28 mEq/L 8.4-10.2 mg/dL 95 -106 mEq/ L 1.3 -2.1 mEq/L 27-4.5 mg /dL 3.5 - 5.0 mEq /L 136 -145 mEq /L

0.65-1.05 mmol/L 0.87-1.45 mmol/L 3.5- 5.0 mmol/L 136-145 mmol/ L

3.5 - 5.0 g/dL 35 -100 U/ L 8 - 20 U/L 25 125 U /L 8 - 20 U/L 0-0.3 mg /dL 0.1-1.0 mg/dL 7-18 mg/dL 3) Obstruction stridor, foreign bodies

-

Physical Exam • weight, height, BP, HR, respiratory rate, and Oa saturation • focused physical exam of the CNS, CVS, and respiratory systems • general assessment of nutrition, hydration, and mental status • airway assessment is done to determine intubation difficulty ( no single test is specific or sensitive) and ventilation difficulty cervical spine stability and neck movement - upper cervical spine extension, lower cervical spine flexion (“sniffing” position - see Figure 6C, A8 ) Mallampati classification (see Figure 1 ) “3-3-2 rule’(see Figure 2 ) 3 of patient s own fingers can be placed between the incisors ( incisor distance) 3 fingers along the floor of the mandible between the mentum and hyoid bone ( hyoid-mental distance) 2 fingers in the superior laryngeal notch (thyroid -hyoid distance) thvromental distance ( distance from the mentum to the thyroid notch in midline with neck extended ); «

u

Aryepiglottic •::

-

90%

• small decrease in saturation below SaO’ of 90% corresponds to a large drop in PaO’ • in intubated patients, O ’ is delivered via the ETT • in patients not intubated, there are many O: delivery systems available; the choice depends on O’

requirements ( FiO’) and the degree to which precise control of delivery is needed • cyanosis can be detected at Sa02 10% of blood volume is lost children have a high HR and low BP • CO is dependent on HR , not SV because of low heart wall compliance ) therefore, bradycardia severely compromises CO

.

Temperature Regulation

• vulnerable to hypothermia • minimize heat loss by use of warming blankets, covering the infant’s head , humidification of inspired gases, and warming of infused solutions Central Nervous System • MAC of halothane is increased compared to the adult (0.75% adult, 1.2% infant, 0.87% neonate) • NM ) is immature for the first 4 wk of life, and thus, there is an increased sensitivity to non -

depolarizing relaxants

-

• parasympathetics mature at birth , sympathetics mature at 4 6 mo; thus, there is an autonomic

imbalance • infant brain is 12% of body weight and receives 34% of CO (adult: 2% body weight and 14% CO) Glucose Maintenance

• infants < 1 yr can become seriously hypoglycemic during preoperative fasting and postoperatively if feeding is not recommenced as soon as possible • after 1 yr, children are able to maintain normal glucose homeostasis in excess of 8 h Pharmacology • higher dose requirements because of higher TBW ( 75% vs 60% in adults) and greater volume of

distribution

pharynx

.

• barbiturates/opioids more potent due to greater permeability of BBB

Thyroid cartilage

JfA

Cricoid cartilage —+3 Trachea

((

IgbodyCB ^

Vertebral

T0

© Nicole Clough 2014

Child Upper Airway

I

|

i i

o

£ M

I. Large head 2 Newborns are obligate nasal breathers 3. Adenoid and tonsils 4. Larger tongue in proportion to mouth 5. Smaller pharynx 6 Larger and more flaccid epiglottis 7. Larynx is more superior and anterior 8 Narrowest point at cricoid cartilage 9. Trachea Is more narrow and less rigid

Figure 18. Comparison of paediatric vs. adult airway

+

Toronto Notes 2023

A 29 Anesthesia

• muscle relaxants • non-depolarizing

immature NM ), variable response depolarizing must pre - treat with atropine or may experience profound bradycardia and /or sinus node arrest due to PNS > SNS (also dries oral secretions) more susceptible to arrhythmias, hyperkalemia , rhabdomyolysis, myoglobinemia, masseter spasm, and malignant hyperthermia

Uncommon Complications

ETT Siring in Paediatrics Diameter (mm) of tracheal tube in children after 1 year - (age/4) 4 length (cm) of tracheal tube - (age/ 2 ) * 12

See landmark Anesthesiology trials table lor more information on a study by Su n et a I.. 2016 which details tbe association between a single general anesthesia exposure prior age 3G months and

.

neurocognitive outcomes in later childhood.

Malignant Hyperthermia •hypermetabolic disorder of skeletal muscle •due to an uncontrolled increase in intracellular Ca 2 39°C lavage open body cavities, stomach, bladder, rectum; apply ice to surface; infuse cold saline IV • stop cooling if temperature is 50%, or maximum dose 17 rngfkg given Maintenance infusion: 1 4 mg/min Avoid if prolonged QT or CHF

.

Consider • Adenosine only if regular and monomorphic • Antiarrhythmic infusion • Expert consultation

Amiodarone IV Dose: First dose ISO mg over 10 min Repeat as needed if VT recurs Follow by maintenance infusion of 1 mg/mm for first 6 h

No If refractory, consider

7 • Vagal maneuvers • Adenosine (il regular ) • (JBIocker or calcium channel

• Underlying cause

• Need to increase energy

level for next cardioversion

blocker

• Addition of anti-arrhythmic drug • Expert consultation

• Consider expert consultation

Figure 22. Adult tachycardia with a pulse algorithm Reprinted with permission: ACLS Provider Manual. Copyright

Sofalol IV Dose : 100 mgll Smgi’kgl over 5 min Avoid if prolonged QT


120 msec Broad notched R naves In leads I. aVl. VS, and V6 Deep broad S waves in leads VI-2 Secondary SI T changes|- ve in leads with broad notched R waves -*ve in VI -2) are usually present IBBB can mask ECG signs of Ml IBBB: lead VI negative V6 positive and notched

ORS duration >120 msec Positive ORS in lead V1 ( rSR ' or occasionally broad R wave ) Broad S waves in leads I. V5 6 ( 40 msec) Usually secondary I wave inversion in leads V1- 2 Frontal axis determination using only the first GO msec RBBB: VI is positive ( rSR 'l, V6 has broad S wave

.

-

.

Left Anterior Fascicular Block ( LAFB ) (Left Anterior Hemiblock )

-

- -

Left Posterior Fascicular Block ( LPFB ) ( Left Posterior Hemiblock )

Figure 7. Axial reference system Each lead contains a ( * ) area displayed by the bold arrows Impulses traveling toward the positive region of the lead result in an upward deflection in that lead. Normal QRS axis is between -30° and < 90°

.

Left Bundle Branch Block

Bifascicular Block

-

RBBB Pattern Right Axis Deviation (110° to 180° ) left Axis Deviation ( 30 ° to 90*| Small 0 and prominent R in leads I and aVl Small R and prominent S in leads I and aVl Small 0 and prominent R Small R and prominent S in leads II. III. and aVF Small 0 and prominent R in leads II. III and aVF The lirsl 60 msec (1.S small squares) of the ORS shows the pattern of LAFB or LPFB Bifascicular block refers to impaired conduction in two ol the three fascicles, most commonly a RBBB and left anterior hemiblock : the appearance on an ECG meets the criteria for both types of blocks

V5

VI

r*

.

.

-

Additional criteria IV strain pattern (asymmetric SI depression and I wave inversion in leads I. aVL. and V 4 V6) Left atrial enlargement N . B. The greater the number of criteria , the more likely the diagnosis is IVH . II only one voltage criteria present , it is called minimal voltage criteria lor IVH ( may be a normal varianl )

V5

VI

Nonspecific Intraventricular Block • QRS duration >120 msec • absence of definitive criteria for LBBB or RBBB Table 2. Hypertrophy/Chamber Enlargement Lett Ventricular Hypertrophy S in Vt * R in V5 or V6 >3S mm above age 40 ( »40 mm tor age 31 - 40. »45 mm for age 21 30) RinaVL »11 mm Rini -* Sin III > 25 mm

Right Bundle Branch Block

Right Ventricular Hypertrophy Right axis deviation

R /S ratio »1 or qR in lead Vt RV strain pattern: SI segment depression and I wave inversion in leads

-

VI 2

Left Ventricular

Hypertrophy V5

VI

-

left Atrial Enlargement

Right Atrial Enlargement

Brphasic P wave with the negative terminal component of the P wave in lead V1 »1 mm wide and »1 mm deep P wave »100 msec, could be notched in lead II ( "P mitrale")

P wave »2.5 mm in height in leads il. Ill, or aVf (“ P pulmonale ” )

Right Vontricular Hypertrophy

r

l

I

l

I© .

.

Figure 8 Complete LBBB RBBB, LVH, and RVH ( please see online examples for the full range of waveforms and the text for additional characteristics)

+

Toronto Notes 2023

C9 Cardiology and Cardiac Surgery

ISCHEMIA/INFARCTION

• look for the anatomic distribution of the following ECG abnormalities (see Table 3 ) • ischemia ST segment depression T wave inversion (most commonly in V1-V6) injury/infarct transmural (involving the epicardium ) ST elevation in the leads facing the injured / infarcted area subendocardial - marked ST depression in the leads facing the affected area may be accompanied by enzyme changes and other signs of Ml

• •

"

LEAD II

It - . -

-

T

"

Left Atrial Enlargement

I

'

Acute days ( avg. 3-5 hours)

r

Right Atrial Enlargement

LEAD II

Vfv

1

y

Recent weeks-months

Old months-ycars ( avg. >6 months) Persistent Qs

T wave inversion

ST segment elevation

J

L

VI

J

I

Figure 10. LAE, RAE ( please see online examples and the text for characteristics)

Figure 9. Typical ECG changes with infarction Note that 0 waves may gradually appear over time (not shown here)

• ST elevation

new ST elevation in two contiguous leads of >0.1 mV (in all leads other than leads V 2-V3) for leads V 2-V 3: £0.2 mV in men £40 yr, £0.25 mV in men T ) enhances the toxic effects of digitalis

+

Toronto Notes 2023

CIO Cardiology and Cardiac Surgery'

• hypercalcemia • shortened QT interval ( more extracellular Ca ' means shorter plateau in cardiac action potential )

-

• hypocalcemia

• prolonged QT interval (less extracellular Ca 2+means longer plateau in cardiac action potential ) 1

T wave

-4A I

K

Figure 11. Hyperkalemia

L-

J

I Uwave

U/V

Figure 12. Hypokalemia

Hypothermia • sinus bradycardia severe, prolonged QRS and QT intervals • when • Al;ib with slow ventricular response and other atrial / ventricular dysrhythmias • Osborne ) waves: “ hump-like” waves at the junction of the|point and the ST segment Pericarditis • early: diffuse ST segment elevation ± PR segment depression, upright T waves • later: isoelectric ST segment, flat or inverted T waves

Figure 13. Osborne J waves of a hypothermic patient

• ± tachycardia

Drug Effects • digitalis ( cardiac glycoside ) poisoning rare in 2021; 100/ min ) )

• normal QTc is 360- 450 msec for males and 360 - 460 msec for females • increased (> 450 msec for males and >460 msec for females ): risk of Torsades de Pointes ( lethal

•

tachyarrhythmia; rare if 1 mm ) in leads without diagnostic Q waves (other than VI oraVR ) * increasing nervous system symptoms (e.g. ataxia, dizziness, or near syncope ) signs of poor perfusion (cyanosis or pallor) technical difficulties in monitoring ECG or sBF

• • risks

-

Most Commonly Used Treadmill Stress Test Protocols • The Bruce Protocol: 7 stage test with each stage lasting 3 min. With each successive stage, the treadmill increases In both speed (2.7 km/h to 9.6 km/h ) and grade (10% with a 2% increase per stage up to 22%) The Modified Bruce Modified Naughton Protocol: for older individuals or those with limited exercise capacity

.

.

Important Contraindications to Exercise Testing • Acute Ml aortic dissection pericarditis, myocarditis, PE

.

. Severe ASto.exerciseHTN

.

arterial

adequately

• Inability

Important Prognostic Factor Duke Treadmill Score ( DTS) Weighted Index Score Treadmill exercise time using standard Bruce protocol • Maximum net ST segment deviation (depression or elevation ) • Exercise induced angina provides diagnostic and prognostic information (such as 1 yr mortality) DTS •exercise time (5 x MaxST) (4 x angina index ) Angina index: 0 ( no angina), 1 (angina but not exercise limiting), 2 (exercise limiting angina ) DTS z5: 0.25% 1 yr mortality DTS 4 to 10:1.25%1 yr mortality DTS < 11: 5.25% 1 yr mortality

.

-

-

-

-

-

-

-

-

Aim Mem Med 1987:106:193 800

• sustained VT

death, Ml, arrhythmia, hemodynamic instability, and orthopaedic injury (< 1-5/10000 superv ised tests)

LJ

Patients with normal imaging ( nuclear perfusion or stress echo) studies at peak stress have a 50% stenosis • contraindications: allergy to contrast dye; severe renal dysfunction; irregular heart rhythm or

tachycardia which may impact image quality • risks: radiation exposure; and contrast induced nephropathy

Magnetic Resonance Imaging • description

offers high spatial resolution, eliminates the need for iodinated contrast, and does not involve exposure to ionizing radiation often used with gadolinium injection to assess myocardial scar

n LJ

• indications

valuable in assessment of congenital cardiac anomalies, abnormalities of the aorta, assessment of viable myocardium , and assessment of cardiomyopathies most accurate measure of ejection fraction especially valuable for assessing RV

+

Toronto Notes 2023

C19 Cardiology and Cardiac Surgery • contraindications

metallic foreign bodies/implants (e.g. pacemaker, 1CD, CRT, cerebral aneurysm clips, metal shrapnel, piercings) kidney dysfunction due to gadolinium contrast medium • risks hazards posed by certain metallic devices inside patients

CARDIAC DISEASE

Arrhythmias Mechanisms of Arrhythmias Alterations in Impulse Formation

:
100 bpm ( usually 140 200) ventricular flutter: if rate approximately 300 bpm and monomorphic sinusoidal pattern “sustained VT” if it lasts longer than 30 s or requires termination due to hemodynamic instability FCG characteristics: wide regular QRS tachycardia (QRS usually > 140 msec) AV dissociation, bizarre QRS pattern also favour diagnosis of VT: left axis or right axis deviation , nonspecific intraventricular block pattern, monophasic orbiphasic QRS in VI with RBBB, QRS concordance in V1-V6 occasionally, during VT, supraventricular impulses may be conducted to the ventricles; these impulses generate QRS complexes with normal /aberrant supraventricular morphology ( I.e. “ventricular capture" ) or summation pattern ( i.e. “ fusion complexes") by itself, nonsustained VT (30 s) is an emergency requiring immediate treatment hemodynamic compromise: treat VT with electrical cardioversion and ACLS no hemodynamic compromise: treat VT with electrical cardioversion, amiodarone, Type 1A agents (e.g. procainamide, quinidine ) • every patient with sustained VT/ Vl ih and comorbid structural heart disease, in the absence of reversible causes, should be considered for 1CD implantation to prevent SCD '

s

A

jj;ij

Figure 32. VT (monomorphic)

Table 7. Wide Complex Tachycardia: Clues for Differentiating VT vs. SVT with Aberrancy* Clinical Clues

Arrhythmias that may present as a Wide QRS Tachycardia • VT (this is most common especially in older patients or those with structural heart disease) • SVT with aberrant conduction (rate related) • SVT with preexisting BBB or nonspecific intraventricular conduction defect • AV conduction through a bypass tract in WPW patients during an atrial tachyarrhythmia (e.g . atrial fluttec atrial tachycardia ) • Antidromic AVRT in WPW patients (see Pre-Exatotion Syndromes. C2S )

ECG Clues

,

Presenting symptoms

Not helpful

History of CAD and previous HI

VT

AV dissociabon Capture or fusion beats

Physical exam Cannon “a" waves Variable S1

VI

Carotid sinus massage adenosine terminates arrhythmia

SVT"

VT VT

ORS width »140 msec

VT

Extreme axis deviation (left or right superior axis)

VI

Positive OPS concordance

VI

(P wave across chest leads)

Negative OPS concordance

May suggest VI

(S wave across chest leads)

Axis Shift during arrhythmia

VT (polymorphic)

•If patient >65 yr and previous Ml or structural heart disease, then chance of VT >95*« "May terminate VT in some patients with no structural heart disease

Torsades de Pointes • a variant of polymorphic VT that occurs in patients with baseline QT prolongation “ twisting of the points” • looks like usual VT except QRS complexes “ rotate around the baseline,” changing their axis and

amplitude usually starts following a post extrasystolic pause ( “pause dependent” ) • ventricular rate >100 bpm, usually 150 -300 bpm usual onset after a post-PVC pause associated with “pause dependent" QT prolongation ) • etiology: occurs in association with prolonged QT intervals • congenital long QT syndromes • drugs: e.g. class 1A ( quinidine ), class 111 ( sotalol ) , phenothiazines ( TCAs), erythromycin, quinolones, antihistamines • electrolyte disturbances: hypokalemia, hypomagnesemia • nutritional deficiencies causing above electrolyte abnormalities • treatment: IV magnesium , temporary pacing (5 blocker, correct the underlying cause of prolonged QT • electrical cardioversion and ACLS if hemodynamic compromise •

Figure 33. Torsades de pointes

Ventricular Fibrillation • chaotic ventricular arrhythmia, with very rapid irregular ventricular hbrillatory waves of varying morphology without clear QRS complexes terminal event , unless advanced cardiac life support ( ACLS ) procedures are promptly initiated to • maintain ventilation and CO, and electrical defibrillation is carried out • most frequent cause of sudden death • refer to ACLS algorithm for complete therapeutic guidelines

-

VW\ A A Figure 34. VFib

LJ

55

^

+

Toronto Notes 2023

C28 Cardiology and Cardiac Surgery

Sudden Cardiac Arrest Definition

• cessation of cardiac electrical activity with circulatory collapse ( loss of pulses) and gasping respirations or lack of spontaneous breathing

• patient becomes suddenly unresponsive • presenting rhythms may be PEA , asystole, VFib ( less commonly pulseless VT ) Etiology

• the likelihood of an underlying cardiac cause is proportional to age at time of arrest

• cardiac causes (especially CAD ) are more likely in older adults •

-

non cardiac causes are more likely in children and young adults (< 35 yr )

Table 8. Etiology of Cardiac Arrest myocardial Ischemia

Cardiac Causes SHMI NS1EMI Coronary spasm coronary dissection Anomalous coronary artery

Non- Cardiac Causes Vascular

Pulmonary embolism

Aortic dissection Aortic rupture Stroke

HF Scar

Neurologic

Non-lschemic Cardiomyopathy

Dilated CM Hypertrophic CM Infiltrative CM myocarditis Arrhythmogenic RV CM Hypertensive CM VHD with IVfailure

Hemorrhagic

Subarachnoid Intracranial Gastrointestinal

Valvular Heart Disease

AS MR

Infection

Sepsis Pneumonia

Heritable ion channel disorders

long 01 syndrome Brugada syndrome

Respiratory

Respiratory arrest

Primary Arrhythmogenic

Acquired 01prolongation Idiopathic Complete heart block

Other

Tension pneumothorax Substance overdose Ketoacidosis Trauma

Congenital Heart Disease

Tetralogy olFallot

Ischemic Cardiomyopathy

Sudden unexplained death in

epilepsy Neurogenic

WPW

»1

Post- Surgical scar

Management

• acute: resuscitate according to ACLS guidelines (see Anesthesia , A 32)

resuscitation can be grouped into those with and without shockable rhythms

• activation of emergency systems and high -quality chest compressions are essential for any bystander

• investigate underlying causes using cardiac catheterization , electrophysiologic studies, echocardiography

patients with ST -elevation require emergent coronary angiography and revascularization patients without ST elevation can still have clinically relevant coronary lesionsand therefore benefit from coronary angiography on a non-emergent basis • initiate targeted temperature management to optimize neurologic recovery regardless of presenting

See Urdu it Cardiac Inals for more information on COACT. ninth dethilstte1-yr clinical outcomes ol

atgiogreplty timing on survival in resuscitated cardiac

arrest patients nrithourt SIEMI.

-

rhythm • treat underlying cause • antiarrhythmic drug therapy: amiodarone, lidocaine, p blockers • 1CD for secondary prevention

Electrophysiologic Studies • invasive test for the investigation and treatment of cardiac rhythm disorders using intracardiac catheters • provide detailed analysis of the arrhythmia mechanism and precise site of origin when ECG data are nondiagnostic or unobtainable • bradyarrhythmias: define the mechanisms of SA node dysfunction and localize site of AV conduction block ( rarely performed ) • tachyarrhythmias: map for possible ablation , assess indudbility of VT prior to ICD implant

rn LJ

+

Toronto Notes 2023

C 29 Cardiology and Cardiac Surgery

Electrical Pacing • the decision to implant a pacemaker usually is based on symptoms of a bradvarrhy thmia or tachyarrhythmia with intermittent bradycardia precluding rate limiting medications

Pacemaker Indications •SA node dysfunction ( most common): symptomatic bradycardia ± hemodynamic instability •common manifestations include: syncope, presyncope, or severe fatigue •SA node dysfunction is commonly caused by: intrinsic disease within the SA node (e.g. idiopathic degeneration, librosis, ischemia, or surgical trauma), abnormalities in autonomic nervous system

function, and drug effects

• AV nodal - infranodal block: Mobitz II, complete heart block Pacemaker Complications

•complications related to surgical implantation include venous access ( pneumothorax, hemothorax,

air embolism ), pacemaker leads ( perforation , malposition ), packet hematomas, and infection; rarer complications include venous stenosis or thrombosis, and tricuspid regurgitation •complications specific to the pacemaker include a failure to pace, failure to sense, pulse generator failure, pacemaker syndrome, lead fractures, and pacemaker-mediated tachycardia Pacing Techniques • temporary: transvenous ( jugular, subclavian, femoral ) or external (transcutaneous) pacing • permanent: transvenous into RA, apex of RV, or both •single or dual chamber: can sense and pace atrium , ventricle, or both • rate responsive, able to respond to physiologic demand • biventricular pacing ( cardiac resynchronization therapy ): leads are guided to RV and LV to stimulate

both ventricles

Implantable Cardioverter Defibrillators • SCI) usually results from Vl-ib, sometimes preceded by monomorphic or polymorphic VT

• ICDs detect ventricular tachyarrhythmias and are highly effective in terminating VT/ VFib and in aborting SCD

• mortality benefit vs. antiarrhythmics in secondary prevention and selected patients for primary

prevention

• CRT'- D may' be of benefit in patients with LBBB, prolonged QRS, and LVEF 100 pg/ mL), NT ProBNP ( >300 pg / ml ), uric acid

-

• urinalysis • ECU: look for chamber enlargement, arrhythmia, ischemia / infarction • CXR: cardiomegaly, pleural effusion, redistribution, Kerley B lines, bronchiolar-alveolar culling • echo: systolic function ( LVEP), diastolic function (E /A ratio, E/e’), cardiac dimensions, wall motion abnormalities, RV systolic pressure (from TR jet ), valvular disease, pericardial effusion radionuclide angiography: LVEP • • myocardial perfusion scintigraphy ( thallium or sestamibi SPE(.T )

Additional Diagnostic Investigations

• cardiac catheterization • cardiopulmonary' exercise testing other tests (CMR, MPI, MUGA, CT scan )

.

wave)

Anemia Rheumatic heart disease and other valvular disease Thyrotoxicosis Failure to take medications (very common) Arrhythmia (common) Infection/Ischemia/Infarction (common) Lung problems (PE. pneumonia COPD) Endocrine (pheochromocytoma hypcraldosteronism) Dietary indiscretions (common)

.

-

-

-

-

HEART FAILED HTN (common) Endocarditis/environment (e.g. heat

.

Acute Treatment of Pulmonary Edema • treat acute precipitating factors (e.g. ischemia, arrhythmias) L Lasix* (furosemide ) 40-500 mg IV M morphine 2-4 mg IV: decreases anxiety and preload ( venodilation ) N nitroglycerin: topical / IV /SL use with caution in preload dependent patients (e.g. right HP or RV infarction ) as it may precipitate CV collapse O oxygen: in hypoxemic patients • P positive airway pressure (continuous positive airway pressure (CPAP)/bilevel positive airway pressure ( BiPAP )): decreases preload and need for ventilation when appropriate P position: sit patient up with legs hanging down unless patient is hypotensive • in ICU setting or failure of LMNOPP: other interventions may be necessary nitroprusside IV hydralazine PO sympathomimetics dopamine - low dose: selective renal vasodilation ( high potency D1 agonist) medium dose: inotropic support ( medium potency pi agonist ) high dose: increases SVR (low potency pi agonist ), which is undesirable * dobutamine - pi-selective agonist causing inotropy, tachycardia, hypotension (low dose) or HTN ( high dose); most serious side effect is arrhythmia, especially AEib phosphodiesterase inhibitors ( milrinone) inotropic effect and vascular smooth muscle relaxation (decreased SVR), similar to dobutamine • consider pulmonary artery catheter to monitor PCWP if patient is unstable or a cardiac etiology is uncertain ( PCWP >18 indicates likely cardiac etiology ) • mechanical ventilation as needed • rarely used , but potentially life saving measures: IABP reduces afterload via systolic unloading and improves coronary perfusion via diastolic augmentation

-

Precipitants of HF

-

LVAD /RVAD

cardiac transplant Long- Term Management

• overwhelming majority of evidence- based management applies to H FrEF • currently no proven pharmacologic therapies shown to reduce mortality in Hl pEE; control risk factors for HTpEE (e.g. HTN ) • prevent fluid overload with appropriate diuretic strategies

-

Conservative Measures

• symptomatic measures: oxygen in hospital, bedrest , elevate the head of bed

• lifestyle measures: diet, exercise, DM control, smoking cessation , decrease EtOH consumption, patient education, sodium, and fluid restriction • multidisciplinary' H E clinics: for management of individuals at higher risk, or with recent hospitalization

The most common cause of right HF is left HF

Measuring NT- proBNP BNP is secreted by Vs due to IV stretch and wall tension Cardiomyocytes secrete BNP precursor that is cleaved into proBNP After secretion into Vs proBNP is cleaved into the active C terminal portion and the inactive NT- proBNP portion

-

.

-

NT proBNPIevels

Wirt) HF very likely

*pe

50 50-75


75

450 900 »1800 >

>

.

.

IMlaUons: Age body hjtrtuv WMI lunctton PI

*

Features of HF on CXR HERB- B Hea rt enlargement (cardiothoracic ratio >0.50) Pleural Effusion Re -distribution (alveolar edema) Kerley B lines Bronchiolar-alveolar cuffing

n LJ

Patients on p - blocker therapy who have acute decompensated HF should continue (5- blockers where possible (provided they are not in cardiogenic shock or in severe pulmonary edema)

+

Toronto Notes 2023

013 Cardiology and Cardiac Surgery

Non-Pharmacological Management • from 2021 CCS guidelines

• restrict salt intake to 2-3 g/d • monitor daily weight for patients with HI', fluid retention, or congestion that is difficult to control with diuretics or renal dysfunction • restrict daily fluid intake to approximately 2 L/d for patients with fluid retention or congestion that is difficult to control with diuretics • cardiac rehabilitation: participation in a structured exercise program for N YHA class 1-111 after clinical status assessment to improve quality of life (HF-ACT10N trial)

-

.

Pharmacological Therapy ACEI /ARB: HAAS blockade ACE1: slows progression of LV dysfunction and improves survival all symptomatic patients functional class 11-1V all asymptomatic patients with LVEF 5.2 mmol/ L

-

rn

LJ

+

Toronto Notes 2023

C44 Cardiology and Cardiac Surgery

• SGLT 2 inhibitor: empaglillozin, canagliflozin, dapaglitlozin « recommended for treatment of patients with stable HErEE, irrespective of T 2 DM recommended in mild to moderate HErEE with concomitant T2DM to improve symptoms and reduce mortality

Treatment of CHF .Chronic ACEI *

• pblockers'

Mineralocortlcold receptor antagonists* • Diuretic •

HFrEF Management 1. ARNI ( or if on ACE1/ARB substitute to ARNI ) 2. p - blockers 3. MRA

.

ARNI Inotrope Antiarrhythmic

•

.

.

4 SGLT 2 inhibitor

t

• i Anticoagulant 'Mortality benefit

HFpEF Management

1. ARB 2. Systolic/ Diastolic Hypertension Management according to CHER Guidelines ( 2017) 3. MRA ( if serum K* < 5.0 mmol/ L and eGl R >30 ml/ min )

Ivabradine and Outcomes in Chronic Heart failure ( SHIFT ): A Randomized Placebo-Controlled Stud y Lanced 2010:376:11-17 Study : Randomised , double - blind , placebocontrolled. parallel- group trial. Population Patients with symptomatic Hfand IVEF of 35 % or loner, in sinus rh ythm with HR greater than or equal to JO bpm , had been admitted to hospital lot HF within pres ions year , on stabe background

Surgical Management • revascularization is the most frequently performed operation in HE patients with the aim to restore blood flow to hibernating myocardium ( 3.0 mUkf 'mm Increase in peak Oz consumption with no NTHA class reduction. Results:4S|37%) of 123 patients on mavacamten is. 22 (12%) of 128 on placebo met the primary endpoint Patients on maiacamten had greater reductions In post-eiercise LVOT gradient and greater increase in peak Oz consumption.34% more patients in the mavacamten group improved by at least 1 NYHA class. Safety and tolerability were comparable to placebo. Conclnsion: Mavacamten improved exercise capacity. LVOT obstruction, NYHA functional class, and health status in patients with HOCM.

-

.

RCM vs. Constrictive Pericarditis Present similarly but constrictive pericarditis is treatable with surgery

RCM

.

Constrictive Pericarditis

.

•

.

iltry

• no putsusparadoxus

.•

systolic murmurs LVH • . : :- ':d J _ ( ntiacardiac pathology ) urjo- and endocardial later gadolinium enhancement ( LGE) elevated BNP '

. .

'

r i .: in somecases

y

1

• pulsus paradoxus

.. -may -be:present Jf

iy :

no LVH

• pericardial

calcification

•

.

and per.catdral thickening pericardial late gadolmiom enhancement ( LGE ) reduced BNP

+

Toronto Notes 2023

CSO Cardiology and Cardiac Surgery Management

• exclude constrictive pericarditis

• control HR, anticoagulate if AFib • treat underlying disease: (e.g. cardiac amyloidosis, cardiac sarcoidosis, hemochromatosis) • supportive care and treatment for CHF, arrhythmias, and prevention of SCI) when indicated • judicious use of diuretics (excess volume reduction reduces filling pressures versus pathologic requirements triggering hypoperfusion ) • cardiac transplant: might be considered for CHF refractory to medical therapy Prognosis

• depends on etiology

Key Investigations

• Echo: may show respiratory variation in Wood (low in constrictive

. :may constrictive . MRI : pericarditis

CT show very thickened pericardium and calcification in pericarditis best modality to directly visualize pericardium and myocardium

Left Ventricular Noncompaction Cardiomyopathy Definition • failure of LV compaction leading to endomyocardial trabeculations that increase in number and prominence • characterized by abnormal trabeculations in the LV, most frequently at the apex Etiology

• genetics are incompletely understood • mutations have been mainly observed in genes coding sarcomeric, cytoskeletal and mitochondrial proteins

• can occur in healthy individuals (e.g. athletes and pregnancy ) as well as concomitantly with con genital heart diseases and other cardiomyopathies ( i.e. HCM, RCM, DCM, ARVC ) • can be reversible

Clinical Manifestations • if occurring in absence of concomitant cardiomyopathy and congenital heart disease, LV non compaction can be benign • symptoms range from SOBOL to rest symptoms • many patients are asymptomatic • ventricular arrhythmias or complete AV block ( presents as syncope and sudden death ) • thromboembolic events

• more likely when systolic dysfunction and LV dilatation are present

Investigations

• directed by primary pathology when LV non -compaction is comorbid with congenital disease or other

cardiomyopathies • TTL and cardiac MRI • most common diagnostic method is the ratio of the thickness of the non compacted layer to that of the compacted layer ( greater than 2:1 at the end of diastole) • role of routine genetic screening remains in question typically performed in the setting of LV non - compaction with comorbid cardiomyopathy

-

Management • at-risk first-degree relatives are recommended to undergo screening • therapy is largely driven by concomitant myocardial dysfunction , arrhythmias, and congenital heart

disease • ICD is an option if patients have syncope or documented VT • antiplatelets or systemic anticoagulation should be considered in adults, especially when the LV or atria are dilated Prognosis

• dependent on LV function and presence of comorbid conditions (e.g. congenital heart disease and cardiomyopathy)

Cardiac Transplantation • treatment for end-stage heart failure • median survival is 12 yr

• matching is according to blood type, body size and weight (should be within 25%), HLA tissue matching, and geographical considerations (to minimize ischemic time ) Indications for Surgery •severe cardiac disability despite maximal medical therapy (e.g. recurrent hospitalizations for CHF, NYHA 111 or IV, peak metabolic oxygen consumption < 14 mL / kg/ min in absence of p blocker ) with a

-

•symptomatic cardiac ischemia refractory to conventional treatment (e.g. unstable angina not life expectancy of 12 18 mo

amenable to CABG or PCI with LVEF < 20-25%; recurrent, symptomatic ventricular arrhythmias)

+

Toronto Notes 2023

C51 Cardiology and Cardiac Surgery

• high - risk HFSS

HFSS is an algorithm that incorporates the patient s HR, serum sodium, ischemic cardiomyopathy, LVEF, peak myocardial oxygen consumption , MAP, interventricular conduction

delay

-

-

-

-

-

patients with medium risk ( HFSS 7.2 8.1, 73% l yr survival ) and high risk ( HFSS 5 Wood units, transpulmonary gradient < 18 mmHg, or systolic pulmonary artery pressure >60 mmHG ) • major systemic illness • mental illness or other cognitive factors likely to affect ability to adhere to post-transplant regimens • repeated non adherence to medications • severe COED ( i.e. I EVI < 1 L) • severe symptomatic cerebrovascular disease

.

for End -Stage Heart Failnre

-

KJH 2001:345:1435 1443 Int leased survival of 23% vs. i% with WAD vs. medical management of Hf after 2 yr . Heartmate VAD has a biologic surface and therefore, does not require long-term anticoagulation but confers a higher risk of infection.

.

-

Relative Contraindications • active systemic infection • acute PUD • age >70 yr • DM with end -organ disease • lack of family/ social support • obesity ( >35 kg / m 2) • significant symptomatic carotid disease or PVD

Canadian Cardiovascular Society Focused Position Statement Update on Assessment 5 m/s or mean pressure gradient > 60 mm Hg)iIV dysfunction Stage D: symptomatic: can be severe AS or very severe AS; criteria also exist for low - flow, low gradient AS with reduced LVEF and for low gradient AS with either normal IVEF or paradoxical low flow severe AS

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Definition Leakage of blood across the aortic valve into the LV (i.e. aortic insufficiency). May be primary or secondary AR Etiology Supravalvular:aortic root disease (Marfan syndrome, atherosderosisand dissecting aneurysm, connective tissue disease) Valvular: congenital (bicuspid aortic valve, large VSD) IE Acute Onset: IE aortic dissection, trauma, failed prosthetic valve Pathophysiology Volume overload * LV dilatation » increased SV high sBPand low d8 P * increased wall tension * pressuie overload * LVH (low dBP •decreased coionary perfusion) Symptoms Pathophysiology Outflow obstruction * increased EDP •» concentric LVH * LV failure CHF subendocardial ischemia Usually only becomes symptomatic late in disease when HE symptoms S 0B0 E, dyspnea orthopnea PHD, syncope, and/or angina develop as a result of IV lailurc Symptoms Physical Exam Exertional angina, syncope,dyspnea. PHD orthopnea, peripheral edema, exertional dyspnea, decreased exercise tolerance, HF symptoms, presyncope, syncope Waterhammer pulse, bisferiens pulse.femoral brachial sBP >20 mmHg (Hill 'stest: wide pulse Physical Exam pressuie), hyperdynamic apex, displaced PMI heaving apex Harrow pulse pressure,brachial-radial delay, pulsus parvus et tardus, sustained PMI Auscultation: early decrescendo diastolic murmur at LLSB (cusp pathology ) or RLSB (aortic root Auscultation:crescendo - decrescendo SEM radiating to right davideand carotid,musical guality at pathology): best heard sitting, leaning forward, on full expiration; soft S1 absent S2, present S3 apex (Gallavardin phenomenon) S 4 soft S2 with paradoxical splitting S3 (late) (late) Investigations Investigations ECG: LVH and strain LB8 B. LAE AFib ECG: LVH LAE CXR: post stenotic aortic root dilatation, calcified valve, LVH LAE CHF CXR: LVH, LAE aortic root dilatation echo: etiology, valve area, valve morphology, hemodynamics LV sice, systolic function, prognosis echo /TIE: ctiologylscverity quantify AR leaflet or aortic root anomalies IV sice, systolic function timing of intervention prognosis, timing of intervention Other: low -dose dobutamine stress testing, CT imaging/aortic valve calcium score, and exercise TEE CMR or cardiac catheterization if > moderate AR, suboptimal/inconsistent TIE: systolic testing ( contraindicated il symptomatic) function, heart volumes,aortic site, AR severity Cardiac catheterization lab|Cath lab): if >40 yr and surgical candidate - to assess for ischemic Treatment Calcific AS: statin based on standard risk score for atherosclerotic prevention heart disease Stages A C: treat HTH Exercise testing: hypotension with exercise Asymptomatic:serial echos (repealed based on seveiity) avoid exertion Treatment Symptomatic:avoid nitrateslarterial dilatois and ACEI in severe AS Asymptomatic:serial echos, afterload reduction (e.g. ACEI nifedipine, hydralazine) Symptomatic: avoid exertion, treat CHF Proceduial intervention considered in stage D stage C and other specific situations Surgery il: symptomatic severe AR: chionic, severe AR with LVEF < 55%; severe AR and otherwise Procedural Options SAVR: if < 65 yr old and > 20 yr life expectancy, or if 1AVR contraindication undergoing cardiac surgery; other specific situations Surgical Options - Conduct prior to pregnancy (if AS significant) TAVR : if >80 yr old if

Etiology rheumatic disease (most common), non -rheumatic calcilication congenital Definition Severe MS: mitral valve area (MVA) "1.5 cm 2. diastolic pressure half- time >150 ms Pathophysiology MS » fired CO and LAE •increased LA pressure •PVR and CHF; worse with AFib (no atrial kick), tachycardia ( decreased atrial emptying time) and pregnancy (increased preload) Symptoms S060E orthopnea, fatigue, decreased exercise tolerance, palpitations, peripheral edema, raalai Hush, pinched and blue lacies (severe MS) Physical Exam Af ib, left parasternal lift, palpable diastolic thrill at apex: if AFib no “a* wave on JVP; if sinus, piominenl “a” wave may be found on JVP Auscultation: mid diastolic rumble atapex; best heard with bell in left lateral decubitus position following exertion: loud S1, OS following loud P 2 (heard best during expiration), long diastolic murmur, and short A 2 OS interval correlate with worse MS Investigations ECO: HSR , AFib, LAE ( Pmitrale) RVH. RAD CXR: LAE. CHF, mitral valve calcification echo / TTE: diagnosis/severity, hemodynamics, valvular lesions, valve analomy/morphology LA thrombus if percutaneous mitral balloon commissurotomy being considered Exercise testing: rheumatic MS and resting echo inconsistent with symptoms Cath lab:if concurrent CAD and patient >40 yr (male) or >50 yr (female) Treatment Avoid exertion, fever (increased LA pressure): treat AFib and CHF; increase diastolic filling time O-blockers digitalis) Vitamin K antagonist anticoagulation: in rheumatic MS if AF previous embolism, or LA thrombus Heart rate control ( for some patients) Intervention if: symptomatic, severe MS Invasive Options Percutaneous mitral balloon commissurotomy (PMBC): symptomatic, severe rheumatic MSwith acceptable morphology < moderate MR and no LA thrombus ( may be reasonable in other specific situations) Mitral valve surgery (repair, commissurotomy,or replacement): symptomatic, severe rheumatic MS with contraindicalion/limited access for PMBC. previous failure of PMBC, or otherwise undergoing cardiac suigery (note: lestenosis in 50% of patients In 8 yr after open mitral commissurotomy) Nonrheumatic,calcific MS: if severe MS and severe symptoms, valve intervention can be contemplated pending discussion with patient abouthigh procedural risk

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Etiology MVP congenital dell leallets IV dilatationiancurysm (CHF DCM myocarditis) IE abscess Marfan 's syndrome, HOCM. acute Ml myxoma, mitral valve annulus calcification, chordae /papillary muscle traumafische mia/rupture (acute), rheumatic disease, leaflet perforation Definition Leakage of blood across the mitral valve from the LV into the LA; can be primary or secondary. Can use Carpenlier 's classification Pathophysiology Reduced CO * increased IV and LA pressure * LV and LA dilatation » and pulmonary HID Symptoms Dyspnea. PND, orthopnea, palpitations, peripheral edema, decreased exercise tolerance, SOBOE Physical Exam Displaced hyperdynamic apex, left parasternal lid apical thrill Auscultation: holosystolic murmur atapex radiating to axilla * mid diastolic rumble,loud S2 (if

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pulmonary HTN) S3 Acute MR : sudden acute and hemodynamic instability (possibility duringfpost Ml)

Investigations ECG: LAE, left atrial delay (bifid P waves), * LVH

CXR: LVH. LAE, pulmonary venous HTN echo /TTE: etiology and severity of MR LV/RV function, leaflets, pulmonary artery pressure, vegetations/abscesses, papillary musdc /choidal rupture LA sice,mitral valve apparatus, extent of remodelling TEE:can be helpful with acute MR or if considering transcalheter interventions: also used when TTE findings are insufficient/inconsistent; assess for MR severity/mechanism and IV function Swan Gant Catheter : prominent LA "v" wave Other: CMR, exercise testing, stress nudear / PET, stress echo, and serum biomarkers /novel measurement of LV function Treatment Acute MR: vasodilator therapy (use limited by systemic hypotension):intra aortic balloon counter pulsation or percutaneous circulatory assist device may be employed Asymptomatic: serial echos Guideline directed management and therapy lor patients with severe MR and IVsystolic dysfunction or HFrEF ( e.g. ACEt ARBs, beta blockers, aldosterone antagonists ARNIs, biventricular pacing) intervention if: acute MR with CHF, papillary muscle rupture;severe MR with symptoms or LV systolic dysfunction; AFib; increasing LV siiefprcsence of IV dilatation: pulmonaiy hypertension; decreasing exercise tolerance: can be reasonable in other situations if low mortality risk (95%) or if otherwise undergoing CABG Procedural Options Mitral valve surgery (preferably repair ) is indicated and lifesaving in acute, severe, symptomatic, primary MR Valve repair (preferred over replacement if degenerative disease is the etiology): >75% of patients with MR and myxomatous MVP annuloplasty rings, leaflet repair,chordae translers / shorteningf replacement Valve replacement if: failure of repair,heavily calcified annulus Advantage of repair: low rate of endocarditis, no anticoagulation, less chance of re - operation Transcalheter cdgclo - edgc repair ( TEER ): reasonable in patients with severe, symptomatic primary MR with high/prohibitive surgical risk or in severe, symptomatic secondary MR if associated with LV dysfunction

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C59 Cardiology and Cardiac Surgery

Toronto Notes 2023

Table 18. Valvular Heart Disease Tricuspid Stenosis

Tricuspid Regurgitation

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Etiology Rheumatic disease, congenital, carcinoid syndrome, fibroelastosis; usually accompanied by MS (in rheumatic heart disease), autoimmune disorders, atrial mysomas, blunt trauma, mctastascs, congenital,drug -associated valvulopathy Definition Tricuspid orifice narrowing: blood flow from the RA into the RV is obstructed Pathophysiology Increased RA pressure •right HF » CO decreased and fined on exertion Symptoms Peripheral edema, fatigue, palpitations Physical Exam Prominent “a * waves in JVP positive abdominojugular reflux. Kussmaul's sign, diastolic rumble 4th left intercostal space Investigations ECG: RAF CXR: dilatation of RA without pulmonary artery enlargement echo: diagnostic Cardiac catheterization: large R A “a" wave (12- 20 mm Hg); diastolic, mean pressure gradient of 4 -8 mm Hg (Increased RA pressure with a slow decrease in early diastole * diastolic pressure gradient is classic for 1$) CMR: RV sice/ function Treatment Preload reduction (diuretics) for severe, symptomatic IS (caution: may exacerbate low oulpul) Treatunderlying etiology Slow HR Surgery: usually performed at time of other cardiac surgery (e.g. mitral valve surgery for rheumatic MS) Surgical Options Valvotomyusing 13 balloons Valve surgery: repair or replacement (open or transcatheter options for replacement) Usually bicuspid surgery favoured over percutaneous balloon tricuspid commissurotomy or valvuloplasty

Etiology RV dilatation.IE (particularly due to IV drug use), rheumatic disease, iatrogenic (deviceleads, endomyocardial biopsy), congenital (Ebstein's anomaly),pulmonary HTN. RV overload, DCM. annular dilation, leaflet tethering RA dilatation, ischemic heart diseases, other (trauma, carcinoid, drugs, irradiation) Definition leakage of blood across the tricuspid valve (i e. bicuspid insufficiency ): can be primary or secondary Pathophysiology RV dilatation » TR ( and further RV dilatation) * right HF Symptoms Peripheral edema, fatigue, palpitations SOBOE. ascites Physical Exam elevated JVP.“cv" waves in JVP. positive abdominojugular reflux, holosystolic murmur at LLSB accentuated by inspiration, left parasternal lift Investigations ECG: RAE, RVH. AFib CXR: RAE, RV enlargement echofllE: diagnostic assess lor ctiology / severity of TR IVC and right heart sice RV systolic function, left - sided disease and pulmonary artery systolic pressure Invasive measurements ( to address inconsistencies): cardiac index, right -sided diastolic pressure, pulmonary artery pressures, pulmonary vascular resistance, ventriculography Treatment Preload reduction (diuretics): reasonable if right sided HF related to severe TR Therapies to treat HF etiology reasonable if right -sided HF related to severe secondary TR Surgery if: severe TR (stages C and D) and undergoing cardiac surgery for a left- sided valve: can be reasonable in other specific situations Surgical Options Annuloplasty (i.e. repair:rarely replacement)

Pulmonary Stenosis

Pulmonary Regurgitation

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Etiology Usually congenital, rheumatic disease (rare), carcinoid syndrome

Definition Stiffening /narrowing of the pulmonic valve: blood llow into the pulmonary artery from the RV is obstructed Pathophysiology Increased RV pressure * RVH * right HF Symptoms Chest pain, syncope, fatigue,peripheral edema Physical Exam Systolic murmur at 2nd left intercostal space accentuated by inspiration; pulmonary ejection click ; right -sided S4 Investigations ECG: RVH CXR: prominent pulmonary arteries, enlarged RV echo: diagnostic Treatment Balloon valvuloplasty if severe symptoms Surgical Options Percutaneous or open balloon valvuloplasty

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Etiology Pulmonary HIH, IE rheumatic disease, tetralogy of Fallot (post - repair ), defective valvular coaptation, annular dilatation, fibrinoid deposits Definition Insufficient closure of the pulmonicvalve during diastole:reversal of flow into the RV Pathophysiology Increased RV volume » Increased wall tension * RVH •right HF Symptoms Chest pain, syncope, fatigue, peripheral edema Physical Exam Early diastolic murmur al USB: Graham Stecll (diastolic) murmur at 2 nd and 3rd lell intercostal space (increasing with inspiration) Investigations ECG: RVH CXR: prominent pulmonary arteries if pulmonaiy HTH; enlarged RV echo: diagnostic Treatment Rarely requires treatment: valve replacement (rarely done) Surgical Options Pulmonary valve replacement

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C60 Cardiology and Cardiac Surgery

Table 18. Valvular Heart Disease Mitral Valve Prolapse

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Etiology Myxomatous degeneration ol chordae: thick, bulky leaflets that crowd orifice: associated with connective tissue disorders: pectus excavatum; straight back syndrome, other MSK abnormalities; decreased venous return -> decreased diastolic ventricular filling decreased CO -> hypotension and venous congestion

»

•

.

•

Hypotension Increased JVP Muffled heart sounds

Signs and Symptoms

• tachycardia, hypotension, increased ) VP • tachypnea, dyspnea, shock , muffled heart sounds • pulsus paradoxus ( inspiratory fall in sBP >10 mmHg during quiet breathing ) •|VP “x” descent only, blunted “y ” descent • hepatic congestion/ peripheral edema • severity of signs/symptoms depend on rate of accumulation , volume of pericardial contents, pericardial distensibility, cardiac filling pressures, and chamber compliance Investigations

• ECCi: electrical alternans ( pathognomonic variation in R wave amplitude), low voltage

• CXR: enlarged cardiac silhouette; slow-accumulating effusions • GT/GM R : less available; usually only necessary if Doppler echo is infeasible • echo ( diagnostic modality of choice): pericardial effusion ( size, location, hemodynamic impact ), swinging of the heart , compression of cardiac chambers ( RA and RV ) in diastole, etc. -> echo also used for the purpose of guiding pericardiocentesis • cardiac catheterization ( rare) Treatment

• urgent drainage: needle pericardiocentesis recommended ( with echo or fluoroscopic guidance); surgery ( i.e. pericardiotomy ) is an alternative drainage approach (e.g. with purulent pericarditis or in an urgent situation involving bleeding into the pericardium ) • avoid diuretics and vasodilators ( these decrease venous return to already under filled RV -> decrease LV preload -> decrease CO) as well as mechanical ventilation • IV fluid may increase CO • treat underlying cause

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C66 Cardiology and Cardiac Surgery

A. No pathology

B. Cardiac tamponade { inspirationI

Ventricular wall collapse on inspiration Pericardial effusion

Interventricular septum

Pericardium

( pericardial sac

F— Pericardial fluid

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pericardial fluid )

C. Cardiac tamponade (expiration )

0. Pericardiocentesis

-Improvement in

cardiac output on

expiration

Resolution of ventricular wall collapse

Pericardial effusion

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- Pericardial fluid

pressure

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Removal of excess pericardial fluid

chambers

©Jennifer Lee 2021

Figure 53. Cardiac tamponade pathophysiology

Constrictive Pericarditis Definition • loss of pericardial elasticity caused by granulation tissue formation; leads to restricted ventricular

filling Etiology

• chronic pericarditis resulting in fibrosed, thickened, adherent, and /or calcified pericardium • any cause of acute pericarditis may result in chronic pericarditis • major causes are idiopathic, post-infectious (viral, bacterial pericarditis/ purulent pericarditis, TB), radiation, post cardiac surgery, uremia, Ml, collagen vascular disease • any pericardial disease process can cause constrictive pericarditis; risk of progression to constrictive pericarditis is based on the etiology of the pericardial disease

-

Pathophysiology • rigid, fibrous pericardium impairs ventricular filling during diastole -» decreased venous return to the heart -» rise in systemic venous pressure -> signs and symptoms of right-sided HF (classically with preserved ventricular function and otherwise no myocardial disease) in advanced cases, there can be systolic dysfunction if myocardial fibrosis or atrophy present

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C67 Cardiology and Cardiac Surgery

Toronto Notes 2023

Signs and Symptoms

• dyspnea, fatigue, palpitations • abdominal pain • may mimic CHF (especially right sided HI ') • venous congestion, ascites, hepatosplenomegaly, edema , pleural effusions • increased|VP, Kussmaul 's sign ( paradoxical increase in ) VP with inspiration ), Friedreich ’s sign ( prominent “ y” descent) • BP usually normal (and usually no pulsus paradoxus) • precordial examination: ± pericardial knock (early diastolic sound ) • see Table 19 for differentiation from cardiac tamponade

-

-

Investigations

DDx Pulsus Paradoxus

• Most etiologies of RV failure except restrictive cardiomyopathy (e.g. acute RV Ml )

• Constrictive pericarditis ( rarely)

• Severe obstructive pulmonary

disease (e.g. asthma ) Pneumothorax PE • Cardiogenic shock • Cardiac tamponade • Effusive Constrictive pericarditis

..

-

• HCG: non-specific findings low voltage, flat T wave, ± A Fib

• CXR: pericardial calcification, effusions • echo/CF/CMR: pericardial thickening, calcification ± characteristic echo- Doppler findings ( Note: CMR is discouraged if patient is hemodynamically impaired ) • cardiac catheterization: indicated if other, non -invasive imaging modalities are insufficient to make diagnosis; assess for equalization of end -diastolic chamber pressures • diagnosis: right HF symptoms + diastolic filling impairment caused by constriction (documented on SI imaging modality including echo, CT, CMR, and /or catheterization) • note: in up to 20% of patients, constriction can occur even with normal thickness of the pericardium ( pericardiectomy equally efficacious in these patients) Treatment

• surgery ( pericardiectomy): mainstay treatment for chronic, permanent constrictive pericarditis • medical therapy: can be used in 3 situations 1. for specific pathologies/etiologies (e.g. TB) 2. for transient constriction that is temporarily caused by pericarditis, or new constriction diagnosis with evidence of inflammation of the pericardium ( use anti-inflammatories) 3. supportive when high / prohibitive surgical risk ( goal is to relieve congestive symptoms with diuretics, salt restriction) • prognosis best with idiopathic or infectious cause and worst in post-radiation • death may result from HF Table 19. Differentiation of Constrictive Pericarditis vs. Cardiac Tamponade Characteristic

Constrictive Pericarditis

JVP

V

Kussmaul's sign

Present

»V

Cardiac Tamponade

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Absent

Pulsus paradoxus

Uncommon

Pericardial knock

Present

Absent

Hypotension

Variable

Severe

Always

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C68 Cardiology and Cardiac Surgery

Extracorporeal Circulation lOrtic cross- clamp Systemic flow line

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C69 Cardiology and Cardiac Surgery

Cardiopulmonary Bypass Overview

• CPB is commonly used in cardiac and thoracic aortic surgeries to obtain a still, bloodless surgical field by circumventing the heart and lungs while supplying blood to the systemic circulation • essential functions of CPB: oxygenation , ventilation, circulation, temperature control Components • the standard components of a CPB circuit: arterial cannula (aortic, femoral, or axillary ) and line (3/8” heparin coated tubing ) oxygenator ( membrane oxygenator, defoamer, and heat exchanger) pump ( peristaltic/ roller or centrifugal) venous cannula ( RA, SVC and IVC, or femoral) and line (1/2” heparin- coated tubing) venous reservoir ( rigid high capacitance reservoir or closed soft reservoir)

-

Mechanics

• venous blood is drained into venous reservoir. The blood is oxygenated , and CO i is eliminated , heated , or cooled ( if applicable) and returned to the systemic circulation via the arterial cannula heparin is first administered so that pump suckers can be turned on when the patient's ACT is > 400 s and CPB initiated when ACT is > 480 s

is measured every 30 min while on CPB and additional heparin boluses are administered • ACT to maintain ACT 480 s

> anticoagulation is reversed following separation of CPB by administering protamine which neutralizes heparin the rate of blood draining into the venous reservoir is determined by the: CVP, height differential between venous cannula and venous reservoir, luminal radius of venous cannula and tubing, presence of air within the tubing arterial cannulation is typically performed at the distal ascending aorta , distal to the aortic cross clamp, with alternative sites for cannulation including the aortic arch, innominate artery, subclavian artery, axillary artery, femoral artery, and LV apex optimal flow rate is calculated to achieve a cardiac index of 2.4 L / min / m patient parameters measured during CPB: ECG, BP, CVP, SaO 2, ETC02, peripheral and core temperature, urine output, ABG CPB pump parameters measured during CPB: blood flow rate, roller pump/centrifugal speed , gas flow, pump blood temperature, heat exchanger water temperature, arterial line pressure, arterial and venous line 02 saturations, delivered O 2 concentration Complications • reaction to non endothelialized foreign surfaces: systemic inflammatory response, hemolysis,

-

coagulopathy • vessel injury from cannulation: aortic dissection and embolization of aortic debris ( e.g. porcelain aorta) • heparin -related: heparin -associated thrombocytopenia, heparin -induced thrombocytopenia ( HIT) • systemic embolization: cerebrovascular accident, renal and splanchnic hypoperfusion includes biologic and nonbiologic microemboli as well as air /gas / bubble emboli cardiotomy reservoir must be filtered to reduce risk of microemboli

Cardiac and Neurological Protection during Cardiopulmonary Bypass Myocardial Protection Techniques • myocardial protection reduces myocardial ischemia during CPB by reducing myocardial oxygen consumption and maintaining oxygenated myocardial perfusion • methods of myocardial protection to reduce oxygen demands include: unloading the heart (CPB), stopping the heart (cardioplegic diastolic arrest ), cooling the heart (core hypothermia , cold saline external washing, hypothermic cardioplegia solutions) • cardioplegia ( given continuously or intermittently) induces diastolic arrest by altering myocytes' resting potential and ionic gradients via concentrated K + solutions

• crystalloid cardioplegia

extracellular solutions ( high sodium ) (e.g. St. Thomas' solution , del Nido solution) increase extracellular K+ concentration to prevent cardiomyocyte repolarization intracellular solutions (low sodium ) lower extracellular Na + concentration thereby blocking

depolarization blood cardioplegia: autologous cold blood combined with tailored crystalloid solutions in various ratios »

blood typically comprises majority of overall solution (e.g. 8:1, 4:1, 2:1 )

Special Consideration of Blood

Conservation for Jehovah's Witness (Clients • Preoperatively: • Administer erythropoietin • Stop all anticoagulant and antiplatelet medications for 7 d, if possible

• Intraoperativety: • Continuous cell salvage circuit Meticulous hemostasis .• OPCAB

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• Pharmacological adjuncts (tranexamic acid or aprotinin ) • Postoperatively: • Low threshold for rcsternotomy due to bleeding

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C70 Cardiology and Cardiac Surgery

Cerebral Protection • cerebral protection techniques are required when CPB cannot supply the head vessels, such as during

surgery on the aortic arch • methods of cerebral protection to reduce oxygen demands include: hypothermia ( most important ) and anterograde / retrograde cerebral perfusion Deep Hypothermic Circulatory Arrest • deep hypothermic circulatory arrest reduces cerebral metabolism and oxygen consumption to the point that CPU can be discontinued • ( 3(M 0 min safe circulatory arrest at 20°C; 15 60 min safe circulatory arrest at 16“C ) concurrent ACP enables circulatory arrest at higher temperatures than DHCA alone • liECi monitoring occurs throughout to confirm adequate cerebral protection • mannitol ( reduces cerebral edema ) and steroids ( decrease cerebral inflammation ) are used

--

adjunctively complications related to deep hypothermic circulatory arrest include: coagulopathy and platelet dysfunction, systemic inflammatory response, neurological injury secondary to ischemia in watershed areas ( neurologic dysfunction may be persistent or transient depending on etiology)

Common Medications Table 20. Commonly Used Cardiac Therapeutics Mechanism of Action

Indications

Contraindications

Inhibit ACE mediated conversion of angiotensin I to angiotensin II (AT II), causing peripheral vasodilation and decreased aldosterone synthesis

HTN. CAD, CHE, post Ml, DM

Bilateral renal artery stenosis pregnancy, caution in decreased GER

Dry cough (10%) hypotension, fatigue, hyperkalemia, renal insufficiency, angioedema

Bloch AT II receptors, causing similar effects as ACEI

Same as ACEI, although evidence is generally less lor ARBs: often used when ACEI arc not tolerated

Same as ACEI

Similar lo ACEI but do not cause dry cough

Sacubilril inhibits neprilysin which leads to vasodilation and natriuresis Valsartan ( ARB) see above

HFrEF

Angioedema pregnancy

aliskiren

Directly blocks renin thus inhibiting the conversion of angiotensinogen to angiotensin I;this also causes a decrease in AT II

HTN (exact role of this drug remains unclear ) Not recommended as initial therapy

atenolol, metoprolol, bisoprolol, propranolol, labetalol, carvedilol, accbutolol

Block p - adrenergic receptors, decreasing HR , BP contractility, and myocardial oxygen demand; also slow conduction through the AV node

HTN CAD, acute Ml, post - MI, CHF (start low and go slow ), AFib, SVT

Bcnzothiazcpines Phenylalkylamincs (non - dihydropyri dines)

dllliacem

Block smooth muscle and myocardial calcium channels causing effects similar to

HIN CAD, SVT AFib, diastolic dysfunction

Dihydropyrldines

amlodipine (Notvasc ' ) nifedipine (Adalaf ), felodipine ( Plendil )

Drug Class

Examples

Side Effects

ANGIOTENSIN CONVERTING ENZYME INHIBITORS ( ACEI )

enalapril ( Vasotec '), perindopril (Coversyl ' ), ramipril (Allaccs) lisinopril ( Zestril ' )

.

-

.

.

ANGIOTENSIN IIRECEPTOR 8 L 0CKERS ( ARBs)

.

candesartan irbesartan, losartan olmesarlan lelmisarlan valsartan

.

.

.

.

ANGIOTENSIN RECEPTOR - NEPRILYSIN INHIBITOR ( ARNI)

sacubilril/ valsarlan (Entreslo ' )

.

.

Angioedema hyperkalemia, hypotension, renal

insufficiency

-

DIRECT RENIN INHIBITORS ( ORIs)

P -BLOCKERS P1 antagonists

.'

pifp2 antagonists a1 B1fp 2 antagonists P1 antagonists with intrinsic sympathomimetic

.

.

.

Pregnancy severe renal impairment

Diarrhea, hyperkalemia (higher risk if used with an ACEI) rash, cough, angioedema, reflux, hypotension, rhabdomyolysis, seizure

Sinus bradycardia, 2nd or 3rd degree heart block,

Hypotension, fatigue, light - headedness depression, bradycardia, hyperkalemia, bronchospasm impotence, depression of counterregulatory response to hypoglycemia, exacerbation of Raynaud 's phenomenon, and claudication

.

hypotension Caution in asthma, claudication Raynaud's phenomenon, and decompensated CHF

.

.

activity

.

CALCIUM CHANNEL BLOCKERS verapamil

.

0 -blockers

.

Sinus bradycardia, 2nd or 3rd degree heart block, hypotension CHF

Hypotension, bradycardia, edema

Severe AS and liver failure

Hypotension, edema Hushing, headache, light - headedness

.

Also vasodilate

.

Block smooth muscle calcium channels causing peripheral vasodilation

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Table 20. Commonly Used Cardiac Therapeutics Drug Class

Examples

Mechanism of Action

Indications

Contraindications

Side Effects

Pioposed mechanisms include: osmotic diuresis and natriurcsis reducing preload: vasodilation leading to reduced afterload: myocardial metabolic stabilnatron

Dapaglilloiin trial (DAPAHF) Indicates potential use in HFrEF with DM /non - OM, with multiple other SGLI 2 inhibitors trials underway. Although dapaglilloiin has received guideline recommendations in Canada, US and EU lor use in HFrEF, no SGLT 2 inhibitors have formal approval for HFrEF without DM by Health Canada HFpEF ( see EMPEROR -Preserved

Severe CKO (dapagliflozin contiaindKated in patients with cGER < 30 ml/ mm /U3m;) 11DM history of OKA advise holding during sick days

Veasl inlections Urinary trad Infections, hypoglycemic episodes, diabetic ketoacidosis, decreased bone mineral density

Sulfa allergy,pregnancy

Hypotension, hypokalemia, polyuria

Hypovolemia, hypokalemia

Hypovolemia, hypokalemic metabolic alkalosis

SODIUM - GLUCOSE COTRANSPORTER - 2 ( SGLT 2 ) INHIBITORS

canaglillocm dapaglillonn empaglillocln erluglillocin

.

. .

.

trial)

DIURETICS

Reduce (In' reabsorption in the distal convoluted tubule ( OCT)

HTN (drugs ol choice for uncomplicated HTN)

furosemide (Lasix )

Blocks HafK'- ATPase in thick ascending limb of the loop of Henle

CHE pulmonary or peripheral edema

spironolactone

Antagonize aldosterone receptors

HTN CHE, hypokalemia

Renal insufficiency, hyperkalemia, pregnancy

Edema, hyperkalemia, gynecomastia

Inhrbit Nd/ K'- AIPasc , leading to increased intracellular Na andCa concentration, and increased myocardial

CHE, AEib

2nd or 3rd degree AV block , hypokalemia

AV block, junctional tachycardia, bidirectional VT bradyarrhythinlas, blurred or yellow vision ( van Gogh syndrome), anorexia N/V

Thiazides

hydrochlorothiazide, chlorthalidone, metolazone

Loop diuretics

Aldosterone receptor antagonists

eplenerone

-

.

.

INOTROPES

digoxin ( Lanoxin ' )

-

^

.

contractility Also slows conduction through the AV node ANTICOAGULANTS

Coumarins

warlarin (Coumadin ' )

.

AFrb LV dysfunction, prosthetic Antagonizes vitamin K, valves, venous thrombosis leading to decreased synthesis of dolling factors II, VII IX and X

.

Recent surgery or bleeding

bleeding diathesis, pregnancy

..

Heparins

Antithrombin III agonist, Unfractionated heparin LMWHs: dalteparin enoxapaun, leading to decreased clotting linzaparin factor activity

Direct thrombin inhibitors

dabigatran

Direct factor Xa inhibitors

.

.

Bleeding (by tar the most important side elfect), paradoxical thrombosis, skin necrosis

Acute MI/ ACS: ( when immediate anticoagulant effect needed). PE, venous thrombosis

Recent surgery or bleeding bleeding diathesis thrombocytopenia, renal insufficiency ( for LMWHs)

Competitive, direct thrombin inhibitor, thrombin enables fibrinogen conversion to fibrin during thecoagulation cascade

AEib, venous thrombosis, PE

Severe renal impairment Bleeding,Gl upset recent surgery,active bleeding Idarucizumab: FDA approved agent for reversal of dabigatran for bleeding

rivaroxaban apixaban edoxaban

Direct, selective and reversible inhibition of factor Xa in both the intrinsic and extrinsic coagulation pathways

AEib, venous thrombosis PE

ASA ( Aspirin 1 )

Irreversibly acetyl ales platelet COX -1,preventing thromboxane A 2 - medialed platelet aggregation

.

.

.

.

Bleeding, osteoporosis, heparin - induced thrombocytopenia (less in LMWKs)

Hepatic disease, active bleeding, bleeding diathesis, pregnancy, lactation Andeianet alfa FDA approved agent for reversal of apixaban and rivaroxaban for bleeding

Bleeding, elevated liver enzymes

Active bleeding or PUD

Bleeding, Gl upset, Gl ulceration, impaired renal perfusion

Acute Ml post Ml post PCI, CABG

Active bleeding or PUD

Bleeding, thrombolic thrombocytopenic purpura, neutropenia (liclopidine)

Acute Ml, particularly if PCI is planned

Recent surgery or bleeding, bleeding diathesis

Bleeding

See fable 10. C34

Bleeding

ANTIPLATELETS Salicylates

.

Ihienopyridines

clopidogrcl (Plavu ' ) liclopidine (liclid )

P 2Y 12 antagonist (block platelet ADP receptors

Nucleoside analogues

licagrelor (Brillinta )

P 2Y12 antagonist (but diflerenl binding site than Ihienopyridines)

Glycoprotein llb / llla inhibitors

eptifibatide, tirohban abeiximab

.

Block binding of fibrinogen to

Gp lib I, lia

..

CAD acute Ml, post - MI, post -

PCI CABG

.

.

THROMBOLVTICS alteplase, reteplase. tenecteplase streptokinase

.

Convert circulating Acute STEMI plasminogen to plasmin which lyses cross-linked fibrin

.

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C72 Cardiology and Cardiac Surgery

Table 20. Commonly Used Cardiac Therapeutics Examples

Mechanism of Action

nitroglycerin

Relax vascular smooth CAD MI CNf (isosorbide muscle, producing venous and dinitrate plushydralatine) arteriolar dilation

Drug Class

Indications

Contraindications

Side Effects

NITRATES

. .

.

Concurrent use of cyclic

Headache, dimness guanosine monophosphate weakness, postural phosphodiesterase inhibitors, hypotension angle closure glaucoma, increased intracranial pressure

LIPID LOWERING AGENTS

.

Stalins

atorvaslalin (Lipitor ) pravastatin (Pravachol:i rosuvastalin ( Crestor ' ) simvastatin (Zocor 3 ) lovastatin (Meracor 5 )

Inhibit hydroxy 9 -methylglutaryl - CoA (HMG CoA) reductase, an enzyme which catalyzes the rate limiting step in cholesterol synthesis

Dyslipidemia (1" prevention ot CAD) CAD, post - Ml|2“ prevention of CV events)

Cholesterol absorption inhibitor

eietimibe ( Ezetrol 3 )

Inhibits gut absorption ol cholesterol

Decreases low density lipoprotein but does not reduce

Miscellaneous

fibrates bile acid sequestrates,

PCSK 9 inhibitor

evolocumab alirocumab

.

.

.

.

-

liver or muscle disease

Myalgia, rhabdomyolysis, abdominal pain

liver or renal impairment

Myalgia, rhabdomyolysis abdominal pain

.

mortality

. nicotinic acid

Primarily in familial hypercholesterolemia Monoclonal antibody that inhibits PCSKETs inhibitory action on the recycling of LDL receptors, thereby increasing the number ol IDl receptors on the surface of liver celts

Hypercholesterolemia

Gt side effects common Hypersensitivity reaction to drug

Mild reactions to site ol injection, nasopharyngitis

Antiarrhythmics ! i 2 slow Ctf influx '

a

5 3 _ a §

D Na ' influx

3

K -efflux

threshold

Na influx

s TIME

Figure 55. Representative cardiac action potential

Table 21. Antiarrhythmic ' Drugs ( Vaughan - Williams Classification) Class

Agent

Indications

Side Effects

Mechanism of Action

la

quinidine procainamide disopyramide

SVT VT

Torsades de Pointes (all la), diarrhea Lupus-like syndrome Anticholinergic effects

Moderate Nr channel blockade Slows phase 0 upstroke Prolongs repolarization. slowing

lb

lidocaine mexiletine

VI

Confusion, stupor,seizures Gl upset, tremor

Mild Na 'channel blockade Shortens phase 3 repolarization

Ic

propafenone

SVT. VT AFib

Exacerbation olVT (all Ic) Negative inotropy (all tc) Bradycardia and heart block (all Ic)

Upstroke

llecainide encatnide

.

conduction

propranolol meloprolol etc.

.

III

IV

amiodarone" solalol

verapamil diltiazem

.

SVT. AEib

Bronchospasm negative inotropy, bradycardia, AV block, impotence, fatigue

SV 1. VI

Amiodarone: photosensitivity , pulmonary toxicity, hcpalotoxlcity thyroid disease, increased INR Amiodarone and sotalol: Torsades de Pointes, bradycardia, heart block, p-blockerside elfects

AFib SVI V 1

.

SV 1 AFib

.

.

Bradycardia AV block Hypotension

p blocker Decreases phase 4 depolarization Blocks K* channel

.

Piofongs phase 3 repolarization which prolongs refractory period

rn LJ

CCB Slows phase 4 spontaneous depolarization,slowing AV node

conduction

+

'All antiarrhythmics have potential to be proarrhythmic "Amiodarone has class I, II III and IV properties

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C73 Cardiology and Cardiac Surgery

Table 22. Actions of a and p Adrenergic Receptors

p RECEPTORS

a RECEPTORS

Target System

at

Cardiovascular

Constriction olvascular smooth muscle Constriction of skin,

.

skeletal muscle and splanchnic vessels Increase myocardial contractility Decrease HR

a2 Same as o1

Peripherally act to modulate vessel tone Vasoc onstrict and dilate; oppose o1vasoconstrictor activity

31

32

Increased myocardial contractility Accelerate SA node conduction Accelerate ectopic

Decreased vascular smooth muscle tone

pacemakers

Bronchodilation

Respiratory Dermal

Pilomotor smooth muscle contraction Apocrine constriction

Ocular

Radial muscle contraction

Gastrointestinal

Inhibition of myenteric

Ciliary muscle relaxation

plexus Anal sphincter contraction

Pregnant uterine contraction Penile and seminal vesicle ejaculation Urinary bladder contraction Stimulate liver gluconeogenesis and glycogenolysis at the liver

Genitourinary

Metabolic

Smooth muscle wall relaxation

Stimulation ol renalrenin release

Bladder wall relaxation Uterine relaxation

Same as ol Fat cell lipolysis

Fat cell lipolysis Glycogenolysis

Gluconeogenesis Fat cell lipolysis

Adapted from the Family Practice Notebook ( vrww.tpnotebook.com NEU194.htm)

Table 23. Commonly Used Drugs that Act on a and p Adrenergic Receptors p RECEPTORS RECEPTORS Mechanism ol Action

a1

u1andn 2

o2

31

31 and 32

32

Agonist

Phenylephrine Methoxamine

Epinephrine Norepinephrine

Clonidine Methyldopa

Norepinephrine

Isoproterenol Epinephrine

Albuterol Terbutaline

Propranolol

Buloiamine

Antagonist

Praiosin Phentolamine Phenoxybentamine

Vohimbine Mirlatapine

Dobutamine Meloptolol Acebutolol Alptenolol Atenolol

Timolol Nadolol Pindolol

Esmolol

Carvedilol

.

Adapted from the Family Practice Notebook ( Yrww tpnotebook .corn/NEU194.htm)

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C7 1 Cardiology and Cardiac Surgery

Landmark Cardiac Trials Trial Name

Reference

Clinical Trial Details

ACME

HEJM 1992;326:10 -16

ARRIVE

Lancet 2018:392:1036-46

Tillc: A Comparison ol Angioplasty with Medical Therapy in lire Treat men! of Single - Vessel Coronary Arlery Disease Purpose: Compaic the effects of percutaneous transluminal coronary angioplasty (PICA ) on angina and exercise tolerance in patients with stable single - vessel disease Methods: Patients with exercise - induced myocardial ischemia and epicardial arlery stenosis were randomized to PICA or medical therapy, and repeat exercise testing performed at 6 mo. Results: PICA was successful in 80% of patients, reducing mean % stenosis from 76% to 36%. At 6 mo, 64% PICA patients were angina free. compared with 46% of medically heated patients. PTCA - treated patients had longer exercise durations (2.1 vs. 0.5 min. P- 0.0001) than medically treated patients. Conclusions: PICA offers earlier and better relief of angina than medical therapy in patients with single - vessel disease. Title: Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE ): A Randomised. Double- blind Placebo- controlled Trial Purpose: Assess efficacy and safety of ASA versus placebo in patients with moderate risk of a first CV event. Methods: Patients with moderate CV risk were randomized to receive ECASA or placebo tablets, once daily. The primary endpoint was a composite of time to CV death, MI. UA. stroke, or TIA. Results: The primary endpoint occurred in 4.29% of ASA- treated patients versus 4.48% of placebo - treated patients (hazard ratio 0.96; 95% Cl 0.81 to 1.13: P'0.6). The overall incidence of adverse events was similar between groups (82.01% in ASA group versus 81.72 % in placebo group). Conclusions: Among patients at moderate risk of CHD. the use of ASA was not beneficial. ASA was not associated with a reduction in adverse CV events.

ASCOTLLA

lancet 2003:361:1149 58

Tide: Prevention of Coronary and Stroke Events with Atorvaslatin in Hypertensive Patients who have Average or Lower than Average Cholesterol Concentrations, In the Anglo Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm ( ASCOT lla): A Multicenlre Randomised Controlled Trial Purpose: Assess benefits ol cholesterol lowering In primary prevention ol CHD in hypertensive patients. Methods: Hypertensive patients aged 40 79 were randomized to atorvastatin 10 mg or placebo. The primary endpoint was non - fatal Ml and fatal CHD after 5 - yr follow - up. Results: 100 primary events occurred in the atorvaslatin group compared to 154 events in the placebo group at a median lollowup of 3.3 yr (hazaid ratio 0.64; 95% Cl 0.50 lo 0.83; P'0.0005). Fatal and non - fatal stroke, total CV events and total coronary events were also lowered in the atorvastatin group. Conclusions: In hypertensive patients with risk factors for CHD and average cholesterol levels, atorvastatin reduced non- fatal Ml, fatal CHD. fatal/ non - fatal stroke, coronary events but not all- cause mortality.

BARI 2D

HEJM 2009:360:2503 15

Title: A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease Purpose: Determine optimal treatment for patients with I2DM and stable ischemic heart disease. Methods: Patients withT 2DM and heart disease were randomized to prompt revascularization with intensive medical therapy, or intensive medical therapy alone. Primary endpoints weremortality. Ml. orstroke Results: 5- yr survival did not differ significantly between groups ( 88.3% in revas.cularizalion group vs. 87.8% in the medical therapy group: P 0.97). In the PCI group, there were no significant differences in primary endpoints, while in the CABG group , rates of CV events were significantly lower with revascularization than medical therapy (22.4% vs. 30.5%: P'0.01). Conclusions: There was no significant difference in the rates of death and major CV events between prompt revascularization and medical therapy.

ISCHEMIC HEART DISEASE

.

'

CAPRIE

Lancet 1996:348:1329 39

.

Title: A Randomised Blinded. Trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE ) Purpose: Assess the relative efficacy of clopidogrel and ASA in reducing risk of clinical thrombotic events. Methods: Patients with atherosclerotic vascular disease were randomized to clopidogrel 75 mg once daily or ASA 325 mg once daily. Pnmaiy endpoints were a composite ol ischemic stroke. Ml or vascular death. Results: Patients treated with clopidogrel had a 5.32 % annual risk of stroke. Ml or death, compared with 5.83% ol ASA palients (p'0.043). There were no ma|0i differences In terms of safety. Conclusions: In atherosclerotic vascular disease , clopidogrel reduced the rales of stroke. Ml or vascular death compared lo ASA.

.

.

CARE

HEJM 1996:335:1001 09

Title: Ihe Effect of Piavaslatin on Coronary Events after Myocardial Infarchon in Patients with Average Cholesterol levels Purpose: Determine the elleds of cholesterol lowering in palients with coronary disease and average cholesterollevels. Methods: Patients with Ml who had plasma cholesterol levels < 240 mg were administered either 40 mg pravastatin or placebo. The primary endpoint was a fatal coronary event or fatal Ml. Results: The primary endpoint occuired in 10.2% of the pravastatin- treated patients and 13.2% of placebo - treated patients (95% Cl 9% to 36%: P- 0.003). There were no significant differences in overall mortality or mortality from nonvascular causes. Pravastatin lowered the rate ol coronary events more among men than women. Conclusions: Pravastatin reduced Ml and stroke in patients with previous Ml and average cholesterol.

COURAGE

HEJM 2007:356:1503 -16

Title: Optimal Medical Therapy with or without PCI for Stable Coronary Disease Purpose: Compare initial strategy of PCI plus intensive pharmacological therapy and lifestyle intervention against optimal medical therapy alone, in patients with stable coronary disease . Methods: 2287 patients with myocardial ischemia and significant CAD were randomized to PCI with optimal medical therapy, or optimal medical therapy alone. The primary outcome was all- cause mortality and non- fatal Ml. Results: There were 211 primary events in the PCI group and 202 in the optimal medical therapy group (hazard ratio for PCI, 1.05; 95% Cl 0.87 tol.27: P'0.62). There were no significant differences between groups in the composite of death. Ml , stroke, or hospitalizations for ACS. Conclusions: Compared with optimal medical therapy alone. PCI plus medical therapy did not reduce all - cause mortality and non - fatal Ml. and it did not reduce the incidence of major CV events.

CURE

HEJM 2001:345:494 502

Title: Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without Si- Segment Elevation Purpose: Evaluate efficacy and safely of clopidogrel with ASA in patients with ACS without ST- elevation. Methods: 12562 palients who presented within 24 h ol symptom onset were randomized lo clopidogrel or placebo in addition to ASA lor 3 - 12 mo. The primary endpoint was a composite ol CV mortality, non - fatal Ml or stroke. Results: The primary endpoint occuired in 9.3% ol clopidogrel patients and 11.4 % ol patients in the placebo group |RR 0.80: 95% Cl 0.72 lo 0.90; P' 0.001). Ihcrc were significantly more patients with bleeding in the clopidogrel group than Ihe placebo group ( 3.7% vs. 2.7%: RR 1.38: P'0.001) . Conclusions: Clopidogrel plus ASA reduced death from CV causes, non - falal Ml . or stroke but increased bleeding complications .

.

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C75 Cardiology and Cardiac Surgery

Trial Name

Reference

Clinical Trial Details

EUROPA

Lancet 2003;362:782 -88

Title: Efficacy of Perindopril in Reduction of Cardiovascular Events Among Patients with Stable Coronary Artery Disease:Randomised. Double-blind Place bo- controlled, Multicentre Trial (The EUROPA Study) Purpose:Assess whether ACEI reduced CV risk in a low risk population with stable coronary disease. Methods: Alter a run in of 4 vrk, in which all pabents received perindopril, 12218 patients were ran do mired to perindopril 8 mg 00 or matching placebo. The primary endpoint was CV death. Ml. or cardiac arrest Results: 8% of perindopril patients experienced a primary endpoint, compared with 10% of placebo pabents. These benefits were consistent in all subgroups and secondary endpoints. Conclusions: With stable CAD and no CH F, perindopril reduced CV death, Ml and total mortality.

.

-

-

.

European Coronary Surgery Study

NEJM 1988;319:332-37

Title: Twelve - Year Follow -up of Survival in the Randomized European Coronary Surgery Study Purpose: Evaluate survival rates in men with good LVEF after CA 8G or medical therapy. Methods: 767 men were randomized to early CABG or medical therapy. Results: At the prodded S yr follow - up period, there was a significantly higher survival rate in the surgical group than in the medical treatment group (92.4% vs. 83.1%, P‘0.0001). Conclusions: CABG resulted in higher survival than medical therapy at 5 - yr follow - up but not at 12 yr follow - up.

EXCEL

NEJM 2019;381:1820 - 30

Title: Five -Year Outcomes after PCI or CABG for Left Main Coronary Disease Purpose: Assess long - term outcomes after PCI with contemporary drug - eluting stents, as compared with CABG in patients with left main CAD. Methods:1905 patients with left main CAD of low/intermediate anatomical complexity were randomized to PCI or CA 8G. The primary outcome was a composite of death, stroke or Ml. Results: At 5 yr, the primary outcome occurred in 22.0% of PCI pabents and 19.2% of CABG patients ( 2.8% difference: 95% Cl - 0.9 to 6.5: P‘0.13). Rates of CV death and Ml were not significantly different between groups. All cerebrovascular events were less frequent after PCI than CABG ( 3.3% vs. 5.2%; 95% Cl - 3.8 to 0). Conclusions: Among patients with left main CAD there was no significant difference between PCI and CABG in terms of the composite outcome of death stroke, or Ml at 5 yr .

-

.

.

.

HPS

lancet 2002;360:7- 22

-

Title: MRC /BHF Heart Protection Study of Cholesterol lowering with Simvastatin in 20,536 High risk Individuals: A Randomised Placebo - controlled Trial Purpose: Assess effect of IDl- lowerlng with simvastatin on vascular disease, in patients of normal LDL -C. Methods: 20536 adults with coronary disease or DM were randomized to simvastatin 40 mg daily or placebo.Primary outcomes were mortality, and fatal or non- fatal vascular events . Results: Alt -cause mortality was significantly reduced (12.9% in simvastatin patients vs. 14.7% in placebo). There were significant reductions in the first event rate for non- fatal Ml (8.7% vs. 11.8%; Por bleeds at 9 d.and Ml at 30 and 180 rt

.

.

.

PEGASUS - IIMI 54

NEJM 2015:372:1791- 800

Title: long - Term Use of Ticagrelor in Patents with Prior Myocardial Infarcton Purpose:Investigate the safety and efficacy of bcagreloc after an ACS. Methods: 21162 patients who had a prior Ml were randomised to ticagrelor 90 mg SID. or placebo. The primary endpoints were a composite of CV death. Ml. or stoke. The primary safety endpoint was thrombolysis in Ml and major bleeding. Results: Kaplan - Meier event rates showed that ticagrelor reduced event rates at 3 yt.at 7.77% for the beatment group and 9.04% in the placebo group (hasard rabo 0.85: 95% Cl 0.75 to 0.96: P'0.008). Rates of major bleeding were higher with ticagrelor than with placebo (P 0.001). ‘ Conclusions: Ticagrelor on top ol ASA reduces CV events in patients with a history of Ml.

PLATO

NEJM 2009:361:1045 57

Title: Ticagrelor vs. Clopidogrel in Patients with Acute Coronary Syndromes Purpose: Evaluate the efficacy of ticagrelor vs. dopidogrel in patients with an ACS. Methods: 18624 patients admitted to hospital with ACS. with or without ST - eleiaton. were randomized to ticagrelor (180 mg loading. 90 mg twice daily after) or clopidogrel (300- 600 mg loading;75 mg daily after). The primary endpoint was a composite of vascular death. Ml.orstok. Results: The primary endpoint occurred in 9.8% of patents receiving ticagrelor compared with 11.7% of patients receiving clopidogrel (hazard ratio 0.84: 95% Cl 0.77 to 0.92: P 0.001). The rate of death was also reduced with ticagrelor (4.5% vs. 5.9%:P 0.001).There ‘ ‘ were no significant differences in the rates of major b'eedmg. Conclusions:In ACS patents with either STEMI or KSTEMI.regardless of reperfusion strategy ticagrelor reduced mortality.Ml. and stroke without increased bleeding compared to clopidogrel.

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Trial Name

—

PROVE IT TIMI 22

Reference

Clinical Trial Details

NEJM 2004;350:1495- 504

Title: Intensive vs. Moderate Lipid Loweringwith Statins alter Scute Coronary Syndromes Purpose: Determine the optimal LDL-C level in patients undergoing statin therapy (or reduction in risk of CV events. Methods: 4162 patients hospitalized with ACS in the preceding 10 d were assigned to pravastatin 40 mg daily or atorvastalin 80 mg daily . The primary end point was a composite of all cause mortality Ml, US revascularization, and stroke. Results: Event rales were 26.3% in the pravastatin group and 22.4% in the atorvastalin group ( P * 0.005; 95% Cl 5 lo 26% ) Ihe study established the superiority ol Ihe more intensive regimen Conclusions:In patients hospitalized lor ACS high dose atorvastalin reduced all- cause mortality Ml. unstable angina, revascularization, and stroke compared with pravastatin.

.

-

.

TRITON TIMI 38

NEJM 2007:357:2001-15

.

.

.

Title: Prasugrel vs.Clopidogrel in Patients with Acute Coronary Syndromes Purpose: Compare clopidogrel and prasugrel in preventing thrombotic complications of ACS and PCI. Methods:13608 patients with ACS and scheduled PCI were randomized to prasugrel (60 mg loading 10 mg maintenance) or clopidogrel (300 mg loading 75 mg maintenance). Ihe primary endpoint was CV death, non- fatal Ml or non -latal stroke. The safety endpoint was

.

.

.

major bleeding. Results: Ihe primary endpoint occurred in 12.1% ol clopidogrel patients and 9.9% ol prasugrel patients ( hazard ratio 0.81; 95% Cl 0.73 to 0.90: P 1000 Da) are not as easily absorbed by passive diffusion ) • pH and drug ionization drugs are usually weak acids (e.g. ASA ) or weak bases ( e.g. ketoconazole) and thus exist in ionized and non -ionized forms in the body non - ionized ( uncharged ) forms cross cell membranes more readily by passive diffusion than

..

V

ionized (charged ) forms the ratio of ionized to non ionized forms is determined by body compartment pH and drug pKa (as per the Henderson - Hasselbalch equation ) • total surface area for absorption (e.g. small intestinal villi are the primary site of absorption for most orally -administered drugs) • drug transporters

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CP 1 Clinical Pharmacology Bioavailability (F) • definition: proportion of dose that reaches systemic circulation in an unchanged state and is available to access the site of action

-

absorption or significant first pass effect • lower F usually reflects limited drug • IV dose has 100 % bioavailability ( I;= l ) First- Pass Effect • definition: metabolism ( i.e. biotransformation ) of the drug prior to reaching systemic circulation, resulting in reduced F • can occur with PO administration of a drug: G1 tract (absorption with possible metabolism ) -> portal vein to liver ( possible first pass metabolism ) > systemic circulation • with rectal administration , 50% of drug absorbed in the colon goes through the portal system

-

Drug Transporters • there are many drug transporters that can affect the uptake or efflux of drugs from cells and

organelles, and affect drug absorption, distribution, and elimination • P-glycoprotein ( P-gp) is a transport protein of clinical relevance as it is found in a wide variety of body tissues ( including the small intestinal epithelium , proximal tubule, bile canaliculi, and BBB ) where it acts as a multidrug efflux pump and provides a “ natural defence mechanism" against drugs and xenobiotics • P-gp limits the absorption and enhances the elimination of its many P -gp substrates (e.g. digoxin, etoposide, paclitaxel, tacrolimus, cyclosporine, apixaban ) • some drugs (e.g. most macrolide antibiotics) inhibit P-gp, leading to increased serum concentrations of P-gp substrate drugs; P -gp inducers (e.g. rifampin, St. John’s wort ) increase efflux activity leading to decreased serum concentrations • some tumours overexpress P gp leading to multidrug resistance to chemotherapeutic agents • other members of the ATP Binding Cassette ( ABC ) superfamily and the Solute Carrier (SLC ) superfamily of drug transporters also affect drug absorption; members of the SLC superfamily generally function as uptake drug transporters

-

Distribution • definition: movement of drugs between different body compartments and to their sites of action • major body fluid compartments include plasma , interstitial fluid, intracellular fluid , and transcellular fluid (e.g. CSF, peritoneal, pleural) • tissue compartments include fat, muscle, and brain Factors Affecting the Rate and Extent of Drug Distribution • physical and chemical properties of the drug ( e g. P»/ w, pKa , and size)

• pH of fluid • binding to plasma proteins • binding within compartments ( i.e. depots)

.

• regional blood flow • drug transporters Plasma Protein Binding • some drug molecules in the blood exist in an equilibrium of two forms: 1 . bound to plasma protein: acidic drugs bind to albumin, basic drugs bind to al acid

glycoprotein

-

2. free ( unbound ): can leave the circulation to distribute into tissues and exert an effect, subject to metabolism and elimination • bound fraction is determined by drug concentration, binding affinity, and plasma protein concentration ( number of binding sites) • reduced number of binding sites (e.g. hypoalbuminemia ) or saturation of binding sites (e g. competition / displacement ) may result in increased concentration of free drug, which is often cleared with no harmful effects, although toxicity is possible

.

Volume of Distribution

• Vd: the apparent volume of fluid into which a drug distributes • a calculated value ( Vd ) = amount of drug in body ( i.e. dose administered ) initial plasma drug concentration

• a theoretical value that does not correspond to an actual physiologic volume; Vd can greatly exceed TBW anatomical fluid volume thought to be • Total Body Water (TBW ) represents the maximal accessible to a drug (~ 40 L for average adult ) • small Vd ( plasma drug concentration • may be determined for a particular organ (e.g. liver or kidney ), but if not specified , represents the total

=

body clearance rate determined from the sum of individual clearance rates or by determining ke x Vd , where ke is the elimination rate constant equal to In 2 / half life

-

Elimination Kinetics

• first-order kinetics ( most common type)

• constant proportion of drug eliminated per unit time

some drugs can follow first-order kinetics until elimination is saturated (usually at large doses) at which point the Cl is less than would be predicted for a given concentration shows linear relationship when plotted on a graph of concentration (log) vs. time (linear) the concentration axis is converted to a log scale to allow for easier mathematical calculations • non linear or zero order kinetics ( less common , applies to a few drugs in the therapeutic range (e g. alcohol, phenytoin , Aspirin*) and is more commonly associated with overdose) constant amount of drug eliminated per unit time, regardless of concentration; the concept of half life does not apply saturation of various ADME processes creates non -linear kinetics, with first-order exhibited at lower concentrations and zero-order exhibited at higher concentrations after saturation the complexity of dosing drugs with non -linear kinetics has resulted in the creation of drugspecific nomograms to aid clinicians in dosing, with these drugs often being the target of TDM »

-

.

-

-

. . phenytoin, theophylline)

(e g

Loading and Maintenance Doses

• loading doses are used when an immediate effect is needed , with parenteral administration being the most common way of giving a large dose to “fill up" the volume of distribution • maintenance doses can be given after a loading dose, but are most commonly initiated without a loading dose steady-state levels are achieved after approximately five half-lives can be given as either a continuous infusion ( rare ) or more commonly as intermittent oral doses

Pharmacodynamics • study of “ what the drug does to the body"

• definition: study of the effects of the drug on the body Dose-Response Relationship • graded dose- response relationship: relates dose to intensity of effect

Efficacy

• the maximum biological response produced by a drug

• measured by Emax ( the maximal response that a drug can elicit or under optimal circumstances) Potency • measured by EC50 (the concentration of a drug needed to produce 50% of Emax); ED50 if dose is used • a drug that reaches its EC50 at a lower dose is more potent (e.g. in l'igure 1, drug A is more potent than drug B)

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E of A and C

C

A

Potency:

..

A > B >C ( both B and C are less potent than A )

E ofB

-

Efficacy:

30

A'C > B

logldose )

ECaofA

EC sa Of C

ECuofB logldose)

A -» C increasing dose of reversible © Jason Raina

competitive antagonist

At each dose of antagonist, increasing the concentration of agonist can oveicome the inhibition

Figure 1. Log(dose ) - response curve illustrating efficacy and potency

Figure 2. The log(dose)- response curve for reversible competitive antagonism

Effects of Drugs on Receptors Agonists

• drugs that mimic the effects of the endogenous ligand and evoke a response when bound to the receptor affinity: the ability and strength of the agonist to bind to the receptor (e.g. the (32 agonist salbutamol has greater affinity for {52 receptors than pi receptors, thus it binds preferentially to p2-receptors) efficacy : the ability to replicate endogenous response via the receptor interaction (e.g. binding of salbutamol to p2 receptors results in smooth muscle relaxation ) drug efficacy is often determined under ideal conditions whereas drug effectiveness is a better measure of how the drug works in real- world situations • full agonists: can elicit a maximal effect at a receptor (e.g. methadone and morphine on the p opioid receptor system ) • partial agonists: can only elicit a partial effect , irrespective of the concentration at the receptor; also known as a ceiling effect ( i.e. reduced efficacy compared to full agonists ) (e.g. buprenorphine on the p opioid receptor system )

-

-

-

-

Antagonists

• drugs that bind to receptors without activating them; they reduce the action of an agonist drug or of an endogenous ligand

• chemical antagonism: direct chemical interaction between agonist and antagonist prevents agonistreceptor binding (e.g. chelating agents for the removal of heavy metals, such as charcoal) • physiological /functional antagonism : drugs that produce opposite physiological effects (e.g. insulin decreases blood glucose levels through its action at insulin receptors vs glucagon raises blood glucose levels through its action at glucagon receptors) • pharmacological antagonism: antagonist binds to the same site as the agonist or an alternative effector site and reduces the ability of the agonist to bind • competitive antagonism: antagonist binds directly to the active site on a given receptor, without activating it ( i.e. zero efficacy) and blocks or displaces the agonist from the active site • reversible competitive antagonists: bind non -covalentlv to the receptor, thus increasing concentrations of agonist may overcome the antagonist (e.g. naloxone is a competitive antagonist to morphine or heroin) irreversible competitive antagonists: form a covalent bond with the receptor and cannot be displaced , thus irreversibly blocking other substrates from binding (e.g phenoxybenzamine forms a covalent bond witn adrenergic receptors preventing adrenaline and NE from binding ) • non - competitive antagonism: antagonist ( negative allosteric modulator ) binds to an alternate site on the receptor which is distinct from the active site, producing allosteric effects that alter the ability of the agonist to bind

80% ol all ADRs

B (Bizarre)

Nol dose - related

Reachons unrelated lo the known pharmacological actions of the drug, generally with a genelic basis E.g.drug hypersensitivity syndromes Immunologic reactions (e.g. penicillin hypersensitivity), and idiosyncratic reactions ( e.g. malignant hyperthermia)

.

-

C (Chronic)

Dose - and lime related

Related lo cumulative doses tlfeds are well - known and can be anticipated (e.g. alypical femoral Iradutc Irom bisphosphonates. retinal toxicity from hydroxychloroquine)

D (Delayed)

Time -related

Occurs some lime after use of drug (e.g. cardiovascular toxicity following doxorubicin therapy) May also be dose -related

E (End of use)

Withdrawal

Occurs alter cessation ol drug use ( e.g opioid withdrawal resulting from opioid dependence)

F ( Failure)

Unexpected failure ol therapy

the expected died is nol produced. This is often due to pharinacogenetic valiants ( e.g. failure to biosclivate a prodrug such as dopidogrel)

.

Tips to Reduce Drug- Related Adverse Events in the Elderly • Be mindful of longstanding medications that have never been adjusted for patient age or renal or hepatic function • Consider whether medications initiated during hospital admission are needed long term (and whether the discharge dose is appropriate for maintenance) • Avoid polypharmacy by decreasing the dose of or discontinuing medications that are causing side effects or are no longer indicated • Verify adherence to medications before automatically increasing the dose of subtherapeubc treatment • When prescribing medications, preferentially use those with a high Tl • Review the patient's problem list and reconcile current medications to avoid duplication or inappropriate dosing/frequency

Antibiotic Allergies •What is the Risk of

Cross-Reactivity? • In clinical practice cross reactivity between drugs presents a problem for both patients and physicians • In Use case of penicillin allergy, crossreactivity to cephalosporins is less than 2%. However, in patients who have a history of hue anaphylactic reaction, cross-reactivity is closer to 40% depending on the side chain • Cross- reactivity between penicillins and carbapencms is M

Investigations • consider a skin biopsy • hepatitis C serology if patient has risk factors Management

• topical or intralesional corticosteroids • short courses of oral prednisone ( rarely) • phototherapy, oral retinoids, or systemic immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) for extensive or recalcitrant cases

Pityriasis Rosea Clinical Features

• acute, self -limiting eruption characterized by red, oval plaques / patches with central scale that does not extend to edge of lesion • long axis of lesions follows skin tension lines ( i.e. Langer lines ) parallel to ribs producing “ Christmas tree" pattern on back • varied degree of pruritus • most start with a “ herald " patch which precedes other lesions by 1 -2 wk • common sites: trunk, proximal aspects of arms and legs Pathophysiology

-

• suspected HHV 7 or HHV -6 reactivation Investigations

• none required Management

-

• none required ; clears spontaneously in 6 12 wk • symptomatic: topical corticosteroids if pruritic, cool compresses, emollients

Psoriasis Classification 1. plaque psoriasis 2. guttate psoriasis 3. erythrodermlc psoriasis •4. pustular psoriasis 5. inverse psoriasis

Skin Treatments lor Chronic Plaque Psoriasis Cochrane 08 Syst Rev 2013:00005028 P urpose: lo renew the eflectneness tolqribility. and safety of topical treatments for chronic plaque

.

psoriasis.

Methods: This renew identified RCls comparing active topical treatments to either placebo or litemm 0 analogues (used alone or m combination ) in people with chronic plaque psoriasis. Results: 1)0 studies including a total ol 34808 participants were included in this review. Conclusion : Both topical coticosteroids and vitar 0 analogues were effective in treating throne plaque psoriasis ol the body . Corticosteroids showed benefits over vitamin 0 analogues in treating chronic plaque psoriasis of the scalp, treatments combining vitamin 0 analogues and topical corticosteroids were mote eHective than using eithervitamm D analogues or corticosteroids alone. Vitamin D analogues did result in more local adverse events than topical corticosteroids, the most common event being skin irritation or burning. People were moeelikely to discontinue using vitamin Oanalogues than topical

corticosteroids.

Calcipotriol is a Vitamin D Derivative Dovobet calcipotriene combined with betamethasone dipropionate and is considered to be one of the most potent topical psoriatic therapies '

Pathophysiology • not fully understood , genetic and immunologic factors • shortened keratinocyte cell cycle correlates with lit I - and '1 hi 7- mediated inflammatory response

+

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Toronto Notes 2023

D 21 Dermatology Epidemiology • 1.5-2%, M F • all ages: peaks of onset: 20-39 yr and 50-60 yr • polygenic inheritance: 8% with one affected parent, 41% with both parents affected • risk factors: smoking, obesity, alcohol, drugs, infections, physical trauma ( Koebner phenomenon )

=

Differential Diagnosis

See landmark OematologyTriaIsiab 'e far mote information on the BE VIVID trial compiling the efficacy and safety a!a 52 wk treatment irith bimekicomah vs. p ' acebo vs.usteknemab in patiects with mpderate to severe Dlaqne psp- asis.

-

• mycosis fungoides (cutaneous T cell lymphoma ), seborrheic dermatitis, tinea, nummular dermatitis,

lichen planus Investigations • none required; biopsy if atypical presentation

PLAQUE PSORIASIS

Clinical Features • chronic and recurrent disease characterized by well- circumscribed erythematous papules/ plaques

-

with silvery white scales • often worse in winter ( lack of sun ) • Auspitz sign: bleeds from minute points when scale is removed • common sites: scalp, extensor surfaces of elbows and knees, trunk (especially buttocks), nails, pressure areas Management • depends on severity of disease, as defined bv BSA affected or less commonly PASI • mild (10% BSA ) goal of treatment is to attain symptom control that is adequate from patient’s perspective

.

• phototherapy if accessible systemic or biological therapy based on patient’s treatment history and comorbidities topical steroid ± topical vitamin D3 analogue as adjunct therapy Table 14. Topical Treatment of Psoriasis Treatment

Mechanism

Emollients

Reduce fissure formation

-

Salicylic acid112%

Comments

Remove scales

Tar ( LCD: liquor car bonis detergens)

inhibits OKA synthesis, increases celt turnover

Messy, poor long term compliance

Topical corticosteroids

Reduce scaling, redness and thickness

Use appropriate potency steroid in different areas for degree of psoriasis

Vitamin D analogues: calcipotriene/ calcipotriol (Dovonex Silkis )

Reduces keratmocyte hyperproliferation

-

.

Betamethasone calcipotriene (Dovobei )

Combined corticosteroid and vitamin 0 analogue. See above mechanisms

Not to be used on face or folds

Tazarotene (Tazorac I (gel/cream)

Retinoid derivative,reduce scaling

Irritating

Table 15. Systemic Treatment of Psoriasis Treatment

Considerations

Adverse Effects

Acitretin

More effective when used in combination with phototherapy

Alopecia, cheilitis, teratogenicity, hepatotoxicity, photosensitivity,epistaxis xerosis,hypertriglyceridemia

Used for intermittent control rather than continuously Avoid using for >1yr

Renal toxicity, hypertension, hypertriglyceridemia, immunosuppression, lymphoma

Cyclosporine

.

Methotrexate

Has been used for over 50 yr

Bone marrow toxicity, hepatic cirrhosis, teratogenicity

Apremilast (Otezla : )

Extremely safe

6Iupset headache, loose stool, weight loss

PUVA

Highly effective in achieving remission Avoid >200 sessions in lifetime

Pruritus,burning, skin cancer

Broadband UVB and NB- U VB (311- 312 nm)

UVB is muchless carcinogenic than PUVA.N8 - UVB has not Rare burning been shown to increase the risk of skin cancer

Figure 10. Psoriasis distribution

Mechanism of Biologies “-mab" - monoclonal antibody u *

rT LJ

cept" - receptor

+

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Toronto Notes 2023

D22 Dermatology

Table 16. Biologies Approved in Canada Treatment

Dosing Schedule

Route

Adalimumab|Huniira ' }*

SC SC

50 mg twice per wk for 3 mo, then 50 mg every wk 80 mg » 1 then 40 mg at wk 1 and every 2 wk thereafter

InfliximablAemicade )*

IV

Uslckinumab (Slelara ' )*

SC

5 mg /kg al wk 0.2, 6. and every 8 wk the reader 45 mg or 90 mg at wk 0.4 , and every 12 wk Iherealter 300 mg al wk 0, 1, 2, 3.4, and every month Iherealter 160 mg at wk 0, then 80 mg at wk 2, 4, 6, 8.10, 12, then 80 mg every 4 wk thereafter

EtanercepfEnbrel - }* '

.

SecukinumablCosentyi ' )* SC SC Ixekizumab (Taltz : )*

Brodalumab (Siliq )

-

SC SC

100 mgatwkO, 4. and every 8 wk thereafter 210 mg at wk 0.1, 2 and every 2 wk thereafter

Ccrtolixumab pcgol

SC

400 mg every 2 wk

Guselkumab|Tremfya : )

Effectiveness Action + +

-

Anti INF

-

Anti INF

-

Anti INF

Anli I112/23 +

Anti IL 1 / A

+ +4++

Anti IL 17A

+*+++

Anti IL 23

-

-

mAb IL-17R ( brodalumabis a monoclonal antibody that targets the IL 17 receptor

-

(ClmiiaT

. .

150 mg al wk 0, 4 and every 12 wk Iherealter 100 mg at wk 0.4 and every 12 wk thereafter 320 mg at wk 0.4. 8.12.16 , and every 8 wk thereafter

SC Risankiiomab (Skyriu ) Tildrakizumab ( IIUMYA ) SC Bimekizumab ( BIM 2 ELX [ ) SC '

'Can

Anti INF

-

Aziti IL 23 Anti 1123 ++*•+

Anti - IL 17A/ IL 17F

also be used to treat psoriatic arthritis

GUTTATE PSORIASIS (“RAIN DROP- LIKE”)

Clinical Features • discrete, scattered salmon pink small scaling papules • sites: diffuse, usually on trunk and legs, sparing palms and soles • often antecedent streptococcal pharyngitis

-

Management • UVB phototherapy, sunlight, lubricants, topical steroids • penicillin V, erythromycin, or azithromycin ifCiAS on throat culture

ERYTHRODERMIC PSORIASIS

Clinical Features generalized erythema ( >90% of BSA ) with fine desquamative scale on surface associated signs and symptoms: arthralgia, pruritus, dehydration, electrolyte imbalance • aggravating factors: lithium, p -blockers, NSAlDs, antimalarials, phototoxic reaction , infection • •

Management • potentially life threatening, requires immediate medical care • IV fluids, monitor fluids and electrolytes, may require hospitalization • treat underlying aggravating condition • cyclosporine, acitretin , methotrexate, UV, biologies

-

PUSTULAR PSORIASIS

Clinical Features • sudden onset of erythematous macules and papules which evolve rapidly into pustules, can be painful

• may be generalized or localized • patient usually has a history of psoriasis; may occur with sudden withdrawal from steroid therapy Management • methotrexate, cyclosporine, acitretin, UV, biologies

INVERSE PSORIASIS

Clinical Features • erythematous plaques on flexural surfaces such as axillae, inframammary folds, gluteal fold, inguinal folds • lesions may be macerated

LJ

Management • low potency topical corticosteroids • topical vitamin D analogues (e.g. calcipotriene, calcitriol ) • topical calcineurin inhibitors ( e.g. tacrolimus, pimecrolimus)

+

• phototherapy

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D 23 Dermatology

Toronto Notes 2023

PSORIATIC ARTHRITIS

• 20-30% of patients with psoriasis also suffer from psoriatic arthritis • psoriatic patients with nail or scalp involvement are at a higher risk for developing psoriatic arthritis • see Rheumatology. RH 25

Vesiculobullous Diseases

s

Bullous Pemphigoid Clinical Features

• chronic autoimmune bullous eruption characterized by pruritic, tense, subepidermal bullae on an erythematous or normal skin base

• can present as urticarial plaques without bullae

• common sites: flexor aspect of forearms, axillae, medial thighs, groin, abdomen , mouth in 33% Pathophysiology

• IgG produced against dermal-epidermal basement membrane proteins ( hemidesmosomes) leading to subepidermal bullae Epidemiology

-

• mean age of onset: 60 80 yr, l '= M Investigations

• immunofluorescence shows linear deposition of lgCi and C3 along the basement membrane • anti - basement membrane antibody ( IgG ) ( pemphigoid antibody detectable in serum ) Prognosis • heals without scarring, usually chronic

• rarely fatal Management

-

-

• prednisone 0.5 1 mg/ kg /d until clear, then taper ± steroid sparing agents (e.g. azathiopri ne ,

cyclosporine, mycophenolate mofetil ) • topical potent steroids (dobetasol ) may be as effective as systemic steroids in limited disease • tetracycline + nicotinamide is effective for some cases • immunosuppressants such as azathioprine, mycophenolate mofetil, cyclosporine • For refractory cases: 1Vlg, rituximab, dupilumab, or omalizumab

Pemphigus Vulgaris

g

Clinical Features

• autoimmune blistering disease characterized by flaccid , non - pruritic intraepidermal bullae/ vesicles on an erythematous or normal skin base • may present with erosions and secondary bacterial infection • sites: mouth (90%), scalp, face, chest, axillae, groin, umbilicus • Nikolsky’s sign: epidermal detachment with shear stress • Asboe- Hansen sign: pressure applied to bulla causes it to extend laterally Pathophysiology

Pemphigus Vulgaris vs. Bullous Pemphigoid VUlgariS = Superficial, intraepidermal. flaccid iesions PemphigoiD - Deeper, tense lesions at the dermal -epidermal junction

-

• IgG against epidermal desmoglein l and -3 lead to loss of intercellular adhesion in the epidermis Epidemiology

• 40 -60 yr, M = F, higher prevalence in Jewish, Mediterranean , Asian populations • paraneoplastic pemphigus may be associated with thymoma, myasthenia gravis, malignancy, and use of D-penicillamine Investigations

• immunofluorescence: shows intraepidermal IgG and G3 deposition • circulating scrum anti - desmoglcin IgG antibodies Prognosis • lesions heal with hyperpigmentation but do not scar • may be fatal unless treated with immunosuppressive agents

Pemphigus Foliaceus An autoimmune intraepidermal blistering disease that is more superficial than pemphigus vulgaris due to antibodies against desmoglein 1 a transmembrane adhesion molecule. Appears as crusted patches, erosions and/or flaccid bullae that usually start on the trunk . Localized disease can be managed with topical steroids. Active widespread disease is treated like pemphigus vulgaris

-.

+

Management

• prednisone 1 -2 mg/ kg until no new blisters, then 1 -1.5 mg / kg until clear, then taper ± steroid -sparing agents (e.g. azathioprine, cyclophosphamide, cyclosporine, 1 Vlg, mycophenolate mofetil, rituximab)

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-

D24 Dermatology

Toronto Notes 2023

Dermatitis Herpetiformis Clinical Features • grouped papules/vesicles/ urticarial wheals on an erythematous base, associated with intense pruritus, burning, stinging, excoriations • lesions grouped, bilaterally symmetrical • common sites: extensor surfaces of elbows/ knees, sacrum, buttocks, scalp

Pathophysiology

• transglutaminase IgA deposits in the skin alone or in immune complexes leading to eosinophil and neutrophil infiltration • almost all carry human leukocyte antigen ( HLA ) DQ2 or DQ8, other haplotypes include B8, DR 3, and DQWZ

-

• 90% have gluten sensitive enteropathy, 20% have intestinal symptoms of celiac disease • 30% have thyroid disease; increased risk of intestinal lymphoma in untreated comorbid celiac disease; Fe/folate deficiency' is common

.Epidemiology 20-60 yr, M:F=2:l Investigations

• biopsy • immunofluorescence shows IgA deposits in perilesional skin Management

• dapsone (sulfapvridine if contraindicated or poorly tolerated ) • gluten free diet for life: this can reduce risk of lymphoma

-

Porphyria Cutanea Tarda Clinical Features • skin fragility followed by formation of tense vesicles/ bullae and erosions on photo-exposed skin • gradual healing to scars, milia • periorbital violaceous discolouration , diffuse hypermelanosis, facial hypertrichosis • common sites: light-exposed areas subjected to trauma, dorsum of hands and feet, nose, and upper

trunk Pathophysiology

• uroporphyrinogen decarboxylase deficiency leads to excess heme precursors • can be associated with hemochromatosis, alcohol abuse. DM, drugs (estrogen therapy, NSAIDs), HIV, hepatitis C, increased iron indices Epidemiology • 30-40 yr, M >F Investigations

-red fluorescence under Wood’s lamp ( UV rays) • 24 h urine has elevated uroporphyrins • stool contains elevated coproporphyrins • immunofluorescence shows IgE at dermal-epidermal junctions

• urine and HC15% shows orange

Management

• discontinue aggravating substances (alcohol, estrogen therapy ) • phlebotomy to decrease body iron load • low dose hydroxychloroquine

Drug Eruptions

Classification by Naranjo et al. has 4 criteria:

t Temporal relationship between drug

Exanthematous

exposure and reaction

2. Recognized response to suspected z :- z

EXANTHEMATOUS DRUG REACTION

LJ

3. Improvement after drug withdrawal 4. Recurrence of reaction on re challenge with the drug Definite drug reaction requires all 4 criteria to be met Probable drug reaction requires 41 3 to be met Possible drug reaction requires only #1

-

Clinical Features

• morphology: erythematous macules and papules ± scale • spread: symmetrical, trunk to extremities • time course: 7 14 d after drug initiation, fades 7 14 d after withdrawal

-

G

Diagnosis of a Drug Reaction

-

-

+

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Toronto Notes 2023

D25 Dermatology

. commoncommon

Epidemiology cutaneous drug reaction; increased in presence of infections most causative agents: penicillin, sulfonamides, phenytoin • Management

• weigh risks and benefits of drug discontinuation • antihistamines, emollients, topical steroids DRUG- INDUCED HYPERSENSITIVITY SYNDROME ( DIHS) /DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS ( DRESS)

w

Drug Hypersensitivity Syndrome Triad

Fever Exanthematous eruption Internal organ Involvement

Clinical Features

• morphology: morbilliform rash involving face, trunk, arms; can have facial edema • systemic features: fever, malaise, cervical lymphadenopathy, internal organ involvement (e.g. hepatitis, arthralgia, nephritis, pneumonitis, lymphadenopathy, hematologic abnormalities, thyroid abnormalities) • spread: starts with face or periorbitally and spreads caudally; no mucosal involvement • time course: onset 1-6 wk after first exposure to drug; persists wk after withdrawal of drug Epidemiology • rare: incidence varies considerably depending on drug • common causative agents: anticonvulsants (e.g. phenytoin, phenobarbital, carbamazepine, lamotrigine ), sulfonamides, and allopurinol • 10% mortality if severe, undiagnosed, and untreated Management

• discontinue offending drug ± prednisone 0.5 mg / kg /d , consider cyclosporine in severe cases • may progress to generalized exfoliative dermatitis /erythroderma if drug is not discontinued

Urticarial DRUG- INDUCED URTICARIA AND ANGIOEDEMA

Clinical Features

• morphology : wheals lasting >24 h unlike non -drug induced urticaria, angioedema ( face and mucous membranes)

• systemic features: may be associated with systemic anaphylaxis ( bronchospasm , laryngeal edema , shock )

-

• time course: h d after exposure depending on the mechanism Epidemiology

• second most common cutaneous drug reaction • common causative agents: penicillins, ACE1, analgesics/anti-inflammatories, radiographic contrast media Management • discontinue offending drug, treatment with antihistamines, oral corticosteroids, epinephrine if

anaphylactic SERUM SICKNESS- LIKE REACTION

Clinical Features

• morphology: symmetrical cutaneous eruption (usually urticarial ) • systemic features: malaise, low grade fever, arthralgia, lymphadenopathy • time course: appears 1 -3 wk after drug initiation, resolves 2 -3 wk after withdrawal Epidemiology

-

• more prevalent in children (0.02 0.2%) • common causative agents: cefaclor in children; bupropion in adults Management

L

• discontinue offending drug ± topical /oral corticosteroids

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-

-

D26 Dermatology

Toronto Notes 2023

Pustular ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP) Clinical Features

• morphology: extensive erythematous, edematous, and sterile pustules • systemic features: high fever, leukocytosis with neutrophilia • spread: starts in face and intertriginous areas, spreads to trunk and extremities • time course: appears I wk after drug initiation, resolves 2 wk after withdrawal Epidemiology • rare: 1 5/ million • common causative agents: aminopenicillins, cephalosporins, clindamycin, calcium channel blockers

-

Management

• discontinue offending drug and systemic corticosteroids

KE

Bullous STEVENS-JOHNSON SYNDROME (SJS )/TOXIC EPIDERMAL NECROLYSIS (TEN)

Clinical Features

• morphology: prodromal rash ( morbilliform / targetoid lesions ± purpura , or diffuse erythema ), confluence of flaccid blisters, positive Nikolsky sign (epidermal detachment with shear stress), full thickness epidermal loss; dusky tender skin, bullae, desquamation /skin sloughing, atypical targets • classification: BSA with epidermal detachment: < 10% in SJS, 10 30% in SJS/ TEN overlap, and >30% in TEN spread: face and extremities; may generalize; scalp, palms, soles relatively spared; erosion of mucous membranes ( lips, oral mucosa, conjunctiva, GU mucosa ) • systemic features: fever ( higher in TEN ), cytopenias, renal tubular necrosis/AKl, tracheal erosion, infection, contractures, corneal scarring, phimosis, vaginal synechiae • time course: appears 1 3 wk after drug initiation; progression 40, malignancy, initial BSA detached >10%, tachycardia >120 bpm. serum urea >10 mmol/L serum glucose >14 mmol/L, serum bicarbonate 2 should be transferred to intensive care or bum unit

Score at admission is predictive of survival: 94% for 0- 1, 87% for 2.53% for 3.25% for 4, and 17% for zS

• risk factors: SLE , HIV /A IDS, HLA - B1502 ( reaction most prevalent in East Asians, associated with

carbamazepine), HLA - B5801 ( reaction most prevalent in Asian and White populations, associated with allopurinol ) • common causative agents: drugs ( allopurinol, anti-epileptics, sulfonamides, NSAlDs, cephalosporins) responsible in 50% of SJS and 80% of TEN; viral or mycoplasma infections • prognosis: 5% mortality in SJS, 30% in TEN due to fluid loss and infection Differential Diagnosis • scarlet fever, phototoxic eruption, GVHD, SSSS, exfoliative dermatitis, AGEP, paraneoplastic

pemphigus

Management

• discontinue offending drug • admit to intermediate /intensive care/ burn unit

• supportive care: IV fluids, electrolyte replacement, nutritional support, pain control, wound care, sterile handling, monitor for and treat infection • IVIg, cyclosporine, or etanercept

Other FIXED DRUG ERUPTION

Systemic ImmunomodutatingTherapies for Stevens Johnson Syndrome and Toxic Epidermal He crolysis: A Systematic Review and Mela analysis JAMA Dermatol 2017:153:514 522 Purpose: To examine possible immunomodulating treatments for SJS/IEH and estimate mortality effect compared to suppo Hue tare. Methods: Systematic renew ol randomited and nonraodomindstudietofl systemic

-

-

-

mmunomodulating therapies or suppotlnre cere

lot SJS/IEH.

Results: Ninety- six strides with 3248 patients

were included in the final analysis. Glucocorticoids were associated writha survival benefit for patients {aggregate - OR Oi 95% Cl 0.3-101). Though findings were limited In a small number of patients overall, cyclosporine was associated with significant benefit (OR 0.1: 95% Cl 0.0 0.4). No beneficial effects were observed with other therapies, including IVIg. Conclusion: ( hough based on limited evidence, glucocorticoids and cyclosporine were most promising as SJS/ fEN immunosuppressive therapies.

.

-

Clinical Features

• morphology: sharply demarcated erythematous oval patches on the skin or mucous membranes • spread: commonly face, mucosa, genitalia, acral; recurs in same location upon subsequent exposure to the drug ( fixed location )

n

LJ

Epidemiology • common causative agents: antimicrobials (tetracycline, sulfonamides), anti-inflammatories, psychoactive agents ( barbiturates), phenolphthalein

+

Management

• discontinue offending drug ± prednisone I mg / kg/d x 2 wk for generalized lesions • potent topical corticosteroids for non -eroded lesions or antimicrobial ointment for eroded lesions

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D27 Dermatology

Toronto Notes 2023

PHOTOSENSITIVITY REACTION

Clinical Features

• phototoxic reaction: “exaggerated sunburn” (erythema, edema, vesicles, bullae) confined to sunexposed areas

• photoaliergic reaction: pruritic eczematous eruption with papules, vesicles, scaling, and crusting that may spread to areas not exposed to light

Pathophysiology

• phototoxic reaction: direct tissue injury • photoaliergic reaction: type IV delayed hypersensitivity Epidemiology • common causative agents: chiorpromazine, doxycycline, thiazide diuretics, procainamide Management

• sun protection ± topical /oral corticosteroids

Heritable Disorders Ichthyosis Vulgaris Clinical Features

• xerosis with fine scaling as well as large adherent scales (“fish-scales” ) • affects arms, legs, palms, soles, back, forehead, and cheeks; spares flexural creases • improves in summer, with humidity, and as the child grows into adulthood Pathophysiology • genetic deficiency in filaggrin protein leads to abnormal retention of keratinocytes ( hyperkeratosis )

• scaling without inflammation

Epidemiology

• 1:300 incidence • autosomal dominant inheritance • associated with AD and keratosis pilaris

Investigations

• electron microscopy: keratohvalin granules Management • immersion in bath and oils followed by an emollient cream, humectant cream, or creams/otl containing urea or a- or (5- hydroxv acids • intermittent systemic retinoids for severe cases

Epidermolysis Bullosa Clinical Features

• blisters and erosions on skin and mucous membranes following minor trauma • extracutaneous manifestation may occur in severe disease and include intraoral blistering and erosions, naii abnormalities, esophageal strictures, and genitourinary abnormalities Pathophysiology

• group of rare inherited diseases caused by mutations in genes coding for structural proteins involved in basement membrane of skin Differential Diagnosis • friction blisters, epidermolysis bullosa acquisita Investigations

• skin biopsy for immunofluorescence mapping

n «. J

Management

• symptomatic management • avoid inducing friction on skin • place padding on furniture • wear loose clothing and appropriate footwear • maintain cool ambient room temperature

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D28 Dermatology

Toronto Notes 2023

Neurofibromatosis (Type I; von Recklinghausen’s Disease) Clinical Features • diagnostic criteria includes 2 or more of the following, if parent not diagnosed with NF1: 1.6 or more cafe-au-lait patches>1.5 cm in an adult or 6 or more cafe-au-lait macules >0.5 cm in

prepubertal individuals 2.axillary or inguinal freckling 3.2 or more iris hamartomas ( lisch nodules) 4.optic glioma 5.2 or more neurofibromas of any type or one plexiform neurofibroma 6. distinctive bony lesion (sphenoid wing dysplasia or thinning oflong bone cortex ) 7. heterozygous pathogenic NH variant with a variant allele fraction of 50% in normal tissue • a child of a parent who meets the diagnostic criteria above needs I or more to be diagnosed with NT 1 • associated with pheochromocytoma, astrocytoma, bilateral acoustic neuromas, bone cysts, scoliosis, precocious puberty, developmental delay, and renal artery stenosis • skin lesions less prominent in neurofibromatosis Type 11 ( see Paediatrics. PS9) Pathophysiology • autosomal dominant disorder with excessive and abnormal proliferation of neural crest elements (Schwann cells, melanocytes), high incidence of spontaneous mutation • linked to absence of neurofibromin (a tumour suppressor gene)

Epidemiology • incidence 1 in 3000

Investigations • Wood 's lamp to detect cafe au lait macules in patients with pale skin

- -

Management • refer to orthopaedics, ophthalmology, plastics, and psychiatry • follow- up annually for brain tumours (e.g. astrocytoma ) • excise suspicious or painful lesions • see Paediatrics, PS9

Oculocutaneous Albinism Clinical Features

hvpopigmentation of skin and hair, including eyebrows and eyelashes, compared to family members and persons of same ethnicity • ocular involvement: decreased retinal pigmentation , impaired vision, photophobia, nystagmus, strabismus •

Pathophysiology • group of genetic disorders of melanin biosynthesis • autosomal recessive Epidemiology • 1 in 20000 • varies across ethnic groups Investigations •

often clinical diagnosis, may consider molecular testing

«

Interventions lor Vitiligo tore ne D 8 Syst Rev 2315 ACK C3263 P urpose: To assess the effects of eisirg interceptions used mtte treregeiertcf rttgo. M ethod: Systematic rerew of 8CTs essess rg the effects of vitiligo treatments (tog ce tree erts. light therapies, oral treatments surgcel ceiscds). Primary outcomes mere goaity of hie and >JSt

—

,

Management

• sun protection • close surveillance for skin cancers with whole body skin examinations

Vitiligo Clinical Features • primary pigmentary disorder characterized by depigmentation • acquired destruction of melanocytes characterized by sharply demarcated white patches • associated with streaks of depigmented hair, chorioretinitis • sitest extensor surfaces and periorificial areas ( mouth, eyes, anus, genitalia ) • Koebner phenomenon, may be precipitated by trauma Pathophysiology • acquired autoimmune destruction of melanocytes

re- pigmentation.

Results: Ninety-six RCts wits 4512 pa - tc parts

were deemed el igihle. of nit id only 25 reported on the pnmary outco raes and were Snaly edoded. 8e - pignentation was better msanseasoo therapy (calcipotnpl ptos PtfVi. than Pint alone hydiocort soreU -P.tyate pin euiaec laser vs. excimer laser alone: oral mmpaseof prednisolone ( 0MP|pins narrowband UVB is. ON ? alone: acathioomeirtt PtfHc. PUUae-e: ,

8 -methos ypsore en (8 -M0P|ptasst igttvs. psoralen ). Jnoo -signficant increase a pnoortma of participants with >75% ra-pgirertatic mas noted n favour nf NB-UVB compared to Finn. Compared to PUM. the MV -UVB group reported lomer i -utesces of nausea and erythema. Put not itch eg. Conclusions: Snne studies support existing therapies for v tligo menagement t utfo. om-up s needed to assess permanence nf re-p gmentanop and higher quality RCTs need to be condcctel '

-

Activate Windows 80% on sun exposed sites • typical latency period of 20 -50 yr between time of U V damage and onset of BCC also associated with previous scars, radiation, trauma , arsenic exposure, or genetic predisposition (Gorlin Syndrome)

shave biopsy; otherwise punch or cxcisional biopsy may be more appropriate

Surgical Margins

• Smaller lesions: electrodessication

Epidemiology • most common malignancy in humans • 75% of all malignant skin tumours in > 40 yr old, increased prevalence in the elderly • risk factors: M > F, skin phototypes I and 11 , chronic cumulative sun exposure, ionizing radiation , immunosuppression, arsenic exposure

•

Differential Diagnosis • •

benign: sebaceous hyperplasia , intradermal melanocytic nevus, dermatofibroma malignant: nodular MM , SCC, merkel cell carcinoma ( MCC)

and curettage with 2 3 mm margin of normal skin Deep infiltrative lesions: surgical excision with 3-5 mm margins beyond visible and palpable tumour border, which may require skin graft or flap; or Mohs surgery, which conserves tissue and does not require margin control

Management

see Table 22 , Management of Nonmelanoma Skin Cancers • follow - up for new primary disease or recurrence • 95% cure rate if lesion < 2 cm in diameter or if treated early

•

Table 22 . Management of Nonmelanoma Skin Cancers Indications

Disadvantages

Imiquimod 5% cream (Aldara - )

Superficial BCCs. Bowen's Disease

Side effects: erythema, edema , ulceration and scaling

Cryotherapy

Superficial BCCs. Bowen's Disease Advantages: minimal equipment, simple to perform , cost- effective, no restriction of activity after surgery

Margin around cancer may not be free, potential for scarring , minimally painful , no skin tissue for diagnosis

Treatment Treatment Options Category Topical

5- lluorouracil ( Efudex Procedural

Surgical

| Superficial

BCCs . Bowen 's Disease

Side effects: pain , burning , swelling

Photodynamic therapy

Superficial BCCs Advantages: low cost , tolerable side effect profile

Side effects: pain

Radiation therapy

Advanced cases of BCC.SCC Advantages: if lesions are located in cosmetically sensitive area

Side effects: alopecia , pigmentary changes, fibrosis, atrophy, buccal mucositis, gingivitis, telangiectasias

Shave excision and electrodessication and curettage

.

Most types of BCCs Bowen's Disease

-

Advantages: minimal equipment needed , simple to perforin , cost effective, no restriction of activity after surgery

.

Not used for morpheaform BCC margin around cancer may not be free, slow healing, possible scarring

Mohs surgery

BCC and SCC lesions on the face or in areas that are difficult to reconstruct Advantages: highest cure rate, good cosmetic results, healthy skin tissue

Iraditional surgical excision

SCC

Activity restriction alter surgery if skin graft /flap needed, healthy tissue around

Advantages: margin around cancer more likely to be free than shave excision , tissue is available for diagnosis, cosmetic satisfaction

cancer must be removed

Vismodegib

Metastatic BCC , Gorlin Syndrome ( multiple BCCs)

Side effects: muscle spasms , hair loss, abnormal taste, weight loss, nausea ,

Expensive, highly technical, resource intensive, activity restriction after surgery if skin graft/ flap needed

ri

LJ

is preserved

Medical Therapy

+

amenorrhea

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Toronto Notes 2023

D ll Dermatology BOWEN’S DISEASE ( SQUAMOUS CELL CARCINOMA IN SITU)

Clinical Features

• sharply demarcated erythematous patch / thin plaque with scale and /or crusting

• often 1 -3 cm in diameter and found on the skin and mucous membranes

-

• evolves to SCC in 10 20% of cutaneous lesions and >20 % of mucosal lesions Management • see Table 22 , Management of Nonmelanoma Skin Cancers, D40 SQUAMOUS CELL CARCINOMA

Clinical Features

• hyperkeratotic indurated , pink /red /skin -coloured papule/plaque/ nodule with surface scale/crust ± ulceration • more rapid enlargement than BCC • exophytic (grows outward ), may present as a cutaneous horn • common sites: face, ears, scalp, forearms, dorsum of hands Pathophysiology

• malignant neoplasm of keratinocytes ( primarily vertical growth ) • predisposing factors include: cumulative UV radiation, PUVA , ionizing radiation therapy/

exposure, chemical carcinogens (such as arsenic, tar, and nitrogen mustards), HPV 16 or 18, im mu nosuppression • may occur in previous scar (SCC more commonly than BCC) Epidemiology • second most common type of cutaneous neoplasm in less pigmented skin types • most common cutaneous neoplasm in patients with Type 6 skin, typically in non-photoexposed sites • primarily on sun-exposed skin in the elderly, M >F, skin phototypes I and 11, chronic sun exposure • SCC is the most common cutaneous malignancy in immunocompromised patients such as in organ transplant recipients, with increased mortality as compared to non-immunocompromised population

Differential Diagnosis

• benign: wart, psoriasis, irritated seborrheic keratosis

• pre- malignanl: AK, Bowenoid papulosis • malignant: keratoacanthoma , Bowen 's disease, BCC, amelanotic melanoma Management

• see table 22 , Management o/ Nonmtlanoma skin Cancers , D id • lifelong follow up ( more aggressive treatment than BCC)

-

Prognosis

• good prognostic factors: early treatment, negative margins, and small size of lesion • rate of metastasis from primary SCC is 2-5% • higher risk of metastasis if diameter >2 cm, depth >2 mm, recurrent, involvement of bone/muscle/ nerve, location on scalp/ears/ nose/lips, immunosuppressed, caused by arsenic ingestion, or tumour arose from scar/chronic ulcer/burn/genital tract /sinus tract KERATOACANTHOMA

Clinical Features • rapidly growing, firm , dome shaped , erythematous or skin coloured volcano like nodule with central keratin filled crater

•

may spontaneously regress

-

• sites: sun - exposed skin Pathophysiology

• epithelial neoplasm with atypical keratinocytes in epidermis • low grade variant of SCC Etiology • HPV, U V radiation, chemical carcinogens (tar, mineral oil ) Epidemiology • most common in > 50 yr old, rare in < 20 yr old

Differential Diagnosis • treat as SCC until proven otherwise

• nodular BCC, MCC, hypertrophic solar keratosis, verruca vulgaris

(ft

-

Interventionsfor IK Cochrane D8 Syst Rev 2012:2:C 004415 Purport: la assess thetffiucy of trejirrentsfor AK . Methods: Systematic rev eve ot KCIs. Results: A total of 83 RCTs (10036 patients) were Included evaluating 24 treatments.Cryotherapy, diclofenac 5 fluorouracil imiqiimd ingenol

.-

.

.

.

mebutate photodynamic therapy, resurfacing and trichloroacetic acid peel mere all effective at treating AK and generally comparahte with one another.Skin irritation was more common with diclofenac and S fluorouracil. Photodynamic therapy andimiqoimod treatment resulted in better cosmetic appearance. Conclusion:for individual lesions, photodynamic therapy is more effective than cryotherapy, for field directed treatments. S-Duorouracrl. diclofenac imiquimod and ingenol mebutate had comparable

n LJ

-

-

+

efficacy.

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D12 Dermatology

Toronto Notes 2023

Management

• surgical excision or saucerization (shave biopsy) followed by electrodesiccation of the base, treated similarly to SCC • intralesional methotrexate or 5-fluorouracil injection

Malignant Melanoma Clinical Features • malignant characteristics of a mole: “ABCDE” mnemonic • sites: skin, mucous membranes, eyes, CNS • 2/3 arise de novo without an associated nevus • abnormal dermoscopic features

Does this Patient have a Mole or Metanoma?

—

Clinical Subtypes of Malignant Melanoma Listed from most to least common subtype • superficial spreading melanoma ( 60 70% of all melanomas)

-

• atypical melanocytes initially spread laterally In epidermis then invade the dermis • irregular, indurated , enlarging plaques with red / white/ blue discolouration , focal papules or nodules • ulcerate and bleed with growth • subtype most likely associated with pre-existing nevus

ABCDE checklist Asymmetry Border (irregular and/or indistinct) Colour (varied) Diameter (increasing or >6 mm) Enlargement , elevation, evolution (i.e. change in colour, size, or shape) Sensitivity 92% (Cl 82- 96%) Specificity 100% (Cl 54 -100%)

-

JUU 199l;2tt:WS W1

• nodular melanoma ( 15-30% of all melanomas ) • atypical melanocytes that initially grow vertically with little lateral spread • uniformly ulcerated, blue-black, and sharply delineated plaque or nodule

1 mm thick OR 1 mitoses/mm2 (Stage IB or higher melanoma patients should

.

be offered a sentinel lymph node biopsy) • Assess sentinel node at time of wide

excision

Pathophysiology • malignant neoplasm of pigment-forming cells (melanocytes and nevus cells)

Epidemiology

• I in 75 (Canada ), I in 50 ( US ) • risk factors: increasing age, fair skin , red hair, positive pcrsonal / family history, familial dysplastic nevus syndrome, large congenital nevi ( >2() cm ), any dysplastic nevi, > 50 common nevi, immunosuppression , sun exposure with sunburns, tanning beds • most common sites: back ( M ), calves ( F) • worse prognosis if: male, on scalp, hands, feet, late lesion , no pre-existing nevus present Differential Diagnosis • benign: nevi, solar lentigo, seborrheic keratosis, dermatofibroma, spitz nevus • malignant: pigmented BCC, dermatofibrosarcoma protuberans

Management

• excisional biopsy preferable ( margin determined by Breslow depth ), otherwise incisional biopsy,

sentinel lymph node dissection controversial • remove full depth of dermis and extend beyond edges of lesion only after histologic diagnosis • beware of lesions that regress - tumour is usually deeper than anticipated • high dose ll'N for stage 11 ( regional), chemotherapy (cis-platinum, BCG ) and high dose ll' N for stage Ill (distant) disease • newer chemotherapeutic regimens, immunotherapy, and vaccines in metastatic melanoma • radiotherapy may be used as adjunctive treatment

-

Set Landmark Dermatology trials tabic lot nott reformation on the Inal by Hodi elal. 2010. which

d Claris improved survival with Iprlimmnab in patterns vnth metastatic melanoma .

-

+ See Landmark Dermatology Trials table for more information on the DDIH 3 trial comparing the efficacy ofBRJkf kinase inhibitor vemurafemb (PlX4032) to dacubaiine in patients with metastatic melanoma.

-

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D43 Dermatology

Toronto Notes 2023

Table 23. American Joint Committee on Cancer Staging System Based on Breslow ’s Thickness of Invasion Tumour Depth

Stage

Approximate 5 Yr Survival

II 20 x 109/ L with Sezary »

cells can be considered to have evolved from mycosis fungoides ( not initially meeting diagnostic

criteria ), but more commonly arises de novo associated with intense pruritus, alopecia, palmoplantar hyperkeratosis, and systemic symptoms (fatigue, fever)

• high mortality Pathophysiology

• clonal proliferation of skin-homing CD4 T-cells Epidemiology • seen in >50 yr, M:T ratio is 2:1 Differential Diagnosis

-

• tinea corporis, nummular dermatitis, psoriasis, DLL, Bowen 's disease, adult T Cell leukemia lymphoma ( ATL)

-

Investigations

• skin biopsy ( histology, “lymphocyte antigen cell ” markers, TcR gene arrangement ) • blood smear looking for Sezary cells or flow cytometry (e.g. CD4:CD8 > 10 is characteristic but not diagnostic of Sezary) • imaging (for systemic involvement)

Management

• Mycosis fungoides

depends on stage of disease early stage: topical steroids, topical chemotherapy, topical retinoids, topical imiquimod, local radiation , and/or PUVA, NB UVB (311 313 mm ) advanced stage: biologies, low dose methotrexate, systemic retinoids, PUVA • Sezary syndrome » oral retinoids and Il'N extra - corporeal photopheresis • may need radiotherapy for total skin electron beam radiation • may maintain on U V therapy other chemotherapy agents

-

-

-

-

r -I

KAPOSI SARCOMA

LJ

Definition • an angioproliferative neoplasm that requires infection with human herpesvirus 8 ( HHV-8) • 4 types based on the clinical circumstance at which it develops • classical: develops in middle or old age in individuals of Mediterranean descent •» endemic: seen in sub Saharan indigenous Africans iatrogenic: associated with immunosuppressive drug therapy and renal allograft recipients AIDS associated

+

-

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Toronto Xotes 2023

Dll Dermatology

Clinical Features • purplish, reddish blue, or dark brown / black macules, plaques, and nodules on the skin • skin nodules can range in size from very small to several centimeters in diameter, and lesions may ulcerate and bleed • lesions typically present on the distal extremities • also atfects the gastrointestinal tract and lymphatics leading to secondary lymphoedema Epidemiology • incidence is 0.02% to 0.06% of all malignant tumours, M > F

Differential Diagnosis

• well - differentiated angiosarcoma, benign lymphangiomatosis, hypertrophic lichen planus Investigations • biopsy • PCR - can identify HHV 8 DNA sequences

-

Treatment

• surgery', cryotherapy, laser surgery, photodynamic therapy, topical retinoids, immunomodulators for superficial macules and plaques • radiation therapy, systemic chemotherapy

Diseases of Hair Density Hair Growth • hair grows in a cyclic pattern that is defined in 3 stages ( most scalp hairs are in anagen phase ) 1.growth stage = anagen phase 2. transitional stage = catagen stage 3. resting stage telogcn phase • total duration of the growth stage reflects the type and location of hair: eyebrow, eyelash , and axillary hairs have a short growth stage in relation to the resting stage • growth of the hair follicles is also based on the hormonal response to testosterone and dihydrotestosterone ( DHT ); this response is genetically controlled

=

Non- Scarring (Non- Cicatricial) Alopecia

Hair Regrowth Potential Ability to regrow hair depends on location of inflammatory infiltrates on hair follicle as stem cells are located at the upper part (bulge region) of the hair follicle • Scarring alopecia: Inflammatory infiltrates found in upper part of hair follicles, destroying stem cells • Non scarring alopecia: Hair follicle is not permanently damaged, and therefore spontaneous or treatment induced regrowth is possible

-

-

ANDROGENETIC ALOPECIA

Clinical Features

-

-

• male or female pattern alopecia

• males: fronto- temporal areas progressing to vertex, entire scalp may be bald • females: widening of central part, “Christmas tree” pattern

Pathophysiology

• action of DHT on hair follicles

-

Autoimmune • Alopecia areata Endocrine • Hypothyroidism • Androgens Micronutrient deficiencies

Epidemiology • males: early 20s-30s • females: 40s-50s

Iron .• Zinc

Management

.

• camouflage techniques (i.e. wigs, hair extensions, powders, concealing lotions or sprays ) • topical minoxidil ( Rogaine*) solution or foam to reduce rate of loss/ partial restoration • females: spironolactone (anti-androgenic effects), cyproterone acetate ( Diane-35*) • males: finasteride ( Propecia*) (5-a - reductase inhibitor ) 1 mg /d

• oral minoxidil • procedural ( hair transplant, platelet - rich plasma ) TELOGEN EFFLUVIUM

Clinical Features • uniform decrease in hair density secondary to hairs leaving the growth (anagen ) stage and entering the resting (telogen ) stage of the cycle Pathophysiology

• variety of precipitating factors ( i.e. post - partum , psychological stress, major illness ) • hair loss typically occurs 2-4 mo after exposure to precipitant • regrowth occurs within a few mo but may not be complete

-

ODx of Non Scarring ( Non Cicatricial) Alopecia

Toxins

• Heavy metals • Anticoagulants • Chemotherapy

Vitamin A Trauma to the hair follicle • Trichotillomania • Tight ponytail or braiding styles Other • Syphilis Severe illness Childbirth

..

Precipitant!of Telogen Effluvium

hair follicles out of anagen and into telogen St ress and Scalp disease (surgery) Endocrine (hypothyroidism , post partum ) Nutritional (iron and protein deficiency) Drugs (acitretin, heparin , lithium IFN 8 blockers, valproic acid SSRIs)

"SEND"

-

-

.

+

. .

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D45 Dermatology

Toronto Notes 2023

ANAGEN EFFLUVIUM

Clinical Features • hair loss due to insult of hair follicle impairing its mitotic activity (growth stage) Pathophysiology

• precipitated by chemotherapeutic agents ( most common ), other medications ( bismuth, levodopa,

colchicine, cyclosporine), exposure to chemicals ( thallium, boron, arsenic) • dose-dependent effect • hair loss 7-14 d after single pulse of chemotherapy; most clinically apparent after 1-2 mo • reversible effect; follicles resume normal mitotic activity few wk after agent stopped

(§) Hair Loss

ALOPECIA AREATA

Clinical Features

• autoimmune disorder characterized by patches of complete hair loss often localized to scalp, but can affect eyebrows, beard, eyelashes, etc. • may be associated with dystrophic nail changes - fine stippling, pitting • “exclamation mark ” pattern (hairs fractured and have tapered shafts, i.e. looks like “!”)

TOP HAT Telogen effluvium, Tinea capitis Out of iron, zinc Physical: trichotillomania , tight ponytail or braiding styles Hormonal: hypothyroidism, androgenic Autoimmune: SLE alopecia areata Toxins: heavy metals, anticoagulants, chemotherapy, vitamin A, SSRIs

.

• may be associated with autoimmune conditions: pernicious anemia, vitiligo, thyroid disease,

Addisons disease

• spontaneous regrowth may occur within mo of first attack (worse prognosis if young at age of onset

and extensive loss) • frequent recurrence often precipitated by emotional distress • alopecia totalis: complete loss of hair on scalp • alopecia universalis: complete loss of scalp hair, eyelashes, eyebrows, and body hair

-

Non scarring alopecia: intact hair follicles on exam * biopsy not required ( but may be helpful) Scarring alopecia: absent hair follicles on exam •* biopsy required

Management

• excellent prognosis for localized disease • topical corticosteroids and intralesional triamcinolone acetonide (corticosteroids) can be used for isolated patches • topical immunotherapy (diphencyprone, anthralin ) • systemic immunosuppressants for refractory or extensive disease • immunomodulatory (diphencyprone, anthralin ) • newer treatments: janus kinase inhibitors

Alopecia Areata Subtypes Alopecia totalis: loss of all scalp hair and eyebrows Alopecia universalis: loss of all body hair

OTHER

• trichotillomania: impulse - control disorder characterized by compulsive hair pulling with irregular patches of hair loss, and with remaining hairs broken at varying lengths

• traumatic (e.g. tight braiding styles, wearing tight ponytails, tight tying of hair coverings)

Scarring (Cicatricial) Alopecia Clinical Features • irreversible loss of hair follicles with fibrosis Etiology

• physical: radiation , burns • infections: fungal, bacterial , I B, leprosy, viral ( HSV )

• primary inflammatory - subdivided into lymphocytic, neutrophilic, and mixed lymphocytic: lichen planus (lichen planopilaris) - white scale around hair follicles, up to 50% have lichen planus at other body sites DLL ( note that SIL can cause an alopecia unrelated to DLL lesions which are non scarring ) central centrifugal cicatricial alopecia (CCCA ): seen in up to 40% of Black women, starting at central scalp; one of the most commonly diagnosed scarring alopecias, may be associated with hair care practices keratosis follicularis spinulosa decalvans ( autosomal dominant, X-linked )

-

neutrophilic: folliculitis decalvans - discharge of pus and blood, tufting of hair follicles dissecting cellulitis of the scalp - follicular papules, pustules, nodules, and abscesses develop on the scalp • mixed acne keloidalis nuchae - dome-shaped papules, pustules, and plaques on the occipital scalp • morphea: “coup de sabre” with involvement of centre of scalp *

ri

Investigations

• biopsy from active border

+

Management

• infections: treat underlying infection

• inflammatory: topical / intralesional steroids, anti-inflammatory antibiotics, antimalarials, immunosuppressants (e.g. cyclosporine)

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D 16 Dermatology

Toronto Notes 2023

Postmenopausal Hair Changes

• estrogen regulates the growth and cycling of hair follicles • hormonal changes (e.g. reduced estrogen ) during menopause leads to decreased hair diameter, growth rate, and percentage of hairs in the anagen phase; moreover, chronological age affects hair density • these compounded effects of the two factors above ( hormone changes and aging ) may lead to a perception of decreased scalp hairs in middle-aged women

Nails and Disorders of the Nail Apparatus Table 24 . Nail Changes in Systemic and Dermatological Conditions Definition/ Etiology

Associated Disease

Clubbing

Proximal nail plate has greater than 180" angle to nail fold, watch-glass nails, bulbous digits

Cyanotic heart disease, bacterial endocarditis, pulmonary disorders Gl disorders, etc.

Koilonychia

Spoon shaped nails

Iron deficiency, malnutrition. DM

Onycholysis

Separation of nail plale from nail bed

Psoriasis, dermatophytes, thyroid disease, repetitive

Onychogryphosis

Hypertrophy ol the nail plate producing a curved,

Poor circulation,chronic inflammation, tinea

Nail Abnormality NAIL PLATECHAN 6 ES

.

trauma daw like delormity

Onychohemia

Subungual hematoma

Onychomycosis

Fungal infection of nail (e.g. dermatophyte, yeast mould)

HIV DM peripheral arterial disease

Onychomadesis

Hail plate detachment from proximal nail fold due to severe trauma that produces a complete arrest of nailmatrix activity

Manicures, ecrema,chronic paronychia, severe or febrile illness, erythroderma

Trauma to nail bed

.

. .

SURFACE CHANGES

-

V Shaped Nicking

Distal margin has Y - shaped loss of the nail plate

Darier's disease (keralosisfollicularis)

Pterygium Inversum Unguis

Distal nail plale docs not separate from underlying nail bed

Scleroderma

Pitting

Punctate depressions that migrate distally with

Psoriasis (random pattern), alopecia areata ( geometric, grid-shaped arrangement), eczema

growth Transverse Ridging

Transverse depressions, often more in central portion of nail plate

Serious acute illness slows nail growth (when present in all nails Beau's lines), eczema, chronic paronychia, trauma

-

Transverse White lines

8 ands of while discolouration

Poisons, hypoalbuminemia (Muchtcke ’s lines)

Onychorrhexis

Brittle nails leading to longitudinal ridging

Lichen planus, psoriasis, normal aging, fungal infection

COLOUR CHANGES

.

Yellow

Tinea, ( aundice tetracycline, pityriasis rubra pilaris, yellow nail syndrome, psoiiasis tobacco use

Green

Pseudomonas

.

Black

Melanoma,hematoma

Brown

Nicotine use, psoriasis, poisons, longitudinal melanonychia (more common in FitzpalrickV and VI)

Splinter Hemorrhages

.

Extravasation of blood from longitudinal vessels of ftauma, bacterial endocarditis, blood dyscrasias nail bed blood attaches to overlying nail plate and psoriasis moves distally as it grows

.

Oil Spots

8rown- yellow discolouration

Psoriasis

Leukonychia

White nails

Hypoalbuminemia, chronic renal failure

Terry 's Nails

White proximal nail, darker distal nail with ground glass appearance, no lunula

liver cirrhosis

NAIL FOLD CHANGES Herpetic Whitlow

HSV infection of distal phalanx

HSV infection

Paronychia

Local inflammation of the nail fold around the nail bed

Acute: painful infection Chronic: constant welting (e.g. dishwashing thumbsucking)

Nail Fold Telangicctasias

Cuticular hemorrhages, roughness, capillary

Scleroderma, SIE dermalomyosltrs

.

.

changes

r

T

LJ

LOSS OF HAILS

Temporary Loss

Occurs without scarring

Trauma (especially toenails or fingernails after large subungual hematoma) Beau's lines after severe illness

Permanent Loss

Occurs with scarring

Lichen planus ( pterygium), genetic abnormalities

.

+

(rare)

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D47 Dermatology

Toronto Notes 2023

Adnexal Disorders HIDRADENITIS SUPPURATIVA

Definition

• a chronic inflammatory skin condition that is a result of poor occlusion of the pilosebaceous units within intertriginous zones Clinical Features

• primary lesions are inflammatory nodules

• presence of sinus formation, clusters of open comedones (double tombstone comedones), and hypertrophic scarring of intertriginous areas • sites: occurs primarily in the intertriginous areas of the axillae ( most common site), inguinal area , inner thighs, perianal and perineal areas, mammary and inframammary regions, buttocks, pubic region, scrotum , vulva, trunk, and occasionally the scalp and retroauricular areas • additionally significant hyperpigmentation and keloid formation can be seen in more pigmented skin types Pathophysiology

• follicular occlusion , follicular rupture, and an immune response Epidemiology • affects 1-4% of the population, 1;>M • onset of symptoms occur between puberty and age 40, typically in 2nd or 3rd decade • increased incidence in people of African descent • associated with smoking and excess weight Differential Diagnosis

• folliculitis, furuncles, carbuncles, acne vulgaris, Crohn’s disease, granuloma inguinale, pyoderma gangrenosum Investigations

• clinical diagnosis Treatment

behavioural: patient self - management including avoidance of skin trauma , smoking cessation , and weight management • pain management with NSAIDs • mild disease: local therapy with topical clindamycin , intralesional corticosteroid injections , topical «

resorcinol • moderate to severe disease: antibiotic therapy (oral tetracyclines, clindamycin and rifampin

combination, dapsone), oral retinoids, hormonal therapy, surgery ( punch debridement ), laser and light-based therapies ( C02 laser and Nd:YAG) • refractory moderate to severe disease: TNF-a inhibitors such as adalimumab and infliximab, systemic glucocorticoids, and cyclosporine PRIMARY HYPERHIDROSIS Definition

• secretion of sweat in amounts greater than physiologically needed for thermoregulation Clinical Features

• focal, visible, excessive sweating of at least 6 mo without apparent cause • symptoms typically develop during childhood or adolescence and persist throughout life • symptoms occur only during waking hours (diurnal ) • focal symptoms typically localized to the palms, soles, and axillae, and less commonly the scalp and

face Pathophysiology

• abnormal or exaggerated central response of the eccrine sweat glands to normal emotional stress n

Epidemiology • affects 1 5% of the population

L J

Differential Diagnosis • excessive heat, medications (e.g. antidepressants, antipyretics, cholinergic agonists, hormonal agents), menopause, and spinal cord injuries (autonomic dysreflexia, orthostatic hypotension, posttraumatic syringomyelia)

+

-

• most patients have a family history of hyperhidrosis

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D48 Dermatology

Toronto Notes 2023

Investigations

• clinical diagnosis, iodine starch test Treatment

• antiperspirants, botulinum toxin, microwave thermolysis, topical glycopyrronium bromide, suction curettage, systemic agents (oral glycopyrrolate, oral oxybutynin ), iontophoresis, or endoscopic thoracic sympathectomy

Oral Diseases LEUKOPLAKIA

• see Laikoplukiii , D39 RECURRENT APHTHOUS STOMATITIS

Clinical Features • also known as “canker sores” • painful , shallow, typically less than 5 mm in diameter, round to oval shaped , covered by a creamv-

whitc pseudomembrane with an erythematous halo

• sites: labial and buccal mucosa, floor of the mouth , ventral surface of the tongue, soft palate, and oropharyngeal mucosa

Pathophysiology

• dysfunction in the immune system resulting in immunologically mediated damage to epithelial cells • triggered by trauma, infectious agents, genetic factors, HIV infection , and hormonal fluctuations • early lesions can show a neutrophilic vessel-based submucosal infiltrate Epidemiology • women more commonly affected than men • peak prevalence in ages 20-30 Differential Diagnosis

-

• Behcet syndrome, SLE, gluten sensitive enteropathy, HSV Investigations

• diagnosis is made clinically Treatment • oral hygiene: soft toothbrush, waxed tape-style dental floss, soft-tipped gum stimulator for plaque

removal, and nonalcoholic mouthwash

• reduce traumatic factors inside the mouth such as biting cheeks or lips, and sharp/ rough dental restorations • pain control: lidocaine viscous 2%, diphenhydramine liquid (12.5 mg / 5 mL), dyclonine lozenges • severe refractory’ cases: colchicine

e.J

+

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Toronto Notes 2023

DllJ Dermatology

Skin Manifestations of Systemic Disease Table 25. Skin Manifestations of Internal Conditions Disease

Related Dermatoses

Raynaud's Phenomenon DDx

AUTOIMMUNE DISORDERS

Behcet's Disease

Painful aphthous ulcers in oral cavity t genital mucous membranes, erythema nodosum, acneiform papules

Buerger 's Disease

Superficial migratory thrombophlebitis, pallor, cyanosis, gangrene, ulcerations, digital resorptions

Dermatomyositis

Periorbital and extensor violaceous erythema,heliotrope with edema Gottron's papules (violaceousflattopped papules with atrophy), periungual erythema, telangiectasia, calcinosis culis

Polyarteritis Nodosa

Subcutaneous nodules, stellate purpura, erythema, gangrene, splinter hemorrhages, livedo reticularis, ulceration

.

Reactive Arthritis

Keratoderma blennorrhagica (on leet), balanitis circinata (on male penis)

Rheumatic Fever

Petechiae, urticaria, erythema nodosum, rheumatoidnodules, evanescent rash

Scleroderma

Raynaud's, non-pitting edema, waxy/shiny/tense atrophic skin (morphea), ulcers, cutaneous calcification, periungual telangiectasia, acrosderosis salt - and pepper pigmentation

SLE

Malar erythema, discoid rash (erythematous papules or plaques with keratotic scale, follicular plugging, atrophic scarring on lace, hands, and arms), hemorrhagic bullae,palpable purpura, urticarial purpura, patchy / diffuse alopecia, mucosal ulcers, photosensitivity

Crohn's Disease/ UC

Pyoderma gangrenosum, erythema nodosum Sweet's syndrome

.

COLD HAND Cryoglobulins/Cryofibrinogens Obstruction /Occupational Lupus erythematosus, other connective tissue disease DM / Drugs Hematologic problems (polycythemia, leukemia, etc.) Arterial problems (atherosclerosis) Neurologic problems (vascular tone) Disease of unknown origin (idiopathic)

-

.

ENDOCRINE DISORDERS

Addison's Oiscasc

Generalired hyperpigmcntalion or limited to skin folds, buccal mucosa, and scars

Cushing's Syndrome

Moon lades, purple striae, acne, hyperpigmcntalion, hirsutism, atrophic skin with telangiectasia

DM

Infections (e g boils, carbuncles, candidiasis S. aureus, derma to phytoses, tinea pedis and cruris, infectious ecrematoid dermatitis), pruritus, eruptive xanthomas, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic foot, diabetic bullae,acanthosis nigricans, calciphylaxis

Hyperthyroidism

Moist, warm skin, seborrhea, acne, nail atrophy, hyperpigmentation, toxic alopecia, pretibial myxedema, acropachy onycholysis

Hypothyroidism

Cool, dry, scaly, thickened, hyperpigrncnled skin; toxic alopecia with dry coarse hair, brittle nails, myxedema, loss of lateral 113 eyebrows

.

..

.

.

HIV - RELATED

.

.

.

. .

Infections

Viral (e.g. HSV H 2V, HPV CMV Molluscum contagiosum, oral hairy leukoplakia), bacterial ( impetigo, acneiform folliculitis, dental caries, cellulitis, bacillary epithelioid angiomatosis, syphilis), fungal (candidiasis, histoplasmosis, cryptococcus, blastomycosis)

Inflammatory Dermatoses

Seborrhea, psoriasis, pityriasis rosea, vasculitis Kaposi's sarcoma, lymphoma, BCC, SCC, MM

Malignancies

Acanthosis Nigricans An asymptomatic dark thickened velvety hyperpigmentation of flexural skin most commonly around the neck. Associated with DM obesity, and other endocrine disorders, and malignancy It is a cutaneous marker of tissue Insulin resistance

MALIGNANCY

Adenocarcinoma

Gastrointestinal Ccrvix / anus/rcctum

Peutz - Jeghers: pigmented macules on lips/oral mucosa Paget 's disease: eroding scaling plaques ol perineum

Carcinoma Breast G! Thyroid Breast /lung/ovary

Paget 's disease: eczematous and crusting lesions ol the skin ol the nipple and usually areola ol the breast Palmoplanlar keratoderma: thickened skin of palms/soles Sipple's syndrome:multiple mucosal neuromas Dermatomyositis:heliotrope erythema of eyelids and violaceous plaques over knuckles

Lymphoma / leukcmia Hodgkin's Acute leukemia

Ataxia telangiectasia: telangiectasia on pinna, bulbar conjunctiva Ichthyosis: generalized scaling especially on extremities Sweet's syndrome Bloom's syndrome: butterfly erythema on face, associated with short stature

Multiple Myeloma

Amyloidosis: large, smooth tongue with facial petechiae and waxy papules on eyelids, nasolabial folds, and lips

OTHERS

.

.

.

Renal Disease

Pruritus, hyperpigmcntalion spider nevi palmar erythema, white nails ( ferry's nails), porphyria culanea tarda, xanthomas, hair loss, jaundice Pruritus, pigmentation, half and hall nails, perforating dermatosis,calciphylaxis

Pruritic Urticarial Papules and Plaques of Pregnancy

Erythematous papules or urticarial plaques in distribution of striae distensae: buttocks, thighs, upper inner arms,and lower back

Cryoglobulinemia

Palpable purpura in cold exposed areas Raynaud's, cold urticaria, acral hemorrhagic necrosis, bleeding disorders, associated with hepatitis C inlection

Liver Disease

.

r

“i

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D50 Dermatology

Toronto Notes 2023

Paediatric Exanthems •

see Paediatrics. P62

Miscellaneous Lesions Angioedema and Urticaria Angioedema

deeper swelling of the skin involving subcutaneous tissues; often involves the eyes, lips , and tongue may or may not accompany urticaria • hereditary or acquired forms • hereditary angioedema (does not occur with urticaria ) onset in childhood; 80% have positive family history • recurrent attacks; 25% die from laryngeal edema • triggers: minor trauma , emotional upset, temperature changes • types of acquired angioedema • •

acute allergic angioedema ( allergens include food, drugs, contrast media, insect venom , latex) non -allergic drug reaction ( drugs include ACEI)

• acquired Cl inhibitor deficiency • treatment • prophylaxis with danazol or stanozolol for hereditary angioedema • epinephrine pen to temporize until patient reaches hospital in acute attack Urticaria • also known as “hives” • transient, red , pruritic well -demarcated wheals

each individual lesion lasts less than 24 h second most common type of drug reaction • results from release of histamine from mast cells in dermis • can also result after physical contact with allergen

DDx for Urticaria

MAD HIVES

Malign ancy Allergic Drugs and foods Hereditary Infection Vasculitis Emotions Stings

•

•

Table 26. Classification of Urticaria Type

Etiology

Acute Urticaria >213 of cases Attacks last

4 . Polvic/Rotrovosical ( Pouch of Douglas ) bladder ( Bl

r -i

free fluid ( F )

LJ

+ Figure 2. Four areas of a FAST

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ER6 Emergency Medicine

Toronto Notes 2023

PHYSICAL EXAM ( see Traumatology , ER7) Head and Neck • palpation of facial bones, scalp

Chest

• inspect for midline trachea and flail chest • auscultate lung fields • palpate for subcutaneous emphysema Abdomen

• assess for peritonitis, abdominal distention , and evidence of intra -abdominal bleeding • DRE for Cil bleed , high - riding prostate, and anal tone Musculoskeletal

• examine all extremities for swclling, deformity, contusions, tenderness, ROM • check for pulses ( using Doppler probe) and sensation in all injured limbs • log roll and palpate thoracic and lumbar spines • palpate iliac crests and pubic symphysis and assess pelvic stability ( lateral, AP, vertical ) Neurological • tiCS

• full cranial nerve exam • alterations of rate and rhythm of breathing are signs of structural or metabolic abnormalities with progressive deterioration in breathing indicating a failing CNS • assess spinal cord integrity • conscious patient: assess diistal sensation and motor function • unconscious patient: response to painful or noxious stimulus applied to extremities

Signs of Increased ICP • Deteriorating IOC ( hallmark) • Deteriorating respiratory pattern • Cushing reflex (high BP low HR irregular respirations) • lateralizing CNS signs (e g cranial nerve palsies, homiparcsis)

.

.

..

• Seizures

• Papilledema (occurs late) • N/V and headache

INITIAL IMAGING

• non -contrast CT head / face/C - spine ( rule out fractures and bleeds) • CXR • FAST' (see Figure 2, ER5 ) or CT abdomen /pelvis ( if stable) • pelvis x-ray

-

Non contrast head CT is the best imaging modality for intracranial injury

Ethical Considerations Consent to Treatment: Adults

• see Ethical. Legal , and Organizational Medicine. ELOM 11 • Emergency Rule: consent is not needed when a patient is at imminent risk from a serious injury AND obtaining consent is either: a ) not possible, OR b) would increase risk to the patient assumes that most people would want to be saved in an emergency • any capable and informed patient can refuse treatment or part of treatment, even if it is life-saving • be aware of who the legal substitute decision maker (SDM ) is and contact them early • exceptions to the Emergency Rule - treatment cannot be initiated if: a competent patient has previously refused the same or similar treatment and there is no evidence to suggest the patient’s wishes have changed (e.g. after an SDM has been contacted to clarify patient’s wishes) an advanced directive is available (e.g. do not resuscitate order) NOTE: refusal of help in a suicide situation is NOT an exception; care must be given • if in doubt, initiate treatment • care can be withdrawn if necessary at a later time or if wishes are clarified by family Consent to Treatment: Children

• treat immediately if patient is at imminent risk • parents/guardians have the right to make treatment decisions, up to the age of 16 ( beyond age 16, the patient can be considered an emancipated minor) • if parents refuse treatment that is considered life saving or will potentially alter the child’s quality of life, CAS must be contacted - consent of CAS is needed to treat

-

s Witnesses .Jehovah Capable adults have the right to '

refuse medical treatment

.

• May refuse whole blood. pRBCs platelets, and plasma even if

-

considered life saving

• Should be questioned directly about

the use of albumin, immunoglobulins, hemophilic preparations • Do not allow autologous transfusion unless there is uninterrupted extra corporeal circulation • Usually ask for the highest possible quality of care without the use of the above interventions (e.g. crystalloids for volume expansion, attempts at bloodless surgery) • Patient will generally sign hospital forms releasing medical staff from liability • Most legal cases involve children of Jehovah 's Witnesses; if life saving treatment is refused, contact CAS

-

Other Issues of Consent

• consent is required for HIV testing and /or administration of blood products

• however, if delay in substitute consent for blood transfusions puts patient at risk, transfusions can be

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given Duty to Report

• law may vary depending on province and /or state • e.g. gunshot wounds, suspected child abuse, various communicable diseases , medical unsuitability to drive, risk of substantial harm to others

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ER 7 Emergency Medicine

Toronto Notes 2023

Traumatology • epidemiology 4.9 million deaths are caused by injuries worldwide ( data from 2016 ) in Canada , traumatic injuries contributed more than 269000 hospitalizations and 17000 deaths ( data from 2018) • leading cause of death in patients < 45 yr 4 th highest cause of death in North America • causes more deaths in children / adolescents than all diseases combined

Always completely expose and count the number of wounds

• trimodal distribution of death • minutes: death usually at the scene from lethal injuries • early: death within 4 - 6 h “golden hour" ( decreased mortality with trauma care ) • days weeks: death from multiple organ dysfunction , sepsis, VTE, etc, • injuries fall into two categories • blunt ( most common ): M VC, pedestrian automobile impact, motorcycle collision, fall , assault , sports • penetrating ( increasing in incidence): gunshot wound , stabbing, impalement

-

-

-

Considerations for Traumatic Injury • important to know the mechanism of injury to anticipate traumatic injuries • always look for an underlying cause ( alcohol , medications, illicit substances, seizure, suicide attempt , medical problem ) • always inquire about HI , loss of consciousness, amnesia, vomiting, headache, and seizure activity

Cardiac Box: sternal notch, nipples, and xiphoid process: penetrating injuries inside this area should increase suspicion ol cardiac injury

Table 5 . Mechanisms and Considerations of Traumatic Injuries Mechanism of Injury

Special Considerations

Associated Injuries

MVC

Vehide(s) involved: weight, sire, speed , damage location of patient in vehicle Use and type of seatbelt Ejection of patient Irom vehicle Entrapment of patrentunder vehicle Airbag deployment Helmet usein motorcycle collision

Head on collision: head / facial , thoracic (aortic), lower

-

Pedestrian Automobile Impact

High morbidity and mortality Vehicle speed is an important factor Site of impact on car

1 storey *12 ft » 3.6 m Distance of fall: $0% mortality at 4 storeys and 96% mortality at 7 storeys Landing position ( vertical vs. horizontal )

Falls

-

extremity Uleral /l bone collision: head , C spine, thoracic, abdominal , pelvic, and lower extremity Rear end collision: hyper- extension of C spine (whiplash injury) Rollover : all of the above may be associated injuries

-

-

-

-

Adults tend to be struck in lovrer legs ( lower extremity injuries), impacted against car ( truncal injuries), and thrown to ground ( HI ) Vertical: lower extremity , pelvic, and spine fractures; HI Horizontal : facial , upper extremity, and rib fractures: abdominal , thoracic, and HI

High- Risk Injuries • MVC at high speed, resulting in ejection from vehicle • Motorcycle collisions • Vehicle vs. pedestrian crashes • Fall from height >12 ft (3.6 m)

Vehicle vs. Pedestrian Crash • In adults look for triad of injuries • Waddell's triad • Tibia -fibula or femur fracture • Truncal injury • Craniofacial injury

Head Trauma • see Neurosurgery. XS35

Specific Injuries

• fractures • Dx: non -contrast head CT and physical exam A. skull fractures vault fractures linear, non -depressed most common - typically occur over temporal bone, in area of middle meningeal artery (commonest cause of epidural hematoma ) depressed open (associated overlying scalp laceration and torn dura , skull fracture disrupting paranasal sinuses or middle ear ) vs. closed basal skull fractures typically occur through floor of anterior cranial fossa ( longitudinal more common than transverse) can be a radiological or clinical diagnosis associated with Battle’s sign , racoon eyes, hemotympanum, and / or (.'ST otorrhea / rhinorrhea B. facial fractures (see Plastic Surgery, PL31 ) • neuronal injury beware of open fracture or sinus fractures ( risk of infection ) • severe facial fractures may pose risk to airway from profuse bleeding

-

Signs of Basal Skull Fracture • Battle's sign (bruised mastoid process)

• Hemotympanum • Raccoon eyes (periorbital bruising) • CSF rhinorrhea/otorrhea

-

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ER8 Emergency Medicine

Toronto Notes 2023

• scalp laceration

can be a source of significant bleeding achieve haemostasis, inspect and palpate for skull bone defects ± CT head ( rule out skull fracture) • neuronal injury A. diffuse • mild TB1 = concussion (GCS 13 15, patients are awake, may be confused but able to communicate and follow commands ) • transient alteration in mental status that may involve loss of consciousness • hallmarks of concussion: confusion and amnesia, which may occur immediately after the trauma or minutes later • loss of consciousness ( if present ) must be less than 30 min and post traumatic amnesia must be less than 24 h • diffuse axonal injury mild: coma 6-24 h, possibly lasting deficit moderate: coma >24 h, little or no signs of brainstem dysfun ction severe: coma >24 h, frequent signs of brainstem dysfunction B. focal injuries contusions • intracranial hemorrhage (epidural, subdural, intracerebral )

•

-

-

ASSESSMENT OF BRAIN INJURY History

• prehospital status • mechanism of injury

Signs of Severe Head Injury .Warning GCS 8
90 ) • treat other injuries • early neurosurgical consultation for acute and subsequent patient management after imaging • seizure treatment /prophylaxis benzodiazepines, phenytoin, phenobarbital • treat suspected raised 1CP: intubate ( neuroprotective RSI where possible) calm ( sedate) if risk for high airway pressures or agitation paralyze if agitated • hyperventilate ( 100% 02) to a pCO:of 30 35 mmHg • elevate head of bed to 20“ adequate BP to ensure good cerebral perfusion give mannitol Ig/ kg infused rapidly (contraindicated in shock/renal failure) or 3 ml./ kg of hypertonic (3%) saline

-

Canadian CT Head Rule lancet 2001:357:1391-1396 C THeadis oily required lor patients with minor HI with airy one of the following High -Risk (for neurological intervention) . GCS score'15 at 2 h alter injury • Sospeded open or depressed skull fracture • Any ugn of basal tiiull fracture ( hemolympanurn. 'raccoon' eyes . CSF otonhealihinorrhea . Battle's vgn ) Venting ;2 episodes

.. *

ge *65 p Medium-Risk (lor brain injury on Cl) • trimesa before unpact > 30 min (i.e. cannot recal events just before impact) • Dangerous raecbansm ( pedestrian strode by UVt. occupant ejected Iron motor vehicle tadl from height » 3 ft or five stairs) Minor HI redefined as witnessed loss of consciousness, definite amnesia or witnessed disorientation i n a patient with a GCS score of 13-15. ,

.

. hiving a bleeding tfcwdef. taring Couitudai an otntoa open skull Iroctuie. HI:CanadianCl Head Rule does nut apply lot mn

Irautvi uttv lot CCS «13.090s «16 foe patlwnh on jnd of

Of

_

r^

i J

Disposition

• neurosurgical 1CU admission for severe HI • in a hemodynamically unstable patient with other injuries, prioritize most life-threatening injuries and maintain cerebral perfusion • for minor HI not requiring admission, provide 24 h HI protocol ( regular assessment of the patient for signs of loss of consciousness, confusion or amnesia ) to competent caregiver, follow up with concussion and /or sports clinic as even seemingly minor HI may cause lasting deficits

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ER9 Emergency Medicine

Toronto Notes 2023

Mild Traumatic Brain Injury Epidemiology

• TBI results in 1.7 million deaths, hospitalizations, and ED visits each year ( US)

75% are estimated to be mild TBI; remainder are moderate or severe ( see Neurosurgery, NS37) • highest rates in children 0 4 yr, adolescents 15 19 yr, and elderly >65 yr «

-

-

Clinical Features

• somatic; headache, sleep disturbance, N / V, blurred vision • cognitive dysfunction ; attentional impairment, reduced processing speed , drowsiness, amnesia • emotion and behaviour: impulsivily, irritability, depression • severe concussion: may precipitate seizure, bradycardia , hypotension , sluggish pupils

Extent o( retrograde amnesia correlates with severity ol injury

Etiology

• falls, M VC, struck by an object, assault, sports Investigations

• neurological exam

• concussion recognition tool (see parachute.ca )

• imaging - CT as per Canadian CT Head Rules, or MR1 if worsening symptoms despite normal CT Treatment

• close observation and follow- up; for patients at risk of intracranial complications, give appropriate discharge instructions to patient and family; watch for changes to clinical features of more severe TBI (see above), and if change, return to ED • hospitalization with normal CT ( CCS < 15, seizures, bleeding diathesis), or with abnormal CT • pharmacological management of pain, depression, headache • follow Return to Flay/ Return to Learn guidelines

For minor paediatric HI ( up to 16 yo with CCS z13 and injury within the last 24 h ), use Canadian Assessment of Tomography for Childhood Head Injury (CATCH) rule to determine need for CT CT head required if any of the following findings are exhibited • CCS 3 ft or 5 stairs, fall from bicycle with no helmet)

.

.

Prognosis

• most recover with minimal treatment athletes with previous concussion are at increased risk of cumulative brain injury • repeat TBI can lead to life- threatening cerebral edema or permanent impairment

.

Spine and Spinal Cord Trauma • assume cord injury with significant faUs (>12 ft ), deceleration injuries, blunt trauma to head, neck, or

back

Every Patient with One or More of the Following Signs or Symptoms should be Placed in a C Spine Collar Midline tenderness Neurological symptoms or signs • Significant distracting injuries

• spinal immobilization (cervical collar, spine board during patient transport only) must be maintained until spinal injury has been ruled out • vertebral injuries may be present without spinal cord injury; normal neurologic exam does not exclude spinal injur}' • cord may be injured despite normal C-spine x-ray (spinal cord injury without radiologic abnormality) • injuries can include: complete/ incomplete transection, cord edema, spinal shock

.

History

.

• mechanism of injur}', previous deficits, SAMPLE • neck pain, paralysis/ weakness, paresthesia

. abdominal ecchymosis,

-

.

HI • Intoxication • Dangerous mechanism History of altered LOC

Physical Exam

ABCs

tenderness • neurological: complete exam, including mental status • spine: maintain neutral position , palpate C- spine: log roll, then palpate T spine and L spine, assess rectal tone when palpating, assess for tenderness, muscle spasm , bony deformities, step off, and spinous

•

:

-

-

process malalignment

-

. -

Of the investigations CT is the best modality to assess C Spine injuries. If unavailable and significant trauma is suspected, protect C Spine and transfer for definitive imaging. If minor trauma of C Spine may consider x ray imaging

- .

-

• extremities: check capillary refill , suspect thoracolumbar injury with calcaneal fractures Investigations • bloodwork: CBC, electrolytes, Cr, glucose, coagulation profile, cross and type, toxicology screen

.

imaging CT of the spine; if not available, protect spines and transfer for definitive imaging indications C spine injury » unconscious patients ( with appropriate mechanism of injury ) neurological symptoms or findings deformities that are palpable when patient is log rolled back pain

-

Cauda Equina Syndrome can occur with any spinal cord injury below T10 vertebrae look for incontinence, anterior thigh pain , quadriceps weakness, abnormal sacral sensation , decreased rectal tone, and variable reflexes

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ER10 Emergency Medicine

Toronto Notes 2023

bilateral calcaneal fractures (due to fall from height ) concurrent burst fractures of the lumbar or thoracic spine in 10% ( T 11 L 2) MRI ( for soft tissue injuries) if appropriate

-

-

-

The Canadian C Sp< neRule JAMA 200 l:286:1841 48 For AlertlGCS Score 181 and Stable Trauma Patients where C Spine Injury is a Concern

Can Clear C- Spine if:

= -

-

1. Any high risk (actor that mandates radiography? Age >fi5 vt

• oriented to person , place, time, and event

• no evidence of intoxication • no posterior midline cervical tenderness • no focal neurological deficits • no painful distracting injuries (e.g. long bone fracture)

or

Oangerous mechanism*

or

Paresthesias in extremities No

Management of Cord Injury

-

2. Any low risk factor that allows sale assessment oIROM ? Simple rear end MVCt

• immobilize • evaluate ABCs

-

• treat neurogenic shock ( maintain sBP > 100 mmHg ) • insert NCi ( for decompression of paralytic ileus ) and holey catheter ( only if no concerns about urethral

or

Sitting position in ED

or or

injury)

• complete imaging of spine and consult spine service • continually reassess high cord injuries as edema can travel up cord • if cervical cord lesion, watch for respiratory insufficiency low cervical transection (C5 T1) produces abdominal breathing ( phrenic innervation of diaphragm still intact but loss of innervation of intercostals and other accessory muscles of breathing ) high cervical cord injury (above C4) may require intubation and ventilation • if patient is in shock, treat with: warm blanket, Trendelenburg position (occasionally), volume infusion, consider vasopressors

Yes

No

Radiography

Ambulatory at any time Delayed ( not immediate ) onset ofneck pain

or

-

Absence of midline C-spine tenderness Unable

Yes i. Able to actively rotate neck ? >45* left and right

.| Able

Approach to C-Spine Imaging •CT of the spine is the screening modality of choice • C -Spine CT can detect 97-100% of injuries • compared to radiography, CT scans allows for more rapid clearance of the C- Spine • MRI of C -Spine is the preferred technique for soft tissue injuries (spinal cord lesions, intervertebral

discs, and spinal ligaments) • CT of C Spine is the preferred modality. If only C Spine x rays are available, radiography can be assessed as follows

-

-

-

Table 6. Interpretation of Lateral View : The ABCS A

Adequacy and Alignment Follow the anterior and posterior contour lines Translation ol the vertebra >3.8 mm and angulation ol >11 dcgiccs is consideicd significant loi spinal instability Next , follow the spinolaminar line: Ihe diameter between the posterior cortex and the spinolaminar line should be >18 mm Fanning of spinous processes suggests posterior ligamentous disruption Widening olfacet joints Check atlanto occipilal joint line extending interiorly horn cirrus should transect odontoid Atlanto axial articulation , widening ol predental space ( normaI: < 3 mm in adults , 48 h, major urine extravasation, renal pedicle injury, all penetrating wounds and major lacerations, infections, renal artery thrombosis

-

• ureter

ureteroureterostomy • bladder

extraperitoneal

-

minor rupture: Foley drainage x 10 14 d major rupture: surgical repair

In the case of gross hematuria, the genitourinary system is investigated from distal to proximal (i.e. urethrogram, cystogram etc.)

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+

intraperitoneal

• urethra

anterior: conservative, if cannot void, Eoley or suprapubic cystostomy and antibiotics posterior: suprapubic cystostomy (avoid catheterization ) ± surgical repair

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ERI 5 Emergency Medicine

Toronto Notes 2023

Orthopaedic Injuries

.

• see Orthopaedic Surtterv ( see Shoulder OR 2 Knee OR34, Wrist OR 23, Ankle OIOII ) Goals of ED Treatment • diagnose potentially life / limb- threatening injuries • reduce and immobilize fractures ( cast / splint ) as appropriate • proside adequate pain relief • arrange proper follow - up if necessary

History • use SAMPLE, mechanism of injury may be s'ery important

Description of Fractures

SOLARTAT Site Open vs. closed Length Articular Rotation Translation Alignment/Angulation Type e.g. Salter-Harris. etc.

Physical Exam

• look ( inspection ): “ HEADS" = swelling, erythema , atrophy, deformity, and skin changes (e.g. bruises ) • feel ( palpation ): all joints / bones for local tenderness, swelling, warmth , crepitus, joint effusions, and subtle deformity • move: joints affected plus those above and below injury active ROM preferred to passive • neurovascular status: distal to injury ( before and after reduction )

acute extremity pain.

LIFE- AND LIMB-THREATENING INJURIES

Methods: K1 unhiding 416 patients « ith "ipdeiate ta severe acute eitremity pam . Participants lecened

-

Table 10. Life - and Limb-Threatening Orthopaedic Injuries Life - Threatening Injuries (usually blood loss) Limb - Thieatening Injuries ( usually interruption of blood supply) Major pelvic fractures Traumatrcampulations Massive long bone injuries and associated fat emboli syndrome Vascular injury proximal to knee/elbow

Fracture/dislocation ol ankle (talar AVN ) Crush injuries Compartment syndrome Open fractures Dislocations ol knee/hip fractures above knee /elbow

Open Fractures

• communication between fracture site and external surface of skin - increased risk of osteomyelitis • remove gross debris, irrigate, cover with sterile dressing formal irrigation and debridement often done in the OK • control bleeding with pressure ( no clamping ) • splint • antibiotics ( 1st generation cephalosporin and aminoglycoside) and tetanus prophylaxis • standard of care is to secure definitive surgical management within 6 h , time to surgery may vary from case to- case

-

tiled ol a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Eitremity Pain in the ED JAMA 2017:318 :1661 166P Purpose: lo compare the efficacy ol 4 aratjesns on

ibupiolen 400 mgard acetaminophen 1000 mg: oiycodone S mg and acetaminophen 325 mg: hydrocodone 5 mg and acetam nophen 300 mg; or codeine 30 mg and acetaminophen 300 mg. Ihe primary outcome was the difference m decline in pain 2 h after ingestion. Pain was assessed using an 11- point numerical rating scale [ MRS). Results: At 2 h, the mean HRS pain score decreased try 4.3 in the ihuprofen and acetaminophen group: by 4.4 in the oiycodone and acetaminophen group: by 3.5 in the hydrocodoneand acetaminophen group: and by 3.9 in the codeine and acetaminophen group (P 0.053). Conclusions: For patients present ng to the ED with acute eitremity pain, there were no statistically significant or clinically important differeoces m pam reduction at 2 h among single -dose treatment with ibupiolen andacelaminophen or with 3 different opioid and acetaminophen combmationenelgesics.

-

-

Vascular Injuries

• realign limb/apply longitudinal traction and reassess pulses (e.g. Doppler probe ) • surgical consult • direct pressure if external bleeding Compartment Syndrome

• when the intracompartmental pressure within an anatomical area (e.g. forearm or lower leg ) exceeds the capillary perfusion pressure, eventually leading to muscle/ nerve necrosis • clinical diagnosis: maintain a high index of suspicion pain out of proportion to the injury • pain worse with passive stretch • tense compartment • look for “ The 6 Hs” ( note: radial pulse pressure is 120 /80 mrnHg while capillary perfusion pressure is 30 mrnHg, seeing any of the 6 Ks indicates advanced compartment syndrome , therefore do not wait for these signs to diagnose and treat ) • in the unconscious patient , a Stryker compartment pressure monitor can be used • requires prompt decompression: remove constrictive casts, dressings; emergent fasciotomv may be needed

When Dealing with an Open Fractuie. Remember " STAND"

Splint Tetanus prophylaxis Antibiotics Neurovascular status (before and after ) Dressings (to cover wound)

Vascular injury/ compartment syndrome Is suggested by “ The 6 Ps” Injury

Compartment Syndrome •

6 Ps Pulse discrepancies Pallor Parcsthesia /hypoesthesia Paralysis Pain (especially when refractory to usual analgesics) Polar ( cold)

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F.RI6 Emergency Medicine

Toronto Notes 2023

UPPER EXTREMITY INJURIES • anterior shoulder dislocation axillary nerve (lateral aspect of shoulder ) and musculocutaneous nerve (extensor aspect of forearm ) at risk seen on lateral view: humeral head anterior to glenoid • many techniques for reduction (e.g. traction , scapular manipulation ), immobilize in internal rotation, repeat x- ray, out- patient follow - up with orthopaedics

¥ Lateral view

with forceful Injury, look for fracture • Colics' fracture

• distal radius fracture with dorsal displacement from “ Kail on Outstretched Hand " ( I OOSH ) • anteroposterior film : radial shortening, radial deviation , radial displacement • lateral film: dorsal displacement, volar angulation '

reduce, immobilize with splint , out- patient follow- up with orthopaedics or immediate orthopaedic referral if complicated fracture if involvement of articular surface, consider outpatient fracture clinic or orthopaedic referral if unsatisfactory reduction in ED • scaphoid fracture • tenderness in anatomical snuffbox , pain on scaphoid tubercle, pain on axial loading of thumb negative x ray: thumb spica splint, repeat x ray in I wk ± CT scan / bone scan positive x ray: thumb spica splint x 6 8 wk , repeat x ray in 2 wk • treat based on clinical suspicion even in absence of radiological scaphoid fracture risk of AVN of scaphoid if not immobilized outpatient orthopaedic follow - up

-

-

-

-

LOWER EXTREMITY INJURIES • knee injuries • see Ottawa Knee Rules • ankle and foot fractures see Ottawa Ankle and l oot Rules

A- P view 1. Dorsal tilt 2. Dorsal displacement 3. Ulnar styloid fracture 4 Radial displacement 5. Radial tilt 6. Shortening

| £ 23

S

1

Lunate

Radius

-

14 si

Scaphoid

Trapezium

Triquetrum

• avulsion of the base of 5th metatarsal occurs with inversion injury • supportive tensor or below knee walking cast for 3 wk • calcaneal fracture associated with fall from height associated with axial loading (other injuries may involve ankles, knees, hips, pelvis, lumbar

J

Figure 6. Codes’ fracture

Ulna

'

CN

Trapezoid

Pisiform* Hamate /

" Capitate

i

Metacarpal bones ( 1-51

spine) SEIishova Marcus

A luiec x-ray examination is required only for acute injury patients with one or more of:

Figure 7. Carpal bones

^

• Age 55 yr or older • Tenderness at head of fibula

• Isolated tenderness ol patella • Inability to Ilex to 90 '

• Inability to bear weight both immediately and in the ED Hour steps) Figure 8. Ottawa knee rules

-

.

Adapted Irom: SUell 16. Wells GA. Hoag RH et aL JAMA 1997:278:2075 2079.

LATERAL VIEW

An ankle radiographic series is required only if there is any pain in malleolar zone and any of these findings:

Malleolar Zone

A. Posterior edge or tip of lateral

Midlout Zone

malleolus

- C.

,

Base ol 5th metatarsal

MEDIAL VIEW B. Posterior edge or tip of medial

MalleolafZODt

malleolus

Midfoot Zone

D. Navicular

1. Bony tender ness at A or 2 Bony tenderness atB or 3. Inability to bear weight both immediately and in ED A radiographic seriesis required only if there is any pain in midfoot zone and any of these findings:

1 Bony tender ness atC or 2 Bony tenderness atD or 3. Inability to bear weight both immediately and in ED

+

ENataiie Cormier 2016

(

Figure 9. Ottawa ankle and foot rules

.

. et al. JAMA 1994:271:827-832.

Adapted Irom: Stiell 16. Mcknight RO Greenbetg 6 H

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ER17 Emergency Medicine

Toronto Notes 2023

Wound Management Goals of ED Treatment

-

• identify injuries and stop any active bleeding direct pressure

Acute Treatment ol Contusions

• wound examination and exploration • cleansing ± antibiotic and tetanus prophylaxis • closure and dressing

RICE Rest Ice Compression

• manage pain

Elevation

Tetanus Prophylaxis • both tetanus toxoid ( I'd ) and immunoglobulin ( TIG ) are safe in

pregnancy

Table 11. Guidelines for Tetanus Prophylaxis for Wounds Clean , Minor Wounds

-

All Other Wounds'

Vaccination History

Tdaporld *

TIG

Tdap or Id1

TIG

Unknown or fewer than 3 doses

Yes

Ho

Yes

Yes

3 or more doses

Hoi

Ho

Ho

'

Ho

'Such as, but not limited to, wounds contaminated with dirt, feces, soil, and saliva: puncture wounds; uvulslons; and wounds resulting from missiles, crushing, burns, and frostbite ’Tdap Is preferred to Td for adults who have never received Tdap. Single antigen tetanus toxoid (IT ) Is no longer available In the United Stales SYes It more than ten years since the last tetanus toxoid containing vaccine dose ' Yes if more than five years since the last tetanus toxoid containing vaccine dose :1 28 Source: MM WR 1991:40( No. RR 10|

. ..

--

- -

High Risk Factors for Infection Wound Factors • Puncture wounds • Crush injuries • Wounds >12 hold • Hand or foot wounds Patient Factors • Age >50 yr • Prosthetic joints or valves ( risk of endocarditis) • Immunocompromised

Bruises

• non - palpable = ecchymosis • palpable collection ( not swelling ) = hematoma following blunt trauma • assess for coagulopathy (e.g. liver disease ), anticoagulant use Abrasions partial to full thickness break in skin • management • clean thoroughly with brush to prevent foreign body impregnation ± local anesthetic antiseptic ointment ( Polysporin* or Vaseline*) for 7 d ± tetanus prophylaxis

Lacerations • see Plastic Suruerv PL8, sidebar PL 24 • consider every structure deep to a laceration injured until proven otherwise • in hand injury patients, include the following in history: handedness, occupation, mechanism of injury, previous history of injury • physical exam • think about underlying anatomy • examine tendon function actively against resistance and neurovascular status distally • clean and explore under local anesthetic; look for partial tendon injuries • x-ray or U /S wounds if a foreign body is suspected (e.g. shattered glass) and not found when exploring wound (remember: not all foreign bodies are radiopaque ), or if suspect intra -articular involvement • management • disinfect skin / use sterile techniques • irrigate copiously with normal saline or tap water

.

analgesia ± anesthesia maximum dose of lidocaine 7 mg/ kg with epinephrine 5 mg / kg without epinephrine • in children , topical anesthetics such as LET (lidocaine, epinephrine, and tetracaine), distraction provided by Child Life Specialist or parent; and in selected cases a short-acting benzodiazepine ( midazolam or other agents ) for sedation and amnesia are useful • secure hemostasis • evacuate hematomas, debride non viable tissue, remove hair and foreign bodies • ± prophylactic antibiotics (consider for animal / human bites, intra-oral lesion, or puncture wounds to the foot ) suture unless: delayed presentation (>24 h), puncture wound, mammalian bite, crush injury, or retained foreign body • take into account patient and wound factors when considering suturing • advise patient when to have sutures removed • cellulitis and necrotizing fasciitis (see Plastic Suruerv, El.16)

•

Suture Use and Duration Suture to:

Close with Nylon or Other Nonabsorbable Suture

-

.

Approx Duration (d)

Face

6-0 or 5 0

5

Hot Joint

4-0

Joint

34)

Scalp

40

7 10 7

Mucous Membrane

Absorbable fray!)

N/A

N.B. Patientson steroid therapy may need sutures for longer periods of lime

Early wound irrigation and debridement are the most important factors in decreasing infection risk

-

Q

Alternatives to Sutures • Tissue glue , Steristrips -

LJ

• Staples

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ER18 Emergency Medicine

Toronto Notes 2023

Approach to Common ED Presentations Abdominal Pain Table 12. Selected Differential Diagnosis of Abdominal Pain Emergent

Usually Less Emergent

.

Perforated viscus, bowel obstruction , ischaemic bowel, appendicitis strangulated hernia, I8 D flare, esophageal rupture, peptic ulcer disease Hepatobiliary Hepatic/splenic injury pancreatitis, cholangitis, spontaneous bacterial

Gl

.

peritonitis

Diverticulitis, gastroenteritis, GERD, esophagitis, gastritis, IBS Biliary colic, cholecystitis, hepatitis

.

Genital

Female: Ovarian torsion , ectopic pregnancy, tubo ovarian abscess Male: Testicular torsion

Female: PIO, ovarian cysl salpingitis , endometriosis Male: epididymitis, prostatitis, orchitis

Urinary CVS

Pyelonephritis

Renal colic, cystitis Pericarditis

Respirology Metabolic

PE empyema OKA sickle cell crisis, toiin Addisonian crisis

Other

Significant trauma, acute angle closure glaucoma

Ml, aortic dissection, AAA

.

.

Pneumonia

.

.

Tonic ingestions (e.g. acetaminophen , Iron HSAIDs, etc ), lead poisoning, porphyria

.

.

Abdominal wall injuty herpcs roster, psychiatric, abscess, hernia , mesenteric adenitis

• differential can be focused anatomically by location of pain: right upper quadrant, left upper quadrant, right lower quadrant, left lower quadrant, epigastric, periumbilical, diffuse

.•

History pain: OPQRST review symptoms from genitourinary, gynecological, gastrointestinal, respiratory, and cardiovascular systems • abdominal trauma /surgeries, most recent colonoscopy, most recent endoscopy, last FOBT/ F1T test Physical Exam

• vitals, abdominal ( including DRE, CVA tenderness), pelvic/genital, respiratory, and cardiac exams as indicated by history

Investigations

• ABCs, do not delay management and consultation if patient unstable • labs: CBC, electrolytes, glucose, BUN /Cr, U /A t liver enzymes, Ll Ts, lipase, fi hCG, ECG, troponins, ±

-

VBCi / lactate • AXR: if suspicious of foreign body or SBO (small bowel obstruction ) in low resource setting. Can also use if frequent SBOs and usual conservative management • CXR upright: look for pneumoperitoneum (free air under diaphragm ), lung disease • U /S: all gynaecologic structure, testicles, biliary' tract, ectopic pregnancy, appendicitis in children and young adults, nephro urolithiasis in young patients, AAA , free fluid: in select cases, can proceed to CT if U /S if non diagnostic but there is high clinical suspicion • CT: SBO, trauma, AAA, pancreatitis, nephro / urolitniasis, appendicitis, and diverticulitis

-

-

-

Management

• NPO, IV, NG tube (if SBO), analgesics, consider antibiotics and anti-emetics

• growing evidence that small amounts of opioid analgesics improve diagnostic accuracy of physical exam of surgical abdomen • consult as necessary: internal medicine, general surgery, vascular surgery, gynecology, etc. Disposition

• admission: surgical abdomen, workup of significant abnormal findings, need for IV antibiotics or pain control • discharge: patients with a negative lab and imaging workup who improve clinically during their stay; instruct the patient to return if severe pain , fever, or persistent vomiting develops n\ LJ

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ER19 Emergency Medicine

Toronto Notes 2023

Acute Pelvic Pain Etiology

• gynecological

ovaries: ruptured ovarian cysts ( most common cause of pelvic pain ), ovarian abscess, ovarian torsion (rare, 50% will have ovarian mass) fallopian tubes: salpingitis, tubal abscess, hydrosalpinx uterus: leiomyomas ( uterine fibroids ) especially with torsion of a pedunculated fibroid or in a pregnant patient (degeneration ), P1D other: ectopic pregnancy ( ruptured /expanding/leaking), spontaneous abortion (threatened or incomplete), endometriosis and dysmenorrhea, sexual or physical abuse non gynecological (see causes of lower abdominal pain above)

-

•

-

History and Physical Exam

• pain: OPQRST • associated symptoms: vaginal bleeding, discharge, dyspareunia , bowel and /or bladder symptoms • pregnancy and sexual history, including oligo/amenorrhea , menorrhagia , and fibroids • vitals • gynecological exam: assess for cervical motion tenderness/ “chandelier sign" (suggests P1D) • abdominal exam Investigations

• (J-hCG for all women of childbearing age • CBC and differential, electrolytes, glucose, creatinine, BUN, culture and sensitivity, PTl'/ lNR • U /A to rule out urologic causes • vaginal and cervical swabs for culture and sensitivity if performing a pelvic exam or urine NAAT for ST1 testing if no pelvic exam is performed • pelvic and abdominal U /S: evaluate adnexa , thickness of endometrium, pregnancy, free fluid or masses in the pelvis • Doppler llow studies for ovarian torsion

Gynaecological Causes of Pelvic Pain • Ovarian cyst • Dysmenorrhea • Mittclschmorz • Endometriosis Ovarian torsion Uterine fibroids/neoplasm • Adnexal neoplasm P1D * cervicitis

.. .

Management

• general: analgesia , determine if admission and consults are needed

U/S is the preferred imaging modality in the assessment of acute pelvic pain

• specific:

•

ovarian cysts

unruptured or ruptured, and hemodynamically stable: analgesia and follow-up ruptured with significant hemoperitoneum: may require surgery ovarian torsion : surgical detorsion or removal of ovary uncomplicated leiomyomas, endometriosis, and secondary dysmenorrhea can usually be treated on an outpatient basis, discharge with gynecology follow- up P1D: broad spectrum antibiotics, recommend low threshold to treat empirically

Disposition • referral: gynecological or obstetrical causes requiring surgical intervention, requiring admission, or oncological in nature • admission: patients requiring surgery, IV antibiotics / pain management • discharge: negative workup and resolving symptoms; give clear instructions for appropriate follow up

-

Altered Level of Consciousness

Possible Causes of Coma AEIOU TIPS

Acidosis/Alcohol Epilepsy

Infection Oxygen ( hypoxiaf /Opiates Uremia Temperature / Trauma (especially head ) Insulin ( too little or too much) Psychogenic/ Poisoning Structural or space occupying lesion

-

Definitions • altered mental status: collective, non specific term referring to change in cognitive function, behaviour, or attentiveness, including: delirium (see Psychiatry, PS23) dementia (see Psychiatry, PS24 ) lethargy: state of decreased awareness and alertness ( patient may appear wakeful ) stupor: unresponsiveness but rousable coma: a sleep-like state, not rousable to consciousness

-

rT LJ

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F.R 20 Emergency Medicine

Toronto Notes 2023

Coma ( GCS ] '' '

Compression •Supra/infratentorial tumour

•Sub/epidural

Direct • Brainstem infarct or hemorrhage

hematoma

.

Figure 10 Etiology of coma

MANAGEMENT OF ALTERED LOC

History

• obtain collateral from family, friends, police, paramedics, patient record , MedicAlert * bracelet, etc. • onset and progression antecedent trauma , seizure activity, fever • abrupt onset suggests CNS hemorrhage/ischaemia , cardiac cause, or poisoning progression over hours to days suggests progressive CNS lesion or toxic/ metabolic cause • determine patient’s baseline LOC • past medical history (e.g. similar episode(s), depression, overdose )

.

Classically, intubate if GCS 42 ngl troponin 15- 42 ngl

2 pis Ipt Opts

troponin 14 rgl

’ Risk (actors: Diabetes meHia. current or recent ('- 30 days) smoker, hypertension, hypercholesterolemia , and lamiy history ol coronary artery disease 0 to 3 points tow risk (0.6% to 17% risk Ol mayor adverse cariiac events): 4 lo 6 points intermediate risk (16.6% risk):7 to 10 points hirfi risk (503% risk)

=

=

=

-

r >

LJ

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F.R 22 Emergency Medicine

Toronto Notes 2023

Table 15 . Comparison of Chest Pain Diagnoses

Acute Coronary Syndrome

Classic History

Classic Findings

Hew or worsening pattern of retrosternal squeezing/ pressure pain, radiation toarm /neck dyspnea, worsened by exercise, relieved by rest N/ V syncope

New or worsened murmur hypotension, diaphoresis, pulmonary edema

.

.

. .

Pulmonary Embolism

Pleuritic chest pain ( 25%), tachycardia, hypoxemia; dyspnea:risk (actors tor evidence ol DVI venous thromboembolism

Acute Pericarditis Viral prodrome,anterior precordial pain, pleuritic, relieved by sitting up and

Management and

ECG:ischaemia|15 -lead if hypotensive AV node involvement or inferior Ml), serial troponin I (sensitive 6 8 halter onset ), CXR

ABCs Aspirinanticoagulation and emergent cardiology consult to consider percutaneous intervention or thrombolytic

Wells' criteria: D - dimer, Cl pulmonary angiogram, ventilation - perfusion ( V /0) scan:leg Doppler CXR

ABCs, anticoagulation: consider airway management and thrombolysis if massive PE (hypotension and cardiovascular collapse)

Disposition

.

.

ECG: sinustachycardia, diffuse SI elevation, PR depression in II, III avf and V4 6: reciprocal PR elevation and SI depression in aVRiVI: echocardiography

Friction rub

.

leaning forward

Pneumothorax

Diagnostic Investigations

Hemithoraxwilh Clinical diagnosis decreased/ absent breath CXR: posteroanterior sounds, hyper - resonance: view,lateral, expiratory deviated trachea and views - lung edge, loss of

Iraumaorspontaneous pleuritic chest pain often

in tall, thin, young male athlete

.

HIN; systolic BP difference •20 mmHg or pulse deficit between arms: aortic regurgitant murmur

extremities in context olHTN

Cl angiogram: CXR - wide mediastinum, left pleural effusion, indistinct aortic knob. > 4 mm separation of intimal calcification from aortic shadow 20% normal

.

.

.

Cardiac Tamponade

Dyspnea, cold extremities Beck 's triad •hypotension ± chest pain: often a recent elevated JVP, muffled

Esophageal Rupture

cardiac intervention or symptoms of malignancy, connective tissue disease Sudden onset seveve pain alter endoscopy, fovcctul vomiting, labour, or convulsion, or in context of corrosive injury or cancer

hear! sounds; tachycardia, pulsus paradoxus >10

recurrent, large pericardial effusion, or non viral cause (e.g. SlE renal failure, requires surgery)

Tracheal deviation is away from tension or towards non tension pneumothorax

ABCs, if unstable, needle to 2nd ICS at mid-clavicular line:urgent surgical consult/ thoracostomy 4 th intercostal space and chest tube

Dots thisPatient with Chest Pain have Acute Coronary Syndrome!: The RationalClinical E lamination Systematic Review JAMA 2015:314:1955-1965 Purpose: loreriew accuracy of the initial history, physical examination, ECC, and risk scores incorporating these elements with the first cardiacspecific troponin. Methods Systematic rev ew of prospective studies among pahenls admitted to the ED with symptoms

ABCs, reduce 8P and HR; classify type A (ascending aorta, urgent surgery) vs. 8 (nol ascending aorta, medical) on Cl angiogram and

Results Prior abnormal stress lesl ( specificity 94%: IR 3.1 55% Cl 2.04.!), peripheral artery disease (speo6crty 9!%:LR 2.! 95% CM.5 4.8),and pain rad at rg to both arms (specificity 96 %; LR 2.6 95% Cl 1.8- 3.!) were most suggestive of ACS. Ihe most soggestve ECC findings were Sl- segnent depression and any evidence of rsetaemia. The History,ECG,Age. Risk factor!Iropori n (HEART) (LR 13.95% Cl1-24) and thelhrombotysis in Ml ( TIMI) risk scores (IR 68. 95% Cl S.2-8.9) were bolh predicb ve of ACS n the high-risk scores. Conclusions Among patients with suspected ACS presenting to the EO the initial history, physical fid ' ration, and f CC alone did not confirm or eichide thedaguosrsof ACS. Instead, the HEARI or IIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information.

-

.

mmHg

Subcutaneous

.

urgent consull

ABCs, cardiac surgery or cardiology consult,pericardiocentesis if unstable, treat underlying cause

CXR: pleural effusion ( 75%)

ABCs, early antibiotics, resuscitation, tboracics consull HPO consider chest tube

.

emphysema, findings consistent with sepsis

pneumomediastinum ; Cl or water soluble conlrasl

.

.

Hone acutely

Herpes Zoster

Abnormal skin sensation itching,1 tingling / pain preceding rash by 1 5 d

Hone if early; maculopapular rash developing into vesicles and pustules that crust

Clinical diagnosis; direct ABCs, anti virals (if < 80 yr. Anginal equivalents include dyspnea, diaphoresis, fatigue, nomretrosternal

present in 25% of Ml)

-

.

Tachycardia, diaphoresis tremor

Diagnosis of exclusion

.

. .

ABCs NSAIDs tcsl orthopaedics consultation lot fractures

ABCs, arrange social supports, rule out suicidality and consider psychiatry consult

.

Conservative vs Interventional Treatment lor Spontaneous Pneumothorax HEJM 2020:382:405-415 Purpose: Detrtmme whether conservative management isan acceptable alternative to interventional management lor uncomplicated, moderate to -laige primary spontaneous pneumothoiax. Methods Open label, rmulticenter,noninleriority triaL Patients 14-50 y r were recruited with a Hist -known,unilateral, moderate-to-targe primary spontaneous pneumothorax. Patients (n - 316) were randomly assig~ ed to immediate interventional management of the pneumothorax or a conservative observational approach and were followed for 12 mo. fhe primary outcome was long re -expansion within 8 wk Resells Re expansion wilhinS wk occurred m 129 of 131 patients with interventional management and in 118 of 125 wnthcoRservative management (P 0.02, for nomnfeciority).Conservative management resulted m a lower risk ol serious adverse events or pneumothorax recurrence than interventional management Conclusions:The trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior lo interventional management with a lower risk of seriousadverse events.

-

.

-

r -i

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ER23 Emergency Medicine

Toronto Notes 2023

Table 16. Common Life - Threatening ECG Changes ECG Findings

Pathology

Dysrhythmia Torsades depointes Ventricular tachycardia Ventricular flutter Ventricular fibrillation

Ventricular complexes In upward- pointing and downward - pointing conlmuum |1G 0 250 bpm) 3 or more consecutive premature ventricular beats (>100 bpm. 0R 5 >120 ms) 5mootb sine wave pattern of similar amplitude (> 200 bpm) Erratic ECG tracing, no identifiable waves

Conduction

2nd degree heart block (Mobil:type II)

PR interval stable, some ORSs dropped

3rd degree heart block

Prolonged ORS complex (> 0.12 s) RSR' in VS or V6 Total AV dissociation, but stable P - P and R - R intervals

left bundle branch block

MonophasiclandV 6 May see ST elevation Difficult to interpret, new L 8 BB is consideredSIEMI equivalent

Ischaemia SI elevation in leads associated with injured area ol hcarl and reciprocal lead changes (depression)

SIEMI

Metabolic Hyperkalemia

Initially, tall l- waves Followed by PR prolongation, ORS widening, loss of P waves Finally, sinusoidal pattern and pulse electrical activity (PEA )fVFib/Asystole

P wave flattening ORS complex widening and flattening U waves appear Flattened I waves Supraventricular tachycardia Slow ventricular response

Hypokalemia

Digitalis Toxicity

Frequent premature ventricular contractions At risk for AV blocks and ventricular irritability

Syndromes

.

Brugada

RBB 8 with St elevation in VI. V 2 and V 3 Susceptible lo deadly dysrhythmias, including VFib

Wellens

Marked T wave Inversion In V 2 and V 3 Left anterior descending coronary stenosis

tong 01 syndrome

01 interval longer than ff> ol cardiac cycle Predisposed to ventricular dysrhythmias

Headache • see

Neurology, N 46

Etiology • common and less serious

common migraine ( without aura )/classic migraine ( with aura ) common: unilateral , throbbing, aggravated by activity, moderate/severe intensity, N / V, photo / phonophobia classic: fully reversible aura symptoms that precede headache, e.g. flashing lights, pins and needles ( paresthesia ), loss of vision , dysarthria treatment: simple analgesics ( NSAlDs, acetaminophen , Aspirin" ), antiemetics, triptans family physician to consider prophylactic treatment tension headache bilateral, non - throbbing, not aggravated by routine physical activity, mild - moderate intensity. can last between 30 min to 7 d triggered with stress, sleep deprivation treatment: modify stressor(s ), simple analgesics ( NSAlDs, acetaminophen , Aspirin*) • less common but potentially fatal subarachnoid hemorrhage ( SAH ) (see Neurosurgery, NS22) sudden onset, “worst headache of life,” maximum intensity within minutes, “ thunderclap headache" increased pain with exertion , N / V, meningeal signs
40 yr Reck pain o< stxfiness Witnessed toss of consciousness Onset during exertion Ihunderdap headache (instantly peaking pain) Limited neck flexion on examination Subarachnoid hemorrhage can he predicted with 100% sensitivity using this rule

«

.

r

^ LJ

• diagnosis

generation CT 100 % sensitive within 6 h of onset ( hyperattenuating signal - new around Circle of Willis)

- LP to look for xanthochromia if suspected SAH and normal CT after 6 h management: urgent neurosurgery consult • increased ICP worse in morning, when supine or bending down , with cough or Valsalva physical exam: neurological deficits, cranial nerve palsies , papilledema

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F.R 2 I Emergency Medicine

Toronto Notes 2023

diagnosis: CT head, LF if suspect idiopathic intracranial hypertension ( risk of blindness if missed) management: consult neurosurgery meningitis ( see

Infectious Diseases , 11317) at least two of the following features suggests that the headache could be due to meningitis: fever, neck stiffness , altered mental status possible clinical /laboratory findings: nausea , focal neurologic signs, seizure, papilledema , petechial rash, high CSI: WBC count, growth of organism in blood culture investigations: rule out increased ICP (CT head , mental status normal , no neurological signs, no papilledema ), if ruled out then perform diagnostic LP treatment: early empiric antibiotics ( high dose ceftriaxone t vancomycin ± ampicillin if > 50 y/o or immunocompromised) ± acyclovir ± steroid therapy (administer based on clinical suspicion, DO NOT wait for LP) giant cell arteritis/ temporal arteritis (causes significant morbidity, blindness) (see Ophthalmology, OP 36) vasculitis of large and mid - sized arteries , gender 3: 11;: M , most commonly ages >70 yr headache , scalp tenderness, jaw claudication , arthralgia , myalgia , fever , malaise or weight

loss

temporal artery tender on palpation, RAPD, optic disc edema on fundoscopy labs: elevated ESR . CRP temporal artery biopsy is gold standard for diagnosis associated with polymyalgia rheumatica treatment: high -dose steroids immediately if suspected, no need to hold treatment until pathology results • cerebral venous sinus thrombosis physical symptoms depend heavily on location, size , and extent of the clot . They may include gradual or sudden onset headache, vomiting, papilledema , visual disturbances, focal neurological deficits , seizures, and acute mental status changes investigations: neuroimaging (e.g. CT head, CT venography ) to assess and r/o other acute processes (e.g. intracranial hemorrhage ), CBC with coagulation studies and /or D -dimer,

Validation of the Ottawa Subarachnoid Hemorrhage Rule in Patients with Acute Headache CMAJ 201?:189:f 1379 E1385 Purpose: Validate the Ottawa S1H Rule m emergency department patients Methods: Prospective cohort study at ( university aftlrated tertiary -care hospital emergency departments in Canada from 2010 2014. Included alert neurotogically intact adult patients with headache peaking within1 hour of onset The rule was scored before investigations. Resnlts:1153/1743 potentially eligible patients were enrolled, 67 had subarachnoid hemorrhage. Ottawa SAH rule had 100% sensitivity and 13.6 % specificity with simitar neuioiinaging rates (87%). Conclusions: the Ottawa SAH Rule was sensitive lor identifying subarachnoid hemorrhage in otherwise alert and neurotogically intact patients.

-

.

-

-

Meningitis • Do not delay IV antibiotics for LP • Deliver first dose of dexamethasone with or before first dose of antibiotic therapy

consider LP to r/o meningitis treatment: anticoagulation ( most commonly LMWH or heparin ) Disposition

•admission: if underlying diagnosis is critical or emergent , if there are abnormal neurological findings, if patient is elderly or Immunocompromised (atypical presentation ), or if pain is refractory to oral

medications

•discharge: assess for risk of narcotic misuse; most patients can be discharged with appropriate analgesia and follow - up with their family physician; instruct patients to return for fever, vomiting, neurologic changes, or increasing pain

Joint and Back Pain

.

JOINT PAIN ( see Rheumatology RH 3) • rule out life - threatening causes e.g . septic joint (sec Orthopaedic Surgery, OKU )

History and Physical Exam • history: recent trauma , drug use (anticoagulants , glucocorticoids ) • associated symptoms: fever, constitutional symptoms, skin lesions, conjunctivitis, urethritis • patterns of joint involvement: polyarticular vs. monoarticular, symmetric vs. asymmetric • inflammatory symptoms: morning stiffness > 30 min, pain/stiffness that ease with activity, mid-day fatigue, soft tissue swelling • non - inflammatory symptoms: morning stiffness < 30 min, stiffness short -lived after inactivity, increasing pain with activity • assess for pain with ROM , localized joint pain , effusion , erythema , warmth , swelling, inability to bear weight, fever; may indicate presence of septic joint Investigations blood work: CBC, ESR, CRP, INR/ PTT, blood cultures, urate joint x-ray ± contralateral joint for comparison • bedside U /S to identify effusion ± joint aspiration • test joint aspirate for: culture, WBC , polynuclear cells , glucose, Gram stain, crystals •

Management

• septic joint: empiric IV antibiotics ± orthopaedic consultation for joint decompression and drainage • crystalline synovitis: NSAlDs at high dose, colchicine within first 24 h , corticosteroids do not use allopurinol for acute flares, as it may worsen acute attack • acute polyarthritis: NSAlDs, analgesics (acetaminophen ± opioids ), local or systemic corticosteroids osteoarthritis: NSAlDs, acetaminophen •

ParcnttralDeiamethasone (or Preventing Recurrence of Acute Severe Migraine Headache SMJ 2008; 336(76S 7):1359 Purpose: Ip examine effectiveness of parenteral corticosteroids for relief of acute severe migraine headache and prevention of recount headaches. Methods: Meta analysis of RCTscomparng corticosteroids (aloneor in comhloahoo with standard abortive therapy] to placebo or any other standard treatment for acute migraine in adults. Results:Seven RCIs met eligibility criteria, at of which used standard abortive therapy and subsequently compared single dose parenteral dexamethasone to placebo. All trialseoarined pain relief and lecuunti ol headache within 72 hr. While dexamethasone and placeboweie comparable for acotepaln reduction ( meanddfereuceO.37 95% Cl 0.20 to 0.94|and sde effect profiles, dexamethasone provided lower recurrence rates (relative risk 9.75, 9.60 to 0.90; number needed

-

.

-

totreat 9). Contusion:Single dose parenteral deiamethasone with standard abnrbve therapy is associated with

a 26% relative reduction in headache recurrence within 72 h.

Sew;

Red Flags for Back Pain

Bo wel or bladder dysfunction Anesthesia (saddle)

Constitutional symptoms K - Chronic disease. Constant pain Paresthesia Age >50 and mild trauma IV drug use /infection Neuromotor deficits

+

soft tissue pain: non - pharmacologic treatment: local heat or cold , electrical stimulation, massage pharmacologic : oral analgesics, NSAlDs, muscle relaxants, corticosteroid injections , topical agents

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ER25 Emergency Medicine

Toronto Notes 2023

BACK PAIN (see family Medicine. I M l 1 ) • rule out extraspinal emergencies: aortic dissection, AAA, PE, Ml , retroperitoneal bleed , pancreatitis • rule out spinal emergencies: osteomyelitis, cauda equina syndrome, epidural abscess or hematoma, spinal fracture, or malignancy

History and Physical Exam • evaluate risk for fracture (osteoporosis, age, trauma), infection ( IV drug user, recent spinal intervention, immunosuppression ), cancer, vascular causes (cardiac risk factors), neurological symptoms ( e.g. saddle anesthesia ) • typical musculoskeletal back pain is moderate, worse with movement or cough with no visceral symptoms • assess vital signs, perform precordial, abdominal, and neurologic examination of lower extremities Investigations • WBC, ESR, CRP, U /A, post -void residual bladder scan • reserve imaging for neurological deficits, metastases, and patients at high - risk of fracture, infection,

cancer, or vascular cause consider x ray ± Cl' if trauma or fracture risk urgent MRI if neurological findings

-

Management

• treat underlying cause • lumbosacral strain and disc herniation: analgesia and continue daily activities as much as tolerated: discuss red flags and organize follow- up • spinal infection: early IV antibiotics and infectious disease consultation • cauda equina syndrome: dexamethasone, early neurosurgical consultation

Seizures • see Neurology, N 18

Definition

• paroxysmal alteration of behaviour and/or EECi changes resulting from abnormal , excessive activity of

neurons • status epilepticus: continuous or intermittent seizure activity for greater than 5 min without regaining consciousness ( life- threatening )

$

Minimum Workup in an Adult with 1st Time Seizure CBC and differential Electrolytes including CaJ + Mg *. PCU1

CT Head

. '

-

Categories

• generalized seizure (consciousness always lost ): tonic/clonic, absence, myoclonic, atonic • partial seizure (focal ): simple partial, complex partial • causes: primary seizure disorder, structural ( trauma, intracranial hemorrhage, infection, increased 1CP), metabolic disturbance ( hypo / hyperglycemia , hypo /hypcrnatremia, hypocalcemia, hypomagnesemia, toxins /drugs ) • differential diagnosis: syncope, stroke/ TIA , psychogenic non -epileptic seizure, migraines, movement disorders, narcolepsv/cataplexy

-

-

History and Physical Exam

• history of seizures, identify potential precipitanls ( illness, alcohol withdrawal , sleep deprivation ) • preceding aura, rapid onset , brief duration, alterations in consciousness, tonic- clonic movements, and post-ictal symptoms would suggest a seizure • common signs include tongue biting ( high specificity), loss of bladder/bowel control, emesis, and

If administering phenytoin , patient must be on a cardiac monitor as dysrhythmias and/or hypotension may occur

m

If IV access is not feasible, midazolam 0.2 mg / kg IM up to 10 mg can be used for initial control of seizure in adults

aspiration

• perform vitals, complete neurologic examination and look for injuries to head, spine, and shoulder ( particularly posterior dislocations )

Table 17. Concurrent Investigation and Management of Status Epilepticus Timing

Steps

Immediate

Protect airway will) positioning: intubate II airway compromised or elevated ICC Monitor: vital signs, ECG oximetry: POCT capillary blood glucose Establish IV access Benzodiazepine lorazepam 2 mg IV at 2 mg,' min up to 10 mg or midazolam 5 mg IM up to10 mg: repeat at 10 min if ineffective: intranasal or I 0 if no IV access Fluid resuscitation IV dextrose it glucose < 60 mg / dl Give 60% glucose 60 ml ( preceded by thiamine 100 mg IM if concerned about alcohol withdrawal ) Obtain CBC electrolytes, Ca 2; Mg 2 - , VBG , serum blood glucose, toxins, and anliepileptic drug levels; p hCG Vasopressor support if sBP "90 or MAP "70 mmHg alter aggressive fluid resuscitation Establish second IV line, urinary catheter If status persists , phenytoin 20 mg / kg IV al 25 50 mg /m in in adults: may give additional 10 mg /kg IV 10 min alter loading infusion II seizure resolves , antieplleptic drug slill required lo prevent recurrence EEC monilonng lo evaluate lor non convulslve status epilepticus

.

-

.

Urgent

-

ri

-

Refractory

If status persists alter maximum doses above, consult ICU and start one or more of : Phenobarbilal 20 mg / kg IV at 50 mg / min Midazolam 0.2 mg /kg IV loading dose and 0.10.4 mg / kg /h Propofol 2 mg / kg IV al 2 5 mg / kg / h then loading dose then 2 10 mg / kg /h Requires definitive airway management indudingiapid sequence intubation and assisted ventilation . Elcctroencephalogiaphy ( EEC ) lor continuous monitoring Investigate underlying cause: consider CT. IP. MRI. ICP monitoring

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Post -Seizure

+

-

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Nate: All interventions should be done os soon os possible dopted from Brophy et al Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012:17:3 -23

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Disposition

• decision to admit or discharge should be based on the underlying disease process identified if a patient had a brief generalized seizure and has returned to baseline function and is neurologicalIy intact, then consider discharge with outpatient follow - up • first time seizure patients being discharged should be referred to a neurologist for follow up • admitted patients should generally have a neurology consult • patient should not drive until medically cleared ( local regulations vary) • complete notification form to appropriate authority regarding ability to drive ( based on local legal requirements) • warn regarding other safety concerns (e.g no swimming, bathing children alone, etc )

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.

.

Shortness of Breath • see Respirologv, R 3 and Cardiology and Cardiac Surgery, C6 High Mortality/ Morbidity

Usually Less Emezgent Chronic obstructive, interstitial or restrictive lung disease

Cardiac

Airway obstruction ( foreign body, epiglottitis, abscess, anaphylaxis) Pneumo/hemothorax Gas exchange - pulmonary edema. PE pneumonia , acute exacerbations ol asthma or CORD CHE, Ml valvular disease, tamponade, arrhythmia

Metabolic

Metabolic acidosis NYD. toxin ingestion

Anemia. Hemoglobinopathy

Neuromuscular

Myasthenia gravis , diaphragmatic paralysis

CNS lesion, primary muscle weakness

Other

Deconditioning , respiratory splinting due lo unrelated pain

Anxiety

.

.

paramedics.

-

Pleural effusion Chronic CHE, angina

-

Methods: Double Mind, randomized , non inferiority trial. Subjects whose convulsions had persisted more than S min and were still convulsing alter paramedics arrived were given the study meditation by either IM or IV Infusion. Primary outcome: absence ol stiluses at the timeof arrival in the emergency department without the need for rescue therapy. Results: Seizu resnere absent without rescue therapy in 73% of the IM midaiolam group and m 63.4% ol the IV loratepam group [ P‘0.001 foi nonlnferiority and Superiority). The median times lo active treatment we it 1.2 min in the IM midazolam group and 4.8 min in the IV lorazepam group, with corresponding median timesfrom active treatment tocessatlonofconvutsmnsof 3.3 minaed 1.( min.

-

Table 18. Differential Diagnosis for Dyspnea Respiratory

Intramuscular »5. Intravenous Therapy for Prehospital Stains Epileptirus HE JM 2012:366:591600 Purpose lo investigate the eHkacy of intramuscular (IM|midatolam with that of IV locatepam for children and adults HI statusepileptrcus treated by

-

-

-

.

Adverse event rates were snmlai

Conclusions: For subjects in status epdeptcus. IM midazolam is at least as safe and effective as K (orazepam fur prehospital seizurecessation.

History and Physical Exam • acute SOB is often due to a relatively limited number of conditions; associated symptoms and signs are

key to the appropriate diagnosis substcrnal chest pain with cardiac ischaemia • fever, cough, and sputum with respiratory infections urticaria with anaphyllaxis wheezing with acute bronchospasm environmental or occupational exposures • dyspnea may he the sole complaint and the physical exam may reveal few abnormalities (e.g. PE, pneumothorax ) • vitals including pulse oximetry wheeze and stridor (ventilatory) vs. crackles ( parenchymal),|V P, and murmurs Investigations

• blood work CBC and differential ( hematocrit to exclude anemia ), electrolytes, consider AB(i/ VB(i serial cardiac enzymes and ECG if considering cardiac source PERC or Wells scores to consider appropriateness of D-dimer • imaging CXR ( hyperinflation and bullous disease suggestive of obstructive lung disease, or changes in interstitial markings consistent with inflammation , infection, or interstitial fluid ) CT chest may be indicated in acute dyspnea, specifically when suspicion for thromboembolic disease (i.e. PE) Disposition

• history and physical exam lead to accurate diagnoses in patients with dyspnea in approximately twothirds of cases; the decision to admit or discharge should be based on the underlying disease process identified and its severity non - invasive positive pressure ventilation ( N 1PPV ) should be considered in patients with severe COPD or CHI ', may reduce the need for intubation in this patient population consider intubation in COPD and CHE if NIPPV will not be tolerated ( e.g. decreased LOC, vomiting )

• if discharging, organize follow- up and educate regarding signs to return to hospital

Syncope

ri j

Definition • sudden, transient loss of consciousness and postural tone with spontaneous recovery • usually caused by generalized cerebral or reticular activating system ( brainstem ) hypoperfusion

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Etiology • cardiogenic: dysrhythmia, outflow obstruction (e.g. PE, pulmonary' HTN ), Ml, valvular disease • non -cardiogenic: peripheral vascular ( hypovolemia ), vasovagal, orthostatic, cerebrovascular disorders, CNS, metabolic disturbances (e.g EtOH intoxication )

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History

• gather details from witnesses, and clarify patient’s experience (e.g. dizziness, ataxia, or true syncope) • two key historical features: prodrome and situation (setting, patient posture) • distinguish between syncope and seizure (see Neurology. N 19) • some patients may have myoclonic jerks with syncope NOT a seizure signs and symptoms during presyncope, syncope, and postsyncope (seizure has post ictal period afterwards, syncope does not ). past medical history, drugs think anatomically in differential: pump ( heart ), blood, vessels, brain • syncope is cardiogenic until proven otherwise if there is sudden loss of consciousness with no warning or prodrome syncope is accompanied by chest pain

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Physical Exam

• postural BP and HR

• cardiac, respiratory, and neurological exams • examine for signs of secondary injury caused by syncopal episode (e.g. head injury') Investigations

• EGG ( tachycardia, bradycardia , blocks, Wolff - Parkinson White, long QT interval, Brugada Syndrome,

right ventricular strain, hypertrophic cardiomyopathy), • POCT capillary blood glucose • consider blood work: CBC, electrolytes, BUN / Cr, VBG, troponin, Ca 2|, Mg - ' , p hCG , D-dimer

-

• consider toxicology screen

Management • ABCs, IV, O’, monitor • cardiogenic syncope: admit to medicine/cardiology

-

-

• low - risk syncope: discharge with follow up as indicated by cause ( non cardiogenic syncope may still be admitted )

Disposition

• decision to admit is based on etiology • most patients will be discharged • on discharge, instruct patient to follow up with family physician

•

educate about avoiding orthostatic or situational syncope evaluate the patient for fitness to drive or work patients with recurrent syncope should avoid high risk activities (e g. driving )

-

.

Sexual Assault

s

Epidemiology

• I in 5 women and I in SO men will be sexually assaulted in their lifetime; only 7% are reported General Approach

• ABCs, treat acute, serious injuries; physician priority is to treat medical issues and provide clearance • ensure patient is not left alone and provide ongoing emotional support • obtain consent for medical exam and treatment, collection of evidence, disclosure to police ( notify police as soon as consent obtained ) • Sexual Assault Kit (document injuries, collect evidence) if 80%

Consider steroids ( MDI or P 0)

Disposition

• discharge is safe in patients with FEVI or peak expiratory flow ( PEE ) >60% predicted, and maybe safe if I F VI or PEE 40 60% predicted based on the patient’s risk factors for recurrence of severe attack risk factors for recurrence: frequent FD visits, frequent hospitalizations, recent steroid use, recent exacerbation , poor medication compliance, prolonged use of high dose (3-agonists • p agonist MDI with aerochamber 2 4 puffs q 2 -4 h until symptoms controlled , then PUN • initiate inhaled corticosteroids with aerochamber if not already prescribed if moderate to severe attack, administer prednisone 30 -60 mg /d for 5-10 d with no taper • counsel on medication adherence and educate on use of aerochamber • follow up with primary care physician or asthma specialist

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Cardiac Dysrhythmias

.

• see Cardiology and Cardiac Surgery 09

Bradydysrhythmias and AV Conduction Blocks

• AN' conduction blocks • 1st degree: prolonged PR interval (>200 msec), no treatment required 2 nd degree Mohitz 1: gradual prolongation of PR interval then dropped QRS complex , usually benign Mohitz 11: PR interval constant with dropped QRS complex, can progress to 3rd degree AV block

• 3rd degree: P wave unrelated to QRS complex , PP and RR intervals constant

atropine and transcutaneous/ transvenous pacing ( atropine with caution ) if transcutaneous/ transvenous pacing fails consider IV dopamine, epinephrine • long- term treatment for Mobitz II and 3rd degree block internal pacemaker • sinus bradycardia ( rate 100 bpm ) • causes: increased sympathetic tone, drugs, fever, shock, anemia , thyrotoxicosis, Ml, HF , emotional , pain , etc. • search for and treat underlying cause • regular rhythm ( i.e. not sinus tachycardia ) • vagal maneuvers ( e.g. carotid massage, Valsalva ), adenosine 6 mg IV push , if no conversion give 12 mg, can repeat 12 mg dose once, electrical cardioversion if vagal maneuvers and adenosine unsuccessful • rhythm converts: probable reentrant tachycardia (atrioventricular ( AV ) nodal reentrant tachycardia ( AVNRi ) more common than AV reentrant tachycardia ( AVRT) monitor for recurrence treat recurrence with adenosine or longer acting medications

Elements of Well-Controlled Asthma

Can Respir J 2010:17(1):15- 24 • Daytime symptoms 90, RR

> 20, WBC > 12 sepsis; SIRS and suspected or present source of infection septic shock: sepsis and either initial lactate > 4 or hypotension qSOl-'A score > 2: high risk for in -hospital mortality (see Infectious Diseases. 1020) • although the presence of a positive qSOl'A should alert clinicians to the possibility of sepsis in all resource settings, it should not be used as a single screening tool given its poor sensitivity. • management » early recognition of sepsis and investigations to locate source of infection identify severe sepsis with lactate or evidence of tissue hypoperfusion • sepsis standard operating procedures, initially specified as Early Goal Directed Therapy have evolved to “usual care” which includes a standard approach with components of the sepsis bundle , early identification, lactate, cultures, antibiotics , and fluids treatment priorities: ABCs, monitors, lines aggressive fluid resuscitation; consider ventilatory and inotropic support cultures, then early empiric appropriate antibiotics consider broad spectrum and atypical

-

Surviving Sepsis Campaign 1 Hour Bundle J Intensive Cere Med 2013:44:925428 U pdale sepsis bundle from 3 h to 1 h lime Irene with lime zero being lime of triage B Ihe tO Artms include: • Measure lactate level. Remeasure . I nitial lactate

lt >2 ratl/l • Obtain Mood cultures prior to administration ol antibiotics

• Administer broad spectrum antibiotics Begin rapd administration ol 30 inL ' kg crystalloid for hypotension or lactate > 4 mmol/l Apply vasopressors il the patient is hypotensive during or after fluid resuscitation to maintain MAP >< 5 mmHg

-

-

coverage source control - e.g. remove infected Foley or surgery for ischaemic gut monitor adequate resuscitation with vital signs, inferior vena cava on U /S, and serial measurement of serum lactate in patients presenting with septic shock, goal- directed therapy and aggressive management should not be delayed while waiting for lab values patients failing initial therapy should be resuscitated more aggressively ( e.g. use of vasopressors, glucocorticoids, inotropic therapy, blood transfusion, etc.)

Stroke and Transient Ischaemic Attack • see Neurology, N 51

• definitions • stroke; sudden loss ofbrain function due to ischaemia (87%) or hemorrhage ( 13%) with persistence of symptoms >24 h or neuroimaging evidence TTA: transient episode of neurologic dysfunction from focal ischaemia without acute infarction or neuroimaging evidence • clinical features Table 23. Signs and Symptoms of Stroke

Signs / Symptoms

General

Language / Throat

Vision

Coordination Motor

Decreased LOC changed menial status, confusion,

Dysarthria ,

. swallowing

Diplopia , eye deviation ,

Ataxia , intention Increased lone loss of power spasticity coordination

.

aphasia

difficulty

neglect

asymmetric pupils , visual field defect

tremor , lack of

.

.

Sensation

Reflex

Loss of sensation

Hyperreflexia , clonus

• patients with hemorrhagic stroke resulting in subarachnoid hemorrhage can present with sudden onset thunderclap headache that is usually described as “worst headache of life” and can often recall the exact moment their headache started • stroke mimlckers: seizure, T odd's paresis ( period of partial or complete paralysis following a seizure), migraine, hypoglycemia , peripheral nerve injury, Bell ’s palsy, tumour, syncope, somatic symptom disorder Table 24 . Stroke Syndromes

..SevenAFibCauses of Emboli from

the Heart

Ml • Endocarditis • Valvular disease • Dilated cardiomyopathy • Left heart myxoma • Prosthetic valves

Differentiation of Upper Motor Neuron (UMN) Disease vs. Lower Motor Neuron ( LMN) Disease

Category

UMH Disease LMH Disease

Muscular

Musde

deficit Relleres

groups Increased Increased

Individual musdes

Decreased / absent

Region of Stroke

Stroke Syndrome

Anterior Cerebral Artery

Contralateral hemianesthesia and hemipatesis (legs > aims/face), gall apraxia , altered menial status, impaired

Tone

judgement

Fasciculalions Absent

Contralateral hemianesthesia and hemipatesis (arms / face > legs), contralateral homonymous hemianopsia , ipsilaleral gaze Contralateral homonymous hemianopsia , cortical blindness, impaired memory

Atrophy

Absent/ minimal

Present

Plantar

Upgorng

Downgomg

Wide variety of cranial nerve, cerebellar, and brainstem deficits: vertigo, nystagmus, diplopia , visual field deficits, dysphagia , dysarthria, facia! hypoesthesia syncope, ataxia loss of pain and temperature sensation in ipsilaleral face and contralateral body

Response

Middle Cerebral Artery

Posterior Cerebral Artery Vertebrobasilar Artery

Decreased

Present

.

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Investigations • CBC , electrolytes, blood glucose, coagulation studies ± cardiac biomarkers ± toxicology screen • CT angiography and perfusion of the head and neck • ECG: rule out AE'ib, acute Ml as source of emboli • other imaging: if you are suspicious of a ’ll A a plain CT followed by carotid Doppler, outpatient CT angiography neck and /or head , magnetic resonance angiography ( MKA ) can be arranged based on

local resources Management • ABCs; intubation with RSI if GCS 120 mmHg, MAP > 140 mmHg ) or HTN associated with hemorrhagic stroke transformation, cardiac ischaemia, aortic dissection, or renal

damage; use IV nitroprusside or labetalol • glycemic control serum glucose of 7.8 - 10 mmol / L • cerebral edema control: hyperventilation, mannitol to decrease ICP if necessary

• consult neurosurgery, neurology, medicine as indicated

• following acute event:

antiplatelet agents to: prevent recurrent stroke or stroke after TlAs , e.g. Aspirin* (1 st line); dopidogrel , Aggrenox * ( 2 nd line) consider anticoagulation : if Afib present or if immobile for DVT prophylaxis • follow -up for consideration of carotid endarterectomy, cardiovascular risk optimization

Otolaryngological Presentations and Emergencies

If a patient presents within 4.5 h of onset of disabling neurological deficits >60 min with no signs of resolution, they may be a candidate for thrombolysis. Do brief assessment and order CT head STAT Absolute Exclusion Criteria for Tissue Plasminogen Activator (tPA) • Suspected subarachnoid hemorrhage • Previous Intracranial hemorrhage • Cerebral infarct or severe HI within the past 3 mo sBP >185 mmHg or dBP >110 mmHg • Bleeding diathesis Prolonged PT >15 s or INR >1.7 Platelet count 1000 2000 IU: further workup and /or gynaecology consult abortions: if complete, discharge if stable; for all others, consult gynaecology • 2nd / 3rd trimester pregnancy placenta previa or placental abruption: obstetrics consult for passible admission • postpartum manage ABCs: start 2 large bore IV rapid infusion , type St cross 4 units of blood, consult OB/GYN

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immediately • non pregnant

-if unstable admit to gynaecology for IV hormonal therapy, possible dilation and curettage

• non-structural abnormalities

• tranexamic acid to stabilize clots

»

medroxyprogesterone acetate 10 mg FO once daily xlO d, warn patient of a withdrawal bleed stable structural abnormalities (fibroids, polyps, endometrial thickening , adenomyosis), outpatient gynaecology referral once stable

Disposition • decision to admit or discharge should be based on the stability of the patient, as well as the nature of the underlying cause; consult OB/GYN for patients requiring admission • if patient can be safely discharged, ensure follow-up with family physician or OB/GYN • instruct patient to return to ED for increased bleeding or presyncope

Pregnant Patient in the ED Table 25. Complications of Pregnancy Trimester

Fetal

Maternal

First 1 12 wk

Pregnancy failure Spontaneous abortion Fetal demise Gestational trophoblastic disease

Ectopic pregnancy Anemia Hypcremcsis gravidarum UTlfpyelonephrilis

Second 13 - 27 wk

Disorders of fetal growth Intrauterine growth restriction Oligo/polyhydramnios

Gestational DM Rh incompatibility

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UTlfpyelonephrilis

Cervical Incompetence Third 28- 41 wk

Vasa previa

Preterm labourfpreterm premature rupture of the membranes Prccdampsia (hypertension in pregnancyVedampsia Placenta previa Placental abruption Uterine rupture DVT/PE

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Nephrolithiasis (Renal Colic)

.

• see Urology U 18 Epidemiology and Risk Factors

• 10% of population (twice as common in males) • recurrence 50% at 5 yr • peak incidence 30 50 yr • 75% of stones < 4 mm pass spontaneously within 2 wk, larger stones may require consultation

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Kidney Stones

• 80% calcium oxalate • 10% struvite 10% uric Kid

.

Clinical Features

• urinary obstruction -> upstream distention of ureter or collecting system -> severe colicky pain • may complain of pain at flank, groin , testes, or tip of penis • writhing, N / V, hematuria (90% microscopic), diaphoresis, tachycardia , tachypnea • occasionally symptoms of trigonal irritation (frequency, urgency ) • fever, chills, rigors in secondary pyelonephritis • peritoneal findings/anterior abdominal tenderness usually absent

Obstruction Infection Urological Emergency Urgent urology consult

-

Differential Diagnosis of Renal Colic

• acute ureteric obstruction

• acute abdomen: biliary, bowel , pancreas, AAA • urogynaecological : ectopic pregnancy, torsion / rupture of ovarian cyst, testicular torsion

• pyelonephritis (fever, chills, pyuria, vomiting ) • radiculitis ( LI): herpes zoster, nerve root compression Investigations

Indications for Admission to Hospital

• CBC: elevated WBC in presence of fever may support an infectious cause

, Intractable pain

• non -contrast CT is the study of choice • consider abdominal U /S in females of childbearing age, children, or if patient has another contraindication to CT scanning: may demonstrate stone(s), hydronephrosis, debris in the collecting

. . Intractable

• electrolytes, Cr, BUN to assess renal function • VIA: routine and microscopy ( WBCs, RBCs, crystals), CStS

system , reduced cortical vascularity, abnormal renal parenchyma

• AXR will identify large radiopaque stones ( calcium , struvite, and cystine stones ) but may miss smaller stones, uric acid stones, or stones overlying bony structures; consider as an initial investigation

• Fever (suggests infection ) or other evidence of pyelonephritis Single kidney with ureteral obstruction Bilateral obstructing stones vomiting • • Compromised renal function

in patients who have a history of radiopaque stones and similar episodes of acute flank pain ( CT necessary if film is negative) Management

• analgesics: NSAIDs ( usually ketorolac ( ToradoD, preferable over opioids), antiemetics, IV fluids if

indicated • urology consult indicated, especially if stone >5 mm, or if patient has signs of obstruction leading to renal dysfunction or infection • a - blocker (e.g. tamsulosin ) may be helpful to increase stone passage in select cases Disposition

• most patients can be discharged

• ensure patient is stable, has adequate analgesia, and able to tolerate oral medications • may advise hydration and limitation of protein, sodium, oxalate, and alcohol intake

Ophthalmologic Emergencies .

• see Ophthalmology OF5

History and Physical Exam

• patient may complain of pain , tearing, itching, redness , photophobia, foreign body sensation , trauma • mechanism of foreign body insertion if high velocity injury suspected ( welding, metal grinding, metal striking metal ), must obtain orbital x- rays, U /S, or CT scan to exclude presence of intraocular

-

metallic foreign body • ask about sexual partners and exposure of eye(s) to bodily fluids (semen, urine, blood, vaginal fluids, saliva, etc.) • visual acuity in both eyes, pupils, extraocular structures, extraocular movements, fundoscopy,

tonometry, slit lamp exam, visual fields

Management of Ophthalmologic Foreign Body

• copious irrigation with saline for any foreign body • remove foreign body under slit lamp exam with cotton swab, sterile needle, or electric burr tool • antibiotic drops if indicated (e.g. organic foreign body ) • patching may not improve healing or comfort do not patch contact lens wearers • limit use of topical anesthetic to examination only

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• tetanus prophylaxis • ophthalmology consult if globe penetration suspected Contraindications to Pupil Dilation

Table 26. Differential Diagnosis of Red Eye in the Emergency Department Symptom

Possible Serious Etiology

Light Sensitivity

Iritis, keratitis, abrasion, ulcer

Unilateral

Above* herpes simplex, acute angle closure glaucoma

Significant Pain

Above * sderitis

White Spot on Cornea

Corneal ulcer

Non- Reactive Pupil

Acute glaucoma, iritis

Copious Discharge

Gonococcal conjunctivitis

Blurred Vision

All of the above

• Shallow anterior chamber • Iris-supported lens implant

• Potential neurological abnormality requiring pupillary evaluation

• Caution with CV disease - mydriatics can cause tachycardia

Other Ophthalmologic Emergencies Infectious: Red eye, endophthalmitis, hypopyon Trauma: Globe rupture, orbital blowout fractures, comeal injuries, eyelid laceration, hyphema, lens dislocation, retrobulbar hemorrhage Painful vision loss: Acute iritis, corneal abrasion, globe rupture, lens dislocation, retrobulbar hemorrhage, optic neuritis, temporal arteritis, endophthalmitis, keratitis Painless vision loss: Central retinal vein occlusion, amaurosis fugax occipital stroke

Table 27. Select Ophthalmologic Emergencies Condition

Signs and Symptoms

Management

Acute Angle Closure Glaucoma

Unilateral red, painful eye Decreased visual acuity, halos around lights fixed, mid- dilated pupil N /V Marked increase in intraocular pressure (I0P) (»40 mmHg) Shallow anterior chamber t cells

Ophthalmology consul! for laser iridotomy Medications: AABCDE / EAT PAL o - agonisl: epinephrine 2 agonist:apradonidine pblocker: timolol Cholinomimetic : pilocarpine Diuretic: acetarolamide, mannitol Eicosanoid: latanoprost

Pain, redness, tearing, photophobia, foreign body sensation De - epithelialired area stains with fluorescein dye

Most clear spontaneously within 24 - 48 h If due to foreign body, remove under magnification using local anesthetic and sterile needle, or consult ophthalmology for removal under magnification Topical antibiotic (drops or oinlmenl) Irrigate site of accident with NS with eyelid retracted until neutral pH achieved Sweep fornices Cycloplegic drops and topical antibiotics

Corneal Abrasion

Known exposure to acids or alkali ( worse) Pain, decreased visual acuity Vascularization or defects of cornea Iris andlens damage

Chemical Burn

Orbital Cellulitis

.

.

Retinal Vein Occlusion

Retinal Delachment

.

Red painfuleye decreased visual acuity Headache fever lid erythema, edema, and difficulty opening eye Conjunctival injection and chemosis Pioptosis opthalmoplegia * RAPD Sudden, painless,monocular vision loss RAPD Chciry red spot and retinal pallor on fundoscopy if central retinal artery occlusion

Admission, ophthalmology consult Blood cultures, orbital Cl IV antibiotics Iceflriaxone vancomycin) Drainage of abscess

Painless, monocular, gradual, or sudden vision loss sRAPD On lundoscopy: "blood and thunder " appearance, diffuse retinal hemorrhages, collon wool spols, venous engorgement, swollen oplic disc, macular edema flashes of light, floaters, and curtains of blackness/ pcriphetal vision loss Painless loss of ted reflex , decreased I0P Detached areas are gvey Visible detachment orbital POCUS iRAPD

Ophthalmology consull for retinal lasei pholocoagulation

.

.

Retinal Artery Occlusion

-

Restore blood llow < 2 li Massage globe Decrease I0P ( topical 8 - blockers, Inhaled Ot /CO ) mix, IV Olnroox ", IV mannitol, drain agueous fluid)

anli - VEGf, and/ or corticosteroid injection

Ophthalmology consult lor scleral buckle /pncumallc retinopexy

POCIIS for the Diagnosis of RetinalDetachment: A Systematic Review and Meta Analysis Acad Emerg Med 2019:26:931-939 Purpose: POCUS has been suggested to idenbfy retinal delachment rapidly Ihe primary outcome for this review wasto determine the test characteristics of POCUS for the diagnosis olretioal detachment. Methods: Systematic review and metaanalysis looking for all prospectuetnalsand RCIs assessing Ihe accuracy of POCUS for identifying retinal detachment Results: II studies (n - 844 ) were identified. Overall,ultrasound was 94.2 \ (95% Cl 78.4% to 98.5 \) sensitive and 96.3%|95 % CI 89.2% to 98.83 ) specific for the diagnosis of retinaldetachment with a poutue likelihood ratio of 25 2 (95% Cl 8.1 to 78.0) and a negative likelihood ratio of 0.06 (9S% Cl * 0.01 to 0.2S). Conclusions: POCUS « sensitive and specific lot the diagnosis of retinal detachment.

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.

.

.

e

Visual acuity is the "vital sign" of the eyes and should ALWAYS be assessed and documented in both eyes when a patient presents to the ED with an ophthalmologic complaint

Dermatologic Emergencies Rash Characteristics A . Diffuse Rashes

• Staphylococcal Scalded Skin Syndrome (SSSS ) caused by an exotoxin from infecting strain of coagulase - positive S. aureus mostly occurs in children prodrome: fever, irritability, malaise, and skin tenderness

•

sudden onset of diffuse erythema : skin is red , warm , and very tender flaccid bullae that are difficult to see, then desquamate in large sheets Steven Johnson Syndrome (S]S ) and Toxic Epidermal Necrolysis ( TEN ) see Dermatology D26 caused by drugs (e.g. phenytoin, sulfas, penicillins, and NSAlDs), bone marrow transplantation, and blood product transfusions usually occurs in adults diffuse erythema followed by necrosis severe mucous membrane blistering

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entire epidermis desquamation high mortality (>50%) Toxic Shock Syndrome (TSS)

.

•

see Infectious Diseases ID22 caused by superantigen from S aureus or Group A Streptococcus (GAS) activating T- cells and cytokines patient often presents with onset of shock and multi-organ failure, fever diffuse erythematous macular rash at least 3 organ systems involved: CNS, respiratory, Gl, muscular, mucous membranes, renal, liver, hematologic, and skin ( necrotizing fasciitis, gangrene ) vesiculobullous lesions Erythema Multiforme ( EM ) immunologic reaction to herpes simplex viral prodrome 1-14 d before rash target lesion: central grey bulla or wheal surrounded by concentric rings of erythema and

.

normal skin

Drug reaction with eosinophilia and systemic symptoms ( DRESS) syndrome

B. Discrete Lesions Pyoderma Gangrenosum often associated with 1BD, rheumatoid conditions, leukemia, and monoclonal gammopathies often occurs in arms, hands, feet, or perineal region usually begins as painless macule/vesicle/pustule/ bulla on red/blue base sloughing, leavinga gangrenous ulcer • Disseminated Gonococcal Infection ( DGI ) see Dermatology D38 fever, skin lesions ( pustules/ vesicles on erythematous base 5 mm in diameter ), arthritis ( joint swelling and tenderness), and septic arthritis ( in larger joints, such as knees, ankles,

.

-

and elbows)

most commonly in gonococcus-positive women during menstruation or pregnancy skin lesions usually appear in extremities and resolve quickly ( 7.5 • fluid resuscitate first, then 3 amps NaHCOi/ L of D5 \ V at 1.5.x maintenance • add 20 -40 mEq / L KC1 if patient is able to urinate

rt LJ

+

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ER53 Emcrgcnq- Medicine

Toronto Notes 2023

Table 33. Protocol for Warfarin Overdose INR

Management: Consider Prothrombin Compel Concentrate (Octaplex :. Beriplex:) tor any elevated INR. AND either life - threatening bleeding, or a plan for the pabent to undergo a surgical procedure within the next 6 h (vitamin K takes 4- 6 h post IV administration to work)


20.0

Hold warfarin, vitam nit 10 mg IV over 10 -

5.0

-. ncrease vitar - Kdssng ( g4 h)

f - eeded

Table 34 . Specific Antidotes and Treatments for Common Toxins* Toxin

Treatment

Considerations

Acetaminophen

Decontaminate ( activated charcoal) N-acetyl cysteine

Often clinically silent: evidence of liver /renal damage delayed >24 h fete dose >200 mg'kg (»7.5 g adult) Monitor drug level 4 h post - ingestion; also liver enzymes, INR, PIT SUN Cr Hypoglycemia, metabolic acidosis, encephalopathy poor prognosis 0;alysis may be required to manage in very high overdoses

. .

Acute Dystonic Reaction

Benztropine:12 mg IM IV then 2 mg P0 3 d OR Oiphenhydr amine 12 mg/kg IV then 25 mg P0 010 x3 d

Berutropme (Cogentm |has euphoric effect and the potential for misuse

Anticholinergics

Consider decontammabon (activated charcoal) Supportive care

Special anbdotes available:consult Poison Information Centre

ASA

Consider decontaminabon (activated charcoal) Alkalinize urine:want urine pH >7.5

Monitor serum pH and drug levels closely Monitor Ktevel:may require supplement for urine alkalinization Hemodialysis may be needed if intractable metabolic acidosis, very high levels, or end- organ damage (i.e unable to diurese)

Benzodiazepines

Consider decontamination (activated charcoal) Flumazeml (only use in iatrogenic overdose (operative oversedabon) due to extensive contramdications (mixed overdose. Hx of EtOH.seizures)) Supportive care

p -blockers

Consider decontamination (activated charcoal,consider whole bowel irrigation for extended- release ingestion) IV glucagon. IV calcium chloride. IV high-dose insubn ( with dextrose). IV lipid emulsificabon

Calcium Channel Blockers

Consider deconta- nabon (acbvated charcoal consider Order EC6. electrolytes (especially Ca Mg 2 \ Ha’. K ) whole bowel irrigabon for extended- release ingesbon) IV glucagon [V calcium chloride. IVhigh-dose insulin

.

.

*-.

,

'

.

( with dextrose).IV intralipid

Cocaine

Decontaminate (acbvated charcoal) if oral Aggressive supportive care

3-blockers are contraindicated in acute cocaine toxicity Intralipid for life- threatening symptoms Consider benzodiazepines for any major side effect of cocaine overdose (agitation, hypertension, tachycardia, etc.)

CO Poisoning

See Inhalation Injury fl?47 Supportive care 100“c 0 J ;may require hyperbaric 0

.

Order ECG VBG.Consider lactate and troponin depending on specific presentabon

Cyanide

Hydroxocobalamin Sg IV (Cyanokit ')

Consider in all patients found in a fire

Digoxin

Consider decontaminabon (activated charcoal) Oigoxm -specific antibody fragments

Use for life- threatening dysrhythmias unresponsive to conventional therapy 6 h serum digoxin >12 nmol/L initial K >5 mmol/l ingestion >10 mg|adult) />4 mg (child) Common dysrhythmias include VFib VTach and conduction blocks

Ethanol

Thiamine 100 mg IMilV Manage airway and circulatory support

Mouthwash - 70% EtOH: perfumes and colognes 40 60% EtOH Order serum EtOH level and glucose level: treat glucose level appropriately

Ethylene Glycol/ Methanol

Fomepizole (4-methylpyrazole) 15 mg/kg IV load over 30 mm then 10 mg,rkgq12 hOR Ethanol (10%) 10 mL Vg over 30 min then 1.5 mt/h

CBC. electrolytes, glucose, ethanol level Consider hemodialysis

Heparin

Protamine sulfate 25- 50 mg IV

For unfracbonated heparin overdose only

Insulin IM/SC /

Glucose IV. PO /NG tube Glucagon:1-2 mg IM (if no access to glucose)

Glyburide carries highest risk of hypoglycemia among oral agents Consider ocbeotide for oral hypoglycemics (50 -100 pg SC q6 h|in these cases:consult local Poison Information Centre

MDMA

Consider decontaminabon (acbvated charcoal) Supportive care

Monitor CK: treat rhabdomyolysis with high flow fluids: aggressive eitemal cooling for hyperthermia Review medical history if possible for serotonergic use

Opioids

See Universal Antidotes. f R4i?

TCAs

Consider decontaminabon (acbvated charcoal) Aggressive supportive care NaHCOs bolus for wide ORS seizures

’

10 - 20 vials IV if acute: 3-6 if chronic 1 vial (40 mg) neutralizes 0.5 mg of toxm

.

.

.

.

.

.

-

.

-

.

Oral Hypoglycemic

.

Organophosphate 100% 0

’

endotracheal intubation

r *>

uJ

Flumazeml antidote conbaindicafed in combined ICA and benzodiazepine overdose Also consider cardiac and hypotension support, seizure control Intralipid therapy

+

Succinylcholine

Atropine

Pralidoxime (2 - PAM)

* Call local Poison Information Centre for reporting of cases, specif c doses, and treatment recommendations. Most toxicology cases should involve communication with your local Poison Information Centre

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ER54 Emergency Medicine

Toronto Notes 2023

Alcohol Related Emergencies

.

• see Psychiatry PS29

ft

Acute Intoxication

• slurred speech, CNS depression, disinhibition , lack of coordination • nystagmus, diplopia, dysarthria , ataxia, may progress to coma • hypotension ( peripheral vasodilation ) • if obtunded, rule out head trauma / intracranial hemorrhage

Alcohol levels correlate poorly with intoxication

associated depressants, toxic alcohols

• may also contribute to respiratory/cardiac depression hypoglycemia (screen with bedside glucometer )

•

hepatic encephalopathy: confusion, altered LOO , coma

• precipitating factors: Cil bleed , infection , sedation , electrolyte abnormalities, protein meal • Wernicke’s encephalopathy (ataxia, ophthalmoplegia, delirium )

Alcohol intoxication may invalidate informed consent

post - ictal state, basilar stroke

Withdrawal

• beware of withdrawal signs • treatment

-

-

diazepam 10 20 mg I WEI) or lorazepam 2 4 mg 1V/ PO q 1 h ( if known liver dysfunction ) until two negative CIWA scores • frequency of dosing may have to be increased depending on clinical response may use CIWA protocol and give benzodiazepines as above until CIWA < 10 thiamine 200 mgIM/IV then 50 - 100 mg /d naltrexone & gabapentin if no improvement magnesium sulfate 4 g 1 V over I 2 h (if hypomagnesemic) admit patients with delirium tremens or multiple seizures or persistently high CIWA (symptoms) despite high doses of benzodiazepines

-

Table 35. Alcohol Withdrawal Signs Time Since Last Drink

Syndrome

Description

6 -8 h

Mild withdrawal

Generalized tremor,anxiety, agitation, but no delirium Autonomic hyperactivity (sinustachycardia),insomnia, HIV

1-2 d

Alcoholic hallucinations

Visual (most common), auditory,and tactile hallucinations Vitals often normal

8 h -2 d

Withdrawal seizures

Typically brief generalized Ionic-clonic seizures May have several within a few hours Cl head if focal seizures have occurred

D1

5% of untreated withdrawal patients Severely confused state, fluctuating LOC Agitation, insomnia, hallucinations/delusions, tremor Tachycardia, hyperpyrexia, diaphoresis

-

3 5d

*

CIWA Withdrawal Symptoms • N /V • Tremor • Paroxysmal sweats • Anxiety • Agitation • Visual disturbances Tactile disturbances • Auditory disturbances • Headache • Disorientation • 10 symptoms each scored out of 7 except orientation, which is scored out of 4

.

High mortality rale

Cardiovascular Complications

• H1N • cardiomyopathy: SOB, edema • dysrhythmias ( “ holiday heart” ) • Al'ib ( most common ), atrial flutter, SVT, VTach (especially Torsades if hypomagnesemic/

-

hypokalemic)

Metabolic Abnormalities

• alcoholic ketoacidosis

metabolic acidosis, urine ketones, low glucose, and normal osmolality history of chronic alcohol intake with abrupt decrease/ccssation malnourished , abdominal pain with N / V treatment: thiamine ( 250 500 mg IM / IV prior to dextrose), dextrose, volume repletion ( with NS) • generally resolves in 12 24 h • toxic alcohols ethylene glycol: CNS, CVS, renal findings • methanol early: lethargy, confusion late: headache, visual changes, N / V, abdominal pain, tachypnea toxic alcohols initially produce a high osmolar gap, as the toxic alcohol is metabolized the osmolar gap drops and an anion gap develops leading to a severe metabolic acidosis, the goal of treatment is to block this pathway EtOH co ingestion is protective

--

n LJ

+

-

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ERS5 Emergency Medicine

Toronto Notes 2023

• treatment

urgent hemodialysis required •» fomepizole 15 mg / kg IV bolus ( treatment of choice ) or 10% EtOH IV bolus and infusion to

achieve blood level of 22 mmol/ L ( EtOH loading may be done PO) consider folic acid for methanol, and pyridoxine and thiamine for ethylene glycol - both help reduce conversion to active metabolites • other abnormalities associated with alcohol: hypomagnesemia, hypophosphatemia, hypocalcemia, hypoglycemia, hypokalemia Gastrointestinal Abnormalities

• gastritis

common cause of abdominal pain and Cil bleed in chronic alcohol users

• pancreatitis

serum amylase very unreliable in patients with chronic pancreatitis, may need serum lipase hemorrhagic form ( 15%) associated with increased mortality fluid resuscitation very important

• hepatitis

AST/ALT ratio > 2 suggests alcohol as the cause • peritonitis/spontaneous bacteria ] peritonitis leukocytosis, fever, generalized abdominal pain /tenderness occasionally accompanies cirrhosis paracentesis for diagnosis (common pathogens: t. coli, Klebsiella , Streptococcus ) albumin shown to improve outcomes in sBP patients • G1 bleeds most commonly gastritis or ulcers, even if patient known to have varices consider Mallory Weiss tear secondary to retching often complicated by underlying coagulopathies minor: treat with antacids • severe or recurrent: endoscopy variceal bleeds: octreotide

-

Disposition from the Emergency Department • alcohol before patient leaves ED ensure stable vital signs, can walk unassisted, and fully oriented offer social services to find shelter or detox program ensure patient can obtain any medications prescribed and can complete any necessary follow- up • methanol, ethylene glycol delayed onset , admit, and watch clinical and biochemical markers • T'CAs • prolonged /delayed cardiotoxicity warrants admission to monitored 1CU bed • if asymptomatic and no clinical signs of intoxication: 6 h ED observation adequate with proper decontamination and no ECCi abnormalities • sinus tachycardia alone ( most common finding) with history of overdose warrants observation in ED • hydrocarbons/smoke inhalation pneumonitis may lag 6-8 h consider observation for repeated clinical and radiographic examination • ASA, acetaminophen if borderline level, get second level 2-4 h after first • for ASA, must have at least 2 measurements showing decreasing toxin serum concentration before discharge ( 3 levels minimum ) • oral hypoglyccmics admit all patients for minimum 24 h if hypoglycemic and 12 h after last octreotide dose • observe asymptomatic patient for at least 8 h

• opioids

-

-

administer naloxone, a short acting opioid antagonist, preferably IV in incremental doses (0.2 1 mg) patients in cardiorespiratory arrest following possible opioid overdose should be given 2 mg of naloxone minimum admit and observe for 24h referral to rapid access clinic and offer a naloxone kit

r

-

i

LJ

Psychiatric Consultation • once patient medically cleared, arrange psychiatric intervention if required • beware - suicidal ideation may not be expressed

+

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ER56 Emergency Medicine

Toronto Notes 2023

Psychiatric Emergencies Approach to Common Psychiatric Presentations

. before

$

.

see Psychiatry PS2 seeing patient, ensure your own safety; have security/ police available if necessary • History

• safety

assess suicidality: suicidal ideation (SI ; passive/active), intent, plan , lethal means, past attempts, protective factors assess homicidality: homicidal ideation ( HI ), access to weapons, intended victim , and history of violence • driving and children • command hallucinations • identify current stressors and coping strategies • mood symptoms: manic, depressive • anxiety: panic attacks, generalized anxiety, phobias, obsessive compulsive disorder, post traumatic stress disorder • psychotic symptoms: delusions, hallucinations, disorganized speech , disorgani zed or catatonic behaviour, negative symptoms (affective flattening, alogia, avolition ) • substance use history: most recent use, amount, previous withdrawal reactions • past psychiatric history, medications , adherence with medications, admissions • medical history: obtain collateral if available

-

Key Functions of Emergency Psychiatric Assessment • Is the patient medically stable? • Rule out medical cause • Is psychiatric consult needed? • Are there safety issues (SI HI)? • Is patient certifiable? ( must demonstrate risk ( present/ past test) and apparent mental illness (future

.

test))

-

Physical Exam • complete physical exam focusing on: vitals, neurological exam , signs of head trauma , signs of drug toxicity, signs of metabolic disorder; which could be contributing or causing psychiatric presentation • mental status exam: general appearance, behaviour, cooperation , speech , mood and affect, thought content and form, perceptual disturbances, cognition ( including MMSE if indicated ), judgment, insight, reliability

Psychiatric Review of Systems

MOAPS Mood Organic Anxiety Psychosis Safety

Investigations • investigations vary with age, established psychiatric diagnosis vs. first presentation , history and physical suggestive of organic cause • as indicated: blood glucose, urine and serum toxicology screen, pregnancy test, electrolytes, TSH, AST/ALT, bilirubin, serum Cr, BUN, and osmolality • blood levels of psychiatric medications • CT head if suspect neurological etiology • LP if indicated (anti-NMDA receptor encephalitis)

Acute Psychosis Differential Diagnosis

• primary psychotic disorder (e.g. schizophrenia ) • secondary to medical condition (e.g. delirium ) • drugs: substance intoxication or withdrawal, medications (e.g. steroids, anticholinergics) • infectious (CNS ) • metabolic ( hypoglycemic, hepatic, renal, thyroid ) • structural ( hemorrhage, neoplasm ) • autoimmune ( anti NMDA receptor encephalitis )

-

Management

• violence prevention

remain calm , empathic, and reassuring ensure safety of staff and patients, have extra staff and /or security on hand patients demonstrating escalating agitation or overt violent behaviour may require physical restraint and /or chemical restraint • treat agitation: whenever possible, offer medication to patients as opposed to administering with force ( helps calm and engage patient ) • benzodiazepines: lorazepam 2 mg PO/ IM /SL • antipsychotics: olanzapine 5 10 mg PO/IM, haloperidol 5 mg PO /1 M • treat underlying medical condition • psychiatry or Crisis Intervention Team consult

-

Suicidal Patient Epidemiology

• attempted suicide 1;> M, completed suicide M > l; • second leading cause of death in people < 24 yr • significantly increased incidence among marginalized communities, particularly Indigenous peoples

.

See Psychiatry Common forms, PS62

+

fot certification (involuntary assessment/ admission) considerations

and 2SLGBTQQIA Canadians

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ER 57 Emergency Medicine

Toronto Notes 2023

Management • ensure patient safety : close observation, remove potentially dangerous objects from person and room • assess thoughts ( ideation ), means , action ( preparatory , practice attempts ), previous attempts ,

protective factors • admit if there is evidence of: active intent and organized plan , access to lethal means, psychiatric disorder, intoxication ( suicidal ideation may resolve with few days of abstinence) • patient may require certification (completion of forms I and 42) if unwilling to stay voluntarily • do not start long- term medications in the ED • psychiatry or Crisis Intervention Team consult

Common Paediatric ED Presentations

High- Risk Patients

SAD PERSONS Sex - male Age >45 yr Depression Previous attempts Ethanol use Rational thinking loss Suicide in family Organized plan No spouse, no support system Serious illness

Modified Glasgow Coma Score Table 36 . Modified GCS Modified GCS lor Inlants Eye Opening 4 - spontaneously 3 - to speech 2 to pain 1 no response

Verbal Response

Motor Response 6 - normal, spontaneous movement 5 - withdraws to touch 4 - withdraws to pain 3 - decorticate flexion 2 - decerebrale extension 1- no response

5 - coos, babbles 4 irritable cry 3 cries to pain 2 - moans to pain 1 no response

-

-

Any trauma or suspected trauma patient 40 if preschool age , >30 if school age ), retractions , tracheal tug see Paediatrics, P 3 for age specific vital signs • pulsus paradoxus (rarely used clinically ) • wheezing, grunting, vomiting

Table 37. Stridorous Upper Airway Diseases: Differential Diagnosis Feature

Croup

Bacterial Tracheitis

Age Range |yr )

0.5 4

S 10

28

Prodrome

Mild for days then acutely severe

Hours to days

Mmulcs to hours High

Epiglottitis

Temperature

Low grade

High

Radiography

Steeple sign

Exudates intracheat

Thumb sign

Etiology

Parainfluenza

S. ouieusMS

H. inlluenioe typeb

Barky Cough

Yes

Yes

No

Drooling

Occasionally

No

Yes Yes

Appear Toxic

No

Yes

Intubation/ICU

No but yes if severe (rare)

Yes

Yes

Antibiotics

No

Yes

Yes

NOTE

Oral exam

Oral exam

No oral exam, consult ENT

rT

LJ 1

flow rare with Hib vaccine in common use found as diffuse haziness and irregularity of the anterior wall of trachea: consider imaging only after ruling out epiglottitis

+

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Management

• croup ( usually laryngotracheitis caused by parainfluenza viruses)

• dexamethasone x 1 dose if moderate-severe, add nebulized or MDI epinephrine ( racemic has limited availability )

consider bacterial tracheitis/epiglottitis if unresponsive to croup therapy humidified O’ has no evidence for efficacy • bacterial tracheitis airway maintenance - usually require intubation, ENT consult, ICU start antibiotics (e.g. doxacillin ), pending C &S

• epiglottitis

• •) D's: drooling, dyspnea, dysphagia , dysphonia + tripod sitting

• do not examine oropharynx or agitate patient

• immediate anesthcsia / ENT call - intubate • then IV fluids, antibiotics, blood cultures

Febrile Infant and Febrile Seizures FEBRILE INFANT

• for fever >38°C without obvious focus

• 90 d

toxic: admit, treat, full septic workup non -toxic and no focus: investigate as indicated by history and physical antibiotics (Ceftriaxone or cefotaxime ( if available), add acyclovir or vancomycin when indicated )

FEBRILE SEIZURES see Paediatrics , P88

$

•

Etiology

• children ages 6 mo -6 yr with fever or history of recent fever

Rochester Criteria for Febrile Infants Ages 28 90 Days Old • Helps identify SBI (serious bacterial infection) and guide testing/work up for well- looking febrile neonates • Non toxic looking • Previously well f >37 wk gestational age. home with mother, no hyperbilirubinemia, no prior antibiotics or hospitalizations, no chronic/underlying illness) • No skin, soft tissue, bone, joint, or ear infection on physical exam WBC 5000 15000 bands 40 yr or post -menopausal women • if the following risk factors are present, screen at any age: DM

+

current cigarette smoking or COPD H 'l N ( sBP >140, dBP >90 ), hypertensive diseases of pregnancy obesity ( BM 1 > 30 kg / m ) '

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E5 Endocrinology

Toronto Notes 2023

family history of premature CVD or dyslipidemia clinical signs of hyperlipidemia ( xanthelasma , xanthoma, arcus cornealis) clinical or radiological evidence of AAA • clinical evidence of atherosclerosis • inflammatory disease ( rheumatoid arthritis, SLE , psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease) HIV infection on highly active antiretroviral therapy ( HAART ) CKD (estimated GPR < 60 mL / min /1.73 m -) • erectile dysfunction high - risk ethnicity: South Asian , Indigenous peoples • screen children with a family history of hypercholesterolemia or chylomicronemia • components of screening: • history and physical examination , lipid panel ( total cholesterol, LDL C, HDL cholesterol, TG ),

-

For Statin Follow Up

• Liver enzymes and lipid profile: liver

enzymes measured at the beginning of treatment, then once after therapy initiated. Lipids (once stabilized)

measured annually. Order both if patient complains of jaundice, right upper quadrant pain, dark urine • CK at baseline and if patient complains of myalgia • Discontinue statin if CK >10x upper limit of normal or patient has persistent myalgia

1

-

-

non-HOL cholesterol, B( > , eGFR

optional: urine ACR, ApoB • ApoB each atherogenic particle ( VLDL, IDL, LDL, and lipoprotein A ) contains one molecule of ApoB serum ( ApoB) reflects the total number of particles and may be useful in assessing cardiovascular risk and adequacy of treatment in high - risk patients and those with metabolic syndrome • I.p( a ) levels may help stratify those at intermediate risk , but is not recommended for routine measurement (only measured once in a patient's lifetime ) coronary artery calcium (CAC ) may help stratify those at intermediate risk •

• CRP levels highly sensitive acute phase reactant ( non -specific) may be clinically useful to identify those at a higher risk of CVD than predicted by the global risk assessment

CVD Risk Assessment • Framingham Risk Score ( IRS): I 0 yr risk of major CVD event. Calculated based on gender, age, total cholesterol, HDL - cholesterol, sBRand smoking ( >20%: high - risk; 10 - 19%: moderate risk ; < 10%: low risk ) • Reynolds Risk Score: 10 yr risk of major CVD event . Calculated based on age, sBP, total cholesterol, HDL- cholesterol, high sensitivity CRP, family history of Ml

-

Treatment of Dyslipidemias Approach to Treatment Primary Prevention Low - Risk

Intermediate - Risk

High- Risk

FRS < 10%

FRS 10- 19 9% and LDL C> 3 5 mmol/ L or Non HDL C >$ 2 mmol/ L or ApoB > 1.2 g/ Lor Mon>50 and women > 60 with one additional risk factor low HDL C IFCThigh WC . smoker . HTN or with presence of other risk modifiers: hsCRP > 2.0 mg/ L, CAC > 0 AU. family history of premature CAD , Lp ( a) > 50 mg/ dL (100 nmol/L)

FRS >20%

_

,

i

H

Discuss hoalth behavioural modifications

4

Monitor

.

-

-

See Landmark Endocrinology Trials far more informal!on on the JUPITER trial. It details the effects of statm treatment on cardiovascular events m patients with elevated high -sensitivity CRP levels.

^. ^

?VS,>m2oli/n,utLn?[, ,f 52,80f SiMindcS»

^

HDL

YES

YES

Discuss add - on therapy with patient: Evaluate reduction in CVD risk vs . cost/access and side effects

r ~i

"- J / NO

•Rosponsoto statin Rx •Response to add on lipid lowering Rx •Health behaviour changes

-

Initiate Statin Treatment

nun

-*

-

_

NO Honllh Behaviour Modifications: •Smoking cessation •Diet : it is recommended all individuals adopt a healthy dietary pattern •Exercise : itisrecommended adults accumulate at least 150 mirx/ wk of moderate vigorous intensity aerobic physical activity

-

.

—

Statin thorapy not recommondod for most low risk individuals, oxcoptions includo: a . LDL C >5.0 mmol/L lor ApoB >J 45 g /L or non HDL C >4 2 mmol/ L) or b. FRS is 5 9.9% with LDL C >3.5 mmol/ L (or non HDL C > 4.2 mmol/ Lor ApoB >J .05 g /L), particularly with other C V risk modifiers le. g. FHx , Lpla ) 50 mg/ dL |or 100 nmol/ U or CAC >0 AU ) as the proportional benefitfrom statin therapy may be similar to other treated groups

2021 Canadian Cardiovascular Society Guidelines on the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult Can J Cardiol 2021:S0828 282X ( 21)00165 3 • Patients with clinical atherosclerosis AAA, LDL C £5.0 mmoLL , and most with diabetes or CKD should be started on statin therapy • Lipid/ llpoprotein screening Is recommended in patients >40 yr or at any age for those at increased risk • Non- HOL cholesterol or Apo8 are preferred to LDL-C as lipid parameters for screening in patients with TG >1.5 mmol/L • LP(a ) should be measured once in a person's lifetime as part of initial lipkl screening to assess cardiovascular risk • Lipid -lowering therapy should be intensified with ezetimibe and/or PCSK9 inhibitors in patients with LDL C remaining >1.8 mmol / L (or non HDL cholesterol >2.4 mmol /L or ApoB 20.7 g/l) on a maximally tolerated statin dose

YES

ADD ON Ezotiinibo as 1st line (BAS as alternative )

+

Figure 3a . Treatment approach for primary prevention patients (without a statin indicated conditiont) Adapted from 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult Canadian Cardiovascular Society

.

.

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E6 Endocrinology

Toronto Notes 2023

I

Statin Indicated Conditions

_

Most potients with diabotos: •Ago £t0 •Ago >30 & 0Mx> 15 yrdurotion •Microvasculor disoasu

LDL > 5.0 mmol/ L orApoB >1.4Sg/Loi non - HDL C i 5.8 mmol/L •Familial hypoicholostorolomio or gonotic dyslipidomio

•

_

Most patients with diabotos: >50 and oG FR 3 mg/mmol

•Ago

Atherosclerotic Cardiovascular Disoaso: •Myocardial infarction, ocuto coronary syndromos •Stable angina, documented coronary artery disoaso by ongiography •Stroke, TIA, document carotid disoaso •Peripheral arterial disease, claudication and/or ABI 3.0 cm or previous aneurysm surgery

Rcvicw/Discuss health behavioural modifications

I

Initiate Statin Treatment

If LDL- C £.5 mmol/ L (or < 50% reduction) orApoB 20.85 g / Lor non HDL C 23 2 mmol/L

NO

J

ft

If LO L C . 2 0 mmol/L or ApoB >^ 0.80 g/Lor non HDL C 2.6 mmol/ L on ^ statin dose maximally tolerated

YES

YES

Discuss add - on therapy with patient Evaluoto reduction in CVD risk vs. cost/access and sido offocts

ADD ON E / otimibo or PCSK 9 inhibitor

u.

If LDLC >J.8 mmol/ Lor ApoB 21.70 g/L or non H DLC >2.4 mmol /Lon maximally tolerated statin dose

YES

Discuss intensification of therapy with patient

ADD ON

i

Ezotimibcas 1st lino IBAS as alternative add onto othor diugs )

INTENSIFICATION

Refer to Figure

Treatment Intensification Approach foi Potients with ASCVO

Monitor

t

•

•Rosponso to statin Rx •Response to add on liprd lowering Rx * Health behaviour modifications

un

NO

Figure 3b. Treatment approach for patients with a statin indicated condition Adopted horn 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipldemia lor the Prevention of Cardiovascular Disease in the Adult. Canadian Cardiovascular Society.

I

Patients with Atherosclerotic Cardiovascular Disease If LDLC >1.8 mmol/ Lor ApoB .2).70 g /Lor if non HDL C >2.4 mmol/ L

LDL C 1.8 2.2 mmol/ Lor ApoB 0.70 0.80 g/ Lor non HD L C 2.4 2.9 mmol/ L

LDLC > 2.2 mmol/ Lor ApoB >0.80 g/ L or non HDL C > 2.9 mmol /Lor high PCSK 9i benefit patient

Consider

Consider PCSK 9 inhibitor ezotnmbo

EzotimiboiPCSK9 inhibitor

If TG >1.5 to 5.6 mmol/ L

A

Consider Icosapent ethyl 2000 mg BID

Figure 3c . Treatment intensification approach for patients with atherosclerotic cardiovascular disease (ASCVD) Adapted horn 2021 Canadian Cardiovascular Society Guidelines lor the Management of Dyslipldemia lor the Prevention ol Cardiovascular Olscose In the Adult Canadian Cardiovascular Society.

.

ri LJ

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1

1

..

'

E7 Endocrinology

Toronto Notes 2023

Disorders of Glucose Metabolism Overview of Glucose Regulation •s \ gi lls of the pancreas stimulated to roloaso insulininto the blood

S

Insulin

stream

(

• Body colls take up more glucose / •

A

-

Liver takes up excess glucose and stones it as glycogen

Increase in blood glucose levels

Blood Glucose Level

Decrease in blood glucoso levels

Liver breaks down glycogen stores and

Reduction of Cardiovascular Events with Icosapent Ethyl Intervention Trill - REDUCE IT

-

HLIU 2019;580:11 22 Study Mjtticenter nnUonned, double -blind, bacebo co tio led trial with S yr ot follow - up. Population: 81)9 patients with established CUD or with diabetes and other risk lac tors, who hadbeen relenting statin therapy arid who had a fasting ID revet of 135 - 459 ragfdLard a LDL level of 41-100 mgidL Intervention: Randomly assigned to receive 2 gof icosapent ethyl BID or placebo. Primary Outcome: Composite ol cardiovascular death, nonlatal HI. nonlatal stroke, coronary revascolariiation or unstable angina. Desalts 4 pnmatyendpoint event occurred in t).2% ot the patients in the icosapent ethyl groupiom pared to 22\ of the patients In the placebo group (HR 0.7 S. 95% Ct 0.68-0.83, P 0.001). The rates of additional ‘ ischemic eod points were significantly lower in the icosapent ethyl groupthan in the place hogroup. induing the rate of cardiovascular death.A larger percentage of patients in the icosapent ethyl group than in the place bn group ware hospitaliied for atrial fibrii’ation or flutter (P* 0.004|and serious bleeding occur led in 2.1% of the patients in the icosapent ethyl group as compared to 2.1% in the placebo group (P 0.06) Conclusions Among patients with elevated 16 levels despite statin therapy, the risk of cardiovascular events wassigrufrcanlly lower in the group who received 2 gof icosapent ethyl BIO compared to those whoreceived placebo. See trralfor more details, outlining spec die emb oi nts

-

.

-

rclcascsglucosc into the blood

Glucagon

stimulated to release glucagon into the blood

a culls

-

Figure 4 . Blood glucose regulation

Pre- Diabetes ( Impaired Glucose Tolerance/Impaired Fasting Glucose)

and results.

• 1-5% per yr go on to develop DM • 50 -80% revert to normal glucose tolerance • weight loss may improve glucose tolerance (5 10% of body weight )

-

• increased risk of developing niacrovascular complications • lifestyle modifications decrease progression to DM by 58%

Diagnostic Criteria (Diabetes Canada 2018 Guidelines) (any of the following) • ll - G: I PG 6.1-6.9 mmol / L • 1GT: 2 h 75 g OGTT 7.8-11.0 mmol / L • Ale: 6.0- 6.4%

Diabetes Mellitus Definition

• DM is a heterogeneous metabolic disorder characterized by the presence of hyperglycemia • chronic hyperglycemia of diabetes is associated with relatively specific long term microvascular complications affecting the eyes, kidneys, and nerves, as well as an increased risk for macrovascular complications such as CVD, stroke, and peripheral vascular disease. Diabetes also increases the risk of

-

See Landmark Endocrinology Trials foe more information on the 4 T trial It details the efficacy of complex insulin regimen for patients with T 2DM.

.

heart failure Diagnostic Criteria (as per Diabetes Canada 2018 Clinical Practice Guidelines) any one of the following is diagnostic:

•

Table 4. Diagnosis of Diabetes FPGs7.0 mmoDl Fasting - no caloric intake lor at least 8 h or A1c »6.5% (in adults) Hot lor diagnosis ol suspected MOM.children, adolescents, or pregnant women or 2 hPG in a 75 g OGTT >11.1 mmol/L or Random PG »11.1 mmol/ L Random any lime of the day without regard to the interval since last meal

-

.

• in the presence of hyperglycemia symptoms ( polyuria , polydipsia , polyphagia , weight loss, blurry vision ) , a confirmatory test is not required • in the absence of hyperglycemia symptoms , a repeat confirmatory test ( IPti , A Ic, 2 hP(i in a 75 g OGTT ) on another day is required for diagnosis of diabetes

See Landmark Endocrinology Trials for more information on the UKPDS trial. It compares the safety and efficacy of intensive blood - glucose control with sulphonylurea or insulin vs. conventional treatment on the risk of complications in T 20M. 1

LJ

See Landmark Endocrinology Trials for more information on the DCCT trial. It details the use of intensive insulin injection therapy for the treatment of T1DM in patients with no cardiovascular history or severe diabetic complications.

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E8 Endocrinology

Toronto Notes 2023

Etiology and Pathophysiology Table 5. Etiologic Classification of Diabetes Mellitus

.

Diabetes Canada 2018 Clinical Practice Guidelines

I T1DM immune - med ated or idiopathic cell destruction, usually leading to absolute insulin deficiency (includes latent autoimmune diabetes in adults ( LADA))

^

target

. III.Other Specific Causes of DM

II T2DM occurs when the pancreas does not produce enough insulin or when the body does not effectively use the insulin that is produced


90% of all DM

Etiology

Autoimmune or idiopathic

Complex and multifactorial

Genetics

Monozygotic twin concordance ts 30-40% Associated with HLA class IIDR3 and DR 4. with either allele present in up to 95% of T1DM Certain DO alleles also confer a risk

Monozygotic twin concordance is 70- 90%

Pathophysiology Synergistic effects of genetic,immune,and environmental factors that cause 3 cell destruction resulting in impaired insulin secretion Autoimmune process is believed to be triggered by environmental factors (e.g.viruses, bovine milk protein,urea compounds) Pancreatic cells are infiltrated with lymphocytes resulting m islet cell destruction 80% of 8 cell mass is destroyed before features of DM present Natural History

Greater herilability than T1DM

Polygenic Kon-HLA associated

Impairment of insulin secretion, excess glucose production by the liver, insulin resistance in fat and muscle, impaired renal handling of glucose|SGLT2i). impaired incretin activity ( decreased insulin production, excess glucagon production, enhanced carbohydrate absorption in the gut and increased appetite from the hypothalamus)

insulin resistance

glucose

^

(3 cell function

. -

t ''v /AiAA - ''

insulin

I honeymoon period time

N

.

'

v

*

insulin I

I (S coll

0 cell defect

glucose

(3 cell failure decompensation

.

After initial presentation, honeymoon period often occurs where gtycemic control can be achieved with little or no insulin treatment as residual cells are still able to produce insulin Once these cells are destroyed, there is complete insulin deficiency

Early on glucose tolerance remains normal despite insulin resistance as 8 cells compensate with increased insulin production As insulin resistance and compensatory hyperinsulinemia continue, the 8 cells are unable to maintain the hyper insulinemic state whichresults in glucose intolerance and DM

Circulating Autoantibodies

Islet cell Ab present in up to 60 - 85% Most common islet cell Ab is against glutamic acid decarboxylase|GA 0) Up to 60% have Ab against insulin

i

SGLTO '

.

QrtuQlrfloiin" * ISGLT2i)

—_

SGLT2J

,

Acarbosc Sylfonylurcas Mcglitinidcs

s- i

Q

Highestlevelofevidence ( GradeA

.

.

" Dm sitagliptm, linagiiplm, alogliptm

|t 2?

—

-

SGLT2i'

O

S 2 SGLT2T -s | §

*

benefit'

.

canagliflozm. dapagliflozm. J empagliflozin

:

CVmonadtv

RISK of HF

-

GLP1 RA Weight loss GLPI RA dulaglutide exenatide ER liraglutide. lixisenatide semaglutide SGL2T 1

.E

CV safety, but NO proven cardiorenal

PROVEN

Risk factors

HF

]

I

*

Study: Multi -centre, double- blind KUcompairq liragtutide to placebo control: 9340 patients (drug n 4668 placebo n 46!2| median obserratam 3.8 ft. Outcome:Death from cardiovascular causes, nonfatal Ml. or nonfatal stroke. Resalts: Both groups concurrently received the standard treatment for I20M Ihe lirag jt de group had significantly louver rates of death from cardiovascular causes than control|4.7V vs. 6 %: P“0.00 ?|.Ihe drug group also had lower all-cause mortality |8.2% and 9.6 V R'0.02). Bales ol nonfatal Ml. nonfatal stroke, and kospitaIllation lor heart la Bure were not signhcantly lower In Ihe litagliditfe group. Conclusion: Adding hraglutide to standard treatment lor pabants with 12DM radoced death from cardiovascular cause and all -cause mortality when compared to placebo

- .

T

f

ADD or SUBSTITUTE AHA with demonstrated cardiorenal benefits

CKO

analogue) has any effect on cardovascular risk in patients with T 2 DM whenadded to standard care.

Adjust or advance therapy *

ASCVD, CKO or HF OR age >60 with 2 CV risk factors

ASCVD

Liraglutidc andCardioviscularOutcomes in 12 DM

NEJU 2016; 375:311 322 Rugose lo investigate whether liraglutidc (a ClP-1

Insulin Hypoglycemia

( GiadeBj (CradaCorD)

Initiate only if eGFR >30 ml/min/1.73m‘'

saxagliptin

IDPP4H

Thiarotidinediones Weight gain

rixed dose combinations may be considered to reduce burden

Changes in clinical status may necessitate adjustment of glycemic targets and/or depresciibing Tobacco uso; dyslipcdomio luso of lip< d modifying thorapy or o documented untreated low density lipoprote n ILDLI > 34 mmoVL or high density lipoprotein chalastorol IHDL 0 cl .Ominol/lfor mon and < 1.3 inmoVLfoc womon or triglyceridos > 2.3 mmolU; or hypertension ( use of blood pressure drug or untreated systolic blood pressure ISBPI >140 mmHg or diastolic blood pressure |0 BP| >95 rnmHg) All antihyperglycemic agents ( AHAs) have grade A evidence for effectiveness to reduce blood glucose levels Consider degree of hyperglycemia, costs and coverage, renal function, comorbidity, side effect profile and potential for pregnancy ~ In CV outcome trials performed in people with atherosclerotic cardiovascular disease IASCVDI chronic kidney disease ( CKO ), heart failure ( HF) or at high cardiovascular ( CV) risk ' Vortis ( CV outcome trial for ortuglifloMi) presented at Americon Oiabetes Association ( ADA ) Juno 2020 showed noninferiority for major adverse CV events ( MACE ). Manuscript not published at time of writing A 1C - glycated hemoglobin; DPP 4i - dipeptidyl peptidase 4 inhibitors; eGFR estimated glomerular filtration rate; GLP1 RA - glucagon like peptide 1 receptor agonists; exenatide ER = exenatide extended release HHF - hospitalization for heart failure SGLT2i - sodium - glucose cotransporter 2 inhibitors

.

"

.

.

^

_

.

Figure 9. Treatment approach for patients living with diabetes

Microvascular Complications Diabetic Retinopathy (see Ophthalmology, OP34 for a more detailed description ) Epidemiology

• diabetic retinopathy is the most common cause of incident blindness in people of working age • among individuals with T 1 DM , limb amputation and vision loss due to diabetic retinopathy are independent predictors of early death Clinical Features

• macular edema: diffuse or focal vascular leakage at the macula • non - proliferative ( microaneurysms , intraretinal hemorrhage, vascular tortuosity, vascular malformation ) and proliferative (abnormal vessel growth ) • retinal capillary closure

r

t

L j

Treatment and Prevention • tight glycemic control ( delays onset, decreases progression ), tight lipid control, manage HTN, smoking cessation • ophthalmologic il treatments available ( see Ophthalmolcmv, OP35 for more details ) • annual follow up visits with an optometrist or ophthalmologist to examine whether symptomatic or not through dilated pupils ( immediate referral after diagnosis of T2 DM; 5 yr after diagnosis of 'TlDM for those >15 yr) • interval for follow up should be tailored to severity of retinopathy

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El 6 Endocrinology

Diabetic Nephropathy ( see Nephrology, NP33 for a more detailed description ) Epidemiology • DM -induced renal failure is the most common cause of renal failure in North America 20 10",, of persons with T1 DM ( after 5 10 yr ) and 4 20% with T2 DM have progressive nephropathy

.

-

-

-

Screening • serum creatinine for eGFR, random urine ACR

• ACR is used as albuminuria is considered the earliest clinical sign of diabetic nephropathy ( microalbuminuria ); diagnosis requires persistent elevated urinary albumin ( 2 out of 3 urinary samples required over 3 mo) • 24 h urine collection for protein / albumin is the gold standard but is difficult to perform, inconvenient, and often incorrect; random urine albumin is insufficient as albumin levels vary with urine concentration • begin screening annually at diagnosis for all T 2 DM, and > 5 yr after diagnosis of T 1 DM for

postpubertal patients Treatment and Prevention • appropriate glycemic control • appropriate BP control ( 5 yr after diagnosis of IT DM for post-

3

CO

I

pubertal patients Clinical Features

Peripheral Sensory Neuropathy

Motor Neuropathy

Autonomic Neuropathy

Paresthesias ( tingling , itching ), neuropathic pain , radicular pain , numbness, decreased tactile sensation Bilateral and symmetric with decreased perception ol vibration and pam ' tempcrature; especially hue in Ihe lower evlremilics but may also be present In Ihe hands Decreased ankle reflex Distal predominant as the longest nerves are affected first Classic stocking glove distribution May result in neuropathic ulceration ol loot

Less common than sensory neuropathy end occurs later in the disease process Delayed motor nerve conduction and muscle

Postural hypotension , tachycardia , decreased cardiovascular response to valsalva maneuver Gastroparesis and alternating diarrhea and

-

constipation weaknesslatrophy May involve one nerve trunk ( mononeuropalhy) Urinary retention and erectile dyslunclion 0 m 0It ( mononeur tis multiplex ) Some ol the motor neuropathies spontaneously resolve after 6- 8 wk Reversible CN palsies: III (ptosis/ ophthalmoplegia , pupil sparing ). VI (inability to laterally deviate eye), and VII ( Bell 's palsy ) Diabetic amyotrophy i.e. Bruns Garland Syndrome: refers to pain , weakness, and wasting ol hip flexors or extensors

,

s

Figure 10. Monofilament testing for diabetic neuropathy

Table 12. Clinical Features of Diabetic Neuropathies

-

V

o

,

Treatment and Management

• tight glycemic control • for neuropathic pain syndromes: tricyclic antidepressants ( e.g. amitriptyline ), pregabalin , duloxetine, anticonvulsants (e.g. carbamazepine, gabapentin ), and capsaicin • foot care education • |obst’ fitted stocking and tilting of head of bed may decrease symptoms of orthostatic hypotension • treat gastroparesis with dietary modification , domperidone and /or metodopramide (dopamine antagonists), erythromycin ( motllln receptor agonist ) • medical, mechanical, and surgical treatment for erectile dysfunction (see Urology, U 33)

Pharmacologic Interventions for Painful Diabetic Neuropathy: An Umbrella Systematic Review a ad Comparative Effectiveness Network Meta Analysis Ann Intern Med 2011;141:639 - 49 Purpose: focompare the efficatiesof rarionsoral and topical anatges.esfor diabetic neuropathy. Study Selection: RCIs that assessed pharmacologic treatments lor pa nful diabetic peripheral neuropathy in adults Results: 65 RCIs , r , a eg 12632 patents were included . Ibelolluwng pharmacological agents demonstrated superiority over placebo for short-term pain control: seroton :n and norep inepbrine reuptake inhibitors (SNRIs) lstandaidired mean difference (SMD) 1.36; 95% credible interval (Cil) |1.77 to 0.9S1I, topkalcaps4ii , r (SMD, 0.91; Crl ( MS to -0.0811, tricyclic ante] epressants|ICAs|( SMD. -0.78; Crl|-1.24 to -0.33]), and anticonvulsants (SMD, -0.67:Crl [-0.97 to -0.37]). Spedfe agents included: carbamaiep , e (SMD -1.57; Crl [-2.83 to 0.31[|, renlalaiine (SMD 1.53: Crl ( 2.41 to -0.6511 dularetmelSMO. 1.33: Crl 1182 to 0 86 )). arid amitriptyline (SMD. -0.72: Crl ( 1.35 tn -0.08'J . Conclusion: SNSIs. topical capsaicin. TCAs and anticonvulsants are effective in short-term nanagementdf painful diabetic neuropathy, but their relative cflicacy compared to each other is unknown.

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Other Complications Dermatologic

• diabetic dermopathy: atrophic brown spots commonly in pretibia! region ( “ tibia spots") secondary to increased glvcosylation of tissue proteins or vasculopathy • eruptive xanthomas secondary to increased triglycerides • necrobiosis lipoidica diabeticorum: rare complication characterized by thinning skin over the shins allowing visualization of subcutaneous vessels

Other Players in Glucose Homeostasis These hormones act to increase: Blood glucose levels Glucagon Epinephrine Cortisol Growth hormone

Bone and Joint Disease

• juvenile cheiroarthropathy: chronic stiffness of hand caused by contracture of skin over joints secondary to glycosylated collagen and other connective tissue proteins • Dupuytren's contracture • increased fracture risk in both T 1 DM and T2 DM due to decreased bone quality • adhesive capsulitis (“ frozen shoulder")

-

C Peptide

A short peptide released into the circulation when proinsulin is cleaved

to insulin

Cataracts • subcapsular and senile cataracts secondary to glycosylated lens protein or increased sorbitol causing

osmotic change and fibrosis

-

Use of C pcptide Levels to Distinguish between Exogenous and Endogenous

Infections

Source of Hypetmsulinemia Increased endogenous Decreased or normal = exogenous

• see Infectious Diseases. Diabetic Foot Infections. ID 14

Hypoglycemia Etiology and Pathophysiology • hypoglycemia occurs most frequently in people with DM receiving insulin or certain anti hyperglycemic therapies ( insulin secretagogues ) • in people without DM, care must be taken to distinguish hypoglycemia that occurs in critically ill or medicated patients from hypoglycemia that presents in individuals who are seemingly well each invokes a separate DDx the timing of hypoglycemia may also provide a clue to the diagnosis (e.g. individuals with an insulinoma typically have fasting hypoglycemia whereas those with non insulinoma pancreatogenous hypoglycemia experience predominantly postprandial hypoglycemia ) must be distinguished from pseudohypoglycemia , defined as situations in which either BG >3.9 mmol/ L with clinical signs of hypoglycemia (e.g. fatigue, headache, visual disturbances, or lightheadedness) or BG 1 h away, eat snack including 15 g of carbohydrate and protein

-

©

Hypoglycemia Unawareness (T1DM »> T2DM ) • Patient remains asymptomatic until severe hypoglycemic levels are

reached Often occurs after repeated episodes of hypoglycemia as the patient develops blunted/ minimal autonomic response • Causes: • Decreased glucagon /epinephrine response • History of repeated hypoglycemia or low A1c • Autonomic neuropathy • May not be safe for patient to d rive • Suggest that patient obtain a Medic Alert " bracelet if at risk for hypoglycemia, especially with hypoglycemia unawareness and consider use of advanced monitoring systems (continuous glucose monitor, flash glucose monitor)

•

-

©

Refer to Diabetes Canada 2018 guidelines for advice around diabetes and driving

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Toronto Notes 2023

•when the cause of hypoglycemia is not evident, screen for oral hypoglycemic agents ( ideally all available sulfonylureas and glinides) and measure plasma glucose, insulin, proinsulin, C -peptide,

-

b hydroxybutyrate, and insulin Ab during a spontaneous hypoglycemic episode or a supervised fast of up to 72 h If hypoglycemia occurs only in the postprandial state, evaluate the patient first with a mixed meal test •correct hypoglycemia with injection of 1.0 mg glucagon IV with measurement of plasma glucose response. This will distinguish endogenous and exogenous hyperinsulinism from other causes of hypoglycemia

.

Treatment •for tumoural hypoglycemia , definitive treatment requires resection of the tumour. If that is not possible certain medications can be helpful such as diazoxide for patients with insulinoma for non insulinoma pancreatogenous hypoglycemia and post bariatric bypass hypoglycemia, dietary changes including reducing the amount of carbohydrate intake and small frequent meals may be helpful. For patients who do not respond to nutritional modification or have severe symptoms, acarbose can be utilized •see Emergency Medicine, ER 34 •treatment of hypoglycemic episode in the unconscious patient or patient NPO D50 W 50 mL ( 1 ampule ) IV in 1 3 min or 1 mg glucagon SC or 1 M ( if no IV access is available ) may need ongoing glucose infusion once B(i > 5 mmol/ L

-

-

-

Metabolic Syndrome • postulated syndrome related to insulin resistance associated with hyperglycemia, hyperinsulinemia, HT' N , central obesity, and dyslipidemia obesity aggravates extent of insulin resistance • • complications include DM , atherosclerosis, CAD, Ml , and stroke • women with PCOS are at increased risk for developing insulin resistance, hyperlipidemia, and metabolic syndrome • not to be confused with syndrome X related to angina pectoris with normal coronary arteries (Prinzmetal angina )

Obesity

$ Features of Metabolic Syndrome | - 3 measures to make a Dx )

-

• see family Medicine. 1 M 9

Measure

Men

.

Pituitary Gland

-

Mediterranean

.

>90 cm >80 cm Asian (35 indies) Japanese 31.5 Inches) South ( Central America >1.7 mmol/ L (150 mgfdL ) TO level

Somatostatin Dopamine

I

CRH

GHRH

l

I I

ACTH

Prolactin

1 I

H

Adrenal

SI

—

'

GnRH

FSH

GH

IH

of gonads

Male

I

Androgens |

Breast

Multiple target organs

Figure 11. Hypothalamic-pituitary hormonal axes

-

HDL C level

«1.0 mmol/L ( 40 mg/dl)

Blood Pressure fasting Glucose Level

;130 /8SmmHg

-

100 mg/dl)

>

1.

Female

Estrogens

progesterone

j

o


102 cm >88 cm Canada USA (40 inches) (35 inches) >80 cm Europid. Middle >94 cm Eastern , Sub (37 Indies) (31.5 inches)

i Gonadal germ cells, Multiple target organs

Anterior Pituitary Hormones FLAT PIG FSH LH

r LJ

ACTH

TSH PPL GH

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Toronto Notes 2023

Endocrinology

Hypothalamic Control of Pituitary

trophic and inhibitory factors control the release of pituitary hormones most hormones are primarily under trophic stimulation except FRL, which is primarily under inhibitory control by dopamine . CiH and TSH are stimulated by GHRH and TRH respectively while inhibition by somatostatin is less important for control • transection of the pituitary stalk ( i .e. dissociation of hypothalamus and pituitary ) leads to pituitary hypersecretion of PRL and hyposecretion of all remaining hormones • •

Anterior Pituitary Hormones FSH , LH , ACTH , TSH , CiH , PRL

• •

these hormones are produced , stored , and released from the anterior pituitary but regulated by hormones produced by the hypothalamus

Posterior Pituitary ( Hypothalamic ) Hormones • ADH and oxytocin • peptides synthesized in the supraoptic and paraventricular nuclei of the hypothalamus • although ADH and oxytocin are produced in the hypothalamus, these hormones are stored in and

released from the posterior pituitary Table 14. The Physiology and Action of Pituitary Hormones Physiology

Hormone

Function

IH / FSH

Polypeptide Stimulate gonads via cAMP Ovary: Glycoproteins (same asubunit as TSH and hCG) Secreted in pulsatile fashion LH: production o( androgens ( thecal cells) which are converted to estrogens (granulosa cells): induces luteinization in follicles FSH: growth ol granulosa cells in ovarian follicle: controls estrogen production lestes: LH: production ol testosterone (leydig cells) FSH: production ol spermatocoa (Sertoli cells)

Inhibitory Stimulus

Secretory Stimulus

Estrogen Progesterone Testosterone

Pulsatile GnRH (low frequency pulsation •fSH release, high frequency pulsation LH release)

Inhibin Continuous ( i.e. non pul satile) GnRH infusion

-

-

ACTH

Stimulates growth of adrenal cortex and secretion of its hormones via cAMP

Polypeptide Circadian rhythm ( highest in the morning, lowest at midnight )

Dexamethasone. cortisol, and other glucocorticoids

TSH

Stimulates growth ol thyroid and secretion ol 14 andT 3 viacAMP

Glycoprotein Note: hCG can activate the TSH receptor and therefore have thyroid stimulating activity

thyroid hormones (14 and 13) and analogues, dopamine, somatostatin

cytokines, high dose glucocorticoids

Promotes mi Ik productionand breast tissue

Polypeptide Episodic secretion

Dopamine (only pituitary hormone under tonic inhibition of secretion )

PRL

development

-

-

Corticotropin Releasing Hormone Melyrapone hypoglycemia Vasopressin fever, pain , stress

.

Inhibits gonadotropin secretion

TRH AVP a adrenergicagonist Sleep

Stress, hypoglycemia Pregnancy, breastfeeding Mid menstrual cycle Sexual activity TRH ( primary hypothyroidism ) Drugs: anlipsycholics tricyclic

-

.

.

antidepressants, metoclopramldc domperidone verapamil, methyldopa , opioids, high dose estrogen

.

Has direct effects on peripheral target cells Needed (or linear growth and also has metabolic effects to increase serum glucose Stimulates secretion of IGF -1 by the livec a potent growth and differentiation factor

Polypeptide Acts indirectly through IGF -1|somatomedin -C) synthesized in the liver and has direct effects Serum GH undetectable lor most of the day and suppressed alter meals high in glucose Sustained rise during sleep

Glucose challenge Glucocorticoids Somatostatin Dopamine D 2 receptor agonists in some GH secreting tumours IGF 1 llong loop)

GHRH Insulin induced hypoglycemia Ghrelin Exercise REM sleep Arginine, donidinc propranolol L dopa Sex hormones Dopamine agonists in normal individuals

ADH

Acts at renal collecting ducts on V 2 receptors to cause insertion of aquaporin channels and increases water reabsorption thereby concentrating urine

Octapeptide Secreted by posterior pituitary Osmoreceptors in hypothalamus detect serum osmolality Contracted plasma volume detected by baroreceptors is a more potent stimulus than i osmolality

a serum osmolality

Hypovolemia or a effective circulatory volume t serum osmolality Stress , pain , fever, system CNS disorders

Oxytocin

Causes uterine contraction Breast milk secretion

Nonapeplide Secreted by posterior pituitary

EtOH

Suckling Distention ol female genital tract during labour via stretch receptors

GH

.

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E 20 Endocrinology

Growth Hormone GH Deficiency

• cause of short stature in children (see Paediatrics. P13) • adults exhibit increased fat and decreased lean body mass, decreased bone mineral density, and

fatigue

• diagnosis made with low serum l (il;- l levels in individuals with deficiencies in three or more pituitary

axes, or by failure to increase GH with a provocative test (see above under GH secretory stimulus ); insulin tolerance test to induce hypoglycemia is the gold standard dynamic test • Tx: GH replacement is not always indicated after max linear height and peak bone mass is reached; consider in an adult patient with childhood onset irreversible GH deficiency (some children who are diagnosed with idiopathic GH deficiency will have normal GH responses when tested as adults and do not require GH treatment). GH replacement can also be provided to patients with adult onset GH deficiency who do not have an active malignancy and prefer treatment after a discussion about its potential benefits, adverse effects, and cost GH Excess

Etiology • GH secreting pituitary adenoma, neuroendocrine tumours secreting ectopic GH or GHRH (very rare)

Pathophysiology

• normally GH is a catabolic hormone that acts to increase blood glucose levels • in GH excess states, secretion remains pulsatile but there is loss of hypoglycemic stimulation , glucose suppression , and the nocturnal surge • proliferation of bone, cartilage, soft tissues, organomegaly • insulin resistance and 1GT Clinical Features • leads to gigantism in children ( before epiphyseal fusion ) • leads to acromegaly in adults (after epiphyseal fusion ) • dermatologic (thickening of skin , increased sebum production , sweating, acne, sebaceous cysts ), musculoskeletal (enlargement of hands and feet, coarsening of facial features, thickening of calvarium , prognathism, carpal tunnel syndrome, osteoarthritis), cardiometabolic ( HTN, DM , acanthosis nigricans, cardiomyopathy ), sleep apnea, sexual ( low libido )

Risks Associated with GH Excess

• Cardiac disease (e.g .

.

cardiomyopathy, valvulopathy arrhythmias, CAD) in 1/3 ol patients. Two fold increase in mortality in acromegaly due to acromegaly associated complications such as HTN, diabetes, CVD, and cerebrovascular disease HTN in 1/3 of patients • Increased risk of cancer ( particularly colon cancer )

-

-

.

Investigations

• first line test: serum 1GF-1 (expected to be elevated ) • glucose suppression test is the most specific test (75 g of glucose PO suppresses GH levels in healthy individuals but not in patients with acromegaly) • O', MKI or skull x -rays may show cortical thickening, enlargement of the frontal sinuses, and enlargement and erosion of the sella turcica • MKI of the sella turcica is needed to look for a tumour

.

Treatment

• surgery is the recommended initial therapy for the majority of patients with acromegaly; second line options include somatostatin analogue (octreotide), dopamine agonist (cabergoline), GH receptor antagonist (pegvisomant ), radiation « radiation may be considered in patients whose disease is not controlled by surgery or medical treatment

Prolactin Hyperprolactinemia Etiology • prolactinoma: most common pituitary adenoma • sellar masses, disease with pituitary stalk compression, or damage causing reduced dopamine

inhibition of PKL release • primary hypothyroidism ( increased TRH ), PCOS, acromegaly • decreased clearance due to CKD or severe liver disease ( PRL is metabolized by both the kidney and

liver) • medications with anti-dopaminergic properties are a common cause of high PRL levels: antipsychotics (common ), antidepressants, antihypertensives ( verapamil / methyldopa ), bowel motility agents (metoclopramide/domperidone), H2-blockers, opiates ( morphine ), estrogens (e.g. oral contraceptives) • macroprolactinemia ( high molecular weight PRL also known as big-big PRL ) that has no action but results in falsely elevated serum prolactin • physiologic causes: pregnancy, stress, sleep, nipple stimulation , factors affecting the chest wall

&

Approach to Nipple Discharge • Differentiate between galactorrhea (fat droplets present ) vs. breast discharge (usually unilateral, may be bloody or serous) • If galactorrhea , determine if physiologic (e.g. pregnancy, lactation ) vs. pathologic • If abnormal breast discharge, must rule out a breast malignancy

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Clinical Features

• galactorrhea ( secretion of breast milk in women and, in rare cases, men ), infertility, hypogonadism, amenorrhea, oligomenorrhea, erectile dysfunction

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E 21 Endocrinology

Toronto Notes 2023

Investigations

• serum PRL, l'SH, liver enzyme tests, creatinine, hCG in all women of reproductive age • macroprolactin level in patients with hyperprolactinemia but no symptoms of PRL excess • MRI of the sella turcica when a secondary cause is not identified or when PRL levels suggest that there may be underlying tumoural hyperprolactinemia Treatment • first line: dopamine agonists ( bromocriptine, cabergoline, quinagolide) • surgery ± radiation ( rare) • PRL-secreting tumours are often slow-growing; treatment may not be necessary in the setting of small tumours associated with hyperprolactinemia which does not result in hypogonadism or bothersome

galactorrhea

• if medication -induced , consider stopping medication if possible • in certain cases if microprolactinoma and not planning on becoming pregnant, may consider OCP

Thyroid Stimulating Hormone . see 'thyroid,£24

Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline J Clin Endocr Mctab 2011:96:273 88

• Indications to treat:

• Symptomatic patients.

in particular those with galactorrhea, hypogonadism amenorrhea low libido, or infertility • Aden omas >1 cm or any size causing structural compression • For patients with symptomatic prolactinomas, dopamine agonist therapy should be used to lower prolactin levels, decrease tumour size, and restore gonadal function • Cabergoline should be preferentially used due to higher efficacy in normalizing PRL levels and shrinking pituitary tumours For symptomatic patients with treatment resistant prolactinomas, increase the dose to maximal tolerable dose before referring for

.

.

Adrenocorticotropic Hormone • tee Adrenal Cortex, £ 33

-

-

surgery

Luteinizing Hormone and Follicle Stimulating Hormone Hypergonadotropic Hypogonadism

• hypogonadism due to impaired release of PSH and LH

• Most women with prolactinomas

should discontinue dopamine agonist therapy immediately if they become pregnant (except for patients with large invasive tumours)

Etiology

• congenital: Kallmann syndrome, CHARGE syndrome, GnRH insensitivity • secondary : CNS or pituitary tumours, pituitary apoplexy, hypothalamic - pituitary radiation , drugs (GnRH agonists/antagonists, glucocorticoids, narcotics, chemotherapy, drugs causing hyperprolactinemia , opioids), functional deficiency due to another cause ( hyperprolactinemia , chronic systemic illnesses, eating disorders, hypothyroidism , DM, Cushing’s disease), systemic diseases involving the hypothalamus/ pituitary ( hemochromatosis, sarcoidosis, histiocytosis) Clinical Features

• amenorrhea, low libido, decrease in energy, erectile dysfunction (see Urology. U33), loss of body hair, thin skin, testicular atrophy, decrease in muscle mass, and failure of pubertal development Treatment

• treat underlying cause if present

• combined l SH / LH hormone therapy, hCG, recombinant l SH , or pulsatile GnRH analogue if fertility '

'

desired • symptomatic treatment with estrogen /testosterone hypergonadotropic Hypogonadism • hypogonadism due to impaired response of the gonads to ESH and LH

Etiology

• congenital:

chromosomal abnormalities ( Turner 's syndrome, Klinefelter syndrome, XX gonadal dysgenesis ) enzyme defects ( I 7a- hydroxylase deficiency, 17,20-lyase deficiency) gonadotropin resistance ( Leydig cell hypoplasia, ESH insensitivity, pseudohypoparathyroidism type 1A)

• acquired:

•

gonadal toxins (chemotherapy, radiation ) drugs (antiandrogens, alcohol ) infections (S'l'ls , mumps) gonadal failure in adults (androgen decline and testicular failure in men , premature ovarian insufficiency and menopause in women )

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LJ

Clinical Features

• amenorrhea, erectile dysfunction (see Urology, U33), loss of body hair, fine skin, testicular atrophy, failure of pubertal development, low libido, decrease in energy, and infertility

+

Treatment

• hormone replacement therapy consisting of androgen ( for males) and estrogen and progesterone ( for females) administration

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1

E22 Endocrinology

Toronto Notes 2023

Antidiuretic Hormone Diabetes Insipidus ( see Nephrology. NP12)

Definition

• disorder of ineffective ADH (decreased production or peripheral resistance ) resulting in passage of large volumes of dilute urine Etiology and Pathophysiology

• central Dl: insufficient ADH due to pituitary surgery, tumours, idiopathic/autoimmune, infiltration or lesion of the stalk, hydrocephalus, Langerhans cell histiocytosis, trauma, familial central Dl • nephrogenic Dl: collecting tubules in kidneys resistant to ADH due to drugs (e.g. lithium ), hypercalcemia, hypokalemia, CKD, hereditary nephrogenic Dl • psychogenic polydipsia and osmotic diuresis must be ruled out Clinical Features

• passage of large volumes of dilute urine, polydipsia, and dehydration; hypernatremia can develop with inadequate water consumption or secondary to an impaired thirst mechanism • central Dl: visual field defect , headache, other neurological features , or evidence of other pituitary hormone deficiencies may be present Diagnostic Criteria • fluid deprivation will differentiate true Dl ( high urine output persists, urine osmolality < plasma osmolality) from psychogenic polydipsia • response to exogenous ADH (DDAVP) will distinguish central Dl from nephrogenic Dl Treatment

• central Dl: first line = desmopressin; second line = chlorpropamide, thiazides, NSAlDs, and carbamazepine • nephrogenic Dl: solute restriction, thiazide diuretics Syndrome of Inappropriate ADH Secretion

Diagnostic Criteria

Diagnosing Subtypes of Diabetes Insipidus with Desmopressin Response

-

Concentrated urine Central No effect * Nephrogenic

$

Syndrome of inappropriate ADH secretion (SIADH ) vs. Cerebral Salt Wasting (CSW) CSW can occur in cases of subarachnoid hemorrhage. Na» is excreted by malfunctioning renal tubules, mimicking findings of SIADH: hallmark is hypovolemia

-

• 1) hyponatremia (serum Nat < 135 mEq / L ) with 2 ) plasma hypo osmolality (< 275 mOsm / kg ), 3) urine Na t concentration > 40 mEq/ L, 4) urine osmolality >100 mOsm / kg ), 5) euvolemia ( no edema ), and 6) absence of adrenal, renal, or thyroid insufficiency

Etiology and Pathophysiology • stress ( post-surgical) • malignancy (ectopic ADH production by tumours including small cell carcinoma of the lung, extrapulmonary small cell carcinomas, squamous cell carcinoma of the head and neck) • CNS disease (inflammatory, hemorrhage, tumour, Guillain-Barre syndrome ) • respiratory disease (tuberculosis, pneumonia, empyema ) • drugs (SSRls, vincristine, chlorpropamide, cyclophosphamide, carbamazepine, nicotine, morphine, DDAVP, oxytocin )

Clinical Features

• symptoms of hyponatremia: headaches, nausea, vomiting, muscle cramps , tremors, cerebral edema if severe (confusion, mood swings, hallucinations, seizures, coma )

Treatment

• goal is to increase serum sodium • treat underlying cause, fluid restriction (800-1000 mL/d ), vasopressin receptor antagonists (tolvaptan, conivaptan ), demeclocycline (antibiotic with anti-ADH properties; rarely used ), and furosemide

Pituitary Pathology Pituitary Adenoma (see Neurosurgery. NS17)

Clinical Features

• local mass effects • visual held defects ( bitemporal hemianopsia due to compression of the optic chiasm ), diplopia (due to oculomotor nerve palsies; rare), headaches; increased ICR is rare • hypofunction • hypopituitarism • hyperfunction • PRL (galactorrhea, hypogonadism ), GH (acromegaly in adults, gigantism in children ), ACT H '

(Cushing’s disease = Cushing’s syndrome caused by a pituitary tumour) • tumours secreting TSH are rare

r Important Deficiencies to Recognite

are:

• Adrenal Insufficiency • Hypothyroidism • Concurrent adrenal insufficiency and

+

hypothyroidism should be treated with glucocorticoids first and then with thyroid hormone to avoid adrenal crisis

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E 23 Endocrinology

Toronto Notes 2023

Investigations

(§)

• radiological evaluation ( MKI sella is imaging procedure of choice) • formal visual field testing for tumours compressing the optic chiasm • laboratory tests of hypothalamic - pituitary hormonal function

The Pituitary Hormones Compression of the pituitary by a mass leads to loss of pituitary hormones in the following usual order: T5o Look For The Adenoma Please" GH. LH FSH, TSH, ACTH PRL + posterior pituitary hormones: ADH and oxytocin

Hypopituitarism

.

Etiology (The Eight I’s)

• Invasive

.

pituitary tumours, craniopharyngioma, cysts ( Kathke's deft , arachnoid , or dermoid ), metastascs

• Infarction / hemorrhage

Sheehan’s syndrome ( pituitary infarction due to excessive postpartum blood loss and hypovolemic shock) pituitary apoplexy (acute hemorrhage / infarction of a pituitary tumour; presents with sudden loss of pituitary hormones, severe headache, and altered LOC; can be fatal if not recognized and

treated early) • Infiltrative/ inflammatory sarcoidosis, hemochromatosis, histiocytosis • Infectious

syphilis, tuberculosis, fungal ( histoplasmosis), parasitic (toxoplasmosis)

• Injury

severe head trauma

• Immunologic

autoimmune destruction ( hypophysitis) • Iatrogenic follow ing surgery or radiation • Idiopathic familial forms, congenital midline defects

Clinical Features • symptoms depend on which hormone is deficient: » ACTH: fatigue, weight loss, hypoglycemia, anemia, hyponatremia, failure to thrive, and delayed puberty in children CiH : short stature in children; adults exhibit increased fat and decreased lean body mass, decreased BMD, fatigue TSH: tiredness, cold intolerance, constipation , weight gain LH and 1 SH: oligo or amenorrhea, infertility, decreased facial / body hair and muscle mass in men, erectile dysfunction, delayed puberty Prolactin: usually asymptomatic, inability to breastfeed ADH: symptoms of D1 (extreme thirst, polydipsia, hypernatremia) Oxytocin: usually asymptomatic only needed during labour and breastfeeding

-

-

-

Investigations

-

• 8 am cortisol, PRL, TSH, Free T4, LH, FSH , Estradiol or Testosterone, GH, IGF I, Na +, Osmolality • insulin tolerance test: insulin ( usual dose 0.1 unit / kg of human regular insulin ) -> hypoglycemia -» increased GH and cortisol (normal response) • initial test: cosyntropin stimulation test ( if results equivocal, proceed to insulin tolerance test ) • triple bolus test ( rarely done)

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E2‘l Endocrinology

Toronto Notes 2023

Thyroid Thyroid Hormones

Extra -Thyroidal (actors Impacting Thyroid Hormone Homeostasis:A Review JRM 2015:4|l ):40 -49 • Most peripheral thyroid metabolism occurs in the liver and kdnejs. thus severe twer disease and CKO can ugnifrcantiy alter the 13:T4 ratio. • Alcohol dependence results m hypothalamic pituitaryry to d axis dysiunction demonstrated hy decreased TSH 14, and T3 levels. • Smoking is associated with lower TSH levels in a dose-dependent manner, with heavy smokers 18-12 ciqarettes'd ) beaig associated with more TSH

C- L r

Cap tan

'

Thyroid follicle

Section of the Thyroid Gland

.

Follicular cell

suppression than light smokers [«4 cigarettes/d).

• Heavy metal exposure including lead, mecenry.and cadmmm has been shown to altar thyroid hormone function and peripheral melabohsm.

Follicular cell

&

Coupling t v:

-

Patterns of Hormone Levels

r Hyper r Hyper 1° Hypo y »ypo

JUT - diodotyrosina; L = lysosome; MU - monoiodotyrosine; Tg - thyroglobulin; NIC

. - thyroid paroxidase enzyme

^ sodium iodide cotransporter TP

.

TSH

Il Tr

*

t

t

t

t

*

*

j

Figure 12. Thyroid hormone synthesis

Synthetic Function of the Thyroid Gland • the synthesis of thyroid hormones '14 and '13 by the thyroid gland involves trapping and oxidation of iodide, iodination of thyroglobulin, proteolysis of thyroglobulin , and release of 14 and T3 more than 90% of thyroid hormone secreted by the thyroid is T4 • free T4 (0.02%) and free T'3 (0.3%) represent the hormonally active fraction of thyroid hormones the remaining fraction is bound to TBG, albumin, and transthyretin, and is biologically inactive • T3 is more biologically active (approximately 4 x as potent as 14), but T3 is present in the blood in smaller quantities and has a shorter half life compared to T4 • 85% of '14' is converted to T'3 or reverse T'3 in the periphery by dciodinase enzymes • reverse T 3 is metabolically inactive but produced in times of stress to decrease metabolic activity • most of the plasma T'3 pool is derived from the peripheral conversion of T4 • calcitonin, a peptide hormone, is also produced in the thyroid by the parafollicular cells (C cells) calcitonin functions by inhibiting osteoclast activity and increasing renal calcium excretion '

-

Role of Thyroid Hormones

• thyroid hormones act primarily through modifying gene transcription hy binding to nuclear receptors • diffuse actions, affecting nearly every organ system • tissue-specific effects determined by the expression of the types of thyroid receptor isoform and the local production of T3 • increase basal metabolic rate through increased Na + / K + ATPase activity, increased 02 consumption, increased respiration, heat generation , and increased cardiovascular activity • when present at higher than normal levels, potentiate the actions of GH , catecholamines (epinephrine, norepinephrine ), glucagon, and cortisol, resulting in increased gluconeogenesis, ketogenesis, and proteolysis, mimicking what happens in starvation • increase sensitivity to catecholamines by up- regulating their receptors, but do not alter their blood

concentrations • required for normal growth in the fetus and child, including the CNS, via stimulation of GH release, in

rT \. LJJ

synergism with cortisol

Regulation of Thyroid Function

• extrathyroid

+

stimulation of thyroid by 'TSH, epinephrine, prostaglandins (cAMP stimulators); T3 negatively feeds back on anterior pituitary to inhibit TSH and on hypothalamus to inhibit T'RH

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Toronto Notes 2023

E 25 Endocrinology

• T3 intrathyroid ( autoregulation ) synthesis ( Wolff -Chaikoff effect,|od - Basedow effect ) varying thyroid sensitivity to TSH in response to iodide availability increased ratio ofT3 to T 4 in iodide deficiency

increased activity of peripheral 5’-deiodinase in hypothyroidism increases T3 production despite low T4 levels

Tests of Thyroid Function and Structure TSH • third generation TSH is the best test for assessing thyroid function • hyperthyroidism primary': TSH is low because of negative feedback from increased levels of circulating T4 and 1'3 secondary: increased TSH results in increased 14 and T3

• hypothyroidism »

primary: increased T SH ( most sensitive test ) because of less negative feedback from T4 and T'3 secondary: T SH is low or inappropriately normal with variable response to TRH depending on the site of the lesion ( pituitary or hypothalamic)

Free T4 and Free T3

• standard assessment of thyroid function measures TSH and, if necessary, free T4. Tree T3 should only be measured in the small subset of patients with hyperthyroidism and suspected T3 toxicosis. In this

e .

Thyroid Assessment TSH • Serum free thyroid hormones (T», T3) Antibodies (TRAb TgAb. and TPOAb) • Thyroglobulin (to monitor thyroid cancer ) • Thyroid U/ S when there is a palpable thyroid abnormality or suspected thyroid mass • Nuclear uptake and scan (for hyperthyroidism) • Biopsy (FNA) of thyroid nodules warranting a cytological evaluation

.

.

case, T SH would be suppressed , free 14 normal , and free 1 3 elevated

Thyroid Autoantibodies

• TgAb, TPOAb, and TRAb of the blocking variety are increased in Hashimoto’s disease; normal variant

-

in 10 20% of individuals

• TKAb of the stimulating variety are also referred to as TSI and can cause Graves' disease. TRAb receptor blocking and stimulating antibodies are seen in patients with

Graves' disease

Plasma Thyroglobulin • used to monitor for residual thyroid tissue post-thyroidectomy, e.g. tumour marker for thyroid cancer

recurrence

• detectable or elevated levels may suggest persistent, recurrent , or metastatic disease • assay can be impacted by presence of TgAb. Therefore, both must be tested to ensure accurate thyroglobulin results Serum Calcitonin • not routinely done to investigate thyroid nodules • ordered if suspicion of MTC (e.g. in patients with a thyroid nodule and suspected or confirmed MEN 2 A or 2 B syndromes or those who have a pathogenic mutation in RET gene) • used to monitor for residual or recurrent MTC Thyroid Imaging/Scans • normal gland size 15-20 g (estimated by palpation ) thyroid U /S to measure size of gland , characterize thyroid nodules, facilitate ENA biopsy ( ENAB ) • U/S is the first line tool for identification of thyroid nodules that require ENAB; exception is

.

hyperthyroid patients with thyroid nodules where use of a radioisotope thyroid scan and RA1U

(see below) permits identification of hyperfunctioning nodules, which generally do not need to be

Does this Patient have a Goitre? from The Rational Clinical Examination JAUA 2009: https:// jamaevidence.mhmediial .com/ ccnte t aspi ?l)O0 « ld 8454 secto i d 6 ? S08 Study: Systematic review of articles assessing the accuracy and precision ot theclinical eum I n the diagnosis of a goitre. Results: Clinical diagnosis was based on degree of lateral prominence, visibility,and palpability of the thyroid gland. Nn evidence eiiststo support the superiority of any one method the combined results of 4 stain detail the predictive hbty of assessing grades of thyroid gland weight:

-

-

- -m

,

•

Weight

Reference

US*

95% Cl

0-20 g

Normal

0.15

(0.10-0.21)

1.9 25.0

(11-3.0)

20-40 g 1- 2x

»

>2

40 g

>

(2.6-175)

.

Mtemathrtly defining a goitre asa mass larger than the distal phalanrof the thumb has been shown to have an LR* of 3.0 (95% Cl 25 3.5) and 1R - of 0.30 (95% a:0.24 0.37) in children, and an LR of 4.7 (95% 0 3.6 0) and LR of 0.08 (95% Cl 0.02 0.27) for the presence of a govtre. Conclusions: Use 0!we ightof thyroid tissue Isan appropriate method of dagnosmga goitre, while com paring the six of the thyroid nasslo the distal pbaia n of the thumb may be a useful alternative.

-

-

-

-

-

-

biopsied • radioisotope thyroid scan (Technetium 99) only if 1 ) one or more thyroid nodule (s) and 2) patient is hyperthyroid to determine whether nodules are hot ( functioning -> excess thyroid hormone production ) or cold ( non functioning ) • hot nodule > very low chance of malignancy; treat hyperthyroidism • cold nodule -» further workup required ( U /S, then ENAB if concerning sonographic features)

-

-

. RA1U

test of function: order if patient is thyrotoxic RAIU measures the turnover of iodine by thyroid gland in vivo if t uptake (e g. incorporated ), gland is overproducing thyroid hormone ( hyperthyroid ) if * uptake (e g not incorporated ), gland is leaking thyroid hormone (e.g. thyroiditis), exogenous thyroid hormone use, or excess iodine intake (e.g. amiodarone or contrast dye, which has high iodine content) • see figure 12 for further information regarding the utility of these scans

. ..

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Thyroid Biopsy

• ENA for cytology «

+

differentiates between benign and malignant disease best done under U /S guidance accuracy decreased if nodule is greater than 50% cystic, or if nodule is located posteriorly in the gland

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E26 Endocrinology

Toronto Notes 2023

Table 15. Summary of Diagnostic Testing in Hyperthyroidism and Hypothyroidism Hyperthyroidism

Hypothyroidism

TSH

Decreased in 1° hyperthyroidism Increased in 2° hyperthyroidism

Increased in 1° hypothyroidism Decreased in 2‘ hypothyroidism

Freeti

Increased in 1" hyperthyroidism Increased in 2" hyperthyroidism

Decreased in 1‘ hypothyroidism Decreased in 2‘ hypothyroidism

Antibodies

Graves': TRAb

Hashimoto's: TPOAb, TgAb

RAIU

Increased uptake Graves' Toxic multinodular goitre Toxic adenoma

Decreased uptake Subacute thyroiditis Recent iodine load Exogenous thyroid hormone

Radioisotope Thyroid Scan

Drugs Affecting Thyroid Function Thyroid 2010:20(71:763-770 • Lithium plays in inhibitory role in thyroid hormone release, resulting n chnical hypothyroidism end goitre. AimadaroceTndyred Hypothyroidism glH|: Ant oderone a class III anbarrhythmic drug, contains 2 atoms ol iodine per molecule and is structurahy similar to thyroid hormones, and may exert antagonist effects on lift receptors. It a also shorn to inhibit type I deiodnoses resulting in high T4 acd lnwT3 levels.AIH occurs in 5-15% nf patients on amiodarone.UH can also occur in people without pre exisbng thyso d dysfunction. • Arniodarone Induced ihyrotoxicovs |JU1): occurs In 2-12\ of patents on amiodarone. Iha may be due to either art increased iodine load in patients with a prer.ousty autonomous thyroid such as in Graves' disease and toxic multinodular goitre (AIT type l|or amiodarone- induceddestructive thyroid tis 1 11 type It)

.

.

*

Graves': homogenous diffuse uptake Multinodular goitre:heterogeneous uptake loxic adenoma: single intense area of uptake with suppression elsewhere

-

Thyrotoxicosis Definition

*

• clinical, physiological, and biochemical findings in response to elevated thyroid hormone

Epidemiology

• 1% of general population have hyperthyroidism • I :M= 5: 1

Signs and Symptoms of HYPERthyroidism

Etiology and Pathophysiology

.

THYROIDISM Tremor Heart rate up Yawning (fatigue due to insomnia) Restlessness Oligomenorrhea / amenorrhea Intolerance to heat Diarrhea

Table 16 . Differential Diagnosis of Thyrotoxicosis Disorder

TSH

Free T /Ti

Thyroid Antibodies

RAIU

Other

Decreased

Increased

TRAb

Increased

Homogenous uptake

HYPERTHYROIDISM

Graves' Disease

on scan

Muscle wasting / weight loss

Toxic Nodular Goitre

Decreased

Increased

None

Increased

Heterogeneous uptake on scan

Toxic Nodule

Decreased

Increased

None

Increased

Intense uptake in hot nodule on scan with suppressed uptake in the rest of the gland

Decreased

Increased

Decreased (increases once entering hypothyroid phase, when TSH rises)

In classical subacute painful thyroiditis

THYROIDITIS

.

Subacute, Silent Postpartum

Up to 50% of cases

.

( TPOAb TgAb )

ESR increased

.

Decreased

Exogenous (drugs)

Decreased

Increased

None

Decreased

Low thyroglobulin since endogenous thyroid hoimone production suppressed

Increased (Ti would be decreased if taking Tj)

None

Decreased

Common Etiologies Thyrotoxicosis

EXTRATHYROIDAL SOURCES OF THYROID HORMONE

Endogenous (struma ovarii, ovarian teratoma, metastatic follicular carcinoma)

Irritability Sweating

Hypothyroidism

Graves' Disease

Hashimoto's

Toxic Nodular Goitre

Congenital

Toxic Nodule

Iatrogenic (thionamides.

.

radioactive iodine o< surgery)

Hyperthyroid phase of Hypothyroid phase ol thyroiditis thyroiditis

EXCESSIVE THYROID STIMULATION

Pituitary Thyrotropinoma

Increased or inappropriately normal

Increased

None

Increased

Pituitary Thyroid Hormone Receptor Resistance

Increased or normal

Increased

None

Increased

..

Increased hCG (e g pregnancy)

Pituitary mass; possible PRL or GH

excess Abnormal THRB gene analysis

Decreased

Increased

None

Test is contraindicated

p1

in pregnancy

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Toronto Notes 2023

E 27 Endocrinology Clinical Features Table 17. Clinical Features of Thyrotoxicosis General

Fatigue , heat intolerance, irritability, fine tremor

CVS

Tachycardia. alrial fibrillation, palpitations Elderly patients may have only cardiovascular symptoms, commonly new onset atrial fibrillation

Gl

Weight loss with increased appetite , thirst, increased frequency of bowel movements |hyperdefecalion)

Neurology

Proximal muscle weakness , hypokalemic periodic paralysis (more common in Asian individuals)

GU

Oligomenorrhea , amenorrhea , decreased feitilily

Dermatology

Fine hair, moist and warm skin , vitiligo, soli nails with onycholysis (Plummer ’s nails), palmar erythema, pruritus Graves' disease: clubbing (acropadiy), prelibial myxedema (rare)

MSK

Decreased bone mass, proximal muscle weakness

Hematology

Graves' disease: leukopenia, lymphocytosis , splenomegaly, lymphadenopathy (occasionally)

Eye

Graves’ disease: lid lag. retraction , proptosis, diplopia, decreased acuity, puffiness, conjunctival injection NOTE: Lid lag is a reflection of a hyperadrenergic state and can be present in any form of thyrotoxicosis

Treatment • p blockers for control of adrenergic symptoms • antithyroidals ( thionamidcs): propylthiouracil ( R U ) or methimazole ( MMl ); MMI recommended • to prepare patients with endogenous hyperthyroidism for surgery, for patients with Graves' disease, and for patients with toxic nodules who do not wish to have definitive treatment with

-

radioactive iodine or surgery • radioactive iodine thyroid ablation for Graves' disease and toxic nodules/ adenoma • surgery in the form of hemi, subtotal, or complete thyroidectomy for toxic nodules • surgery in the form of total thyroidectomy for Graves’ disease

Graves’ Disease Definition

• an autoimmune disorder characterized by autoantibodies that stimulate the TSH receptor leading to

hyperthyroidism

Epidemiology • most common cause of hyperthyroidism • occurs at any age with peak in 3rd and 4 th decade • F:M =7:1, 1.5-2% of women in the United States • familial predisposition: 15% of patients have a close family member with Graves’ disease and 50% have family members with positive circulating antibodies • association with HLA - B8 and DR 3 • may be associated with other autoimmune disorders (e.g. pernicious anemia, Hashimoto’s disease )

Graves' Ophthalmopathy

NO SPECS (In the usual order of changes) No signs Only signs: lid lag, lid retraction Soft tissue: periorbital puffiness, conjuctival injection, diemosis Proptosis/ exophthalmos Extraocular (diplopia ) Corneal abrasions (unable to close eyes)

Sight loss

Etiology and Pathophysiology

• autoimmune disorder due to breakdown in thyroid tolerance likely due to a combination of factors including autoreactive B lymphocytes and an imbalance favouring a TH 2 vs. TH 1 immune response • B lymphocytes produce 1 SI that binds and stimulates the I SH receptor, and thus, the thyroid gland • immune response can be triggered by postpartum state, iodine excess, viral or bacterial infections, and glucocorticoid withdrawal • ophthalmopathy ( thyroid associated orbitopathy) is a result of increased connective and extraocular muscle tissue volume due to inflammation and accumulation of glycosaminoglycans, stimulated by TS1, that increase osmotic pressure within the orbit; this leads to fluid accumulation and forward displacement of the eyeball • dermopathy ( pretibial or localized myxedema ) may be related to cutaneous glvcosaminoglycan deposition '

Clinical Features • signs and symptoms of thyrotoxicosis • diffuse goitre ± thyroid bruit secondary to increased blood flow through the gland • ophthalmopathy: proptosis, diplopia, conjunctival injection , corneal abrasions, periorbital puffiness, lid lag, decreased visual acuity ( plus signs of hyperthyroidism: lid retraction, characteristic stare) • dermopathy ( rare ): pretibial myxedema ( thickening of dermis that manifests as non - pitting edema ) • acropachy: clubbing and thickening of distal phalanges Investigations • low TSH

• increased free T4 (and /or increased T3) • positive for TR Ab ( the currently available third - generation T'RAb tests have sensitivity and specificity over 98%, allowing their use for determining the etiology of hyperthyroidism ) • increased RA 1 U • homogeneous uptake on thyroid scan

AL GRAWANY

Other Medications Used in the Treatment of Graves' G lucocorticoids have been useful in the treatment of severe Graves’ hyperthyroidism and thyroid storm, by inhibiting the conversion of peripheral T« to T3 Lithium can also be used to treat Graves' hyperthyroidism. It acts by blocking thyroid hormone release, but its toxicity has limited its use in practice

m

Caution with Thionamides These drugs are highly effective inhibitors of thyroid hormone synthesis, inducing permanent remission in 20-30% of patients with Graves' disease. They are most often employed to achieve a euthyroid state before definitive treatment. Adverse effects include teratogenicity, agranulocytosis, hepatotoxicity. and ANCApositive vasculitis

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Toronto Xotcs 2023

E28 Endocrinology Treatment

• thionamides (antithyroid medications): PTU or methimazole MMI. In 2020, PTU became unavailable in Canada and it is unclear whether it will be available in the future PT U and MMI inhibit thyroid hormone synthesis by inhibiting peroxidase catalyzed reactions, thereby inhibiting organification of iodide, blocking the coupling of iodoty rosines PTU also inhibits peripheral deiodination of T4 to T3 treat for approximately 12 18 mo aiming for a normal TSH and TKAb prior to consideration of treatment discontinuation small goitre, mild hyperthyroidism , and low TRAb titres are good predictors for long- term remission with medical therapy remission ( normal thyroid indices one vr after discontinuation of PTU or MMI ) rates range between 20 30% following 12 18 mo of antithyroid medication major side effects: hepatotoxicity (cholestasis, hepatitis), agranulocytosis, vasculitis minor side effects: minor rash, pruritus MMI is preferred to PTU due to longer duration of action (once daily dosing for most ), more rapid resolution of hyperthyroidism , and lower incidence of side effects in pregnancy: use PTU during first 16 wk of pregnancy and MMI after. MMI is contraindicated in the first trimester due to risk of aplasia cutis; MMI is preferred in the second and third trimester due to the potential risk of hepatotoxicity with PTU in the second and third trimesters • symptomatic treatment with p blockers • thyroid ablation with radioactive 1-131 if PT U or MMI trial does not produce disease remission or patient prefers definitive treatment with RA1 high incidence of hypothyroidism after 1 131 requiring lifelong thyroid hormone replacement contraindicated in pregnancy may worsen ophthalmopathy; concurrent treatment with prednisone if high risk for or if ophthalmopathy present • total or near total thyroidectomy (indicated for large goitres, suspicious nodule for cancer, if patient is intolerant to thionamides and dedines/is not a candidate for RAI ablation , women who wish to conceive in the near future warranting rapid control of hyperthyroidism , uncontrolled hyperthyroidism not responding to anti-thyroid drugs in pregnancy (surgery safest in second trimester), patient preference) • risks: permanent hypothyroidism , hypoparathyroidism , and vocal cord palsy due to potential laryngeal nerve damage • ophthalmopathy/orbitopathy smoking cessation is important prevent drying of eyes and ulceration of cornea by using artificial tears during the day and lubricants at night high dose prednisone or IV methylprednisolone in severe cases • high dose glucocorticoids preferably IV as well as potential orbital decompression surgery for sight threatening orbitopathy orbital radiation, surgical decompression

-

-

-

-

-

-

Prognosis

• course involves remission and exacerbation unless gland is destroyed by radioactive iodine or surgery • total and subtotal thyroidectomy are rapid cures with low - risk of recurrence ( 2% and 10%, respectively) • radioactive iodine is less invasive than surgery, but also results in permanent hypothyroidism and requires precautions in contacts several days after treatment

-

• medical therapy with thionamides is not invasive, but has high recurrence rate at 50% • lifetime follow- up needed

ri L

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E29 Endocrinology

Toronto Notes 2023

Subacute Thyroiditis ( Thyrotoxic Phase) •

there are two main types: painful (de Quervain’s) and painless (silent ) Table 18 . Painful vs. Painless Subacute Thyroiditis Painful Thyroiditis (de Ouervain’s, granulomatous)

Pathophysiology Presumed lo be caused by viral infection or postviral inflammatory process

-

Painless Thyroiditis (silent, autoimmune )

Considered variant ol Hashimoto 's thyroiditis Associated with HLA 0 R 3 Postpartum subtype occurs following pregnancy

Strongly associated with HLA D 35 Thyroid inflammation damages thyroid follicles, resulting in release Also caused by inflammatory damage leading lo unregulated release ol Ii and 1i into circulation ol large amounts ol T 4 and 13 until stores are exhausted Slate ol hypothyroidism often persists until thyroid can generate suflicient thyroid hormones

.

Clinical Features Painful swelling of the thyroid ( may radiate to jaw and ears) transient vocal cord paresis, malaise, fatigue , myalgia , fever Often preceded by IIRTI Painful condition lasts for a week to lew months Signs of hyperthyroidism during hyperthyroid phase (palpitations. tachycardia , stare)

Thyroid enlargement without discomlorl in association with the typical thyroid function test abnormalities consisting of hyperthyroidism , hypothyroidism , and recovery Signs of hyperthyroidism during hyperthyroid phase ( palpitations, tachycardia , stare) Allects women more than men

Laboratory Investigations

Initial elevated Tiandh Near absentRAIU ( SR and CRP often elevated

Initial elevated Ti and I: Near absent RAIU

NSAID/ prednisone for pain

P -adrenergic blockage is usually eflective in reversing

treatment

hypcrmctabollc and cardiac symptoms

fl adrenergic blockage is usually effective in reversing most of the Prognosis

-

most ol the hypermetabolic and cardiac symptoms II symptomatically llypolhyroid , may treat short term

-

If symptomatically hypothyroid , may treat short term with thyroxine with thyroxine Complete spontaneous recovery to normal thyroid lunction in 90% 10 % ol patients may become permanently hypothyroid ol patients Al risk ol recunen! episodes of thyroiditis 10% of patients may become hypothyroid and require permanent replacement

Toxic Adenoma / Toxic Multinodular Goitre Etiology and Pathophysiology • autonomous thyroid hormone production from a functioning adenoma that is hypcrsecreting T4 and

T3

may be singular ( toxic adenoma ) or multiple ( toxic multinodular goitre ( Plummer’s disease)) • more common in elderly people as opposed to Graves' disease which is more common in younger •

individuals Clinical Features multinodular goitre

•

• •

tachycardia , heart failure , arrhythmia , weight loss, nervousness , weakness , tremor, and sweats local neck compression symptoms such as dysphagia, dysphonia, or dyspnea may be present with large goitres

Investigations • •

low TSH , high free T4 and free T 3 thyroid scan with increased RAIU in nodule (s ) and suppression of the remainder of the gland

Treatment • use high dose radioactive iodine (1- 131) to ablate hyperfunctioning nodules • - blockers often necessary for symptomatic treatment prior to definitive therapy • surgical excision may also he used as first - line treatment

p

•

initiate therapy with PTU or MM 1 to attain euthyroid state in individuals who do not wish to have definitive treatment of their disease, in preparation for thyroidectomy, or prior to RA1 in patients at risk for complications due to exacerbation of hyperthyroidism following RA 1 such as the elderly with

cardiovascular disease

Thyrotoxic Crisis/ Thyroid Storm Definition •

medical emergency - acute exacerbation of all of the symptoms of thyrotoxicosis presenting in a life -

threatening state secondary to uncontrolled hyperthyroidism • rare, but serious with mortality rate between 10 - 30%

+

Etiology and Pathophysiology • often precipitated by infection , trauma , or surgery in a hvperthyroid patient

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E30 Endocrinology

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Differential Diagnosis • sepsis, pheochromocytoma, malignant hyperthermia, drug overdose, neuroleptic malignant

syndrome Clinical Features • hyperthyroidism • extreme hyperthermia (S40°C), tachycardia, vomiting, diarrhea, hepatic failure with jaundice, atrial

fibrillation , CHE

• CNS manifestations including agitation , delirium , psychosis, lethargy, seizures, coma Laboratory Investigations

• increased free T4 and T3, undetectable TSH • ± anemia, leukocytosis, hyperglycemia, hypercalcemia , elevated LET* General Measures

• fluids, electrolytes, and vasopressor agents should be used as indicated • a cooling blanket and acetaminophen can be used to treat the pyrexia • propranolol or other (1 blockers can additionally be used, but should be used with caution in patients with decompensated heart failure as they may worsen condition propranolol is frequently used because it decreases peripheral conversion of T4 to T3

-

Specific Measures

• PTU is the anti-thyroid drug of choice and is used in high doses ( 200 mg q4 h ) • give iodide, which acutely inhibits the release of thyroid hormone, 1 h after the first dose of PTU is given sodium iodide I g IV drip over 12 h q 12 h OR Lugol’s solution 10 drops q8 h OR potassium iodide (SSKI ) 5 drops q6 h • hydrocortisone 100 mg IV q8 h or clexamethasone 2 4 mg IV q6 h for the first 24 48 h; inhibits peripheral conversion of T4 to T3

-

-

Hypothyroidism Definition

• clinical syndrome caused by insufficient thyroid hormone production Epidemiology • 2-3% of general population F:M =10:1 • 10 20% of women >50 have subclinical hypothyroidism ( normal '14, TSH mildly elevated ) • iodine deficiency is the most common cause worldwide, but not in North America

.

-

Etiology and Pathophysiology • primary hypothyroidism (90%)

• inadequate thyroid hormone production due to an intrinsic thyroid defect

-

-

iatrogenic: post ablative (1 131 or surgical thyroidectomy ) autoimmune: Hashimoto's thyroiditis hypothyroid phase of subacute thyroiditis drugs: goitrogens ( iodine), PTU , MM I, lithium • infiltrative disease ( progressive systemic sclerosis, amyloid ) • iodine deficiency » congenital (1/4000 births) neoplasia • secondary hypothyroidism: pituitary hypothyroidism • insufficiency of pituitary TSH • tertiary hypothyroidism: hypothalamic hypothyroidism • decreased TRH from hypothalamus ( rare) • peripheral tissue resistance to thyroid hormone ( Refetoif syndrome ) u

f adore Affecting Gastrointestinal Absorption of levothyrorine: A Review Cl* Titer 201); 39|2):3 403 • (I disorders such as cebac disease, atrophic gastritis, lactose intolerance H. pylori infection nay impede levotbyroiine absorption. t i t , - net -fr - ; : v tv : c:. i - q ;:: to significantly reduce exogenous Ibyroid hormone absorption from the Gi tract These wictude proton pump inhibitors H2 receptor antagonists, calcium carbonate, sucralfate, and aluminum bydronde. - te- i t i n a l :: : i I c r a t e s s o o - :: oflerothyrorine. • food, especially soybeans andcoffee hare been shown to leduce absorption of levoUiyroxine significantly. Roughly 80% of lerotfiyroiine is absorbed within 3 h after administration of the drug. Thus, patients Should be educated to take levothyroniae on empty stomach at least 1 b prior to eating breakfast.

«

.

.

.

.

‘

.

-

.

'

.

.

Table 19. Interpretation of Serum TSH and Free T« in Hypothyroidism Serum TSH

FreeTi

Subclinical Primary Hypothyroidism

Increased Increased

Decreased Normal

Secondary Hypothyroidism

Decreased or not appropriately elevated

Decreased

Overt Primary Hypothyroidism

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Clinical Features Table 20. Clinical Features of Hypothyroidism General

Fatigue, cold intolerance , slowing of mental and physical performance , hoarseness, macroglossia

CVS

Pericardial effusion, bradycardia , hypotension. worsening CHF * angina. hypercholesterolemia, hypcihomocystcincmia , myxedema heart

Respiratory

Decreased exercise capacity, hypoventilation secondary to weak muscles, decreased pulmonary responses lohypoxia, sleep apnea due to macroglossia

Gl

Weightgain despite poor appetite. constipation

Neurology

Paresthesia , slow speech, muscle Clamps , delayed deep tendon reflex relaxation |“hung reflexes") , carpal tunnel syndrome , asymptomatic elevated CK . scuures

GU

Menorrhagia, amenorrhea, impotence, pre- menopausal abnormal vaginal bleeding

Dermatology

Facial pulfmess. periorbital edema , cool and pale, dry and rough skin dry and coarse hair, eyebrows thinned ( lateral 1/ 3), discolouration (carotenemia)

Hematology

Anemia: 1D\ pernicious due to piesencc ol anti parietal cell antibodies with Hashimoto' sthyioidilis

,

Subclinical Hypothyroidism: A Review JAMA 2019;322:153-160 Ebckground Up a MS ot the adultpop ialion tiptnencn jubtlinital hypethyro dism, defined a elevated ISH (»4.4 mUfl| with notmalleeeIs ol fiee 14. The deqiee of abnormality that warrants management is controversial. Observations: Sjbtlinical hypotfiyrodism is most often caused byautoimmune thyroiditis, ttmay be associated w th increased nskof OIF and CAD events Further substantial portion of patients with subclinical hypothyroidism progress to overt hypothyroidism,hrdence from large RCIs to support levotbyroiine therapy in these patients is lacking. The rationale for treatment is therefore based on levathyronme 'spotential to prevent cardiovascular events and progress on to overt hypothyroidism Recommendations : Most individuals with subclinical hypothyioidismcan beobsetvedvi thou! treatment. Candidates for levotbyroiine therapy include those with serum ISH levels >10 mU/Land young and middle -aged patients with symptor sof mild hypothyroidism.

-

.

.*

-

Treatment • L-thyroxine (dose range: 0.05-0.2 mg PO once daily, up to 1.6 pg / kg /d) • elderly patients and those with CAD: start at 0.025 mg daily and increase gradually every 6 wk (start loss’, go slow) • after initiating L thyroxine, TSH needs to be evaluated in 6 wk ; adjust dose until TSH returns to

normal reference range

• once maintenance dose achieved, follow up TSH with patient annually • secondary/tertiary hypothyroidism: monitor via measurement of free T4 ( TSH is unreliable in this setting ) CONGENITAL HYPOTHYROIDISM • see Paediatrics, P34

.

.

Signs and Symptoms of HYPOthyroidism

HIS FIRM CAP Hypoventilation Intolerance to cold Slow HR Fatigue

Hashimoto’s Thyroiditis Definition • most common form of primary hypothyroidism in North America • chronic autoimmune thyroiditis characterized by both cellular and humoral factors in the destruction of thyroid tissue • two major forms: goitrous and atrophic; both forms share same pathophysiology but differ in the extent of lymphocytic infiltration, fibrosis, and thyroid follicular cell hyperplasia • goitrous variant usually presents with a small, rubbery goitre and euthyroidism, then hypothyroidism becomes evident • associated with fibrosis • atrophic variant patients arc hypothyroid from onset

Impotence Renal Impairment Menorrhagia /amenorrhea Constipation Anemia Paresthesia

• risk factor for rare primary thyroid lymphoma

Etiology and Pathophysiology • defect in a T-suppressor clone leads to cell - mediated destruction of thyroid follicles • B lymphocytes produce antibodies against thyroid components including thyroglobulin , thyroid peroxidase, TSH receptor, Nat / I symporter

-

Risk Factors • F:M=7:1

• genetic susceptibility: increased frequency in patients with Down's syndrome, Turner's syndrome, certain HLA alleles, cytotoxic T lymphocyte associatcd protein 1 ( CTLA 4 ) • family Hx or personal Hx of other autoimmune diseases • cigarette smoking • high iodine intake

-

-

-

-

Investigations • high TSH, low T4 ( not necessary to measure T3 as it will be low as well ) • presence of TPOAb and TgAb in serum Treatment

r »

-

• if hypothyroid, replace with L thyroxine ( analog of '1'4)

L J

Myxedema Coma Definition

-

+

.

• medical emergency severe hypothyroidism complicated by trauma , sepsis , cold exposure Ml, inadvertent administration of hypnotics or narcotics, and other stressful events • rare; high level of mortality ( up to 40%, despite therapy )

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Clinical Features

• decreased mental status and hypothermia are hallmark symptoms

• hyponatremia , hypotension , hypoglycemia , bradycardia, hypoventilation, and generalized non - pitting edema often present

Investigations

• decreased T4, increased TSH, decreased glucose • check ACTH and cortisol for evidence of adrenal insufficiency

Treatment

• aggressive and immediate treatment required • ABCs: 1CU admission • corticosteroids ( for risk of concomitant adrenal insufficiency ): hydrocortisone 100 mg q8 h • L thyroxine 0.2 0.5 mg IV loading dose, then 0.1 mg IV once daily until oral therapy tolerated: also consider T3 therapy • supportive measures: mechanical ventilation, vasopressors, passive rewarming, IV' dextrose, fluids if necessary ( risk of overload ) • monitor for arrhythmia

-

-

Non-Thyroidal Illness ( Sick Euthyroid Syndrome) Definition

• changes in the regulation of the hypothalamic-pituitarv-thyroid axis, and thyroid hormone metabolism and transport among patients with severe illness, trauma , surgery, or starvation • not due to intrinsic thyroid, pituitary, or hypothalamic disease • initially low free T3 may be followed by low TSH and, if severe illness, low free T4 • with recovery of illness, TSH may become transiently high Pathophysiology • abnormalities include alterations in:

peripheral transport and metabolism of thyroid hormone regulation of TSH secretion • may be protective during illness by reducing tissue catabolism Labs

• initially decreased free T3 followed by decreased TSH and Anally decreased free T4

• with recovery of illness, TSH may become elevated

Treatment

• treat the underlying disease; thyroid hormone replacement has not shown to be benefleial • thyroid function tests normalize once patient is well (initially with a transient increase in TSH ) Non-Toxic Goitre

Definition • generalized enlargement of the thyroid gland in a euthyroid individual that does not result from

inflammatory or neoplastic processes Pathophysiology

• the appearance of a goitre is more likely to present during adolescence, pregnancy, and lactation due to increased thyroid hormone requirements • early stages: goitre is usually diffuse • later stages: multinodular non-toxic goitre with nodule, cyst formation , and areas of ischemia, hemorrhage, and ftbrosis Etiology • iodine deftciency or excess • goitrogens: brassica vegetables (e.g. turnip, cassava ) • drugs: iodine, lithium, para aminosalicylic acid

-

• any disorder of hormone synthesis with compensatory growth • peripheral resistance to thyroid hormone Treatment • remove goitrogens

n LJ

• radioiodine therapy ( very high doses required given low iodine uptake, used as last resort in very highly selected cases where the goiter is causing symptoms and surgery is not feasible ) • suppression with L thyroxine ( rarely done ) • surgery may be necessary’ if severe compressive symptoms develop ( rare); patients are often asymptomatic

-

+

Complications • compression of neck structures causing stridor, dysphagia, pain, and hoarseness of voice • multinodular goitre may become autonomous leading to toxic multinodular goitre and hy'perthyroidism

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Thyroid Nodules Definition

• discrete lesion that can be distinguished sonographically from the rest of the thyroid parenchyma • 19-67% prevalence based on incidentally found nodules on U /S Etiology • benign tumours (e.g . follicular adenoma ) • thyroid malignancy

• hyperplastic area in a multinodular goitre • cyst: true thyroid cyst , area of cystic degeneration in a multinodular goitre Investigations

• approach to thyroid biopsy depending on U /S characteristics of the nodule • benign or very small nodules suspicious for thyroid cancer do not require ongoing surveillance • small nodules suspicious for thyroid cancer require up to five years of surveillance • larger nodules suspicious for thyroid cancer require biopsy Thyroid nodule on U/S

Third generation TSH

Normal/elevated TSH

LowTSH

-

Thyroid scan Hot nodule

No biopsy Treat hyperthyroidism

Cold nodule

-

U/S guided biopsy if indicated based on U/S characteristics

1

U/S guided biopsy it indicated based on U/S characteristics Treat hyperthyroidism

Figure 13. Approach to the evaluation of a thyroid nodule

.

Adapted from Of. J Goguen University of Toronto. MMMD 2013

Thyroid Malignancies • see Otolaryngology. OT 37

Adrenal Cortex Adrenocorticotropic Hormone

• a polypeptide ( cleaved from prohormone POMC ) , secreted in a pulsatile fashion from the anterior pituitary with diurnal variability ( peak: 0200 -0400 h; trough: 1800 - 2400 h ) • secretion regulated by CRH and AV'P • stimulates growth of adrenal cortex and release of glucocorticoids, adrenal androgens and , to a very limited extent, mineralocorticoids • ACTH can directly bind to MSH receptors on melanocytes, enhancing melanogenesis

Adrenocortical Hormones Aldosterone • a mineralocorticoid which regulates ECPV through Na '(and C1- ) retention and R ' (and H ’ ) excretion (stimulates distal tubule Na 1/ K+ ATPase) • regulated by the RA AS and hyperkalemia • negative feedback to juxtaglomerular apparatus (|GA ) by long loop (aldosterone volume expansion ) and short loop (angiotensin 111 peripheral vasoconstriction )

Tblood glucose, trauma, infection, emotion, circadian rhythm

i

-

CNS 4

i Hypothalamus a -

-

o

® A\ P

CRH

Q

!©

-

Pituitary 4 - -

i ACTH

—

i Adrenal gland

G

Cult

SL

ri

Figure 14. Regulation of CRH- ACTHadrenal gland axis

+

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Cholesterol

©

I©

©

Progesterone

© 17-hydroxylase © 3-Pdehydrogenase

* Pregnenolone

@ 21-hydroxylase

17-OH-pregnenolone

I®

I© - -

11- deoxycorticosterone

17 OH progesterone

I©

18-hydroxycorticosterone

(f) 17 -pdehydrogenase

1®

£) 5- areductase

(

I©

I®

(jP) 18-hydroxylase

@

Testosterone

|©

|©

Cortisol

Estradiol

OUTSIDE Zona Glomerulosa produces mineralocor tlcoids ( aldosterone)

(ff) Aromatase

Androstenedione

11-deoxycortisol

Corticosterone

(T) 11-hydroxylase

> DHEAS

Layers of the Adrenal Cortex

0 18-oxidase

(

’Most common enzyme defect Dihydrotestosterone

Zona Fasciculate produces glucocorticoids (cortisol) Zona Reticularis produces androgens IDHEA, androstenedione)

INSIDE

I© Aldosterone

Glucocorticoids

Mineralocorlicoids

(zona glomerulosa )

Sex Steroids

( zona fasciculata)

( zona reticularis )

Figure 15. Pathways of major steroid synthesis in the adrenal gland and their enzymes tvolume Tarterial pressure

iuolume iarterial pressure iNa delivery to macula densa Prostaglandins Sympathetic stimulation

Dopamine

Renal Na ' retention

l

I

Stimulation of JGA

i

Renin ( kidney ) Angiotensinogen

Inhibition of JG A

ACE (lung and kidney )

Angiotensin I

Angiotensin II (with negative feedback to inhibit JGA )

1

-

ACE angiotensin converting enzyme JGA - juxtaglomerulai apparatus

* Renal Na retention, K excretion

Aldosterone release Arteriolar vasoconstriction Promotion ol ADH release

Figure 16. Renin-angiotensin- aldosterone axis (see Nephrology, NP4)

Cortisol • a glucocorticoid regulated by the HPA axis • involved in metabolism regulation • supports blood pressure and vasomotor tone • also involved in behavioural regulation and immunosuppression Table 21. Physiological Effects of Glucocorticoids Stimulatory Effects

Inhibitory Effects

Stimulate hepatic glucose production (gluconcogencsis)

Inhibit bone formation; stimulate bone resorption

Increase insulin resistance in peripheral tissues

Inhibit fibroblasts, causing collagen andconnechve tissue loss

Increase protein catabolism

Suppress Inflammation; impair cell-mediated immunity

Stimulate leukocytosis and lymphopenia

Inhibit growth hormone axis*

Increase cardiac output,vascular tone Na ’retention

Inhibit reproductive axis’

Increase PIN release, mine calcium excretion

Inhibit vitamin (Hand inhibit calcium uplakc

.

'Typically only occurs with cortisol excess

Androgens • sex steroids regulated by ACT H; primarily responsible for adrenarche ( growth of axillary and pubic hair) • principal adrenal androgens are: DHEA , androstenedione, and l l hydroxyandroslenedione • proportion of total androgens (adrenal to gonadal ) increases with age

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£35 Endocrinology

Adrenocortical Functional Workup STIMULATION TEST

• purpose: diagnose hormone deficiencies • method: measure target hormone after stimulation with tropic ( pituitary ) hormone Tests of Glucocorticoid Reserve

• Cosyntropin (ACTH analogue) Stimulation Test administer 250 pg cosyntropin 1V /1M, and measure plasma cortisol levels before and 30 and 60 min after administration

«

physiologic response: stimulated plasma cortisol of > 500 nmol / L (>18 pg /dL) at 30 or 60 min physiologic response rate threshold may be lower with newer assays and should be confirmed with local lab inappropriate response: inability to stimulate increased plasma cortisol; peak cortisol levels below 500 nmol / L (18 pg/dL) at 30 or 60 min

SUPPRESSION TESTS

• purpose: diagnose of hormone hypersecretion • method: measure target hormone after suppression of its tropic ( pituitary ) hormone 1. Tests of Pituitary- Adrenal Suppressibility • DXM suppression test • principle: DXM suppresses pituitary ACTH, plasma cortisol should be lowered if HPA axis is normal • screening test: low dose overnight DXM suppression test oral administration of 1 mg DXM between 11 pm and midnight, then measure plasma cortisol levels the following day between 8 am and 9 am physiologic response: plasma cortisol 277 pmol / L is consistent with PA, 111 pmol/L (140 - 277 indeterminant range)

24 hour urine aldosterone

Not performed Not performed

Treatment • inhibit action of aldosterone: spironolactone, eplerenone, triamterene, amiloride ( act on sodium channels) • surgical excision of adrenal adenoma • secondary hyperaldosteronism : treat underlying cause

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E37 Endocrinology

Cushing’s Syndrome Definition • metabolic disorder caused by chronic glucocorticoid excess Etiology • ACTH dependent (85%) bilateral adrenal hyperplasia and cortisol hypersecretion due to: • ACTH-secreting pituitary' adenoma (Cushing’s disease; 80% of ACTH-dependent) • ectopic ACTH-secreting tumour (e.g. small cell lung carcinoma, bronchial, pancreatic islet cell, pheochromocytoma, or medullary thyroid tumour ) • ACTH independent (15%) • primary adrenocortical tumours: adenoma and carcinoma ( uncommon )

-

-

-

Red cheeks, acne,

Dorsalfatpad

moon face

$ :3

\

striae

0 steoporosis

infrequently reported; it is ACTH -independent

Clinical Features

-

• symptoms: weakness, insomnia , mood disorders, impaired cognition , easy bruising, oligo /

amenorrhea , hirsutism, and acne (ACTH dependent ) • signs: central obesity, round face ( “ moon face”), supraclavicular and dorsal fat pads, facial plethora, proximal muscle wasting, purple abdominal striae, skin atrophy, acanthosis nigricans, HTN , hyperglycemia, osteoporosis, pathologic fractures, hyperpigmentation , hyperandrogenism (if ACTH dependent )

Thin arms

and legs

*

,Poor wound„

* l

healing

I 0

r

Large 3 abdomen

bilateral adrenal nodular hyperplasia

• iatrogenic Cushing’s syndrome is likely more common than endogenous cortisol excess but is

Purple

| i

/•/ (Si* ?

L

Figure 18. Clinical features of Cushing’s syndrome

Diagnosis

• rule out excessive glucocorticoid exposure leading to iatrogenic Cushing's syndrome by conducting a thorough drug history before conducting biochemical testing • perform one of: 1) 24 h urine free cortisol ( >2 tests), 2) low dose DXM suppression test, or 3) late night salivary cortisol (S2 tests) • consider reasons for a false positive (e.g. pregnancy, depression, alcoholism, morbid obesity, poorly controlled DM, glucocorticoid resistance, physical stress, malnutrition, anorexia nervosa, intense chronic exercise, hy'pothalamic amenorrhea) • confirm with one of the remaining tests Treatment • adrenal

• adenoma : unilateral adrenalectomy ( curative) with glucocorticoid supplementation postoperatively, tapering slowly until HPA axis has recovered

carcinoma: adrenalectomy in patients with disease localized to the adrenal, adjunctive mitotane for individuals with high-risk for current disease Mitotane ± chemotherapy for patients with

metastatic disease medical treatment: ketoconazole to reduce cortisol, mitotane can be used typically reserved for patients with malignant disease

-

• pituitary' • transsphenoidal resection, with glucocorticoid supplementation postoperatively • if surgery delayed, contraindicated, or unsuccessful, consider medical management e.g.

ketoconazole, mitotane, pasireotide, or cabergoline • ectopic ACTH tumour ( paraneoplastic syndrome ): usually bronchogenic cancer ( poor prognosis) surgical resection, if possible; chemotherapy / radiation for primary tumour • medical treatment with mitotane or ketoconazole to reduce cortisol synthesis. Often required when surgery is delayed, contraindicated, or unsuccessful • treat comorbidities associated with hypercortisolism

Congenital Adrenal Hyperplasia • see Paediatrics. P35

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Hyperandrogenism Definition • state of having excessive secretion of androgens ( DHEA, DHEA-sulfate, testosterone) Etiology and Pathophysiology Table 23. Etiology of Hyperandrogenism Anabolic steroids ACIH androgens, progestational agents -

. .

Medications Androgen Mediated

PCOS Ovarian hyperthecosis theca cell tumours Pregnancy: placental sullatase/aromalase deficiency Congenital adrenal hyperplasia (CAH, late onsel CAN ) tumours ladenoma carcinoma)

Ovarian

Adrenal

.

-

-

Cushing's disease high AC1H Hyperprolactinemia

Pituitary

Clinical Features

Females

• hirsutism

male pattern growth of androgen -dependent terminal body hair in women: back, chest, upper

abdomen , face, linea alba

-

Eerriman Gallwey scoring system is used to quantify severity of hirsutism (score of >8 is abnormal for white/ black women, >9 abnormal for Mediterranean / Hispanic/ Middle-Eastern women, i 2 for Asian women ) scores should be interpreted in the context of the specific patient and acknowledge limitations such as the use of cosmetic hair removal scores between 8 15 are mild , 16 25 moderate, and >25 severe hirsutism

• virilization

-

-

Conditions that do Not Represent True Hirsutism • Androgen-independent hair (e.g. lanugo hair ) • Drug-induced hypertrichosis (e.g. phenytoin, diazoxide, cyclosporine, minoxidil) • Topical steroid use

frontal balding, ditoromegaly, increased muscle mass, deepening of the voice , breast size, infertility, anabolic appearance, acne amenorrhea • Males

• minimal effects on hair, muscle mass, etc.

• inhibition of gonadotropin secretion may cause reduction in testicular size, testicular testosterone production, and spermatogenesis Investigations

• testosterone, DHEA -S as a measure of adrenal androgen production • LH / I 'SH (commonly in PCOS >2.5) • 17-OH progesterone, elevated in CAH due to 21-OH deficiency; check on day 3 of menstrual cycle with a progesterone level • for virilization: CT/ MRI of adrenals and ovaries (identify tumours) • if PCOS, check blood glucose and lipids Treatment

• discontinue causative medications (e.g. oral DHEA, valproate, danazol )

• antiandrogens, e.g. spironolactone • oral contraceptives ( increase sex hormone binding globulin , which binds androgens> estrogens; reduces ovarian production of androgens) • surgical resection of tumour • glucocorticoid ± mineralocorticoid ifCAH confirmed • treat specific causative disorders, e.g. tumours, Cushing's, etc. • cosmetic therapy ( laser, electrolysis)

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Adrenocortical Insufficiency Definition

• state of inadequate cortisol and /or aldosterone production by the adrenal glands Etiology PRIMARY ADRENOCORTICAL INSUFFICIENCY

Table 24. Etiology of Primary Adrenocortical Insufficiency Autoimmune ( 70 90% ) Isolated adrenal insulliciency (Addison 's Disease)

-

Polyqlandular autoimmune syndromes types I and II Antibodies often directed against adienal cniymcs and 3 cortical cones

tuberculosis ( 7 20 % ) ( most common in developing world ) fungal : histoplasmosis, paracoccidioidomycosis HIV CMV Syphilis Alncan trypanosomiasis

Inlections

.

Infiltrative

Metastatic cancer|lung > slomach > csophagus >coion > brcast ): lymphoma Sarcoidosis, amyloidosis, hemochromatosis

Vascular

Dilateral adienal hemorrhage ( risk increased by heparin and warfarin ) Sepsis ( meningococcal. Pseudomonas) Coagulopathy in adults or Walethouse f riderichsen syndrome in children Ihiombosis embolism , adrenal infarction Inhibit cortisol: kcloconarole etomidatc megestrol acetate Increase cortisol metabolism: rifampin , phenylpin barbiturates Adrenoteukodystrophy and adrenomyeloneuiopathy Congenital adrenal hypoplasia (impaired steroidogenesis) familial glucocorticoid deficiency oi resistance Defective cholesterol metabolism

.

Drugs

Others

.

.

.

SECONDARY ADRENOCORTICAL INSUFFICIENCY

• inadequate pituitary ACTH secretion • multiple etiologies (see Hypopituitarism , t 23 ), including withdrawal of exogenous steroids Clinical Features Table 25. Clinical Features of Primary and Secondary Adrenal Insufficiency ( Al) Primary Al (Addison's or Acute Al )

Secondary Al

Skin and Mucosa

Dark (palmar crease, extensor surface)

Pale

Potassium

High

Normal

Sodium

Normal or low

Normal or Low

Absent

Metabolic Acidosis

Present

Associated Diseases

Primary hypothyroidism. T1DM vitiligo

Central hypogonadism or hypothyroidism , growth hormone deficiency, Dl

Associated Symptoms

Weakness, fatigue, weight loss, hypotension , salt craving , postural dizziness, myalgia , arthralgia Gl: N /V abdominal pain , diarrhea

Weakness , fatigue, weight loss, hypotension , postural dizziness, myalgia , arthralgia , headaches, visual abnormalities

Diagnostic Test

Cosyntropin Stimulation Test Nigh morning plasma ACTH High renin

Insulin tolerance test Cosyntropin Stimulation Test low or inappropriately normal morning plasma ACTH

.

.

-

Adapted from: Salvatori R. JAMA 2005494:2481 2488

Treatment

-

-

• acute adrenal crisis can be life threatening IV NS 1 L within the first hour followed by continuous IV NS guided by patient requirements; add D5W if hypoglycemic • hydrocortisone 100 mg IV stat followed by 50 mg IV q 6 h • identify and correct precipitating factors • maintenance • hydrocortisone 15 25 mg PO or cortisone acetate 20 35 mg PI ) total daily dose in 2 3 divided doses, highest dose in the morning prednisolone 3 5 mg once daily or 3 5 mg BID can be used as an alternative to hydrocortisone , • especially in patients with reduced compliance • Plorinef * ( fludrocortisone, synthetic mineralocorticoid ) 0.05 0.2 mg PO once daily if mincralocorticoid deficient • stress dosing increase dose of steroids 2 3 fold for a few days during moderate severe illness ( e.g. with vomiting, fever) • major stress (e.g. surgery, trauma ) requires 150 - 300 mg hydrocortisone IV daily divided into 3 doses • medical alert bracelet and instructions for emergency hydrocortisone /dexamethasone IM /SC

-

-

-

-

-

-

-

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Adrenal Medulla Catecholamine Metabolism • catecholamines are synthesized from tyrosine in postganglionic sympathetic nerves ( norepinephrine ) and chromaffin cells of adrenal medulla (epinephrine) • broken down into metanephrines and other metabolites ( VMA, HVA ) and excreted in urine

ABC of Adrenaline Adrenaline activates g - receptors. increasing Cyclic AMP

Pheochromocytoma /Paraganglioma Definition • paragangliomas are rare neuroendocrine tumours that arise from the extra-adrenal autonomic paraganglia (small organs comprised of neuroendocrine cells that secrete catecholamines) • pheochromocytomas are catecholamine-secreting tumours derived from chromaffin cells of the

adrenal gland

Epidemiology most commonly a single tumour of adrenal medulla • rare cause of HTN ( laboratory cutoffs may not always be used

.

activity

V

-

Total Ca2 does not reflect ionized Ca 2 in the following circumstances: • Abnormal albumin levels • Critical illness • Chronic hepatic failure/renal failure When albumin is low, ionized calcium assessment should be performed

* GLAND 4 PARATHYROID

Cholecalcilerol

2

-

i n

tECFCa TECF Calcitriol IECFP02

©

The symptoms and signs of hypercalcemia include: “Bones, stones, groans, and psychiatric overtones”

Figure 19. Parathyroid hormone (PTH) regulation

Hypercalcemia Definition

• total corrected serum ( .'a i * > 2.6 nimol / L OR ionized (.'a 2 * > l .35 nimol / L High Ca 1-

*

Initial investigations: PTH

;

r

i PTH

i

4 Ported to PTHrP I Humoral mediation: Lung cancer. RCC. pheochromocytoma T

1

1 Normal or ROx*I

)

1

r Calcidiol

-

Normal or t PTH

( 25 OH vitamin D )

l

Hypervitaminosis D:

Excessive intake ol vitamin D or its metabolites

T

Vitamin D related

i

t Calcitriol l1,25 ( 0H) ivitamin D )

-

i

Granulomatous disease: eg. tuberculosis, sarcoid, lymphoma ( esp. Hodgkin) which causes extra renal production of calcitriol by macrophages in the lung and lymph nodes Excessive calcitriol intake

-

1 Drugs: Lithium

i

Familial Hypocalcluric Hypercalcemia ( FHH): CaJ‘ receptor gene defect

Primary Hyperparathyroidism: Tertiary Hyperparathyroidism: Solitary adenoma (81% ) Increased PTH after Hyperplasia (15%) prolonged secondary hyperparathyroidism Carcinoma (4% ) due to renal failure MEN 1 and 2a

I

Low vitamin D metabolites

1

Immobilization Malignancy High bone turnover: e.g. hypervitaminosis A, thyrotoxicosis Paget’s disease

.

Milk alkali syndrome: (hypercalcemia, metabolic alkalosis, and renal insufficiency) Drugs: theophylline, thiazide diuretics, estrogen/tamoxifen

r

-

i

LJ

Figure 20. Differential diagnosis of hypercalcemia

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Approach to Hypercalcemia 1. is the patient hypercalcemic? 2. is the PTH high / normal or low? 3. if PTH is low, is phosphate high / normal or low ? 4. if phosphate is high / normal, is the level of vitamin D metabolites high or low? Clinical Features • symptoms depend on the absolute Ca - Value and the rate of its rise ( may be asymptomatic)

Table 28. Symptoms of Hypercalcemia Cardiovascular

Gl

Renal

Rheumatological MSK

Psychiatric

Neurologic

KIN

Constipation Anorexia Nausea Vomiting ( groans) PUD Pancreatitis

Polyuria (Nephrogenic Dl) Polydipsia Nephrolithiasis (stones) Renal failure (irreversible) Dehydration

Goul Pseudogoul Chondrocalcinosis

>3 mmol / L (12 mgfdL)

Hypotonia Hyporeflexia Myopathy Paresis

Arrhythmia

Short 01 Deposition ol Ca ton valves coronary arteries myocardial fibres

.

.

Weakness Bone pain ( bones)

Increased alertness Anxiety Depression Cognitive dysfunction Organic brain syndromes >4 mmol / L|16 mg/dl) Psychosis ( moans)

* ' Hypercalcemic crisis (usually >4 mmol/L or 16 mg / dl): primary symptoms include oliguria /anuria and mental status changes including somnolence and eventually coma * this is a medical emergency and should be treated immediately!

Treatment

• 3.5 mmol / L: severe hypercalcemia requiring urgent correction due to risk of dysrhythmia and coma • aggressive treatment of acute symptomatic hypercalcemia • next treat the underlying cause • mild asymptomatic hypercalcemia: monitor and avoid thiazide, volume depletion, high Ca 'diet, lithium , and bed rest

-

Table 29. Treatment of Acute Hypercalcemia /Hypercalcemic Crisis

.-

.

Increase Urinary Ca 1ictetion

*

FLUIDS FLUIDS FLUIDS! Isotonic saline (4 6 L ) over 24 hr loop diuretic (e.g. furosernide) but only il hypervolemic (urine output >200 ml/h) Calcitonin: 4 lU/ kg IM ' SC q12 h 8 lU/kg IM /SC q6 h Only works lor 48 h can develop tachyphylaxis Rapid onset within 4 - 6 h Before prescribing calcitonin, rein ember loask about lish allergies

.

.

Diminish Bone Resorption

Blsphosphonates (healincnl olchoice) Suggest zolcdionic acid 4 mg IV ovci 15 min or pairudronatc 60 90 nig IV over 2 h Inhibits osteoclastic bone resorption, pi eventing calcium release horn bone Effects on calcium levels aie typically seen at 24 - 48 li alter administration Calcitonin often given in conjunction with bisphosphonale given rapid onset of effect Indicated in malignancy - related hypercalcemia |IV pamldronatc or aoledronlc acid used) II bisphosphonales are contraindicated (i e severe renal impairment), donosumab can be administered concurrently with calcitonin

.

..

Coilicostcioids can be used in hypercalcemia mediated by 1,25 vitamin D. Corticosteroids are polenl inhibitors ol la hydroxylase and therefore, decrease calcitriol production by activated mononuclear cells (e.g in lymphoma, granuloma ) Effects will be seen in 2 5 d

Oecrease Gl Ca ^'Absorption

.

-

Treatment of last resort Indication: severe malignancy - associated hypercalcemia and renal insufficiency or heart failure

Dialysis

The most common cause of hypercalcemia in hospital is malignancy -associated hypercalcemia • Usually occurs In the later stages of disease • Most commonly seen in lung, renal, breast, ovarian, and squamous tumours, as well as lymphoma and multiple myeloma Mechanisms: • Secretion of PTHrP which mimics PTH action by preventing renal calcium excretion and activating osteoclastinduced bone resorption • Cytokines in multiple myeloma • Calcitriol production by lymphoma • Osteolytic bone metastases direct effect • Excess PTH in parathyroid cancer

Before prescribing calcitonin, remember to ask about fish allergies

Differential Diagnosis of Hypercalcemia • Primary hyperparathyroidism • Malignancy: hematologic, humoral, skeletal metastases (>90% from 1 or 2) • Renal disease: tertiary hyperparathyroidism • Drugs: calcium carbonate, milk alkali syndrome, thiazide, lithium, theophylline, vitamin A/D intoxication • Familial hypocakiutic hypcrcakemia • Granulomatous disease: sarcoidosis, tuberculosis, Hodgkin's lymphoma • Thyroid disease: thyrotoxicosis • Adrenal disease: adrenal insufficiency, phcochtomocyloma • Immobilization

Acute Management of Hypercalcemia/ Hypercalcemic Crisis Volume expansion (e.g. NS IV 300500 cc/h): initial therapy • Calcitonin (SC): transient, partial response • Bisphosphonale (IV): treatment of choice, adjust dose if CrCi 7.5 mg of prednisone daily for over 3 mo should be assessed for bone - sparing therapy Mechanism: increased resorption decreased formation + increased urinary calcium loss + decreased intestinal calcium absorption + decreased sex steroid production

Calcium plus Vitamin D Supplementation and Sisk of Fractures 0 steoporosis lot 2015:27:367 -376 Purpose: fo review trials of vitan n D and iikum therapy lor reduung fracture risk in osteoporosis. Study Systematic review searching Mil 2015. mlutine, identified 8 ICIs totaling 30970 participants. SCIs reviewed included healthy adults and ambulatory older adults with medical conditions (excluding cancer). Vitem in D and cakun combination therapy was compared to placebo. Results: Analysis of SCI data revealed that calcium plus vitamin 0 supplementation produced a statistically significant reduction in risk of total fractures (0.85; Cl:0.73-0.98|and in hipfractures (0.70; CL0.56 -0.87). Subgroup analysis was significant for community dwellingoriisfitutioiialized patients.

Conclusions: Systematic analysis suggests that vitamin D and calcium therapy significantly decreases fracture nsk. This study did not specifically look at individuals with osteoporosis, however, d sidl supports that vitamin 0 and calcium should continue to be used as prevenbve treatment for indmduaS at increased riskof fractures.

Dm Hypogonadism Malignancy Secondary to chemotherapy Myelomaseverc: carpopaedal spasm, laiyngospasm focal / generalized seizures

.

Clinical Features

• commonly asymptomatic

• height loss due to col lapsed vertebrae • fractures: most commonly in hip, vertebrae, humerus , and wrist (see Figure 22 , E48 ) fragility fractures: fracture with fall from standing height or less ( does not include fractures of lingers and toes) • Dowager’s hump: collapse fracture of vertebral bodies in mid - dorsal region • x- ray: vertebral compression fractures ( described as wedge fractures, require a minimum of 20% height loss ), “codfishing” sign ( weakening of subchondral plates and expansion of intervertebral discs) • pain, especially backache, associated with fractures Approach to Osteoporosis 1 . assess risk factors for osteoporosis on Hx and physical 2. decide if patient requires BMD testing with dual-energy x - ray absorptiometry ( DEXA ): men and women 265 yr (or younger if presence of risk factors, see Tabic 33, E47 )

3. initial investigations • all patients with osteoporosis: calcium corrected for albumin , CBC, creatinine, ALP, TSH • also consider serum and urine protein electrophoresis if vertebral fractures, celiac workup, and 24 h urinary Ca •'excretion to rule out additional secondary causes • 25 OH - vitamin D level should only be measured after 3 4 mo of adequate supplementation and should not be repeated if an optimal level 275 nmol / L is achieved lateral thoracic and lumbar x - ray if clinical evidence of vertebral fracture ( or in individuals at moderate risk of fracture to help decide if they require medical therapy ) 4. assess 10 yr fracture risk by combining BMD result and risk factors 1) WHO Fracture Risk Assessment Tool ( ERAX) 2) Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment Tool (CAROC ) approach to management guided by 10 yr risk stratification into low, medium, and high - risk 5. for all patients being assessed for osteoporosis, encourage appropriate lifestyle changes (see Table 34 , E47)

-

Vitamin D and Calcium for tbc Prtvtntioa »1 Fracture: ASystcmatic Reviewand Meta analysis J AM It Netw Open 2019: 2 x1917789 Purpose: To investigate if fracture r s < s associated with supplementation with vitamin D alone or vitamin Din combination with calcium. Study Selection: Observational studies with >200 fracture cases and RCTs with >500 participants that reported >10 incident fractures. Results: Vitamin D suppleraentaton alone wasnot associated with a reduced risk of any fracture « hip fracture ( RR, 1.14: 95% Cl.0.98 -1.32). Howerer. combined supplementation with vitamin 0 (400-800 IU daily) and calcium (1000 -1200 mg daily ) was associated with a G % reduction in fracture risk ( RR. 0.94; 95% Cl 0.89 - 0.991 and a IS% reduction of hip fratlure nsk|RR 0.84; 95% Cl, 0.72 0.971. Conclusion VitannDalonewasnotassociatedwdh reduced fracture risk but dally supplementation with a tom bma bon of vitamin 0 and cakium was.

-

.

.

-

-

Clinical Signs of Fractures or Osteoporosis • Height loss >3 cm (Sn 92%) Weight 4 cm (Sp 92%) Rib- pelvis distance 50 yr) All women and men age >65 yr Menopausal women, and men 50- 64 yr with clinical risk factors for fracture: Fragility fracture after age 40 Prolonged glucocorticoid use Other high-risk medication use (aromatase inhibitors, androgen deprivation therapy) Parental hip fracture Vertebral fracture or osteopenia identified on x -ray Current smoking High alcoholintake Low body weight ( 60 kg) or major weight loss (>10% ol weight at age 2 Syr ) Rheumatoid arthritis Other disorders strongly associated with osteoporosis: primary hyperparathyroidism,I10M osteogenesis imperfecta, uncontrolled hyperthyroidism, hypogonadism or premature menopause MS yr ) Cushing's disease, chronic malnutrition or malabsovplion chronic liver disease COPD and chronic inflammatory conditions (c g. inflammatory bowel disease )

-

Younger Adults ( age -, P I H , AI.P, ± imaging ( x ray, BMD ), ± bone biopsy ( gold standard ; only done if results inform treatment )

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Treatment

• prevention

• maintenance of normal serum Ca -’and P04 -*-by restricting P04 Hntake to 1 g once daily • Ca Supplements; PO4 -' binding agents (calcium carbonate, aluminum hydroxide ) • activated vitamin D (calcitriol ) with close monitoring to avoid hypercalcemia and metastatic

calcification

• bisphosphonates and denosumab are not often used for treatment (can worsen the adynamic components of renal osteodystrophy); bone biopsy may indicate if there are signs of increased bone turnover amenable to bisphosphonates

Paget ’s Disease of Bone Definition

• a metabolic disease characterized by excessive bone destruction and repair Epidemiology

• 3% of the population , 10% of population >80 y /0

• consider Paget's disease of bone in older adults with elevated ALP but normal GGT Etiology and Pathophysiology • postulated to be related to a slowly progressing viral infection of osteoclasts, possibly paramyxovirus • strong familial incidence • initiated by increased osteoclastic activity leading to increased bone resorption; osteoblastic activity increases in response to produce new bone that is structurally abnormal and fragile Differential Diagnosis

• osteogenic sarcoma • multiple myeloma • fibrous dysplasia • osteitis fibrosa cystica • metastases Clinical Features • usually asymptomatic ( routine x-ray finding or elevated serum ALP with normal LPTs) • 3 characteristic findings: osteolytic lesions, cortical thickening, pseudofractures (small fissures which develop in the convex surface of long bone) • most commonly affects: skull, thoracolumbar spine, pelvis, and long bones of lower extremities • severe bone pain (e.g. pelvis, femur, tibia ) • skeletal deformities: bowed tibias, kyphosis, frequent fractures • increased risk of osteosarcoma and giant cell tumours

Investigations • laboratory

high serum ALP, normal or high Ca -+ , normal PO43 normal tests LFTs (prothrombin time/ international normalized ratio ( PT/1NR ), activated partial thromboplastin time (aPTT ), albumin, bilirubin) elevated procollagen type 1 N - terminal propeptide ( PINP) (bone formation marker ) • imaging plain x ray of skull and facial bones, abdomen , and tibiae are recommended as initial screening in patients suspected to have Paget's confirmation on x ray required for diagnosis denser bone with cortical thickening characteristic findings: osteolytic lesions, cortical thickening, and pseudofractures burned out Paget’s disease: when the disease has been present for a long time • bone scan to evaluate the extent of disease and identify asymptomatic sites radionuclide bone scintigraphy, in addition to targeted x- ray, are recommended as a means of fully and accurately defining the extent of metabolically active Paget’s disease • MKI or CT are not recommended for diagnosis, but can be used to assess disease complications, particularly if malignancy is suspected "

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Table 37. Paget's Disease- Related Signs Signs Tamo'Shanter

Descriptions

Blade of grass

Lucent leading edge in a long bone seen in lytic phase of Paget 's Radiolucent regions of the skull

-

Appearance ol advanced Paget's disease of the skull overall enlargement of cranium, skull falling overthe facial bones

Osteoporosis circumscripta Jigsaw pattern bone or mosaic pattern bone

Banana fracture Looser zones

Thickened , disorganized trabeculae lead to areas of sclerosis Cories of vertebral body Is thickened Results from thickened , disorganized trabeculae that lead toareas of sclerosis Horizontal pathological fracture seen in bones deformed by Paget's Wide, transverse lucencies traversing through a bone

Ivory vertebra

Diffuse and homogenous increase in opacity ol a vertebral body

Picture frame vertebra Colton wool appearance of bone

Complications

• local fractures; osteoarthritis cranial nerve compression and palsies (e.g. deafness), spinal cord compression osteosarcoma /sarcomatous change in 1 3% * indicated by marked bone pain , new lytic lesions, and suddenly increased ALP • systemic hypercalcemia and nephrolithiasis high output CHE due to increased vascularity

-

Treatment

• goals; decrease pain , decrease rate of remodelling • weight bearing exercise

-

• adequate calcium and vitamin D intake to prevent development of secondary hyperparathyroidism • treat medically if symptomatic or asymptomatic with ALP >3x normal or planned surgery bisphosphonates, e.g. zoledronic acid 5 mg IV per yr (preferred ) OR alendronate 40 mg PO once daily x 6 mo OR risedronate 30 mg PO once daily x 3 mo calcitonin 50 100 U /d SC if unable to tolerate bisphosphonates • surgery for fractures, deformity, degenerative changes • joint replacement surgery and osteotomy are recommended for the treatment of osteoarthritis resistant to medical therapy in patients with Paget 's

-

Male Reproductive Endocrinology Androgen Regulation • testosterone ( from Leydig cells) primarily involved in negative feedback on LH and GnRH, whereas inhibin ( from Sertoli cells) suppresses ESH secretion

GnRH -4 | Pulses

Hypothalamus

Tests of Testicular Function • testicular size ( lower limit = 4 cm x 2.5 cm in adult ). Can use orchidometer to measure testicular volume ( 12 25 mL adult size) LH • , ESH , total, bioavailable, and /or free testosterone

-

Anterior ® Pituitary ,

=

• semen analysis

semen volume, sperm concentration , morphology, and motility are the most commonly used parameters • testicular biopsy' indicated with normal ESH and azoospermia /oligospermia

Hypogonadism and Infertility

^FSH

LH

®-

-

;

® *- -!

Inhibin Testes

tI

® v

Sertoli Cell

t

Leydig Cell

i

—Testosterone

1

Figure 23. Hypothalamo-pituitarygonadal axis

• see Uroloev, U37 • deficiency in gametogenesis or testosterone production Etiology

• causes include primary ( testicular failure), secondary ( hypothalamic- pituitary failure), and idiopathic Diagnosis of Testosterone Deficiency Syndrome (i.e. adult onset primary hypogonadism)

• requires clinical manifestations of testosterone deficiency (see sidebar) AN D documented testosterone levels below the laboratory reference range (confirmed on 2 separate analyses, test needs to be done at 8 9 am when testosterone is usually at its peak ) • rule out secondary causes

Two Distinct Features of Primary Hypogonadism • The decrease in sperm count is affected to a greater extent than the decrease in serum testosterone level Likely to be associated with gynecomastia

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E52 Endocrinology

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History and Physical Examination Ascertain symptoms and signs ol testosterone ( T) deficiency Evaluate for systemic illness, drugs, nutritional deficiency that could lower T

Measure morning lasting total T ( and free T if altered SHBG or borderline total T)

Semen analysis il fertility issue Low total T or Normal or low total T and lowIreeT

.

'r

Confirm by repeating morning lasting total T ( and Iree T)

Normal total T or Normal or low total T and normal Iree T

Low total T or Normal or low total T and low Iree T t

Oiagnosis ol hypogonadism is

r

Consider other causes ol symptoms and signs

confirmed \

Measure LH and FSH

LH and FSH

I

'r

.

* Obtain ka ryotype to

reversible functional causes • Measure prolactin, iron saturation • Evaluate other pituitary hormones (if clinically indicated) • Pituitary MRI (if indicated)

diagnose Klinefelter syndrome (if clinical indication)

.

.

.

Table 38. Classification and Features of Hypogonadism Hypergonadotropic Hypogonadism (Primary Hypogonadism)

Hypogonadotropic Hypogonadism (Secondary Hypogonadism)

Definition

Primary testicular failure t LH and FSH a testosterone and sperm count

Hypothalamic -pituitary axis failure a LH and FSH ( LH sometimes inappropriately normal) a testosterone and sperm count

Etiology

Congenital Chromosomal delects (Klinefelter Noonan) Cryptorchidism Disorders of sexual development (DSD) Bilateral anorchia (vanishing testicle syndrome) Myotonic dystrophy Mutation of FSH or LH receptor gene Disorders of androgen synthesis Germ cell defects Sertoli cell only syndrome leydigcellaplasia / failurc Infection,'Inflammation Orchitis tuberculosis, lymphoma, mumps, leprosy Genilal tract inlection Physical laclors Trauma, heat,irradiation, testicular torsion, vancocelc Drugs Cannabis, alcohol, chemotherapy, ketoconazole glucocorticoid, spironolactone

Congenital Kallman’s syndrome Prader - Willi syndrome Abnormal subunit of LH or FSH Infection Tuberculosis, meningitis Endocrine Adrenal androgen excess Cushing's syndrome Hypo or hyperthyroidism Hypothalamic pituitary disease Itumour hyperprolactinemia, hypopituitarism ) Drugs Alcohol, cannabis, spironolactone, ketoconazole GnftH agonists, androgen / estrogen/progestin use chronic narcotic use Chronic Illness Cirrhosis, chronic renal failure, AIDS Sarcoidosis Langcrhan 's cell histiocytosis, hemochromatosis Critical Illness Surgery Ml head trauma Obesity Idiopathic

Testicular size and consistency (soll/lirm)

Testicular size and consistency (soll/ lirm) Sperm count LH FSH total, and/or bioavatlable testosterone Prolactin levels (and pituilary panel T 4 / 8 AM cortisol) Fe transferrin Mill of hypothalamic - pituitary region

.

-

.

Sperm count LH FSH, total, and/or bioavailable testosterone hCG stimulation (mainly used in paediatrics ) Karyotype

.

. .

Treatment • No specific therapy for majority of cases Treat specific causes • Consider intrauterine insemination, in vitro fertilization (IVF) therapeutic donor insemination, testicular aspiration of sperm, adoption

Figure 24. Diagnostic approach to testosterone deficiency

Diagnosis

.

.

high (primary hypogonadism )

• Consider potentially

.

.

1

LHand FSH low or inappropriately normal ( secondary hypogonadism)

Approach to Male Infertility Infertility: failure of a couple to conceive after 12 mo of regular intercourse without use of contraception in women

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Treatment

• goal: testosterone replacement ( improve libido, muscle mass, strength , body hair growth, bone mass )

• 1M injection, transdermal testosterone patch /gel, oral

side effects: acne, fluid retention, erythrocytosis, sleep apnea, benign prostatic hypertrophy, uncertain effects on cardiac events/ mortality in older men contraindicated in men with prostate or breast cancer, a palpable prostate nodule, prostate specific antigen (PSA) >4 ng / mL, elevated hematocrit, untreated severe obstructive sleep apnea (OSA), severe lower urinary tract symptoms (LUTS), uncontrolled CHE, Ml, or stroke in last 6 mo, or thrombophilia not suggested in men >65 yr, in men with T2 DM with low testosterone concentrations, or in men planning fertility in the near term testosterone therapy only to treat symptoms of hypogonadism , often results in decreased spermatogenesis ( and reduced sperm counts) by further suppression of hypothalamic pituitary gonadal axis and suppression of endogenous testosterone production • goal: fertility treat underlying cause GnRH agonist if hypothalamic dysfunction with intact pituitary, administered SC in pulsatile fashion using an external pump hCG ± recombinant follicle stimulating hormone (rl:SH ) in cases of either hypothalamic or pituitary lesions dopamine agonist (e.g. bromocriptine, cabergoline) if prolactinoma testicular sperm extraction (TESE) or microscopic sperm extraction (MICROTESE) - only if testicular tissues are not functioning

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-

Other Causes of Male Infertility

• hereditary disorders: kartagener syndrome ( primary ciliary dyskinesia ), cystic fibrosis (absence of the vas deferens) • anatomy: hypospadias, retrograde ejaculation • obstruction: vasal occlusion , vasal aplasia, vasectomy, seminal vesicle disease • sexual dysfunction: erectile dysfunction , premature ejaculation , infrequent coitus • surgery: transurethral resection of the prostate (TURF), radical prostatectomy, orchiectomy DEFECTS IN ANDROGEN ACTION

Etiology • complete androgen insensitivity ( CAIS) • partial androgen insensitivity ( FA1S ) • 5 a reductase deficiency

--

• mixed gonadal dysgenesis • defects in testosterone synthesis

• infertile male syndrome • undervirilized fertile male syndrome Clinical Features • depends on age of onset Table 39. Effects of Testosterone Deficiency First Trimester in utero

Incomplete virilization of external genitalia (ambiguous genitalia ) Incomplete development of Wolffian ducts to form male internal genitalia (male pseudohermaphrodism)

Third Trimester /n utero

Micropenis

Prepuberty

Cryptorchidism (failure of normal testicular descent) Incomplete pubertal maturation (high pilch voice, sparse pubic axillary hair , absence of facial hair ) Eunuchoidal body habilus (greater growth of extremity long bones relative to axial bones) Poor muscle development , reduced peak bone mass

Postpuborty

Oecrease in energy, mood , and libido fine wrinkles in corners of moulh and eyes Decrease in pubic /axillary hair, hematocrit , muscle mass, strength , and BMD

Adapted from: UpToDote. 2010: Cecil’s Essentials ol Medicine

Treatment

• hormone replacement or supplementation • psychological support • gonadectomy for cryptorchidism (due to increased risk for testicular cancer)

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Erectile Dysfunction • see U rolottv. U 33

Gynecomastia Definition • true gynecomastia refers to benign proliferation of the glandular component of the male breast , resulting in the formation of a concentric , rubbery, firm mass extending from the nipple(s) • pseudogynecomastia or lipomastia refers to enlargement of soft adipose tissue, especially seen in obese individuals Etiology

Pubertal Gynecomastia This benign condition peaks between ages 13 14 and spontaneously regresses in 90% of cases within 2 yr • Waiting is often the best approach

-

210 mg SC qMonthr 12 mo

Hot flashes Leg cramps Increased risk of fatal stroke, venous thromboembolism Fatigue/headache / Gl injection site reaction Hypocalcemia Atypical femur fractures Osteonecrosis of the jaw

Treatment for postmenopausal women with osteoporosis who are at high risk for fracture Treatmentfor men with primary or hypogonadal osteoporosis who are at high- risk lor fracture Also approved lor glucocorticoid- induced osteoporosis

Paget's disease Orthostatic Prior external beam hypotension or implant radiation Hypercalcemia therapy involving the Dizziness skeleton Leg cramps Bone metastases Metabolicbone diseases other than osteoporosis

Osteopenia Osteoporosis Prevention ol metabolic bone disease

Caution with renal stones

-

1200 mg/ d (including

(MSK) pain Headache Osteonecrosis of the jaw Atypical femur fractures

ol postmenopausal

postmenopausal women at high-risk of fracture Prevent skeletal-related events in patients with

Inhibits PIH secretion

Binds to and inhibits sclerostin (inhibitor ofWnt P'Catcnin pathway) * increased bone lormalion and reduced bone

Contraindications

5 mg IV once yearly 5 mg IV

(osteoclast differentiating factor) inhibits osteoclast formation and decreases bone resorption

Stimulates new bone formation by preferential stimulation of osteoblastic activity over osteoclastic activity

Indications

Treatment of osteoporosis Hypocalcemia Hypersensitivity in postmenopausal women at high risk for fracture (defined as history of osteoporotic fracture or multiple risk factors for fracture)

Vomiting Constipation Dry mouth Headache, joint pain, pain at

injection site May increase risk ofMI 'stroke /CV death Osteonecrosis of jaw Atypical femur

rt L J

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Metabolic Bone Disease Medications Drug Class

Mechanism of Action

Generic Drug Name

Vitamin D

Regulation of calcium and

cholecalciferol (vitamin Or)

Canada Name

US Name (if different)

phosphate homeostasis

ergocalciferol (vitamin Or)

catcitriol ( 1.25|0 H ); D|

Drisdol ! Erdol 5

Dosing

Indications

Contraindications

Side Effects

800 2000 IU d (higher doses required in Insufficiency ot deficiency)

Osteopenia Osteoporosis Prevention of metabolic bone disease

Caution in patients on digoxin (risk of hypercalcemia which may precipitate arrhythmia )

Hypercalcemia Headache HIV Constipation

50000 IU/wk

Osteoporosis in patients with liver dysfunction, refractory rickets, hypoparathyroidism

Hypercalcemia

Hypocalcemia and Start 0.25 pgfd Titrate up by 0.25 yrg /d osteodystrophy in patients with chronic at 4 - 8 vrk intervals to 0.5-1 pgfd renal failure on dialysis

Rocaltrol '

Calcijex -

Malabsorption syndrome

Decreased renal

function

Hypercalcemia

Vitamin 0 toxicity

Hypoparathyroidism

Start 0.25 pg/d Titrate up by 0.25 pg/d at 2 - 4 wk intervals to 0.5 - 2 pgfd

Adrenal Medications Drug Class

Mineralocorticoid Activity

Hydrocortisone

Yes

Generic Drug Nome

Potency Relative to Cortisol

Equivalent Dose (mg )

Duration of Action (1112 in h)

Dosing

Comments

cortef

1.0

20

8

Adrenal Crisis: 50-100 mg IV bolus, then 50 -100 mg q8 h (continuousinfusion x 24 - 48 h) P0 once stable ( 50 mg q8 h x 48 h then taper over 14 d) Chronic Al: 15 - 20 mg PO 8I0 110 (2 / 3 AM 1/ 3 PM )

In high doses, mineralocorticoid side effects may emerge (salt water retention, ECF volume expansion HIH low K metabolic alkalosis)

Adrenal Crisis:75 -3 00 mg / d PO /IM divided q12-24 h Chronic Al: 25 mg/ d divided 8I0 -TID

Pro - drug which is converted to active form as hydrocortisone High doses can result in mineralocorticoid side effects (see above)

Chronic: 0.1 mg daily

Replaces aldosterone in primary adrenal insufficiency

Pro - drug which is converted to active form as prednisolone

solu- Cortef

.

. .

-

.

Cortisone Acetate

Yes

cortisone acetate

0.8

25

oral - 8 IM - 18*

Mineralocorticoid Fludrocortisone

100%

Prednisone

Yes

prednisone

4

5

16 36

Adrenal Crisis: 15- 60 mg/d P 0 once daily or divided BID. 0ID Chrome Al: 5 mg daily

Dexamethasone

No

dexamethasone

30

0.75

36 - 54

Adrenal Crisis: 4 mg IV: repeat q2- 6 hil necessary

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E62 Endocrinology

Landmark Endocrinology Trials Trial Name

Clinical Trial Details

Reference

DIABETES GLP -1 Agonists

LEADER

-

NEJM 2016:375:311 22

Title: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes Purpose: To investigate the cardiovascular effects ol liraglutrde |GIP1 analogue) when added to standard care in palienls with T 20M. Methods: 9340 patients with T 2DM athigh cardiovascular risk were randomly assigned to receive liraglutide or placebo. Results: The primary outcome ( first occurrence of death from cardiovascular causes, nonfatal Ml. or nonlatal stroke) wasobserved in significantly less palienls on liraglutide (13.0%) than placebo (14.9%) (hazard ratio, 0.87:95% confidence interval. 0.78 -0.97; P 50 years old with previous CVD or cardiovascular risk factors were randomly assigned to receive dulaglulide (1.5 mg weekly ) or placebo. Primary composite outcome was first occurrence of nonfatal Ml, nonfatal stroke, or death from cardiovascular causes. Results: During median follow- up of 5.4 years, the primary composite outcome occurred in 12.0% ol patients on dulaglulide vs.13.4% of patients on placebo (hazard ratio (HR), 0.88:95% Cl 0.79 - 0.99: P'0.026). There was no significant difference in all- cause mortality between groups (10.8% in the dulaglulide group vs.12% in the placebo group: HR, 0.90; 95% Cl, 0.80 -1.01: P 0.067). Conclusion: In middle - aged and older adults withI2DM with previous CVD or cardiovascular risk factors, dulaglulide could be considered for managing glycemic control.

-

-

S 6LT 2 Inhibitors

.

EMI'AHEG OUTCOME

NEJM 2015:373:2117 - 28

Title: Empagliflozin Cardiovascular Outcomes, and Mortality in Type 2 Diabetes Puiposc: Io Investigate Ihe effects of empagliflozin on cardiovascular morbidity and mortality in patients with 12DM at high cardiovascular risk. Methods: 7020 patients were randomly assigned to receive empagliflozin (10 mg or 25 mg) or placebo daily. Results: Risk of hospitalization from heart failure, death from any cause, or cardiovascular causes was significantly lower in the pooled empagliflozin group as compared to placebo. There were no significant differences in the rates of Ml or stroke. There were increased rates of genital infection with empagliflozin. Conclusion: Empagliflozin reduced rates of death from any cause and death from CVD in patients with T 2DM at high risk for cardiovascular

CANVAS

NEJM 2017:377:644 57

Title: Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes Purpose: to assess Ihe effects of canagliflozin on cardiovascular, renal, and safety outcomes in patients with T 2 DM , Methods: 10142 patients with 12DM al high cardiovascular risk were randomly assigned to receive canagliflozin or placebo. Primary outcome was a composite of death from cardiovascular causes, nonfatal Ml. or nonfatal stroke Results: Canagliflozin was associated with significantly lower rates of the primary outcome as compared to placebo ( 26.9 vs. 31.5 participants per 1000 patient - years; hazard ratio (HR). 0.86; 95% Cl 0.75 - 0.97: P'0.001 for noninferiority: P - 0.02 for superiority). However, canagliflozin was associated with a greater risk of amputation (6.3 vs.3.4 participants per 1000 patient years: HR 1.97: 95% Cl, 1.41-2.75). Conclusion: Canagliflozin lowered the risk of cardiovascular events but increased the risk of amputation in patients with T 2DM at high cardiovascular risk.

events.

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.

DECLARE TIMI 58

NEJM 2019;380:347-57

-

.

Title: Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes Purpose: To assess the safety and efficacy of the SGLT 2I dapagliflozin in patients with T 2DM who had or were at risk for atherosclerotic CVD. Methods: 17160 patients were randomly assigned to receive 10 mg dapagliflozin daily or placebo. Primary composite safely outcome was MACE (major adverse cardiovascular events), defined by cardiovascular death Ml, or ischemic stroke Ihe primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Results: For the primary safety outcome, dapagliflozin was noninferior to placebo ( P 50%, end - stage kidney disease, or death from renal or cardiovascular outcomes) as compared lo placebo (9.2% vs. 14.5%: hazard ratio 0.61; 95% Cl, 0.51- 0.72: P* 0.001). Effects were similar in palienls with and withoutI2DM. Conclusion: Oapaglillozm therapy resulted in a lower risk of kidney failure and cardiovascular events m patients with CDK with or without I2DM.

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E63 Endocrinology

Trial Name

Reference

Clinical Trial Details

NtJM 2019:381:19952008

Title: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Purpose: To assess the effects of SGLT 2is in patients with heart failure and reduced ejection fraction, with or without 12DM. Methods: 4744 patients with New York Heart Association class II, III or IY heart failure and ejection fraction < 40% were randomly assigned to receive dapagliflorin |10 mg 'd) or placebo, in addition to recommended therapy. Results: Over a median of 18.2 months, dapagliflonn was associated with significantly lower rates of the primary composite outcome ( worsening hurl failure or cardiovascular death) as compared to placebo (16.3 % vs. 21.2%: hazard ratio, 0.74; 95% Cl 0.65 0.85: P'0.0011. Effects were similar in patients with and without I20M. Conclusion: Oapagliflozin therapy resulted in a lower risk ol worsening heart failure or cardiovascular death in patients with heart failure and reduced ejection fraction,with or without T 2DM.

SG112 Inhibitors - Cardiac DAPA - HF

.

.

EMPEROR - Reduced

NEJM 2020:383:1413 - 24

Title:Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Purpose: to assess the effects of SGll 2is in patients with heail failure, including those with a markedly reduced ejection liaction Methods: 3730 palienls with New Yoik Heart Association class II, III or IV heart lailuic and ejection Iradlon ' 40% were landomly assigned lo receive empagliflozin [10 mg >d|or placebo, in addition to iccommended therapy. Results: Over a median of 16 months, empagliflozin was associated v/ ith significantly lower rales of the primary composite outcome (hospitalization for worsening heart failure or cardiovascular death) as compared to placebo (19.4% vs. 24.7%: hazard ratio 0.75; 95% Cl, 0.65 0.86: P'0.001). Effects were similar in patients with and vrithoutI20M. Empagliflozin was also associated with a slower annual rate of decline in estimated GFR ( O.SSvs. -2.28 ml/rriim1.73rnJ/yr; P'0.001). Conclusion: Empagliflozin therapy resulted in a lowei risk ol hospitalization lor worsening heart lailuic or cardiovascular death in palienls receiving recommended therapy loiheart failure, with oi without T 2 DM.

.

.

.

A1c Targets

ADVANCE

NEJM 2008:358:2560 -72

Title:Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes Purpose: To investigate the effects of intensive glucose control on vascular outcomes in palienls with T 2DM. Methods: 11140 patients with 12 DM received intensive glucose control with modified release glidazide [and other drugs necessary to reach target HbA1c - 6,5%| or standard glucose control (taigel HbA1c defined by local guidelines) Results: Intensive glucose control icduccd the incidence ol nephropathy (4.1% vs 5.2%; hazard ratio 0.79; 95% confidence interval (Cl| 0.66 0.93: P- 0.006), but did not significantly reduce major macrovascular events oi death from any cause Severe hypoglycemia was more common in the intensive control group |2.7% vs.1.5%:1.86 Cl [1.42 to 2.40 ]: P 0.001). ‘ Conclusion: Intensive glucose control targeting HbA1c 65 or high risk , add Prevnarr 13 if > 65 and high risk ( A)

-

-

- -

Classification ol recommendation in brackets: A - high quality ot evidence: B - moderate quality ot evidence. For up to date guidelines, see: wvAV.ce nadiantasktorce.ca. References: Guidelines [ Internet) Ottawa (ON ): The Canadian Task Force on Preventive Health Care: c 2019 [cited 2021 [ Available from: https:// Canadian taskloice ca /guldollnei/ Zaltxman A, Oubey V, Iglar K. Update to the Preventive Care Checklist Form : . CFP. 2020 Apr 166(4 ) 270 2.

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Breast Cancer Screening Guidelines 2018 Canadian Task Force on Preventive Care Recommendations

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-

• for women ages 50 74, recommend screening with mammography every 2 3 yr; the decision to undergo screening is conditional on the relative value that a woman places on possible benefits and harms from screening (conditional recommendation; very low certainty evidence) • for women ages 40 49, recommend not screening with mammography; the decision to undergo screening is conditional on the relative value a woman places on possible benefits and harms from screening (conditional recommendation; low certainty evidence ) • recommend not performing clinical breast examinations to screen for breast cancer (conditional recommendation; no evidence ) • recommend not advising women to practice breast self-examination to screen for breast cancer (conditional recommendation; low certainty evidence ) • recommend not using MKl, tomosynthesis, or U /S to screen for breast cancer in women not at increased risk (strong recommendation; no evidence ) • for more information on benign breast lesions and breast cancer, see General Surgery and Thoracic Surgery, GS65

-

Lung Cancer Screening Guidelines 2016 Canadian Task Force on Preventive Health Care Recommendations • for adults ages 55-74 with > 30 pack- yr smoking history who currently smoke or quit < 15 yr ago, recommend annual screening with LDCT up to three consecutive times; screening should ONLY be carried out in health care settings with expertise in early diagnosis and treatment of lung cancer (weak recommendation; low quality evidence ) • for all other adults, regardless of age, smoking history, or other risk factors, recommend not screening for lung cancer with LDCT (strong recommendation ; very low quality evidence ) • recommend that chest x- ray not be used to screen for lung cancer, with or without sputum cytology (strong recommendation ; low quality evidence) i J

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FM5 Family Medicine

Toronto Notes 2023

Colorectal Cancer Screening Guidelines 2016 Canadian Task Force on Preventive Health Care Recommendations • recommend screening adults ages 60 -74 for CRC with FOBT (either gl 'OBT or ITT ) q 2 yr OR flexible sigmoidoscopy q I0 yr (strong recommendation; moderate quality evidence ) recommend screening adults ages 50 59 for CRC with FOB f ( either gl - OB T or ITT ) q 2 yr OR llexible • sigmoidoscopy q 10 yr ( weak recommendation; moderate quality evidence ) • recommend not screening adults ages > 75 for CRC (weak recommendation; low quality evidence) • recommend not using colonoscopy as a screening test for CRC ( weak recommendation; low quality evidence)

-

Men and Women

>

Symptomatic

Diagnostic Workup

I

Asymptomatic regardless of age but positive family history

i HNPCC or FAP Genetic counselling and special screening

I

HNPCC

Colonoscopy every 1 - 2 yr 8egin at age 20 or 10 yr younger than the earliest case in the family, whichever comes first

I

T

One first-degree relative with cancer or adenomatous polyp at ages 60

One second-degree relative or third-degree relative affected

Two or more second-degree relatives with polyps or colon cancer

J

Average risk screening Begin at age 40

Begin at age 40 or 10 yryounger than

the earliest case ol polyp or cancer in the family, whichever comes first

AAPC Colonoscopy annually Begin at ages 16 - 18

Average risk screening

Begin at age 50

I

I - 2 tubular adenomas 2 adenomas: colonoscopy in 3 yr

Incomplete examination, numerous polyps, advanced adenoma, malignant or large sessile adenoma : colonoscopy after a short interval based on clinical judgment

every 5 yr

FAP Sigmoidoscopy annually Begin at ages 10- 12

T

1

Polyps found at colonoscopy

Figure 1. Approach to higher risk screening AAPC = attenuated adenomatous polyposis; FAP = familial adenomatous polyposis; HNPCC = hereditary nonpolyposis colorectal cancer; 1st degree relatives: parents, siblings, children; 2nd degree relatives: grandparents, aunts, uncles; 3rd degree relatives: great grandparents or cousins. Figure printed with permission from Can J Gastroenterol 2004;18:93- 99. Also see: 8C Guidelines [ Internet ]. Victoria ( BC): Guidelines and Protocols Advisory Committee. Colorectal Screening tor Cancer Prevention in Asymptomatic Patients; 2013 Mar 1 [revised 2016 Jun 22; cited 2021 May 27], Available from: https://www 2.gov.bc.ca/gov/content /health/practitionerprofessional- resources/ bc-guidelines/colorectal-cancer- screening

Cervical Cancer Screening Guidelines 2013 Canadian Task Force for Preventive Care Guidelines Recommendations • for women ages 30 -69, recommend Papanicolaou ( Pap) smear or liquid -based cytology for cervical cancer q 3 yr (strong recommendation; high quality evidence ) • for women ages 25 29, recommend Pap smear or liquid based cytology for cervical cancer q 3 yr ( weak recommendation ; moderate quality evidence ) • for women ages >70 who have not been adequately screened, recommend continued screening until 3 negative test results have been obtained ( weak recommendation; low quality evidence ) • for women ages S70 who have been adequately screened ( i.e. 3 successive negative Pap tests in the last 10 yr ), recommend that routine screening may cease • for more information on cervical cancer (see Gynaecology GY48) • note: provincial/ territorial guidelines vary, e.g. Ontario guidelines: women ages > 21 ( recommended ages > 25) who are or have ever been sexually active, recommend screening q3 yr ( if cytology normal ); women who are not sexually active by this age should delay cervical cancer screening until sexually active • a woman may discontinue screening at age 70 if she has an adequate and negative cytology screening history in the previous 10 yr ( i.e. three or more negative cytology tests)

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Toronto Notes 2023

FM6 Family Medicine

Normal

l

ASCUS

Inadequate Adequate sample sample - no TZ

1 Women

Routine

I Repeat

I Routine

screening

cytology

in 3 yr

in 3 mo

screoning in 3 yr

*

LSIL

I

|

i

HPV testing not available

I

HPV -DNA

Colposcopy

testing

± endometrial

i

i

I

2ASCUS

I

*

Repeat cytology Colposcopy in 6 mo

1

i Colposcopy OR

1

1

Repeat cytology in 6 mo

HSIL

Squamous

l

carcinoma!

Colposcopy

1

iASCUS

Negative

other malignant changes

I

Colposcopy

sampling

Positive Repeat cytology in 12 mo

I I

l

Repeat cytology in 6 mo

Negative

I

AGUS/ atypical cndoccrvical colls/ atypical endometrial cells

Colposcopy

Women > 30

ASCUS

Routine

i Routine

4 Colposcopy

screening

I

screening

.

Figure 2 Decision-making chart for cervical cancer screening (not applicable to adolescents) AGUS «= atypical glandular cells of unknovyn significance; ASCUS = abnormal squamous cells of unknown significance; ASC - H = abnormal squamous cells cannot rule out HSIL; HSIL - high grade squamous intraepithelial lesion; LSIL = low grade squamous intraepithelial lesion; TZ = transitional zone Adopted from:Ontario Cervical Screening Cytology Guidelines. May 2012

Prostate Cancer Screening Guidelines 2014 Canadian Task Force for Preventive Care Guidelines Recommendations • for men ages 55-69, recommend not screening for prostate cancer with the PSA test ( weak recommendation ; moderate quality evidence); clinicians should discuss the risks and benefits of screening and its potential consequences with each man in the context of his preferences • for men ages £ 55, recommend not screening for prostate cancer with the PSA test (strong recommendation; low quality evidence ) for men ages S70, recommend not screening for prostate cancer with the PSA test ( strong • recommendation; low quality evidence)

Basis of Recommendation

• the potential small benefit from PSA screening is outweighed by the potential significant harms of the screening and associated follow - up treatment for men ages < 55 or > 70, there is no evidence that screening with the PSA test reduces mortality, whereas there is evidence of harms for men ages 55-69, there is inconsistent evidence of a small potential benefit of screening and evidence of harms

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FM 7 Family Medicine

Toronto Notes 2023

Health Promotion and Counselling • health promotion is the most effective preventive strategy • initial steps should include to respectfully explore the values and purposes of the patient 's habits or

behaviours • it is helpful to be guided by a patient 's present stage of change when having discussions around healthy behaviours • for more information, see www.motivationalinterviewing.org

Motivational Strategies for Behavioural Change Table 2. Motivational Strategies for Behavioural Change Patient's Stage of Change

Physician's Aim

Pre-Contemplation

Encourage patient to consider the possibility of change Raise issue in a sensitive manner Offer (not impose) a neutral eichange of Assess readiness for change information to avoid resistance Increase patient 's awareness of the problem and its risks

Contemplation

Understand patient's ambivalence and encourage change

Physician’s Plan

Canadian Cancer Society Recommendations for Vitamin D Use • Based on CCS research on Vitamin D and the prevention of colorectal and breast cancers • In consultation with their healthcare provider, the Society recommends

Offer opportunity to discuss pros and cons of change using reflective listening

that

• Adults living in Canada should consider taking Vitamin D supplementation of 1000 IU/d during the fall and winter • Adults at higher risk of having

guild confidence and gain commitment to change

Preparation

Action

Explore options and choose course most appropriate for the patient Identify high - risk situations and develop strategies to prevent relapse Continue to strengthen confidence and commitment

Offer realistic options for change and opportunity to discuss inevitabledifficulhes

Help patients design rewards for success Develop strategies to prevent relapse Support and reinforce convictions towards long- term

Offer positive reinforcement and explore ways of coping with obstacles Encourage self -rewards to positively teinforce change

change Maintenance

Help patient maintain motivation Review identified high-risk situations and strategies for preventing relapse Increase self -belief in ongoing change

Discuss progress and signs of impending relapse

Relapse

Help patient view relapse as a learning experience Proride support appropriate to re- entry into the change cycle at the patient's present level of readiness,post-relapse

Offer a non- judgmental discussion about circumstances surrounding relapse and how to avoid relapse in the future Reassess patient's readiness to change

lower Vitamin 0 levels should consider taking Vitamin D supplementation of 1000 IU/d all year round. This includes people: who are older, with dark skin, who do not go outside often, and who wear clothing that covers most of their skin • Babies who are exclusively breast-fed: 400 IU/d

Adapted from:Hunt P.Motivating Change.Nurs Stand 2001:16:45-52, 54- 55

Nutrition General Population • Canada's Food Guide is appropriate for individuals ages > 2 yr • counsel on variety, portion size, and plate layout • guideline I : nutritious foods are the foundation for healthy eating. Vegetables, fruits, whole grains, and proteins should be consumed regularly. Among protein foods, consume plant - based more often (e.g. legumes, nuts, seeds, tofu, fortified soy beverage ). Foods with mostly unsaturated fat should replace those that contain mostly saturated fat. Water should be beverage of choice • nutritious foods to consume regularly can be fresh, frozen , canned , or dried • consider cultural preferences and food traditions. Traditional food improves diet quality among

Indigenous peoples • guideline 2: processed or prepared foods and beverages that contribute to excess sodium, free sugars, or saturated fat undermine healthy eating, and should not be consumed regularly • guideline 3: food skills are needed to navigate the complex food environment and support healthy eating. Cooking and food preparation using nutritious foods should be promoted. Food labels should be promoted as a tool to help make informed choices

Energy Content of Food Carbohydrates: 4 kcat/g Protein: 4 kcal/g Fat: 9 kcal/g Ethanol: 7 kcat/g

• • • •

Calculating Total Daily Energy Expenditure • Roughly 35 kcal/kg/d • Varies by age. weight height sex and activity level • Average 2000-2100 kcal/d for women. 2700-2900 kcal/d for men

.

Handy Serving Size Comparisons • 85 g meat fish, poultry * palm of hand • 250 ml dairy (milk/yogurt) » size

-

of fist • 1 serving of bread/grains * one slice, palm of hand • 125 g rice/pasta » one hand cupped • 250 g of fruitvegetables •» two

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cupped hands

• 28 g cheese full length of thumb • 5 g oit/butter •tip of thumb • 28-57 g nuts/chips/snacks » palm coveted

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F.M8 Family Medicine

Toronto Notes 2023

Eat healthy protein ( e.g. fish, poultry, beans, nuts), limit

Eat plenty of fruits

of ail colours

.

red meat, processed meats and cheese

Use healthy oils

.

Drink water, tea or coffee, limit milk and juice (i.e. 1-2 servmgs/day), avoid sugary drinks

( e.g. olive, canola ),

limit butter, avoid trans fat

g INI

of vegetables

Figure 3. Canada's Food Guide 2019 - plate layout Source:

2019.

v

Eat a variety of whole grains, limit refined grains

Eat plenty and a variety

.

Osteoporosis Canada Recommendations for Calcium and Vitamin D Daily R equipments Vitamin D: 400-1000 IU for individuals 19-50 yr 800-2000 IU for individuals >50 yr or younger adults at high-risk (osteoporosis, multiple fractures, inadequate vitamin D absorption) • Calcium:1000 mg daily from all sources for individuals 19-50 yr and pregnant/lactating women: 1200 mg daily for individuals >50 yr (recommended to obtain caldum from diet whenever possible vs. supplementation)

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8

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.

All Rights Reserved Carvada's Food Guide Health Canada 2019. Adapted and reproduced with permission from the Minister of Health

Cardiovascular Disease Prevention Table 3. Dietary Guidelines for Reducing Risk of Cardiovascular Disease Recommendations Carbohydrates

Complei catbs (legumes,whole grams) should be favoured over smrplecarbs ( white flour/rite, table sugar) Eliminate sugar -sweetened beverages in favour of water

Fruits and Vegetables

Consume a higher proportion of who e. fresh fruits and vegetables Consume leafy green vegetables and berries at least 3 times/wk Consume starchy vegetables (white potatoes,corn,green peas) in moderation

Fats

Consume mono- and polyunsaturated fats in moderation (ion- topical vegetable fats, liquid fats) Minimize tans fat intake (processed'snack foods) Umit saturated fats (processed foods,red meat, cheese, whole milk, butter ) Olive and canola oil are recommended over butterhnargarine/ coconut oil Skim or1% milk is recommended over whole milk

Protein

Consume fish with higher levels of omega-3 fatty adds (salmon,tuna mackerel) Moderate consumption of lean poultry,seafood,and mils Untied meat Minimize consumption of processed meats (det coid cuts, sausage, bacon)

'

,

Salt

s20D0 mg:d

Alcohol

s3 drinks/d on most days for men mat IS'wk 5% body weight was1,77 (55% Cl 1.58 to 1.55: NN1 S 55% CI 4 7) Relative risk lor lots of >10% body weight was 1.51155% Cl 1.65

-

. .

-

.

- . -

.

-

.

-.

-

to 2.16: NM15.55% 0 7 12). Incidence ol I 20 M was lower among pre diabetic intervention participants |RR 0.62. 55% Cl 0.50 to 0.77: MMT 17.55% Cl 1325). Condition: Behavioural and pharmacological treatments for overweight and obese adults may lead to ciimkaOy important reductions in weight and mcidemceOII 2DU in pre-diabetic populations.

-

m

Adverse Medical Consequences of Obesity T2DM • Dyslipvdemia CAD • Osteoarthritis • Stroke OSA HTN • Certain cancers • Gallbladder disease CHF • Low back pain Non-alcoholic statohepatitis • Increased total mortality • Pregnancy complications

. . . .

Extremely high

>

IrtMatat (or Oncmrigkt and Obesity in Adult Populations:A Systematic Review and Meta -

Management

Canadian Adult Obesity Clinical Practice Guidelines (Obesity Canada , 2020) • recognize that people with obesity experience weight bias and stigma, which contributes to increased complications and mortality independent of weight or BMI • Step 1 - Ask: recognize obesity as a chronic disease and obtain patient permission to discuss and help treat this disease in an unbiased manner • Step 2 - Assess: assess the patient using appropriate measures ( i.e. height, weight, WC, and BMI calculation ) and identifying root causes (e.g. biological factors, individual life experiences, psychological factors), complications, and barriers to treatment • Step 3 - Advise: discuss treatment options and work with the patient to create individualized care plans that address root causes of obesity and supports behaviour change nutrition: all individuals can benefit from adopting a healthy, well balanced diet weight loss requires long-term reduction in caloric intake, encouraged by a personalized eating pattern that meets the patient's values, preferences, and nutritional needs medical nutrition therapy should not be used in isolation ( may promote compensatory mechanisms that promote positive caloric intake by increasing hunger ), but instead should be used in combination with other interventions (e.g. psychological, pharmacological, surgical ) physical activity: » consider aerobic physical activity (30 60 min of moderate to vigorous intensity most d / wk ) for adults who wish to achieve small amounts of body weight and fat loss, reduce abdominal visceral fat, maintain weight loss, and /or increase cardiorespiratory fitness resistance training may promote weight maintenance, increased muscle mass, fat free mass, and mobility in adults with overweight /obesity regular physical activity can improve cardiomctabolic risk factors and Improve health related quality of life psychological and behavioural interventions: multicomponent psychological intervention ( behaviour modification , cognitive therapy, and values based strategies to alter diet / activity ) should be incorporated into care plans for weight loss

-

-

-

-

. .

Associations with Low BMI • Osteoporosis • Eating disorders

.

Under -nutrition

• Pregnancy complications

Pharmacotherapy for Obesity • There are currently 3 prescription medications available in Canada that are approved for use in adult patients with BMI 230 kg 'm/oi BMI 227 kg/m 7 and 21 weight- related condition (e.g. HTN T 2DM dyslipldemia) • Note: these medications should be used alongside a reduced-calorie diet and increased physical activity • Contrave ' (naltrexone and bupropion): controls hunger and cravings • Saxenda ’ (liraglutlde): decreases appetite and. therefore, food intake • Xenical ' (orllstat): reduces dietary fal absorption by 30% through inhibition of pancreatic and gastric lipases

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FM10 Family Medicine

Toronto Notes 2023

• pharmacotherapy: liraglutide, naltrexone-bupropion combination, or orlistat (see sidebar Pharmacotherapy for Obesity, FM9) can be used for patients with BMI >30 kg/ m - or > 27 kg/ m -with adiposity- related complications, in combination with medical nutrition therapy, physical activity, and

psychological interventions can be used to maintain weight loss achieved by behaviour changes and to prevent weight regain bariatric surgery: consider for patients with BM1 >40 kg /m ' or BMI >35 kg / m -with > 1 adiposity- related disease (e.g. T2DM) consider for weight loss and /or to control adiposity- related diseases where optimal medical and behavioural management has been insufficient to produce significant weight loss choice of bariatric procedure should be decided according to the patient’s needs, in collaboration with an experienced interprofessional team (suggest against adjustable gastric banding and single anastomosis gastric bypass, due to unacceptable complications and longterm failure) • Step 4 - Agree: agree on goals of therapy with the patient, focusing on the patient’s values to ensure realistic expectations and sustainable behaviour change and health outcomes • Step 5 Assist: follow up and reassess the patient regularly to assist with drivers/ barriers and advocate

-

for improved obesity care

Effects of Popular Diets without Specific Calorie Targets on Weight toss Outcomes: Systematic R eview of Findings from Clinical Trials Nutrients 2017:9:£822 Purpose: Toassess the short-term (6 mo|weight loss outcooes for corrent popular diets in overweight and ooese adu.ts. Methods: A systematic rev:ew wasconducted. All diets in the 2016 I).5. News t Wort d Report Parkings for “Best Weight-Loss Diets’ were eiammed.From the potential 38 diets, el.giole studies breaded trials with a sample s;K >15 per group,internentional clinical trials, intervention periods >12 wk,BMI >25 mg,'m 2, parte ipants ages >18 grand oniecthre measures of pre- and post -intervention. Results: Sixteen articles were included in the review. Diets included the Atkins OASH Glyceric-In dei. Mediterranean Ornish, Paleolithic, and lone rLets. The Atkins diet showedthe most clinically signiheant reduction in we.ght loss in both the short- term end long - term Conclusion : Other diets had limited evidence supporting their effectiveness in producingdin.cally sigmheant short - term and long-term weight loss. Future studies are needed to com pare ar.d evaluate the efficacy of these other diets.

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.

-

Overweight or obese adult

IMPORTANT MESSAGE A modest weight loss of 5-10% of body weight is beneficial Weight maintenance and prevention of weight regain should be considered as long-term goals

Measure BMI Measure waist circumference rf BMI is >25 and 25 kg/m!or waist circumference is above cut off point

Devise goals and lifestyle modification program for weight loss and reduction of risk factors Weight loss goal: 5-10% of body weight or 0.5-1 kg (1-2 lb ) per wk for 6 mo

I Conduct clinical and laboratory

investigations to assess comorbidities:

Blood pressure, heart rate, fasting glucose, lipid profile (total cholesterol, triglycerides. LDL and HDL cholesterol, and ratio of total cholesterol to HDL cholesterol)

Health team to advise lifestyle modification program

l

Lifestyle modification program

Nutrition:Reduce energy intake by 500-1000 keal/d Physical activity:initially 30 min of moderate intensity 3-5 times/wk; eventually >60 min on most days. Add endurance exercise training. (Medical evaluation is advised before starting activity program) Cognitive behavioural therapy

Assess and screen for depression, eating and mood disorders Treat comorbidities and other health risks, if present

*

*

Assess readiness to change behaviours and barriers to weight loss

Effect of Intermittent Energy and Carbohydrate Restriction vs. Daily Energy Restriction on Weight L oss and Metabolic Disease Risk Mathers in Overweight Women BrJNutr 2013:110:1534-1547 Purpose: To determine if intermittent energy and carbohydrate restricton (IECR) may result in greater improvements in insulin sensitivity end weght control than daily energy restriction (0ER|. Methods: Two IECR regimens were tested, induing one which a:owed ad libitum prosin and fat (ECI PF). Overweight women|it-TI5) ages 20 -69 with a family history pf breast cancer were random tsed to an overall 25 % energy restrictor,, or a 25% DER. or an IECR Pf for a 3 mo weight - loss prod and 1mo uf weight maintenance ( IECR a: IECR - Pf for 1d,'wk|. Results: Insulinresistance redjeed with the IECR diets and the IECR PF diet . Reduchons with the IECR diets were significantly greater compared with the OER diet Both IECR groups had greeter reductions a body let compared with the OER group. Owing the weight maintenance phase 1day of IECR or IECR Pf per week maintained the reductions in insula resistance and weight. Conclusion In the short term IECR issuperia io OER with respect lo improved insulin sensitivity and body iat reduction.

-

-

.

.

Satisfactory progress or goal achieved?

Yes

No

No V

'

Regular monitoring

Assist with weight maintenance Reinforce healthy eating and physical activity advice

; Weight maintenance and prevention of weight regain Nutrition therapy Physical activity Cognitive behavioural therapy

Address other risk factors: periodic monitoring of weight BMI. and waist circumference at appropriate primary care visits

vr

Pharmacotherapy BMI >27 kryrrrand risk factors or BMI >30 kgm2 Adjunct to lifestyle modifications: consider if patient has not lost 0.5-1 kg (1-2 lb) per wk by 3-6 mo after Bfestyfe changes

'

Bariatric surgery BMI >35 kg/nrand risk factors or BMI >40 kg/m2 Consider if other weight loss attempts have failed. Requires lifelong medical monitoring

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Figure 4.2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children

+

.

Adapted from: Lau DCW et al. 2006 Canadian clinical practice guidelines or the management and prevention of obesity in adults and children [summary;. CMAJ 2007:17651-513

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Toronto Notes 2023

FM 11 Family Medicine

Dyslipidemia Signs of Hyperlipidemia Atheromata: plaques in the intimal layer of arterial walls • Xanthelasmata: a sharply demarcated yellowish deposit of cholesterol underneath the skin, usually on or around the eyelid • Tendinous xanthoma: lipid deposit in tendon (especially Achilles) • Eruptive xanthoma: hypcitriglyceridemiainduccd reddish yellow, pruritic, and painful papular or nodular rash < Lipemia retinalis: characterized by creamy, white-coloured retinal blood vessels, occurs only with extreme hypertriglyceridemia • Corneal arcus (arcus senilis): lipid deposit in cornea

•

RISK ASSESSMENT. STRATIFICATION AND TREATMENT CONSIDERATION Calculate risk ( unless statin-indicated condition) using the Framin ghant Risk Score ( FRS) or Cardiovascular Life Expectancy Model ( CLEM) Repeat screening every 5 years for FRS 5%

'r

1

Statin-Indicated Conditions

No Pharmacology

Primary Prevention Conditions

Low Risk FRS 20% or L0L-C 3.5 mmol/L or Non-HDL > 43 mmo(/L or alternative method ApoB >).2 g/Lor Men >50 and women >60 with 1 additional risk factor: low H0 L-C, impaired lasting glucose, high waist circumference, smoker, hypertension, or with presence of other risk modifiers: high sensitivity CRP £2.0 mmol/L, coronary artery calcium >0 All, family history ol premature CA 0, high lipoprotein( a) >50 mg/dL

rr

Clinical atherosclerosis Abdominal aortic aneurysm Most diabetes including: Age >40 yr Age >30 yr and 25 yr duration ( type 1 DM) Microvascular disease Chronic kidney disease

LDL- C >5 irimol/L genetic dyslipidemia

To calculate FRS go to https:/ /www. framinghamheartstudy.org/ fhs -risk' functions/cardiovasculnr disease - 10 year -risk/

-

( ilOOnmol/LI

Discuss Behavioural Modifications 1. Smoking cessation 2. Diet adopt a health dietary pattern 3. Exercise: for adults 150 mirVwk of moderate-vigorous aerobics

Initiate Statin Treatment: Treat to Target Approach ( confirm adherence and barriers to use)

-

LDL C 50% reduction or apoB 1 h screen lime nol recommended , engage in reading/ storytelling while sedentary

.

-

Toddler (1 2)

Moving around the home Accumulate >180 min of physical Climbing stairs activity at any intensity spread throughout the dayindudmg energetic Exploring environment play Brisk walking , running , dancing

Sleep: 11-14 h /d of good quality sleep including naps, with consistent bed and wake up times Sit: not restrained ( i.e. in a stroller ) lor >1 h. sedentary screen time not recommended if 1 h, sedentary screen time 60 min /d of moderate to vigorous aerobic physical activity Muscle/ bone strengthening exercises 3 d/wk A variety of structured / unstructured light physical activities for several h / d

Moderate: bike riding , playground playing Vigorous: running , swimming

Sleep: 9 11 h /d ( 5 13 yr), 3 10 h /d (14 17 yr ) uninterrupted, with consistent bed and wake up times Sit: no more than 2 h /d of recreational screen time, limit silting for extended periods

Accumulate 150 min /wk of moderate to vigorous inlensily aerobic physical activity, in bouts ol >10 mm

Moderate: brisk walking, bike riding Vigorous: jogging , cross country skiing

Sleep: 7 9 h/d of good quality sleep, with consistent bed and wake up

Musdc/ bonc strengthening activities using major muscle groups ;2 d / wk

.

Older Adults ( > 65|

-

Accumulate >180 min in a variety of activities at any intensity, including >60 min of energetic play throughout the day

Same as Adults above

Same as Adults above

Physical activities that challenge

Those with poor mobility should perform physical activities to enhance balance and prevent falls

balance

-

-

-

-

-

times

Sit: limit sedentary time to 8 h or less, no more than 3 h /d of recreational screen time, break up long periods ol silting as often as possible Same as Adults above

Epidemiology

• 25% of the population exercises regularly, 50% occasionally, 25% is sedentary Management • assess current level of fitness, motivation , and access to exercise • encourage warm up and cool down periods to allow transition between rest and activity and to avoid injuries • exercise with caution for patients with CAD, DM ( risk of hypoglycemia ), exercise -induced asthma • patients with known CAD should have cardiac assessment prior to commencing exercise • benefits of exercise reduces risk of premature death, heart disease, stroke, HTN, certain types of cancer, T2DM, osteoporosis, and overweight/obesitv • leads to improved fitness, strength, mobility, functional independence, and mental health ( morale and self-esteem )

Smoking Cessation Epidemiology • smoking is the single most preventable cause of premature illness and death • 70% of smokers see a physician each year

• 2012 Canadian Tobacco Use Monitoring Survey on population ages 15 16% are current smokers ( lowest since 1985) • highest prevalence in those ages 20 24 ( 20%) 11% of youth ages 15 19 smoke (decreased from 25% in 2000 ): more males ( 18%) smoke than females ( 14% ); number of cigarettes consumed per day is also decreasing ( 15.0 per day in 2012 vs. 16.2 per day in 2001)

-

-

.

Doses Dura lions, and Modes of Delivery of Nicotine Replacement Therapy for Smoking Cessation Cochrane DBSyst Rev 2019:4:00013308 Purpose: NRI helps With smoking cessation but it is unclear what NRI routines and dosages are most helpful. Theaim wasto establish efficacy of differentfoims deliveries, dosages, and duration of treatment. Methods: Meta - analysis including RCIs of people motivated to quit smoking , comparing one type of NRI vs. another. Results : H gh -certainty evidence that combination NRI [last acting form • patch) results In higher long term quit rates than bugle form . Moderate certa Hy evdence dosages > 21/ 22 mg are equally effective, fivestudies comparing 4 mg gum to 2 mg gum found a benefit ol the higher dose. Nine studies tested the effect of using NRI prior 1o quit day ( preloading ) In comparison to usmg it horn quit day onward: there was moderate certainty evidence of a favourable effect ol preloading on abstinence. Conclusions : There vs high certainty evidence that using combination NRI vs. single- form NRI can increase the chances ol successfully stopping smoking. Higher dosed patchesand gum seemed to result in higher tong term quit rates with moderate quality evidence.

.

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FMM Family Medicine

Toronto Notes 2023

Management

• general approach

identify tobacco users; elicit smoking habits , previous quit attempts, and results he • curious about how the patient relates to smoking. Ask: what purpose does smoking serve in their life at the moment ? 2012 Canadian Action Network for the Advancement, Dissemination and Adoption of Practiceinformed Tobacco Treatment (CAN-ADAPTT) Guidelines tobacco use status should be updated for all patients regularly health care providers should clearly advise patients to quit health care providers should assess patient willingness to quit and offer assistance to those who express interest health care providers should conduct regular follow up to assess response and monitor the patient’s mental health status/other addictions while quitting smoking • medication dosage should be monitored and adjusted as necessary every smoker should be offered treatment • educate patient to watch for withdrawal symptoms: low mood , insomnia , irritability, anxiety, difficulty concentrating , restlessness , decreased heart rate, increased appetite • combining counselling / behavioural therapies and smoking cessation medication is more effective than either alone > 4 counselling sessions, >10 min each, with 6 -12 mo follow- up yields better results 14% abstinent with counselling vs. 10% without counselling approach depends on patient’s stage of change (see Motivational Strategies for Behavioural Change , l ' M 7 ) • willing to quit • provision of social support, community resources ( self help, group, helpline, web based strategies) pregnant patients: counselling is recommended as first line treatment NRT should be made available to pregnant women who are unable to quit using non pharmacologic methods intermittent NRT use ( lozenges, gum ) is preferred over continuous dosing of the patch no strong evidence that either major positive or negative outcomes were associated with gestational use of bupropion or varenicline; consider using only if benefits outweigh risks • pharmacologic therapy I . NRT 19.7% abstinent at 12 mo with NRT vs. 11.5% for placebo no difference in achieving abstinence for different forms of NRT' reduces cravings and withdrawal symptoms without other harmful substances contained in

-

-

-

cigarettes cost of NRT' is comparable, and often lower than cigarettes use with caution: immediately post - Ml , worsening angina, arrhythmia advise no smoking while using NRT public reimbursement for smoking cessation treatment varies across Canada - see https:// www.helpthemquit.ca /treatment/costs-coverage tor more details 2. Antidepressants ( mechanism of action appears to be independent of antidepressant effect ) bupropion SR ( ZybaiT ) 21% abstinent at 12 mo vs 8% for placebo

.

bupropion has similar effectiveness to NRT 3. Varenicline ( Champix* ) partial nicotinic receptor agonist ( to reduce cravings) and partial competitive nicotinic

receptor antagonist (to reduce response to smoked nicotine) more effective than bupropion ( 23% abstinent from 9-52 wk with varenicline vs . 16% with bupropion vs. 9% with placebo) significant side effects ( including nausea , headache, drowsiness, unusual dreams, neuropsychiatric symptoms ) may lower patient compliance Table 6 . Types of Nicotine Replacement Therapy Type

Dosage

Comment

Side Effects

Nicotine Gum (OTC)

2 mg i( »25 cig/d 4 mg if »25 cig /d 1 piece ql 2 h for 1 3 mo (max 24 pieces /d )

Chew until “ peppery" taste then “ park" between gum and cheek to facilitate absorption Continue to chew / paikinteimittently

Mouth soreness Hiccups Dyspepsia Jaw ache ( Most are transient )

Use lor 8 wk 21 mg /d x 6 wk 14 mgfd x 2 wk 7 mg/dx 2 wk 6 16 cartridges /d up lo 12 wk

Starl with lower dose il »10 cig /d Change patch q 24 h and alternate sides

-

Nicotine Patch ( OTC )

Nicotine Inhaler ( OTC )

Nicotine Nasal Spray ( Rx )

-

lor 30 min

Antidepressants lor Smoking Cessation

Coctsrane OB Syst Rev 2020:4 X0000031

P urpose lo attest endente lorthe efficacy, safety, and tolerability of medications with antidepressant properties in assisting long - term tobacco smoking cessation.

Methods: Meta -ana!ysis of RCTs comparing antidepressant mediations to placebo or alternative pharmacotherapy, or the tame medication used » a dillerent way lor smoking cessation . Safety analytes with any for tow - op length was also conducted Results: Compared to placebo, bupropion was associated with increased long- term smoking cessation rates ( HR 1.64, 95% Cl 1.52 to 1.77). higher risk of reported psychiatric adverse events ( RR 125. 95% Cl 1.15 to 1.37), and higher dropout rate due to adverse events of the drug|RR 1.37, 95% Cl 1.21 to 1.561 Bupropion resulted n inferior cessation rates tovarenielmelRR 0.71 95% Cl 0.64 to 0.79) howevei no dilferencein efficacy between bupropion and RSI was found. Add t onally nortriptyline aided sme k g cessation when compared with placebo ( RR 2.03. 95% Ct 1.48 to 2.78). There was insufficient evidence to establish whether combination bupropion and NRT resulted in superior quit rates to NRT alone , or whether combination bupropion and varenicline '

.

.

.

.

-

-

revolted m superior quit rates to varenicline alone. Conclusion fvdence suggests that bupropion nay be helpful and as successful as NRT and nortnptyl me m helping people to quit smoking, but that it isless effective than varenicline.

The 5 A's for Patients Willing to Ouit As k If the patient currently smokes and is willing to discuss cessation Advise the patient to quit Assess willingness to quit Assist in quit attempt( s) Arrange follow - up

The 2-3 Pattern of Smoking Cessation • Onset of withdrawal is 2-3 h after last cigarette • Peak withdrawal is at 2-3 d • Expect improvement of withdrawal symptoms at 2-3 wk • Resolution of withdrawal at 2- 3 mo • Highest relapse rate within 2- 3 mo

Assist Patient in Developing Ouit Plan STAR

Set quit date Tell family and friends (for support) Anticipate challenges (e.g. withdrawal) Remove tobacco - related products (e.g. ashtrays/lighters)

Skin irritation

rT

Insomnia Palpitations Anxiety

Nicotine inhaled through mouth , absorbed in mouth and throat ( not in lungs)

Local irritation Cough

Newer form of NRT

local irritation

LJ

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Cough

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Toronto Notes 2023

FM15 Family Medicine

Table 7. Pharmacologic Treatments for Smoking Cessation Drug

Mechanism

Dosage

Prescribing"

Contraindications

Bupropion

Inhibits re-uptake of dopamine andi' or NE Side effects:insomnia,dry mouth

1.150 mg qAM « 3 d 2.Then 150 rag BID 7-12 wk 3.For maintenance consider 150 mg BID for up to 6 mo

1. Decide on a quit date 2.Continue to smoke for first 1-2 wk of treatment a nd then completely stop (therapeutic levels reached in Ink)

Seicure disorder Eating disorder MAOI use in the past 14 d Simultaneous use of bupropion ( Wellbutrin - ) for depression

Partial nicotinic receptor agonist, and partial competitive antagonist of nicotinic receptor Side effects: nausea, vomiting, constipation, headache, dream disorder,insomnia, increased risk of psychosis, depression,suicidal ideation

10.5 mgqAI4i3 d 2. Then 0.5 mg BIDi4 d 3. Continue 1mg BID 112 wkiadditional 12 wk as

1Decide on a quit date 2.Continue to smoke for first wk of treatment and then completely stop

Caution with pre- existing psychiatric condition

Varenidine

'

*

maintenance

-

Bupropion and varenidine may be used in cor bvnation with KRT

• unwilling to quit • motivational intervention ( 5 Rs) 1. Relevance to patient relevance to patient's disease status or risk, family or social situation (e.g. having children in the home), health concerns, age. gender 2. Risks of smoking short - term: SOB, asthma exacerbation, impotence, infertility, pregnancy complications, heartburn, URT1 - long-term: MI, stroke, COPD, lung cancer, other cancers - environmental: higher risk in spouse/children for lung cancer, SIDS, asthma, respiratory infections

-

-

Physician Advice for Smoking Cessation Cochrane DB Syst Rev 2013:5:CD000t55 fbrpose: lo assess the effectiveness of pirysician advice in promoting smokrrg cessation, compare minimal physician interventions with more intensive interventions, assess the effectiveness of var. oos ads in smoking cessation , and detentne the effect of anti-smoking advice on mortality. Methods: Systematic review of RCTs of smoking cessation advice from a medical practit ooer. Alsstir.er ee was assessed >6 mo after adr ce was first provided. Results: 42 trials with enter 31.000 smokers were identified. Most common settng for advice del very was primary care. A significant increase in qjittirg rates wascotedwith advice vs. no educe|RR US. 95% Cl 1.42-1.941. which was farther increased where the intervention was considered more intensive ( RR 1.84 95% Cl 1.60 2.13: o.s.). Intensive advice showed a small , non significant advantage vs. minmal advice when directly compared|RR 1.37. 95% Cl 1.20 1.56|.A small benefit with folow op visits was also noted , ho statistically signiheant difference in mortality a: 20 yr follow op was found. Conclusion : Smipleadv ce can increase saoi ng cessation rates by 1 3% on hip of the unassisted quit rate. More intensive advxeand providing folow-op support may further increase qurt rates.

.

.

-

-

-

-

-

-

3. Rewards: ( benefits)

-

improved health, save money, food tastes better, good example for children

4. Roadblocks: (obstacles)

fear of withdrawal, weight gain, failure, lack of support 5. Repetition - reassure unsuccessful patients that most people try many times before successfully quitting (average number of attempts before success is 7) • recent quitter highest relapse rate within 3 mo of quitting minimal practice: congratulate success, encourage ongoing abstinence, review benefits and risks prescriptive interventions: address problem ( s) of weight gain, negative mood , withdrawal, lack of support

Alcohol Use • see

Psychiatry , PS.S

Definition • alcohol use disorder diagnostic categories occur along a continuum Epidemiology

• 10 -15% of patients in family practice misuse alcohol • 20 -50% of hospital admissions, 10% of premature deaths, 30% of suicides, and 50% of fatal traffic accidents in Canada are alcohol- related • more likely to miss diagnosis in women, elderly, and patients with high socioeconomic status Assessment • screen for alcohol dependence with CAGE questionnaire if CAGE is positive, further explore for the possibility of alcohol misuse or dependence • assess drinking profile setting, time, place, occasion, with whom impact on family, work, social life quantity-frequency history how many drinks per day? how many days per week? maximum number of drinks on any one day in the past month ? • if identified positive for alcohol use disorder: screen for other drug use identify any medical /psvchiatric complications (e.g. delirium tremens or withdrawal seizures) ask about drinking and driving ask about past recovery attempts and assess current readiness to change

Standard Drink Equivalents

• One standard drink - 13.64 g of pure alcohol

• BeerfCider /Cooler (5% alcohol)

.•

12 oz

-

• Malt liquor (7% alcohol) - 8-9 oz Wine (12-17% alcohol) - 5 oz Fortified wine = 3 oz

-

• Hard liquor (40%) 1.5 oz

CAGE Questionnaire Have you ever felt you needed to Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt Guilty about drinking? Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover? Two "yes" responses is considered positive

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Toronto Notes 2023

FM16 Family Medicine Investigations

Abstinence

Management

Low Risk Drinking 1 mo?

*

ACUTE STRESS REACTION

Recurrent anxious thoughts?

|

PTSD

Excessive worry and apprehension about common concerns yes

6 mo

GAD

£

T

I

SPECIFIC PHOBIA

SOCIAL PHOBIA

T

Setting where it may be difficult to escape PANIC DISORDER WITH AGORAPHOBIA

Rule Out • Cardiac (post Ml, arrhythmias) • Endocrine (hyperthyroidism, diabetes, pheochromocytoma) • Respiratory (asthma, COPD) • Somatoform disorders • Psychotic disorders • Mood disorders (depression, bipolar) • Personality disorder (OCPD) • Drugs ( amphetamines, thyroid preparations, caffeine. OTC for colds/decongestants, alcohol/ benzodiazepine withdrawal)

Are the thoughts J ntrusive, inappropriate and distressing?

I

DISORDER Specific trigger Public setting where ( e.g. Hying, spiders, there migiit be ) negative evaluation blood etc.)

No

t

Patient alraid of another attack and its implications

i

Yes

J[

'r

T

Is patient INo avoiding situation?

i

v

Are they accompanied by a repetitive behaviour meant to neutralize the anxiety? Yes OCD

Differentia! Diagnosis of Wheezing • Allergies, anaphylaxis • Asthma, reactive airway disease GERD • Infections ( bronchitis, pneumonia) • Obstructive sleep apnea COPD • L ess common: congestive heart disease, foreign body, malignancy, cystic fibrosis, vocal cord dysfunction

. .

Excessive worry and apprehension about social situations?

-

Figure 7. Differentiating anxiety disorders using the DSM- V diagnostic criteria

.

.

Adapted from: Evans M Bradwejn J Dunn L. Anxiety Review Panel. Guidelines for the treatment o( anxiety disorders in primary care. Toronto:Queen's Printer of Ontario, 2000.41

Self Management Asthma and COPD Education and Written Action Plan • Education is a key component in management of asthma and COPD • Guided self -management combining education, regular medical review, self -assessment, and written action plans have been shown to reduce hospitalizations, ED visits, and missed days at work or school

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Sample action plans available online: https:/ / cts-sct.ca/

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FM 19 Family Medicine

Toronto Notes 2023

Management

• patient education: emphasize prevalence, good recovery rate of anxiety conditions • with consent, explore lifestyle hahits: exercise, caffeine, alcohol intake, etc. and collaboratively develop a person centered plan (e.g. reduce caffeine at a particular pace ) • psychological: psychotherapy including CBT, exposure therapy, relaxation techniques, and mindfulness strategies • pharmacotherapy: see Psychiatry, PS59 • offer self - help materials, connect with community resources (e.g. support groups), and provide support to family and caregivers

-

Signs of Poorly Controlled Asthma • p2 agonist use >4 x/wk • Asthma - related absence from world school • Exercise induced asthma • Night- time symptoms >1x/wk

What Colour Is Your Inhaler ?

• see

.

salbutamol - Ver tolin

Respirologv. R7

*

Light blue'navy

salmeterot - Serevent ?

Definition

KibeUlOf BriCiayf

lealhight teal Bluehartiile

ICS IkibtasoM - Brwent

Orange/peath

-

• asthma

.

Body /CapColour

Name p 2-Agonists

Asthma /COPD

chronic, reversible airway inflammation characterized by periodic attacks of wheezing, dyspnea , chest tightness, and coughing airways are hyper- responsive to triggers/antigens leading to acute obstructive symptoms including bronchoconstriction, mucous plugs, and increased inflammation cannot be diagnosed at first presentation • PFTs can be done starting at age 6 or when child is able to follow testing instructions • peak flow meters are useful in the office and at home for monitoring COPD group of chronic, progressive, non - reversible lung diseases characterized by limited airflow with variable degrees of air sac enlargement and lung tissue destruction • emphysema and chronic bronchitis are the most common forms

*

'

badesamde - Pnlmicort*

.

White'brown

-

Combined Long-Acting (2-Agonist ICS Ihtiasofle /salmeteiol - Adi& r' Purple discus Bedi'i/nte Dsdesonde loimoleiol, Symb cpTt ' Crey Wut Iktiusooe/ vilanterol- Breo Anticholinergics umettxlirjum - Incruse tiite /green ipratropnim - Atror/ ent 5 Oeet'green tiotiopr ffl - Spina ' thitefti'quoise

'

•

.

Table 8 . Differentiating COPD from Asthma Age of Onset

COPD

Asthma

Usually in 6 th decade

Any age ( but 50 c- of cases are diagnosed in children ages

10 packyr

Not causal, known trigger

Reversibility of Airflow Obstruction

Airflow obstruction is chronic and persistent

Evolution

Slow , progressive worsening ( with peciodic

Airflow obstruction is episodic and usually reversible with therapy Stable, episodic.‘50% will outgrow

History of Allergy

Infrequent

Precipitators

Environmental irritants (air pollution), cigarette Environmental irrilants ( dust , pollen), animal fur. smoking, n-1 antitrypsin deficiency , viral infection, cold air. exercise. URTIs, cigarette smoke, use ol ( blockers,' ASA occupalionai exposure (firefighters, dusty jobs)

Symptoms/ Signs

Chronic cough, sputum, and/or dyspnea

Wheere (hallmark symptom), dyspnea, chest tightness, prolonged expiration, cough which is worse in the cold, at night, and in the early AM

Diffusion Capacity

Decreased ( more so in pure emphysema)

Normal (for pure asthma )

Hypoxemia

Chronic in advanced slages

Not usually present Episodic with severe attacks

Spirometry

May have improvement with bronchodilators bul not universally seen

Marked improvement with bronclrodilalors or steroids

Chest X -Ray

Often normal Increased bronchial markings (chronic bronchitis) and chronic hyperinflation (emphysema) often coexist , bullae

Often normal or episodic hyperinflation Hyperinflation during asthma attack

Management

All: Smoking Cessalion Mild Step 1: SA 8 A as needed (salbulamol) Step 2: SABA as needed » LAAC (i.e. tiolropium) or LABA (e.g. salmeterol) Moderate Step 3: SABA / SAMA LABA or SABA LA 8 A or LAAC: consider inhaled vs. oral steroids

Ongoing patient education, and environmental control SABA taken pm as rescue medication • maintenance meds Mainlenancemedications Mild Step t: low - dose ICS Step 2: Medium / high dose ICS or low - dose ICS plus cither LABA . URA modifier Moderate Step 3: Medium high- dose ICS * either LABA . IT ' modifier Severe Step 4: As above immunotherapyioral glucocorticosteroids pneumococcal vaccination , annual influenia immunization

exacerbations) >

-

-

-

Severe Step 4: Pneumococcal vaccination, annual influenza immunization

50% patients

,

-

-

ICS * inhaled corticosteroids; LAAC * long- ac ling anticholinergic: LABA * long.iictlng P -agonlst; LT modifier •leukotrlene modifier; SABA » short, acting p -agonlst. SAMA short acting muscaiinic antagonist

-

I "-

S Harrs

I

uj

i *

I: 2=

Dbfll

jc

-

ive

'\

Restrictive

n-bl*-? r tv

.«

1 second

tmi matter

-

*

tUNti VOLUME ill

Figure 8. Expiratory flow volume curves (obstructive, normal, and restrictive disease) See Respirologv. R4 Adapted from: Weinberger SE. Principles of pulmonary medicine. 5 th ed. With permission from Elsevier. 2008

More About Inhalers Aerosols (puffers MDI. MDI + spacer ) MDIs should be used with spacers to:

.

-

.

Reduce side effects • Improve amount inhaled

• Increase efficiency of use • DPI (discuss, turbuhaler. and diskhaler) require deep and fast breathing (may not be ideal for children) Nebulizers can be used to convert liquid medications into a fine mist: recommended for use if contraindications to MDIs Currently there is large push in dinica! practice to transition away from the use of MDI inhalers and to move towards using DPI inhalers to reduce the impact of aerosol treatments on the environment • Evohaler MDIs had 20- 30 times larger carbon footprints than the Accuhaler and Elipta DPIs (Thorax 2020 Jan;75(1):82-84.)

. .

When prescribing salbutamol. watch

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+

out for signs of hypokalemia: lethargy,

irritability, paresthesias, myalgias, weakness, palpitations. NN polyuria

.

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FM20 Family Medicine

Toronto Notes 2023

Benign Prostatic Hyperplasia • see U roloav. U 7 Definition

• hyperplasia of the stroma and epithelium in the periurethral transition zone History and Physical

• include current /past health, surgeries, trauma, current medications including OTC

• specific urinary symptoms • physical exam must include DRE for size, symmetry, nodularity, and texture of prostate ( prostate is symmetrically enlarged , smooth, and rubbery in BPH )

Investigations • urinalysis to exclude UT1 and for microscopic hematuria (common sign ) • serum PSA: protein produced by prostatic tissue PSA to screen / test for BPH is no longer used due to the high false positive rate, and is instead used as a marker to guide treatment once diagnosis has been made PSA testing is inappropriate in men with a life expectancy less than 10 yr or patients with prostatitis, UTI • increased PSA in a younger man is more often due to cancer than other causes abnormal DRE or PSA should trigger further assessment discuss test with men at increased risk of prostate cancer ( FHx, Black men ) or who are concerned about development of prostate cancer decision to test PSA in an asymptomatic man ( see Prostate Cancer Screening , PM 6 ) • other tests Cr, BUN, PVR volume by U /S, urodynamic studies, renal U /S, patient voiding diary • tests NOT recommended as part of routine initial evaluation include: cystoscopy, cytology, prostate U /S or biopsy, 1VP, urodynamic studies

Table 9. Symptoms and Complications of BPH Obstructive Symptoms

Irritative Symptoms

Late Complications

Hesitancy (difficulty starting urine flow) Diminution in sire and force of urinary stream Stream interruption (double voiding) Urinary retention (bladder docs not feel completely empty ) Post - void dribbling

Urgency Frequency Nocturia Urge incontinence Dysuiia

Hydronephrosis Loss of renal concentrating ability Systemic acidosis Renal lailure

Overflow incontinence Nocturia

Management

• referral to urologist if moderate/severe symptoms • conservative: for patients with mild symptoms or moderate /severe symptoms considered by the patient to be non - bothersome

fluid restriction (avoid alcohol and caffeine ) avoidance/monitoring of certain medications (e.g. antihistamines, diuretics, antidepressants,

decongestants) pelvic floor/ Kegel exercises; consider referral to pelvic physiotherapist bladder retraining ( scheduled voiding ) • pharmacological: for moderate/severe symptoms a - receptor antagonists ( e.g. terazosin ( Hytrin *), doxazosin ( Cardura*), tamsulosin ( ITomax* ), alfuzosin (Xatral *)) relax smooth muscle around the prostate and bladder neck 5 - a reductase inhibitors (e.g. finasteride ( Proscar* )) « only for patients with demonstrated prostatic enlargement due to BPH

inhibit the enzyme responsible for conversion of testosterone to dihydrotestosterone ( DHT ) thus reducing growth of prostate

antimuscarinic and P -3 agonists

•

recommended for storage symptoms, but avoid in patients with bladder outlet obstruction and /or elevated PVR long acting phosphodiesterase inhibitor recommended in patients with erectile dysfunction

-

desmopressin

-

• surgical

•

r •»

recommended for nocturia as a result of nocturnal polyuria ( watch for hyponatremia in older adults)

u

.

TURP TU 1 P (for prostate < 30 g ) absolute indications: failed medical therapy, intractable urinary retention, benign prostatic obstruction leading to renal insufficiency complications: impotence, incontinence, ejaculatory difficulties (retrograde ejaculation),

+

decreased libido

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FM21 Family Medicine

Toronto Notes 2023

Bronchitis (Acute) Definition

• acute infection of the tracheobronchial tree causing inflammation leading to bronchial edema and mucus formation

.

Differential Diagnosis of Bronchitis URTI • Asthma

Epidemiology

• Acute exacerbation of chronic

• 5th most common diagnosis in family medicine, and most common is URTI

.

bronchitis

• Sinusitis

Etiology • 80% viral: rhinovirus, coronavirus, adenovirus, influenza, parainfluenza, and RSV • 20% bacterial: M . pneumoniae, pneumoniae , ami S. pneumoniae

Pneumonia • Bronchiolitis

• Pertussis • Environmental/occupational exposures

Investigations • acute bronchitis is typically a clinical diagnosis • sputum culture /Gram stain is not useful • CXR if suspecting pneumonia ( cough > 3 wk, abnormal vital signs , localized chest findings) or HE

• Post -nasal drip

.

. . .

Others: GERD CHF cancer, aspiration syndromes, CF foreign body

• PIT with methacholine challenge if suspecting asthma Management

• primary prevention: frequent hand washing, smoking cessation , avoid irritant exposure • symptomatic relief: rest , fluids ( 3 4 L /d when febrile ), humidity, analgesics, and antitussives as required • bronchodilators may offer improvement of symptoms (e.g. salbutamol ) • current literature does not support routine antibiotic treatment for the management of acute bronchitis because it is most likely to be caused by a viral infection antibiotics may be useful if elderly, comorbidities, suspected pneumonia, or if the patient is toxic (see Antimicrobial Quick Reference, FM 54 ) antibiotics in children show no benefit

-

How to Tell if Viral or Bacterial? Bacterial infections tend to give a higher fever, excessive amounts of purulent sputum production, and may be associated with concomitant COPD

Chest Pain • see Cardiology and Cardiac Surgery, C 5 and Emergency Medicine, ER 21

Differential Diagnosis Table 10. Differential Diagnosis of Chest Pain

-

Diagnosis

Clinical Findings

LR+

LR

Acute Ml

Chcst pain radiates to both arms

7.1

0.67

Third heart sound on auscultation

3.2

0.88

Hypotension

3.1

0.96

Chesl Wall Pain

>2 of: localized muscle tension, slinging pain, pain reproducible by palpation, absence of cough

3.0

0.47

GERD

Burning retrosternal pain, acid regurgitation, sour or bitter taste in the mouth: 1 wk trial of high- dose proton pump inhibitor relieves symptoms

3.1

0.30

Panic Disordor/Anxioty State

Single question: In the past 4 wk have you had an anxiety attack ( suddenly feeling fear or panic)?

4.2

0.09

Pericarditis

Clinical tnad of pleuritic chest pain (increases with inspiration or when reclining, and is lessened by leaning forward), pericardial friction rub, and electrocardiographic changes (diffuses ? segmentelevation andPR interval depression without ? wave inversion)

N/ A

N 'A

Egophony

8.6

0.96

Dullness lo percussion

4.3

0.79

Pneumonia

Heart Failure

Pulmonary Embolism

.

.

.

• Age

Red Flags

Fever

2.1

0.71

Clinical impression

2.0

0.24

Pulmonary edema on chesl radiography

11.0

0.48

Clinical impression/ judgment History of heart failure

9.9

5.8

0.66 0.45

History of acute myocardial infarction

3.1

0.69

High prctesl probability based on Wells criteria

6.8

1.8

Moderate pretest probability based on Wells criteria

1.3

0.7

Low pretest probability based on Wells criteria

0.1

7.6

5.3

NIA

Acute Thoracic Aortic Dissection Acute chest or back pain and a pulse differential in the upper extremities

Risk Factors for CAD Major • Smoking • Diabetes • HTN • Hyperlipidemia • Family history of early CAD in first degree relative (males 5/9 with at least one of anhedonia or depressed mood for >2 wk)

(controversial )

MSIGECAPS Depressed Mood M S Increascdfdccreased Sleep Decreased Interest I

SNRI

venlafaxine ( Effexor - ) duloxetine (Cymbalta - ) desvcnlafaxine ( Pristiq ' )

Block serotonin and norepinephrine reuplake

Insomnia , tremors, tachycardia, sweating

SDRI

bupropion ( Wellbutrin )

Block dopamine and NE reuptake

Headache , insomnia , nightmares , seizures, less sexual dysfunction than SSRIs

TCA

amitriptyline ( Elavil - )

Block serotonin and NE

Sexual dysfunction , weight gain tremors, tachycardia , sweating

decreased libido, delayed ejaculation, anorgasmia ), headache, Gl upset , weight loss, tremors, insomnia , fatigue, increase Of interval ( baseline ECG is suggested )

'

G E

Often chosen for lack of sexual side effects, can be used for augmentation of anti -depressant effects with other classes of medication

reuptake

Prognosis

.

Criteria for Depression

Guilt Decreased Energy Decreased Concentration C A Increased /decreased Appetite and weight Psychomotor agitation/ P retardation S Suicidal ideation

Nairow therapeutic window, lethal in overdose

-

• up to 40% resolve spontaneously within 6 12 mo • risks of recurrence: 50 % after 1 episode, 70% after 2 episodes, 90% after 3 episodes

Diabetes Mellitus

.

• see Endocrinology E7 • see 2018 Clinical Practice Guidelines from Diabetes Canada, available from : http:/ /guidelines.diabetes, ca /cpg • see Diabetes Mellitus Patient Care How Sheet from Canadian Diabetes Association, available from: https:// guidelines.diabetes.ca /docs/cpg/Appendi.x-3.pdf DM Related Symptoms

Definition • metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, defective insulin action, or both Classification and Diagnosis • see Endocrinology. E7 Epidemiology

• major health concern , affecting up to 10% of Canadians • incidence of T 2 DM is rising due to increasing obesity, sedentary lifestyle, and age of the population • leading cause of new - onset blindness and renal dysfunction • Canadian adults with DM are twice as likely to die prematurely compared to persons without DM • 1 in 5 Indigenous people in Canada has diabetes

.11 personal

• Hyperglycemia: polyphagia,

polydipsia, polyuria, weight change, blurry vision, yeast infections • Diabetic Ketoacidosis (DKA): fruity breath, anorexia N/V fatigue, abdominal pain Kussmaul breathing, dehydration • Hypoglycemia: hunger, anxiety, tremors, palpitations, sweating, headache, fatigue, confusion, seizures, coma

.

. .

-

Long Term Complications of DM

• Microvascular : nephropathy,

Risk Factors

retinopathy, neuropathy • Macrovasculan CAD, CVD, PVD

DM

or family history of autoimmune disease

• T 2 DM

first degree relative with DM

• ages >40 yr obesity (especially abdominal ), HTN , hyperlipidemia, CAD, vascular disease prior gestational diabetes mellitus, macrosomic baby ( > 4 kg ) • PCOS history of IG F or 1 FG presence of complications associated with DM • presence of associated diseases: FCOS, acanthosis nigricans, psychiatric disorders, HIV medications: glucocorticoids , atypical antipsychotics , HAAKT • both

member of a high - risk population (e.g. Indigenous peoples, Hispanic, Asian, or African descent)

Screening •T 2DM EBG or HbAlc in everyone >40 q3 yr, or at high-risk using the CANR 1SK calculator more frequent and /or earlier testing if presence of I risk factor ( see above ) • gestational diabetes mellitus ( sec Obstetrics. OB29) • all pregnant women between 24 -28 wk gestation

+

A1C Interpretation

• advantages: convenient ( measure any time of day )

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FM 26 Family Medicine

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single sample

• predicts niicrovascular complications • better predictor of CVD than fasting plasma glucose ( FPG ) or two hour plasma glucose in a 75g GCiT'F day to - day variability slow • • reflects long- term glucose concentration •disadvantages:

-

cost

misleading in various medical conditions (e.g . hemoglobinopathies, iron deficiency, hemolytic anemia, severe hepatic or renal disease) altered by ethnicity and aging • standardized, validated assay required • not for diagnostic use in children and adolescents (as the sole diagnostic test ), pregnant women as part of routine screening for gestational diabetes, those with CF, or those with suspected T1DM Goals of Therapy

•see

Endocrinology, F9 and

Clinical Pearl (SMART Goals)

Assessment and Monitoring

SMART

Diabetes Quick Reference Guide A A1C: Optimal Glycemic Control (Usually 50

.

.

• common: functional, PUD, GEKD, gastritis

H pylori Eradication Bismuth Ouadruple Therapy (PBMT) or Concomitant NonBismuth Ouadruple Therapy ( PAMC) for 14 days

History

• symptoms may not be useful in finding cause • associated with eating, anorexia , N / V, alcohol, NSAID use • red flags: vomiting, bleeding /anemia, abdominal mass, dysphagia ( VBAD)

PBMT: 1|PPI standard dose BID 2) Bismuth subsalicylate 524 mg OID 3) Metronidazole 500 mg OID 4) Tetracycline 500 mg OID

Investigations • for new onset dyspepsia: 60 yr should undergo upper endoscopy to rule out organic pathology

PAMC: 1) PPI standard dose BIO 2) Clarithromycin 500 mg BID 3) AmoxidBin 1000 mg BID 4) Metronidazole 500 mg BID

• others: cholelithiasis, irritable bowel syndrome, esophageal or gastric cancer, pancreatitis, pancreatic cancer, Zollinger-Ellison syndrome, and abdominal angina

Management

• lifestyle modifications: decrease caffeine and alcohol intake, avoid citrus food, smaller and more

frequent meals, avoid supine position right after meals, smoking cessation • pharmacologic treatment gastric acid suppression: H 2 blockers, PPls; both are effective for PUD and GERD • TCAs or prokinetics: e g metoclopramide; effective for functional dyspepsia

• H . pylori eradication

..

do not keep patients on PPI without at least 1 trial off the medication per year (https://choosingwiselycanada.org/ perspective/ ppi- toolkit/ ) • for non - responders, upper endoscopy should be considered. If endoscopy is negative, defined as

functional dyspepsia

rn

LJ

+

AL GRAWANY

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Dyspnea • see Respirologv, R3 and Emergency Medicine. ER 26 Definition • uncomfortable, abnormal awareness ofbreathing , a subjective sensation of shortness of breath , or difficulty breathing • when discussing dyspnea with patients, consider using language that is easy for patients to understand such as speaking about “ feeling breathless” or “ having trouble catching your breath ” History and Physical Exam • history associated symptoms ( cough , sputum , hemoptysis, wheezing, chest pain , palpitations, dizziness, edema ) * constitutional symptoms ( night sweats, fever, weight loss) history of asthma , allergies, eczema, ASA / NSAID sensitivity, nasal polyps smoking, recreational drugs, medications occupational exposure, environmental exposure (e.g. pets, allergens, smoke ) travel and birth place (considering areas with increased prevalence of tuberculosis)

• family history of atopy

previous CXR or PFTs • physical exam: vitals, respiratory, precordial , HEENT, signs of anemia / liver failure/ heart failure

. CXR,, ECG

Investigations

Differential Diagnosis of Dyspnea Pulmonary COPD

.

• Asthma • Restrictive lung disease

• Pneumothorax • Congenital lung disease • PE • Malignancy Cardiac HF • CAD • Ml (recent or past) cardiomyopathy • Valvular dysfunction • Pericarditis • Arrhythmia • Hypertrophy Mixed/Other • Deconditioning • Psychological and/or physical trauma • Pain • Neuromuscular • Metabolic condition • Anemia • Functional: anxiety, panic attack, hyperventilation

.

• PFTs ABG acutely if indicated

Management • dependent on cause • send to ED if acute presentation with moderate symptoms • call ambulance if in severe respiratory distress

Dysuria • see Urology, U 10 Definition • the sensation of pain , burning, or discomfort when urinating

Epidemiology • more common in women than men • approximately 25% of women report one episode of acute dysuria per yr • most common in women ages 25-54 and in those who are sexually active • in men, prevalence of dysuria increases with age

UTI Clinical Decision Aid Arch Intern Med 2007:67:2201-2206 • Dysuria • -Leukocytes (on urine dipstick) • +Nitrites (on urine dipstick) If 2 or more criteria met then treat without culture, otherwise culture required prior to treatment.

Risk Factors for Complicated UTI Male • Pregnancy • Recent urinary tract instrumentation Functional or anatomic abnormality of the urinary tract • Chronic renal disease DM Immunosuppression • Indwelling catheter

Etiology • infectious most common cause presents as cystitis, urethritis, pyelonephritis, vaginitis, cervicitis, epididvmo- orchitis, or

.

• non -infectious * hormonal conditions ( hypoestrogenism ), obstruction ( BPH , urethral strictures ), allergic reactions, radiation, drugs /chemicals, foreign bodies, trauma, neoplasm, kidney stones, inflammatory diseases, endometriosis, psychogenic

. .

prostatitis

Cranberries for Preventing Urinary Tract Infections Cochrane OB SystRev 20t2 ;10:CD001321 Purpose: io assess the effectueress of cranberry products in preventing UIIs in susceptible populations. Methods: Ail random iced codrolledtriaIs ( RCTs|or rjuasi dCIsof cranberry products lor the prevention of UIIs were assessed and a meta - analysis of 24 RCTs ( n 44l 3|conducted. Results: Cranberry products did notsign ficanlly reduce the incidence of symptomatic Ullsat 12 mo (IIII 0.86. 9S% CI 0.714.04) compared with placebo! control. Conclusion : Cranberry prodcctsdo not have a significant benefit in th e prevention of symptom atic UIIs over a 12 mo period.

r1 L

-

+

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FM32 Family Medicine

Toronto Notes 2023

Table 13. Etiology, Signs , and Symptoms of Common Causes of Dysuria Infection

Etiology

UTICystitis

KEEPS bacteria {Klebsiella. £ coli. Inlerobacler Proteus mirabilis Pseudomonas.S. saprophyticus )

Signs and Symptoms

.

.

.

.

Urethritis

C. trachomatis. H gonarrhoeae trichomonas Candida.

Vaginitis

Candido EardnereUa trichomonas, C. trachomatis atrophic, herpes,lichen sclerosis

.

Internal dysuria throughout micturition, frequency,urgency incontinence,hematuria, nocturia, back pain,suprapubic discomfort low grade fever (rare)

.

Initial dysuria urethral/ vaginal discharge,history ofSTI

herpes

Prostatitis Pyelonephritis

.

.

.

.

.

Eiternal dysuria /pain, vaginal discharge, irritation, dyspareunia abnormal vaginalbleeding

.

. Internal dysuria. lever, chills, flank pam radiating togroin. f. coli. S. saprophyticus. Proteus mirabiUs. Interobocter. f. coli C. trachomatis. J saprophyticus Proteus mirabitis. Dysuria. lever, chills, urgency, frequency, tender prostate Inter obocter. Klebsiella. Pseudomonas rectal pain

.

Klebsiella Pseudomonas

Prevention of UTIs

• Maintain good hydration

• Avoid feminine hygiene sprays and scented douches

• Empty bladder immediately before and after intercourse • Vaginal estrogen therapy for peri and post menopausal women with recurrent UTIs

-

CVA tenderness. NiV

Investigations

physical are consistent with an uncomplicated UT1, treat empirically with no further investigations • urinalvsis/ dipstick: positive for nitrites and leukocytes • urine R & M: pyuria, bacteriuria, hematuria • urine C&S • CBC and differential if suspecting pyelonephritis • if vaginal / urethral discharge present : wet mount , Gram stain, KOH test , vaginal pH, culture for yeast and trichomonas, endocervical / urethral swab or urine PCR for N.gonorrhoeae and C. trachomatis • radiologic studies and other diagnostic tests if atypical presentation • see Paediatrics, P69 for L IT • if history and

Management

hospitalize if septic or critically ill, and consider hospitalization if persistently high fever, persistent pain , severe weakness, or inability to maintain hydration or tolerate oral feeds • first line treatment of uncomplicated UT' l is TMP/SMX (cotrimoxazole ) I 60 /800 mg BID x 3 d or nitrofurantoin 100 mg BID x 5 d • UTI/cystitis pregnant women with bacteriuria ( 2-7%) must be treated ( first line: amoxicillin, nitrofurantoin, cephalexin ) even if asymptomatic due to increased risk of pyelonephritis, preterm labour, low birth weight , and perinatal mortality. Need to follow with monthly urine cultures and repeat if •

-

still infected patients with recurrent UTIs ( >3/ yr ) should be considered for prophylactic antibiotics • if complicated UT'l, patients require longer courses of broader spectrum antibiotics

• urethritis

•

positive swab or PCR for chlamydia or gonorrhea must be reported to Public Health

• all patients should return 4 -7 d after completion of therapy for clinical evaluation

Epistaxis • see Otolaryngology, 0127

Erectile Dysfunction • see Urology. U 33 Definition • >3 mo of consistent or recurrent inability to attain and /or maintain sufficient penile erection for

sexual performance

Epidemiology 20% of men age 40; 50% of men age 70

•

-

-

Etiology • organic: vascular (90% ) (arterial insufficiency, atherosclerosis), endocrine ( low testosterone, DM ), anatomic (structural abnormality, e.g. Peyronie’s), neurologic ( postoperative, DM ), medications (donidine , antihypertensives, SSRls, tricyclic antidepressants, cimetidine, 5-a- reductase inhibitors) • psychogenic (10%)

Differential Diagnosis of Erectile Dysfunction

PENIS Psychogenic Endocrine (T2DM. testosterone) Neurogenic (T 2DM. postoperative) Insufficiency of blood ( atherosclerosis) Substances

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Table 14. Differentiation Between Organic and Psychogenic ED Characteristic

Organic

Psychogenic

Onset

Acute

Circumstances

Gradual Global

Situational

Course

Constant

Varying

Don-Coital Erection

Poor

Rigid

Morning Erection

Absent

Present

Psychoseiual Problem

Secondary

Long history

Partner Problem

Secondary

At onset

Secondary

Primary

Anxiety and Fear

.

.

Ike Effect of lifestyle Modification and Cardiovascalar Risk Factor Seduction on Erectile (Fpfnctioa A cS li»r Met) 2011:171:17971803 Purpose to evaluate the effectiveness of lifestyle ntenrentions and pharmacotherapy for ca -4oiasc ar|CV|risk factors on sereriiyofereclie tfjsVct 3'PIMethods VeS -analps of RCTs with a foilow-cp of a toa of 6 wk,evaluating lifestyle rntenrention c. pharracoterapy for CV risk factor reduction.Mum ostoce measure iras we.ghted mean differences - tie International Index nf Erectile Dysfunction (Kf -5) score. Results 5 RClswith a total of 740 participants ere octoded. Lifestyle modifications and ptaroacotsecapy for CV risk factor reduction were bo~ associated with significant improvements m sei i function based on IIEF -5 scores (wtgtited mean d fference (»MD| 2.66 95% Cl 1.86-3.47)Eictudmg stain trials, lifestyle modification tentitms were associated with a statistically sgrfeant impronement in sexual function |WMD 1 .L19-151). Coadnsion: Lifestyle modificatons and pranacouetapy fa CV risk reduction are effective in c oramg male sexual function.

-

-

.

.

Walsh PC Campbell MF Retik AB. Campbell's Urology 8!h ed. W.B. Saunders, 2002. Table 46-4

History • comprehensive sexual , medical , and psychosocial history

• review medication and substance use

.

• time course

• last satisfactory erection • gradual or sudden onset • attempts at sexual activity • quantify • presence of morning or night time erections stiffness ( scale of 1 - 10) ability to initiate and maintain an erection with sexual stimulation erection stiffness during sex (scale of 1 -10)

.

«

• qualify • partner or situation specific

.

• loss of erection before penetration or climax • degree of concentration required to maintain an erection percentage of sexual attempts satisfactory to patient and /or their partner significant bends in penis or pain with erection difficulty with specific positions impact on quality of life and relationship Investigations

hypothalamic -pituitary-gonadal axis evaluation: testosterone ( free + total ), prolactin, LH risk factor evaluation: fasting glucose, HbAlc, lipid profile others: TSH , CBC, urinalysis • specialized testing • psychological and /or psychiatric consultation • in - depth psychosexual and relationship evaluation • nocturnal penile tumescence and rigidity ( NPTR ) assessment vascular diagnostics ( e.g. doppler studies, angiography ) • • •

Reasons for Referral to Urology Significant penile anatomic disease • Younger patient with a history of petvic or perineal trauma • Cases requiring vascular or neurosurgical intervention • Complicated endocrinopathies • Complicated psychiatric or psychosoda! problems • Patient or physician desire for further evaluation

Management

Table 15. Management of Erectile Dysfunction

•

Nonpharmacologic

Pharmacologic

Surgical

Lifesty le changes (alcohol, smoking, exercise) Relationship/ sexual counselling Vacuum devices

Oral agents Suppository Hale urethral suppository for erection (MUSE) Injections

Implants

Vascular repair

Rea ignment

pharmacologic treatment phosphodiesterase type 5 inhibitors • testosterone (currently only indicated in patients presenting with hypogonadism and testosterone deficiency (note: breast/ prostate cancer are absolute contraindications)) • a-adrenergic blockers (e.g. yohimbine); currently limited data for use in erectile dysfunction Table 16. Phosphodiesterase Type 5 Inhibitors Examples

Dosing (1 dose/d)

Specifics

Side Effects

Contraindications

sildenafil (Viagra )

25 -

lake 0.5 - 4 h prior to intercourse May last 24 h

Flushing, headache, indigestion

Not to be used in patients taking nitrates

tadalafil (Cialis )

5 - 20 mg/dose

Effects may last 36 h

As above

As above

vardenafil (levitra )

2.5- 20 mgldose

Take 1h prior to intercourse

As above

As above

100 mg, dose

'

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Fatigue Definition

• can describe difficulty or inability to initiate activity, maintain activity, or difficulty with concentration /memory • presentation may vary and the patient’s specific complaint should be clarified, e.g. excessive sleepiness, muscle weakness, decreased exercise tolerance, mood concerns Epidemiology

• 25% of office visits to family physicians

peaks in ages 20-40 F:M =3-4:1 • 50% have associated psychological complaints/ problems, especially if •deficiency, Bn deficiency)

Neurogenic

Myasthenia gravis, multiple sclerosis, Parkinson's disease

D

Drugs

p-blockers,antihistamines,anticholinergics,benzodiazepines, antiepileptics,antidepressants

I

Idiopathic

C A

Chronic illnesses Autoimmune

HF,lung diseases (e.g. COPD, sarcoidosis),renal failure,chronic liver disease SLE, RA mixed connective tissue disease,polymyalgia rheumatica

T E

Toxin Endocrine

Substance misuse (e.g alcohol), heavy metal Hypothyroidism, OM. Cushing's syndrome, adrenal insufficiency, pregnancy

.

.

Common causes are In bold

Investigations • psychosocial causes are common, so usually minimal investigation is warranted • physical causes of fatigue usually have associated symptoms /signs that can be elicited from a focused history and physical exam • investigations are guided by history and physical exam and may include: CBC and differential, electrolytes, BUN , Cr, KSU , glucose, TSH , ferritin , vitamin Bt 2, serum protein electrophoresis, Bence Jones protein , albumin, AST, ALT, ALP, bilirubin , calcium , phosphate, ANA, hCCi urinalysis, CXR ECG additional tests: serologies ( Lyme disease, hepatitis B and C screen, HIV, ANA) and Mantoux skin tests

.

-

P-

Treatment

• treat underlying cause • if etiology cannot he identified ( 1/3 of patients) • validation and follow up, especially with fatigue of psychogenic etiology • supportive counselling, behavioural, or group therapy • encourage patient to stay physically active to maximize function , and consider using motivational

-

interviewing techniques to create person - centred approaches

review all medications, OTC, and herbal remedies for drug-drug interactions and side effects prognosis: after 1 yr, 40% are no longer fatigued

CHRONIC FATIGUE SYNDROME

Diagnosis (IOM, 2015)

• diagnosis requires the following three symptoms:

-

1. a substantial reduction or impairment in the ability to engage in pre illness levels of activity that is: lasting >6 mo accompanied by fatigue of new onset, not alleviated by rest, and not caused by excessive exertion

2. post-exertional malaise * worsening of symptoms after physical, mental or emotional exertion that would not have

+

caused a problem before the illness

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3. unrefreshing sleep' even after a full night of sleep despite the absence of specific objective sleep alterations AND • at least one of the two following manifestations is also required:

cognitive impairment * orthostatic intolerance ' The frequency and severity of these symptoms need to be evaluated Epidemiology • l > M , more common in White individuals than other groups, majority in their 30s • found in 2019:10:C0003200 ftrpos*: lo determiue the effects of eietcise therapy for ado Its with chronic torque syndrome ( CFS ) conjured unth any other intervention or control. Methods: Meta -analyssolKIs invoking adults with CFS as a primary diagnosis who were able to participate m eietcise therapy. Studies compared eietcise therapy to passive control, psychological therapies, adaptive pacing therapy, or pharmacological therapy. Results f rtftciswilh ISIS participants were ci ded . Eietcise therapy lasted 12 to 2t irk. Moderate quality evidence showed exercise therapy was more effective in reducing fatigue vs. passive or no treatment , and was also associated with a positive effect oe daily physical functioning and steep. It also slightly improved physical functioning, depression , and sleep compared to adaptive pacing . Conclusion Exercise therapy may have a positive effect on fatigue m adults with CFS compared to usual care ot passive therapies.

.

• provide support and education that most patients improve over time • non - pharmacological regular physical activity, optimal diet, psychotherapy, family therapy, support groups

• consider using motivational interviewing techniques to create person -centred approaches • pharmacological • to relieve symptoms: e.g. antidepressants, anxiolytics, NSAlDs, antimicrobials ( if indicated based on investigations), anti-allergy therapy, antihypotensive therapy

Fever

.

• see Paediatrics P58 Definition • oral temperature >37.2°C (AM ), 37.7°C ( PM ) • fever in children < 2 yr must be a rectal temperature for accuracy « TM not accurate for measurement until child is >5 yr

Table 18. Differential Diagnosis of Fever Infection

Cancer

Medications

8acterial Viral IB

Leukemia Lymphoma Other Malignancies

Allopurinol

Captopril Cimetidine Heparin

INK

Other Nifedipine Phenytoin

Diuretics Barbiturates Antihistamines

Inflammatory 8o wet Disease Collagen Vascular Disease DVT

Meperidine

History

• fever

peak temperature, type of thermometer, site of temperature measurement , duration time of day response to antipyretics • systemic symptoms weight loss, fatigue, rash , arthralgia, night sweats • symptoms of possible source URT1: cough, coryza , ear pain (consider influenza, COVID 19) UT l / pyelonephritis: dysuria foul smelling urine, incontinence, frequency, hematuria, flank pain • pneumonia: cough, pleuritic chest pain • meningitis: headache, confusion, stiff neck, rash osteomyelitis: bone pain skin: purulent discharge • P1D: discharge, dyspareunia, lower abdominal pain • gastroenteritis: abdominal pain, diarrhea, blood per rectum, vomit

•

'

. -

-

r

medications • PK / DVT: swollen legs, pain in calf, SOB, pleuritic chest pain • history of cancer/family history of cancer • infectious contacts travel history, camping, daycare, contact with TB, foodborne, animals

-

i

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I'M 36 Family Medicine

Possible Investigations • CBC and differential, blood culture, urine culture, urinalysis viral swab including influenza, COVID-19 • stool O&P, Gram stain , culture • CXR, Mantoux skin test , sputum culture • lumbar puncture Management • increase fluid intake • general: sponge bath , light clothing • acetaminophen /ibuprofen as needed • treat underlying cause

Headache Definitions • primary headaches see Neurology. N 46 primary headaches are the most common headaches seen in family medicine including tension headaches, migraines, and cluster headaches secondary causes should be ruled out prior to diagnosing a patient with a primary headache • secondary headaches • caused by underlying organic disease account for < 10% of all headaches, may be life threatening

-

Etiology of Secondary Headaches

• drug: drug withdrawal, medication overuse, drug side effect, and carbon monoxide • infectious: meningitis, encephalitis, abscess • vascular: aneurysm, stroke, subarachnoid hemorrhage, HTN, and temporal arteritis • endocrine: thyroid disease, pheochromocytoma • neoplastic: tumour • trauma: TMJ injury, c -spine injury, head injury, subdural hematoma , and subarachnoid hemorrhage • other: serious ophthalmological and otolaryngological causes Investigations • indicated only when red flags are present and may include: CBC for suspected systemic or intracranial infection ESR or CRP for suspected temporal arteritis neuroimaging (Cl or MR1) to rule out intracranial pathology CSF analysis for suspected intracranial hemorrhage, infection Management

• based on underlying disorder • analgesics may provide symptomatic relief • see Neurology, N 46

Acupuncture for Migraine Prophylaits Coe lane OB Syst Rev 2016:6:C04012 t8 P urpose: lo investigate whether acupuncture is mote effective than no prophylactic treatment, routine are only, or sham acupuncture, and whether it is as effective as prophylactic pharmacological treatment ntermsof reducing headache frequency in adults with episodic migraine. Methods: Meta - ana:ysis of RCIsmthani irum of an 8 wk duration , comparing acupuncture intervention with a no acupuncture toohol (no ptophylaiis rouhne tare sham or pharmacological piophylaiis). lesults: 22 trials with 4985 participants were included . Acupuncture was associated wrth moderate headache frequency redaction compared to no acupuncture (standardized mean difference|SM0) -0.56. 85% Cl 0.65 to - 0.48|. and a reduction of >50% in headache frequency for 41 % and 17% of participants receiving acupuncture and no acupuncture, respectively Ipooied risk laho |tt| 2.40 2.0Sto 2.76; NMI 4.3 lo 6|. Acupuncture showed a small but statistically significant reduction ovet sham troth post - treatment (SMD -0.18. - 028 to -0.08) and post-follow - up (SMD -0.19, -0.30 to 0.09) with >50% headache frequency reduction being achieved in 50% vs. 41 % of those receiving acupuncture and sham, respectively Ipooied RR 1.23 1.11 to 1.36: Mil11.2 to 20 ); these numhers were 53% and 42%, respectively, post-follow- up ( pooled R0125.1.13 to 1.39: NM110.6 to 18). Num her of partcipants dtopprng out and reportuigadveneeffetlsdid not differ significantly between acupuncture and sham groups. Compared to pharmacological ptophylaiis a significant reduction m migraine frequency was noted with drugs (SMD - 0.25, 0.39 to 0.10). but the significance was not maintained at foRow - up. After 6 mo. headache frequency was hahred in 59% of patients receiving acupuncture and 54 % receiving prophylactic dregs (pooled RR 1.11.0.97 to 126). Those receiving acupuncture were less likelyt> drop out due lo adverse effects or lo report adverse events than ( hose receiving drugs.

-

.

. .

-

.

- .

-

.

.

-

Hearing Impairment • see Otolaryngology. 017

Definition • hearing impairment: a raised hearing threshold measured as decibels of hearing loss relative to the

normal population at specific frequencies • hearing disability: hearing impairment that interferes with performing daily tasks Classification conductive ( external sound does not reach the middle ear) • sensorineural (involving the inner ear, cochlea , or auditory' nerve)

-

Conclusion Add ' ngacupuncture losympfomatic treatment of attacks reduces frequency of headaches. Acupuncture is move effective than sham, and is similarly effective lo pharmacological interventions fo< migraine ptophylaiis.

•

• mixed

Migraine Screen

Epidemiology • prevalence increases with age (6% of 35 44 yr, 43% of 65 84 yr ) • 90 % of age - related hearing loss ( presbycusis) is sensorineural • hearing loss detectable by audiology is present in greater than 1 / 3 of people >65 yr

-

Assessment • infants: universal newborn hearing screening program • elderly

-

POUND Pu Isatllc quality Over 4 72 h Unilateral Nausea and vomiting Disabling intensity If >4 present then a diagnosis is likely (Positive likelihood ratio - 24)

-

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• screening tests • whispered votce test * examiner stands 0.6 meters (arm 's length ) behind the patient, whispers a combination of 6 letters / numbers, and asks the patient to repeat the sequence. Test 1 ear at a time while masking the non -test ear simultaneously » tuning fork test ( to distinguish conductive from sensorineural hearing loss) • diagnostic tests (formal audiologic assessment ) • pure tone, air, and bone conduction testing • speech audiometry • impedance audiometry

-

Management

• counsel about noise control and hearing protection programs (grade A evidence) treat patients with unexplained unilateral sensorineural hearing loss urgently with steroids consider blood sugar, CBC and differential, TSH, syphilis testing for unexplained sensorineural hearing loss • consider a CT/MR1 for patients with progressive asymmetric sensorineural hearing loss to exclude vestibular schwannoma (acoustic neuroma ) • refer patients who • have an unknown etiology to an EN T specialist experience sudden sensorineural hearing loss to an ENT specialist for ongoing care • treatment: hearing amplification (e.g. hearing aids), assistive listening devices, and cochlear implants can dramatically improve quality of life

Hypertension

Headache Red Flags SNOOP

Systemic symptoms of illness • Fever • Anticoagulation Pregnancy • Cancer Neurologic signs/symptoms • Impaired mental status • Neck stiffness • Seizures • Focal neurological deficits Onset • Sudden and severe • New headache after age 50 Other associated conditions Following head trauma Awakens patient from sleep • Jaw claudication • Scalp tenderness • Worse with exercise, sexual activity, or Valsalva Prior headache history Different pattern • Rapidly progressing in severity/ frequency

.

. .

.

--

Hypertension guidelines are reviewed and updated annually, for up to date recommendations, please see http://guidelines. hypertension.ca /

.Definitions HTN BP >140/90 mmHg ( office Blood Pressure Measurement (OBPM)); 135/85 mniHg ( ambulatory blood pressure monitoring ( ABPM )/autoniated office blood pressure ( AOBP)) • isolated systolic H TN sBP >140 mmHg and dBP 210 mmHg or dBP >120 mmHg with minimal or no target organ damage • hypertensive emergency • severe HTN (dBP >120 mmHg ) + acute target organ damage

-

-

accelerated HTN significant recent increase in BP over previous hypertensive levels associated with evidence of vascular damage on fundoscopy, but without papilledema malignant HTN sufficient elevation in BP to cause papilledema and other manifestations of vascular damage ( retinal hemorrhages, bulging discs, mental status changes, increasing creatinine) • white coat HTN high clinic BP with normal home BP and 24 h ambulatory BP, caused by anxiety in clinic masked HTN • normal clinic BP with high BP in home and/or ambulatory setting, often provoked by anxiety, job stress, exercise Epidemiology • 22% of Canadian adults suffer from HTN ( prevalence is 52% in the 60-70 age group) • lifetime risk of developing HTN is approximately 90% • 64% of Canadians who have HTN are treated and controlled , while 17% are unaware that they have

Dots this Patient Have Hearing Impairment ? JAIIA 2006:295:416-428 hrpose: lo evaluate bedside clinical maneuvers used to evaluate ttie presence of bearing impairment. Methods: Systematic review of original studies examining the accuracy or pretisaoa of screening questions end tests, Results : 24 studies were Included. Conclusions: tldeily patients acknowledging a bearing impairment require audiometry, while those who indicate they do not have heating impairment should be screened with a whispered - voicetest. A normal whispered votce test requires no further workup, and those unable to perceive the whisper rtquiie audiometry. Weber and bone tests are not suitable loi general hearing impairment screening.

-

• Symptoms of HTN are usually not present ( this is why it is called the - silent killer ") • Patients may have an occipital

headache upon awakening or organspecific complaints if advanced disease

HTN

• 3rd leading risk factor associated with death

risk factor for CAD, HF, cerebrovascular disease, renal failure, PVD

Etiology

• essential HTN (90%, undetermined cause) • secondary HTN ( 10%, known cause ) Predisposing Factors

• family history • obesity (especially abdominal ) • alcohol consumption • stress

Renovascular HTN Suspected if Patient Presenting with 2 or more of: Sudden onset or worsening of HTN and ages >55 or 30

.

Suspect Hyperaldosteronism when HTN refractory to treatment with >3 drugs • Spontaneous hypokalemia • Profound diuretic -induced hypokalemia («3.0 mmol'L) • Incidental adrenal adenomas

• excessive salt intake/ fatty diet • Black ancestry • dyslipidemia Table 19. Causes of Secondary HTN Common Cause

Renal

Renovascular HTN Renal parenchymal disease, glomerulonephritis, pyelonephritis, polycystic kidney

Endocrine

1° hyperaldosteronism Pheochromocytoma Cushing's syndrome Hyperthyroid ism / hyperparathyroidism Hypercalcemia of any cause

Vascular

Coarctation of the aorta Renal artery stenosis

Other Drug Induced

Obstructive sleep apnea isliogcns / OCP MtOls

Steroids lithium

Cocaine

Amphetamines

-

Hypertensive Emergencies • Malignant HTN • Cerebrovascular • Hypertensive encephalopathy • Stroke • Intracerebral hemorrhage SAH • Cardiac • Acute aortic dissection • Acute refractory LV failure • Myocardial infarction/ischemia • Acute pulmonary edema • Renal failure

NSAIDs Decongestants Alcohol

Investigations

• for all patients with HTN : • electrolytes, Cr, fasting glucose and /or HbAlc, lipid profile, 12-lead ECG, urinalysis self- measurement of BP at home is encouraged ( recommended devices listed at www.hypertension .ca ) • for specific patient etiology: DM or chronic kidney disease: urinary protein excretion if suspected renovascular HTN: renal ultrasound, captopril renal scan ( if GFR > 60 mL / min ), MRA /CT'A (if normal renal function ) if suspected endocrine cause: plasma aldosterone, plasma renin (aldosterone-to- renin ratio) measured from morning samples taken from patients in sitting position after resting 15 min discontinue aldosterone antagonists, ARBs, (5- blockers, and clonidine prior to testing if suspected pheochromocytoma: 24 h urine for metanephrines and creatinine • if suspected LV dysfunction : echocardiogram • if clinically indicated or with refractory hypertension : sleep study Diagnosis

• all Canadian adults should have BP assessed at all appropriate clinical visits, oscillometric preferred to manual

.

Elevated BP Reading - Office Home, or Pharmacy

Office Visit - BP >180/110 mmHg

NO

No Hypertension 4-

NO

YES NO

No Diabetes Preferable A 0BP >135/85 mmHg 0R If AOBP Unavailable

Diabetes AOBP or Non -AOBP 2) 30/ 80 mmHg

>

Hypertension

Non- AOBP 2140/90 mmHg YES

Readings ( Out ol Otlice) Preferable ABPM daytime mean ol 2) 35/ 85 mmHg Preferable ABPM 24 h mean oTt-130 80 mmHg

'

YES

ri

OR Home BP Series mean ol >135/85 mmHg

LJ

NO

+

White Coat Hypertension

Figure 12. Diagnostic algorithm for hypertension in adults

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FM39 Family Medicine

Toronto Notes 2023

Treatment • hypertension means high pressure/ strain. Without increasing a patient’s potential distress, consider what may be causing their high pressure or strain. It may be important to support a patient in

reducing sources of stress and worry • treat to target BP: < 140/90 mmHg, 60

factors

sBP > 140 with target organ damage sBP >130 for high - risk populations ( Framingham Risk >20%, ages >50) first-line antihypertensives (consider a single pill combination therapy ) combination therapy principles: if there is an inadequate response to therapy, consider adding another first line

ACEI Not recommended as monotherapy in people of African descent

antihypertensive avoid combining a non - DHP CCB with a (3 -blocker or an ACEI with an ARB monitor potassium and creatinine when administering an AGEI /ARB with a potassium sparing diuretic Table 20. Considerations in the Individualization of Pharmacological Therapy in Adults Condition or Risk Factor Isolated Diastolic HIM with or without Systolic HIM

Recommended Drugs Monotherapy or single pill combination (SPC) Recommended monotherapy choices include thiazide/thiazide like diuretics ( with longer - acting diuretics preferred) P blockers, ACEI ARBs , or long acting CCBs. Recommended SPC choices include combinations of an ACEI with CCB ARB with CCB or ACEI / ARB with a diuretic. (Consider ASA and statins in selected patients)

Alternative Drugs Combinations ol first line drugs

-

-

. -

.

-

.

.

.

Not Recommended/ Notes Not recommended for monotherapy: n - blockers, p - blocker in those >60 yr. ACEI in Black people Hypokalemia should be avoided in those prescribed diuretics. ACEI. ARBs and direct renin inhibitors are potential teratogens, and caution is required if prescribing to women with childbearing potential Combination of an ACEI with an ARB is not recommended

.

-

Thiazide diuretic. ARB or long acting dihydropyridine CCB

Combinations of first tine drugs

Same as above

CAD

ACEI or ARB: p - blockcrs or CCB for

When combination theiapy lor high risk patients ACEI / DHP CCB is preferred

Avoid short acting nifedipine. Combination of an ACEI with an ARB is specifically not recommended. Exercise caution when lowering sBP lo target it dBP is s60 mmHg , especially in patients withlVH

p- blocker and ACEI ( ARB if cannot

Long - acting CCB if P blocker contraindicated or not effective

Recent Ml

tolerate ACEI )

-

left Ventricular Hypertrophy

ACEI . ARB. Ihiazide / thiazide likc diuretics, or long - acting CCB

Cerebrovascular Disease ( stroke /TIA )

ACEI and thiazide /thiazide like diuretic combination

.

-

-

Combination of additional agents

Dihydropyridine CCBs Amlodipine Nifedipine

Felodipine Non-dihydropyridine CCBs Dittiazem \ferapamil

How to Combine Antihypertensive Medications (in general)

ACEI *

Isolated Systolic HIM without other compelling indications

patients with stable angina

Calcium Channel Blockers

-

wp- blocker

iX *

CCB Ac

Diuretic

Non - dihydropyridine CCBs should not be used with concomitant HF Hydralazine and minoxidil

can increase IVH . thusnot recommended

-

Combination of additional agents

L

Treatment of HTH should not be routinely undertaken in

acute stroke unless extreme BP elevation. ACEI and ARB combination after a stroke is not

+

recommended

.

2020 Hypertension Highlights Hypertension Canada. https://hypertension.ca /wp content7uploads / 2018 / 07/Hypertension Guidelines English

-

20 I8 Web.pdf

-

-

-

-

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FM40 Family Medicine

Toronto Notes 2023

Table 20. Considerations in the Individualization of Pharmacological Therapy in Adults Condition or Risk Factor

Recommended Drugs

Alternative Drugs

Not Recommended/ Notes

Heart Failure

ACBI (ARBil ACEI intolerant ) and fl blockcrs Aldosterone antagonists (miner alocorlicoid receptor antagonists) may be added for patients with a recent cardiovascular hospitalization, acute Ml elevated 8 HP or NlproBNP level, or NYHA Class II to

ARB in addition to ACEI Hydralazine/isosorbide dinitrate combine bon if AR 8 or ACEI not

Titrate doses ol ACEI and ARBs to Ihose used in clinical trials Carefully monitor potassium and renal function il combining any of ACEI AR 8 and/or aldosterone antagonist

-

.

toierated/contraindicated

Thiazide /thiazide-like or loop diuretics arc recommended as additive therapy. DHPCCB canalso

.

be used

A combined ARB /neprilysin inhibitor is recommended (in place of an ACEI or ARB ) in symptomatic patients with HIN and HFrEF on standard guideline- based Dyslipidcmia

Does nol affect initial ticatmcnt recommendations

Combination of additional agents

DM with Albuminuria (ACR >2.0 mgfmmol renal disease CVD or additional CV risk factors)

ACEI or ARB

Addition of a dihydropyridine CCB is A loop diuretic could be preferred over a thiazide/ thiazide- considered in hypertensive chronic kidney disease patients like diuretic with extracellular fluid vulume overload

.

Combination of first - line drugs If combination with ACE! is being considered, a dihydropyridine CCB is preferable to a Ihiazide /lhiazide

-

.

therapies

DM without Albuminuria (criteria ACEI ARB, DHP CC 8. or thiazide / listed above) thiazide-like diuretics

.

.

IV symptoms

.

Systematic Review for 2017 ACCfAHA Guidelines for Prevention Detection,( valuation, and Management of High Blood Pressure in Adults Hypertension 201S;71:e116 135 Purpose: Determine evidence for self-measured BP without other augmentation for clinical outcomes and BP control. Determine optimal tligtt for BP lowering during antihyperlcntwe therapy in adults. Oeterm re benefits and harms of different classes ol antihypertensive diugs. Methods: Systematic reviewand meta -analysis osir g PubMedardfMBASf . Results Ihere is a modest but significant rmprovtmeutin sBP in RCIsol self - measured BP vs usual care at 6 but not 12 mo:may be a helpful adjunct to routine office care. sBP lowering to a target of 30 mg/mmol)

ACEI (ARB il ACEI intolerant ), if there is proteinuria Diuretics as additive therapy

Combinations of additional agents

Patients on an ACEI or ARB should have careful monitoring of renal function and potassium. ACEI and ARB combinalioms are nol recommended in palienls without proteinuria

Renovascular Disease

Does not affect initial treatment Combinations of additional agents recommendations Atherosclerotic renal artery stenosis should be primarily managed medically while revascularization should be considered for renal fibromuscular dysplasia

Caution in using ACEI or ARB if bilateral renal artery stenosis or unilateral disease with solitary kidney Renal artery angioplasty and stenting could be considered for palienls with renal artery stenosis and complicated, uncontrolled HIN

.

-

-

2020 Hypertension Highlights, Hypertension Canada, httpsi/rhypertension.ca/ wp contentyuploads /2018/07/Hyperlension-Guidelines- English 2018 Web.pdf

-

Table 21. Common Antihypertensive Medications in Pregnancy and Lactation Pregnancy

Lactation

First line oral drugs

Second line oral drugs

Medications to avoid

Oral drugs

Labetalol Mcthyldopa Long acting oral nifedipine Other 3- blockers ( acebutolol metoprolol pindolol, and propranolol)

Clonidine

ACEIs*

Hydralazine Thiazide diuretics

ARBs'

Labetalol Mcthyldopa Long - acting oral nifedipine

.

.

Enalapril

Caplopril

’ Fclotoiicily ol renal system

Follow - Up assess and encourage adherence to pharmacological and non - pharmacological therapy at every visit • lifestyle modification q 3 - 6 mo

• pharmacological follow - up ql -2 nto until BP under target for 2 consecutive visits, q3 - 6 mo once at target BP • follow-up frequently for patients with svmptomatic/severe HTN , antihypertensive drug intolerance, target organ damage • referral is indicated for cases of refractory HTN , suspected secondary causes, or worsening renal •

failure hospitalization is indicated for malignant HTN

r > L J

+

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FM'II Family Medicine

Toronto Notes 2023

Joint Pain •see Rheumatology, RH4

History

• number of joints involved: monoarticular, oligoarticular, polyarticular

Signs and Symptoms of Inflammatory

morning stiffness (duration ) vs. worse at end of day with activity .• PMHx

WARM ( S) Joints Worse with rest , better with activity Awakening in the latter half of the night Redness around joint Morning stiffness (>30 min) Soft tissue swelling, erythema

• inflammatory vs. non - inllammatory • pattern of joints involved: symmetrical vs. asymmetrical, large vs. small joints, axial skeleton • onset: acute vs. chronic ( >6 wk )

Arthritis

trauma, infection, medications (steroids, diuretics) comorbidities: DM, renal insufficiency (gout), psoriatic arthritis, myeloma, osteoporosis, and OA FHx of arthritis, autoimmune disease • ROS: constitutional symptoms ( neoplasm, septic arthropathy), myalgia, skin /eye/ nail / hand changes,

and GI/GU changes

Physical Exam

• vitals

•specific joint exams to affected areas •systemic features (skin, nails, eyes, hands) Investigations (Guided by the History and Physical Exam) • general: CBC and differential, electrolytes, creatinine • acute phase reactants: ESR, CRP • complement ( C3, C4 ) • urinalysis to detect disease complications ( proteinuria , active sediment ) •serology (tailored to clinical suspicion, see Rheumatology RH 4 ) • antinuclear antibody ( ANA ), negative ANA helps to exclude SLE, positive ANA in subset of RA anti-double stranded DNA (anti-dsDNA), perform anti-dsDNA and anti-smith (anti-Sm ) for SLE if positive ANA human leukocyte antigen B27 ( HLA-B27), more consistent with reactive arthritis than RA anti- histidyl tRNA synthetase autoantibodies (anti Jol ), positive in dermatomyositis and

.

-

polymyositis

--

-

.

• Rash (SLE psoriatic arthritis) • Nail abnormalities (psoriatic, reactive arthritis) • Uveitis (psoriatic, reactive arthritis, ankylosing spondylitis) • Myalgias (fibromyalgia , myopathy) • Weakness ( polymyositis, neuropathy) • Gl symptoms (scleroderma IBO) • GU symptoms (reactive arthritis,

.

anti Sm • anti La antibodies (anti La ), positive in Sjogren's disease anti Sjogren s syndrome related antigen A ( anti SSA / Ro), positive in Sjogren's disease rheumatoid factor ( RhP ), positive in RA and other conditions including Sjogren's disease anti-cyclic citrullinated peptide (anti-CCP), positive in RA •synovial fluid analysis (cell count and differential, culture, Gram stain, microscopy) • radiology ( plain film, CT, MRI, U/S, bone densitometry, bone scan )

--

Systemic Features

• Fever (SLE, infection )

gonococcemia )

-

Treatment

• tailor therapy depending on the specific cause: consider referral to rheumatologist

• non - pharmacologica ): patient education, lifestyle modification , assisted devices, physiotherapy,

occupational therapy • pharmacological: analgesia (acetaminophen , NSAlDs ), anti - inflammatory (disease- modifying anti rheumatic drugs (DMARDs), steroids, antibiotics if osteoarthritis, consider steroid injections, hyaluronic acid injections

Low Back Pain • see Orthopaedic Surgery, OR 28

-

-

•Clinically Organized Relevant Exam (CORE ) Back Tool: https://cep.health /dinical products/ low backpain /

Definition •acute: 12 wk

Epidemiology • 5th most common reason for visiting a physician • lifetime prevalence: 90%, peak prevalence: ages 45 60 • largest WS1 B category and most common cause of chronic disability for individuals 4 episodes/vr, refer urgently for the red flags listed in the side box

+

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FM 18 Family Medicine

Toronto Notes 2023

{

'

{

}

Symptoms ot Sinusitis

>

(

Recurrenl/ ABRS

I

)

>7 tl

CT or refer tor

[

Viral URTI Treat symptomatically

High likelihood of bacterial infection

expert assessment

1.5 x baseline): vancomycin 125 mg P 0 0I0 x 10 -14 d (children: vancomycin 40 mg/kg/d PO divided IID - 0ID x 10 14 d max 500 mg /d)

-

Peptic Ulcer Oiscasc ( non- NSAID related)

H. pylori

PPIP 0 BID •amoxicillin 1000 mg PO BID * clarithromycin 500 mg PO BID * metronidazole 500 mg P0 BID x 7 d OR PPI P 0 BID * bismuth subsalicylate 524 mg P 0 010 * metronidazole 375 mg PO OID * tetracycline 500 mg PO OID x 7 14 d

-

r > LJ

+

PPI: lansoprazole 30 mg or omeprazole 20 mg or panloprazole 40 mg or rabeptazole 20 mg

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FM55 Family Medicine

Toronto Notes 2023

Microorganisms

Antimicrobial

Head and Pubic Lice ( crabs)

Pediculosis humanus capitis Phthicus pubis

permelhrin cream 1%: apply as liquid onto washed hair for 10 min, then rinse: repeal in 1 wk

Vulvovaginal Candidiasis

Candida

Treat only if patient is symptomatic fluconazole 150 mg P011dose miconazole 2% cream (Monislat 7®): one applicator ( 5 g) intravaginally OHS % 7 d Multiple other OTC azole treatments

Bacterial Vaginosis

Overgrowth of : 6. vaginalis M. hominis Anaerobes

If patient isasymptomatic treatment is unnecessary unless high-risk pregnancy, prior IUD insertion, gynaecologic surgery, induced abortion, or upper tract instrumentation 1st line: metronidazole 500 mgP0 BIDx 7 d metronidazole 0.75% gel: one applicator ( 5 g) intravaginally OHS x 5 d clindamycin 2% cream: one applicator ( 5 g) intravaginally OHS x 7 d 2nd line: metronidazole 2 g PO x 1 dose clindamycin 300 ing PO BID x 1 d

Herpes

Herpes simplex virus

1° episode: acyclovir 200 mg P0 five times daily x 5-10 d OR famciclovir 250 mg P0 TID x 5 d OR valacydovit 1000 mg P 0 BIO x 10 d Recurrent Episode: acyclovir 200 mg P 0 five times daily x 5 -10 d famciclovir 125 mg P0 BID x 5 d valacydovit 500 mg P0 8I0 x 3 d or 1000 mg P 0 once daily x 3 d Pregnancy: T episode: acyclovir 200 mg PO 5x /d x 5-10 d Prior infection within previous yr: acyclovir 200 mg P 0 0ID at 36 wk valueydovir 500 mg P0 BIO at 36 vrk

Gonorrhca /Chlamydia

II- gononhoeae C. trachomatis

ceftriaxone 250 mg IM x 1 dose * azithromycin 1 g PO x 1 dose OR doxycydine 100 mg PO BID x 7 d No intercourse for one week after treatment

Mastitis

S. ouceus S pyogenes

doxacillin 500 mg PO 0 ID 17 d cephalexin 500 mg P0 010 x 7 d

Tinea Cruris /Pedis (jock itch / athlete's foot)

trichophyton

dotrimazole1% cream 8ID ketoconazole 2% cream 8ID

Uncomplicated Cellulitis

S. aureus Croup k Streptococcus

Children: 1st line: cephalexin 50 -100 mg /kgfd divided OID x 10 14 d 2nd line: doxacillin 50 mgrkg /d divided 0I0 x 10 14 d clindamycin 25 mg/ kg/ d x 10 -14 d Adults: 1st line:cephalexin 500 mg PO OID x 10 -14 d 2nd line: doxacillin 500 mg PO 0I0 x 10 -14 d clindamycin 300 mg POx 10 -14 d

Condition DERMATOLOGIC

.

.

Landmark Family Medicine Trials Trial Name

Reference

Clinical Trial Details

H Engl J Med 1997; 336:1117-1124

Title: A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure Purpose : To assess the impacts of dietary modifications on blood pressure patterns. Methods: RCT involving 459 patients randomized to receive a control diet, a diet rich in fruits and vegetables, or a combination diet rich In fruits, vegetables and low fat dairy products. Results: The combination diet exhibited the most promising results. In normotensive patients the combination diet reduced systolic and diastolic pressure by 5.5 and 3.0 mmHg more than the control diet, respectively. Amongst patients with hypertension the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mmHg respectively. Conclusion: Thecombinalion diet exhibited promising results for the reduction of blood pressure

HYPERTENSION

DASH

-

.

SPRINT

H Engl J Med 2015: 373:2103 2116

HOPE 3

N Engl J Med 2016: 374:2 021 2031

.

Title: Intensive vs. Standard Blood Prcssute Control Purpose: To assess the effectiveness of various targets for systolic blood pressure with regard to lowering cardiovascular mortality. Methods: RCT including 9361 patients with a systolic blood pressure >130 mmHg and high risk for cardiovascular events. Patients were randomized to a target blood pressure ol 120 mmHg ( standard target) or 140 mmHg (intensive target ). The outcomes ol interest were myocardial infarction, acute coronary syndromes, stroke, heart failure, or death. Results: After 3 yr ol follow up the prevalence of cardiovascular complications were significantly reduced within the intensive treatment group when compared to the standard treatment group - 1.65%/yr and 2.19% /yr.respectively. Conclusion: With regard to patients who are at high risk for cardiovascular events, intensive treatment of their blood pressure resulted in decreased incidence of major cardiovascular complications Title: Cholesterol lowering in Intermediate- Risk Persons without Cardiovascular Disease

Purpose: Toassess the benefits of statins in intermediate- risk populations without cardiovascular disease. Methods: RCT consisbng of 12705 patients who did not presently have cardiovascular disease but were deemed to be at intermediate risk. Patients were randomized to receive either 10mg of rosuvastatin per day or a placebo. The outcome of interest were death by cardiovascular cause, non- fatal myocardial infarction, or non fatal stroke. Results: low - density lipoprotein levels were reduced by 26.5% within the treatment group in comparison to those that received Use placebo Ihe prevalence of vasculai events was significantly reduced within the rosuvastatin group ( 3.7%) when compared to the placebo group ( 4.8%) Conclusion: The use of rosuvastatin inan intermediate- risk group without cardiovascular disease reduced the prevalence of vascular events when compaied to those that did not receive treatment.

-

.

.

Activate Windows

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i

LJ

+

Go to Settings to activate Windows.

FM56 Family Medicine

Toronto Notes 2023

Trial Name

Reference

CHAP

N Engl J Med.

Clinical Trial Details

2022;386|19):1781.

Title: Treatment for Mild Chronic Hypertension during Pregnancy Purpose:Historically,only severe hypertension (BP >160/110 mmHgj was treated. This study aims to assess the benefits of treating mild chronic non severe hypertension ( BP >140 / 90 mmHg). Methods: RCT consisting ol 2408 pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 wk. Patients were randomired to receive the standard medication for severe hypertension in pregnant women or no treatment at all. Primary outcomes were preeclampsia,medically indicated preterm birth («35 v/ k gestation),placental abruption, or fetal/neonatal death Results: The incidence of the primary outcome was substantially lower within the treatment group as opposed to the control group - 30.2% and 37.0% respectively. Conclusion: Targeting a blood pressure below 140/ 90 mmHg using anti - hypertensive medications resulted in improved health and pregnancy outcomes

.

. .

MENOPAUSE / HORMONE REPLACEMENT THERAPY JAMA 2002:288:321-333

Women's Health Initiative Trial

Title: Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women Purpose: loassess the impacts of combined hormone therapy in healthy post menopausal women. Methods: RCT consisting of 16608 postmenopausal women with an intact uterus Participants were randomited to combined estrogen and progesterone,or a placebo. The outcomes of interest were coronary heart disease and breast cancer. Results: Amongst the treatment group there were 286 cases of CH 0 and 290 cases of breast cancer. Conclusion: Results show that the overall health risks exceed the benefits of the combined hormone therapy.

.

.

References .

Abdulla A , Adams H Bone M, etal. Guidance on the management of pain in older people. Age Aging 2013:42:1-67. AGS Panel on Persistent Pain in Older Persons.The management of persistent pain in older persons. J Am Geriatr Soc 2002:50(Suppl6):S 205-S224. American Psychiatric Association. Diagnostic and statistical manual of mental disorders Slh ed Arlington VA: American Psychiatric Publishing 2013 American Psychiatric Association. Heating Major Depressive Disorder: AOuick Reference Guide 2010. Available from: hltps://psychialryonlinc.org/pb/ussels/raw/sitewidc /pracllce guidelines/guidelines /mdd guide pdf. Anderson TJ Gregoire J Pearson GJ, et al.Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2016:32:1263-

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Ar linger S Negative consequences ol uncorrected hearing loss: a review. Int J Audiol 2003:42 Suppl 2:2S17. Bagai A, 1havendiranathan P Detsky AS. Does this patient have hearing impairment ? JAMA 2006:295:416 428. Batal M. DecellesS.A scoping review of obesity among Indigenous peoples in Canada.Journal of Obesity 2019:2019:9741090. Beck E, Sieber WJ. Trejo R.Managementof cluster headaches. Am Fam Physician 2005:71:717724. Bent S. Nallamothu BK. Simcl 01 et al. Ooes this woman have an acute uncomplicated urinary tract infection? JAMA 2002:287:2701- 2710. Brck V Ebderdt C Kaccorowski J.Development of a tool to identify poverty in a family practice setting: a pilot study.Int J Family Med 2011:812:1- 7. British Columbia Medical Association and British Columbia Ministry of Health Services. Osteoarthritis in peripheral joints: diagnosis and treatment. Guidelines 4 Protocol. Advisory Committee, 2008. Available from: https:/ / sagelink.ca/ osteoarthritis peripheral joints. Blinderman C, Billings J Comfort care for patients dying in hospital. N Engl J Med. 2015:373:2549 2561 Brown JP Josse RG. 2002 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMA J 2002:167:51 34. Bruera E, Kuehn H. Miller MJ, etal. The Edmonton Symptom Assessment System ( ESAS): Asimple method for the assessment of palliative care patients.J Pall Care 1991:7:6-9. Burge SK, Schneider FD. Alcohol-related problems: recognition and intervention. Am Fam Physician 1999;59:361-370. Butt P Gliksmanl Beimcss D. et al. Alcohol andhealth in Canada: A summaiy ol evidence and guidelines for low - risk drinking. Ottawa ON: Canadian Centre on Substance Abuse 2011. Available from: https:// www.ccsa.ca/ sitos/defaull/ liles / 2019 - 04 / 2011 $ummary - of Evidcnce- and Guidellnes- foi - low -Ri5k% 20Dimking- en.pdl. Cahill K.StevensS.Perera R etal. Pharmacological interventions for smoking cessation: an overview and network meta - analysis.Cochrane DB Syst Rev 2013:5:1-47. Cahill K.Stead LF Lancaster T. Nicotine receptor partial agonists for smoking cessation.Cochrane DB Syst Rev 2016:CD 006103. CaHe E Thun MJ Pctrelli JM et al. Body mass index and mortality in a prospective cohort of US adults. NE JM 1999;341:1097-1105. CAN ADAPT!. Canadian Smoking Cessation Clinical Practice Guideline. Toronto.Canada: CanadianAction Network lor the Advancement , Disseminalionand Adoption olPractice - Informed lobacco Irealmcnt, Centre foi Addiction and Mental Health. 2011. Available from: https://www.nicotinedependenceclimc.com/ en/ canadaptl/ Publishinglmages/Pages/ CAH - ADAP11- Guidelines;CAN - ADAPH %20Canadian% 20 Smoking%20Cessalion%20Guideline website.pdf. Government of Canada. Canada’s Food Guide (Internet]. 2021 June [cited 2021 June], Available from: https://lood- guide.canada.ca/enf. Diabetes Canada. Canadian Oiabctes Association 2013 Clinical Practice Guidelines [Internet ] 2013. (cited 2020 Jun 22) . Available from: http:/ /guidellnes.diabetcs.ca/8rowse.aspx . Canadian Journal of Cardiology 32.11(2016):1263 -1282.Canadian Health Measures Survey Cycle 2. CHHS CHMS. Statistics Canada. 2012. Available from: http://www.hypertension.ca/en /professional /chep / diagnosis-measuremenl/assessment -of -hypertensive-patients. Canadian Paediatric Society. Use ol selective serotonin re uptake inhibitor medications for the treatment of child and adolescent mental illness (2013). Available from: https:/ / onlinereview.cps.ca/papers/uso - of SSRIs - for - child- adolescent -mental'illness/print ready pdl. Canadian Paediatric Society. Clostridium difficile in pediatric populations (Internet]. 2020 March [cited 2021 June). Available from: hllps://www.cps.ca/en/documents/position/closlridium- dif(icile -in- paediatriepopulations. Canadian Paediatnc Society. Management of acute otitis media in children six months of age and older [Internet!. 3016 February [cited 2021 June]. Available from: https://www.cps.ca /en/ documents/posilion/ acute otitis- media. Canadian Society for Exercise Physiology |CSEP) Canadian 24 - Hour Movement Guidelines: An Integration of Physical Activily.Sedentary Behaviour , and Sleep. Available from: https:// csepguidelines.ca /. Canadian Task Force on Preventive Healthcare. Published Guidelines. Availablefrom: https://canadiantaskforce.ca/guidelines/published-guidelines/. Canadian Task Force For Preventive Health Care. 2015 Obesity Guidelines. Available from:https://canadiantaskforce.ca /guidelines/published- guidelines/ obesity - in- adults/. Canadian Task Force on Preventive Health Care. The Canadian guide to clinical prevenbve health care. Ottawa: Minister of Supply and Services Canada. Available from: https:// www.canadianlaskforcc.ca /. Canadian Task Force on Preventive Health Care. Recommendations for prevention of weight gain and use of behavioural and pharmacologic interventions to manage over - weight andobesity in adults in primary care. CMAJ 2015. DOI: 10.1503/cmaj 140887. Canadian Task Force on Preventive Health Care. Recommendations on screening for depression inadults. CMAJ 2013:185(9):775- 782. Cancer Care Ontario. Ontario Cervical Screening Guidelines Summary [Internet ] 2020 Junc [cilcd 2021 June] Available from: https://www.caiKcicaicontario.ca /en/system/ files foice / denvativc/ DCSPScreeningGuidelines.pdf. Cartwright SL, Knudson MP. Evaluation of acute abdominal pain in adults. Am Fam Physician 2008;77( 7):971- 978. Centor RM, Witherspoon JM. Oalton HP. etal.Ihe diagnosis of strep throat in adults in Ore emergency room. Med Decis Making 1981:1:239 -246. Centre for Effective Practice. Management of Chronic Insomnia [Internet ]. 2017. [cited 2022 Jun], Available from: htlps://ccp health/media /uploaded/ 20170116 Insomnia FINAl.pdf. CHEP (Canadian Hypertension Education Program) Guidelines 2018. Available from: htlp:// www.hypertension.ca/. Cheung AM. Feig DS. Kapral M. et al. Prevention of osteoporosis and osteoporotic fractures in post menopausal women: recommendation statement from Ihe Canadian Task Force on Preventive Health Care. CMAJ 2004;170:1665-1667. Clark MS Jansen XL Cloy JA. Treatment of childhood and adolescent depression. Am Fam Physician 2012;86|5):442 448. Clary P Lawson P. Pharmacological pearls for cnd ol life care. Am Fam Physician 2009;T9(12):1059 1065 Colorectal Screening for Cancer Prevention in Asymptomatic Patients, March 2013. Available from:https:// www 2.gov.bc.ca/gov / conlent/ heallhlpractitioner -professional-resources/ bc -guidelines. College of Family Physicians of Canada. Family Medicine Professional Profile. Mississauga. ON: College of Family Physiciansof Canada; 2018. Comui J, Gucssous I, Farral B. Fatigue: a practical appeoach to diagnosisin primary care. CMAJ 2006:174:765 - 767. Oansangcr ML, Gleason JA Griffith Jl el al. Comparison of the Atkins, Ornish Weight Watchers, and 2 onc diets for weight loss and heart disease risk reduction. JAMA 2005:293:43 53. Derby CA, Mohr BA. Goldstein I el al. Modifiable risk factors and erectile dysfunction:can lifestyle changes modify risk ? Urology 2000:56:302- 306. Desrosiers M, EvansGA. Keith PK, etal. Canadian clinical practice guidelines for acute and chronic rhinosinusitis.Allergy Asthma Clin Immunol 2011:7:1710-1492. Diabetes Canada Clinical Practice Guidelines. New 2018 Guidelines. Available from: http://guidelines.diabetes.ca'cpg. Diabetes Melhtus Patient Care Flow Sheet form. Canadian Diabetes Association. Available from: https://guidelines.diabelcs.ea/ docs/cpg/ Appcndix - 3 pd! Divisions ol Family Practice. Enhanced Primary Care Pathway: Helicobacter Pylori [Internet!2019 [cited 2021 June). 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Domino FJ. The 5-minute clinicalconsult 18tti ed.Lippincolt WilliamsiWilkins 2009. Downar J Goldman R . Pinto R el al.The “surprise question" lor predicting death in seriously ill patients: a systematic reviewand meta -analysis.CMA J 2017:189:5484 -493. Ebell MH. Evidence - based diagnosis: a handbook of clinical prediction rules. Springer 2001. Ebcll MH. Treating adult women with suspected U1I. Am Fam Physician 2006:73:293 298 Eckel RH Jakieic JM Ard JO el al. 2013 AHA/ACC Guideline on lifestyle Management to Reduce Cardiovascular Risk: A Report ol the American College ol Cardiology American Heart Association Task Force on Practice Guidelines. Circulation 2013. Edmonds M.McGuire H, Price J. Exercise therapy for chronic fatigue syndrome.Cochrane D8 Syst Rev 2004:3:1-141. Elmer PJ Obarzanek E Vollmer WM et al. Effects ol comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18 - month results ol a randomized trial. Ann Intern Med 2006:144:485 - 495 Evans M (editor). Mosby's family practice sourcebook: an evidence based approach to care 4 th ed. Elsevier Canada 2006:343 345. Evans M, Bradwejn J, Dunn L. Guidelines for the treatment of anxiety disorders in primary care. Toronto: Queen’s Printer of Ontario 2002. FalloneCA, Chiba N van Zanten SV et al.TheTorontoconsensus for the treatment of Helicobacter pylori infection in adults.Gastroenterology 2016:151:51-69. Fang K, et al. Screen time and childhood overweight/ obesity: Asystematic reviewand meta -analysis. Child Care Health Dev 2019;45:744 -753. Fauci AS Braunwald E Kasper D et al Harrison's principles of internal medicine 17th ed. McGraw - Hill Professional 2008 Fogarty CT Burge S McCord E. Communicating with patients about intimate partner violence: screening and interviewing approaches. Fam Med 2002:34:369 375 Freeman IR. McWhinney 's textbook of family medicine 4!h ed. Oxford University Press; 2016. Furlan AD van Tulder MW, Cherkin DC et al. Acupuncture and dry-needling for low back pain.Cochrane DB Syst Rev 2006:1:CD 001351. Furlan AD Giratdo M Baskwill A et al. Massage for low - back pain. Cochrane D 8 Syst Rev 2015:9:1-113. Genest J McPherson R Frohlich J el al. 2009 Canadian Cardiovascular Society/ Canadian guidelines for the diagnosisand treatment ol dyslipidemia and prevention of cardio vascular disease in the adult - 2009 recommendations. Can J Cardiol 2009:25:567- 579 Gilbert DH Moellering RC, Eliopoulos GM. TheSanford guide to antimicrobial therapy 43rd ed.Sperryvitle: Antimicrobial Therapy 2013. Grades of Recommendation Assessment Development, and Evaluation (GRADE) Working Group. 2011. Available from:http:/7 training.cochrane.org.rpath/grade - approach- evaluatmg- qualily -evidence-pathv/ ay. Graham DJ Staffa JA, Shatin D et al. Incidence of hospitalized rhabdomyolysisin patients heated with lipid-lowering drugs. JAMA 2004;292:2585 -2590. Grindrod KA Houle SKD Fernandes H Traveler 's diarrhea. Can Fam Physician 2019:65:483 486. Guidelines for Adolescent Depression in Primary Care (GLAD PC). Guidelines on identification, assessment andinitial management 2007 Available from: hllp:/ /pedialiics aappubticalions org/content /120/ 5 / e1299 (ull Gupta BP. Murad MH Clifton MM et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction. Arch InternMed 2011:171:1797-1803 Handford C,Hennen B. The gentle radical. Can Fam Physician 2014:60:20 -23. Health Canada. An advisory committee statement: National Advisory Committee on Immunization: prevention of pertussis in adolescents and adults Can Commun Dis Rep 2003;29:ACS5 6. Health Canada. Canadian tobacco use monitoring survey (CTUMS): annual results 2012 Available from: hltp://www.hc- sc gc.ca /h< ps/lobac - labac/rescarclwccherche /stal/ clums esutc 2012 - cng phpWtabl. Health Canada. Natural and non - prescription health products directorate (Internet). 2020 March (cited 2021 Junc ] Availablc from: https:/ / www.canada.ca /en7hcalth- canada /corporatclaboul health Canada / branches- agencies / health products foorJ - tjranch/ nalural - non prescription - health - products -directorate.html. Health Canada. Vitamin D andCalcium: Updated Dietary References Intakes [Internet). 2020 July Idled 2021 June). Available from:https:// www.canada.ca /en/heallh- canada / services/ food-nulrition/heaIthy eating/vita mins minerals/ vitamin- calcium- updated - dietary -relerence-intakes -nutrition.html. Holbrook AM ( Chair : Onlario Musculoskeletal Therapy Review Panel). Ontario treatment guidelines foi osteoarthritis, rheumatoid arthritis, and acute, musculoskeletal injury. Toronto: Oueen 's Printer of Ontario

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Hughes JR, Stead IF Hartmann- Boyce J, et al. Antidepressants foe smoking cessation Cochrane DB Syst Rev 2014:1:1-142 Hui D. Approach to internal medicine.A resource book for clinical practice,3rd ed. Springer Hew York 2012. HuntP. Motivating change.Nurs Stand 2001:16:45- 55. Jepson RG Craig JC. Cranberries foi preventing urinary tract infections. Cochrane DB Syst Rev 2008;10|10):C 0001321 Kaplan A Canadian guidelines for acute bacterial rhlnosinusitis Can Fam Physician 2014:60:227 - 234 Kaplan A. Canadian guidelinesfor chronic rhinosinusilis: clinical summary. Can Fam Physician 2013:59|12):1275- 1281. Kinkade S, long NA. Acute bronchitis. Am Fam Physician 2016;1;94|7):560 - 565. Krauss RM Eckel RH Howard 8. et al. AHA dietary guidelines: revision 2000: Astatement foe healthcare professionals from the nutrition committee of the American Heart Association.Stroke 2000:31:2751-2766. lau D, Oouketis JD, Morrison KM et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMA J 2007;17G:S1 13. leddin 0 J Enns R Hilsden R et al Canadian Association of Gastroenterology position statementon screening individuals at average risk ol developing colorectal cancer. Can J Gastroenterol 2010:24:12 linde K AllaisG Brinkhaus B cl at. Acupuncture for migraine prophylaxis CochraneDB Syst Rev 2009:4 Linde K,Barrett B Wolkart K. et al. Echinacea for preventing and treating the common cold. Cochrane DB Syst Rev 2006;1. Linde K.Berner MM Kris ton L St John's wort for major depression. Cochrane DB Syst Rev 2008:4. linde K Mulrow CD Berner M et al. SI John's wort for depression. Cochrane 08 Syst Rev 2005:2. lilchcnslein AH Appel IJ Brands M et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heait Association Nutrition Committee. Circulation 2006:114:82 96 loo VG DavisI Embil J cl at . Association of Medical Microbiology and Infectious Disease Canada treatment practice guidelines for Clostridium difficile infection JAMMl 2018:3( 21:71 92 lougheed MD lemiere C Ducharme FM, etal. Canadian Thoracic Society 2012 guideline update: diagnosis andmanagement of asthma in preschoolers, children and adults. Can Repair J 2012:19:127 -164. Manson JE Hsia J Johnson KC.etal. Estrogen plus progestin and the risk of coronary heart disease. NEJM 2003:349:523 -534. Marshall HR. Zinc for the common cold. Cochrane DB Syst Rev 20O6;3. MeIsaac WJ. Moincddin R RossS Validation of a decision aid to assist physicians in reducing unnecessary antibiotic drug use for acute cystitis. Arch Intern Med 167:2201- 2206. McPherson R Frohlich J Fodot G cl al. Canadian Cardiovascular Society position statement - Recommendations for the diagnosis and treatment ol dyslipidemia and prevention ol cardiovascular disease Can J Cardiol 2006:22:913 927. Medical care of the dying 4 th ed. Victoria: Victoria Hospice Society 2006. Chapter:Palliative performance scale,version 2.120-121. Montgomery L Scoville C. What is the best way to evaluate acute diarrhea? J Fam Pract 2002:51. Mooie A, Traversy G Reynolds Dl, et al. Recommendation on screening for chlamydia and gonorrhea in primary care for individuals not known to be at high risk CMAJ 2021:193|16):e 549 - c559 Mooie H Summer bell C Hooperl et al Dietaiy advice foe treatment of type 2 diabetes mellilus in adults Cochrane 08 Syst Rev 2007:3 Moyer A Finney JW Brief interventions foe alcohol misuse CMAJ 2015:18717): 502- 506. Murphy J Kennedy EB, Dunn S et al. Cervical screening: a guideline tor clinical practice in Ontario. JOGC 2012:34:453- 458. Nash SD, Cruickshanks KJ, Klein R,et al. The prevalence of hearing impairmentand associated riskfactois: the Beaver Dam Offspnng Study. Arch Otolaryngol Head Heck Surg 2011;137(5):432. National Center on Elder Abuseat the American Public Human Services Association. National elder abuse incidence study. Available from:http://www.aoa.gov/ eldfam/Elder Rights/ Elder Abuse/ AbuseReport Full.

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Public Health Agency of Canada. Section 2: Canadian Guidelines on Sexually liansmilted Infections - Primary care and sexually transmitted infections llnteinel]. 2013 February [cited 2021 June|. Available from: htlpsr /i' www.canada.ca/ en/public- health/services/ infectious - diseasesfsexualhealth -sexually - transmitted - infections / canadian -guidelines / sexuallyliansmitled- infeclions / canadian -guidelines-sexually transmitted -infections -17.html. Public Health Agency of Canada. Section 3: Canadian Guidelines on Sexually Transmitted Infections - Laboratory diagnosis of sexually Iransmilted infections [Internet]. 2017 April [cited 2021 Tune], Available from: https:77www.canada.ca / en/public health/serviccs/infcctious - disieases7sexual - liealth sexually transmitted infections / canadian quidelines7sexually lransmilled- infections / c liC’health /services/infectiouS' diseases /se «ual- heallh -sexually transmitted ' infections /canadian guidelines /sexualty - transniitted infections/canadian guidelincs sexually ltansmillcd inleetions 34 html Public Health Agency of Canada. Syphilis: key information and resources [Internet]. 2020 August [cited 2021 June]. Available from: https : www .canuda.cd'en /public heal th 'services / inleclious diseasesi'sexual health sexually transmitted mlections. canadiaii guidelinevsyphilis.html # at.4. Radin MS.Pitfalls in hemoglobin A1c measurement: when results maybe misleading. J Gen Intern Med 2014;29 (2):388-394. Rambout L. Hopkins L. Hutton B etal.Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic reviewof randomized controlled trials. CMAJ 2007:177:469 - 479. Recommendations for the management of dyslipidcmia and the prevention of cardiovascular disease: Summary of the 2003 update. CMAJ 2003;169:921- 924. Richie AM. Francis Ml. Diagnostic approach to polyarticular joint pain. Am Fam Physician 2003;68(6);1151-1160. Ridker PM.Danielson t . Fonseca FA et al. Rosuvastatin to prevent vascular events in rnen and women with elevated c reactive protein. HEJM 2008:359:2195 - 2207. Roelols PD, Deyo RA. Koes BtV. et al. Non -steroidal anti- inflammatory drugs for tow back pain. Cochrane DB Syst Rev 2008;1. Roush GC. Ernst M.E. Kostis JB, et al. Head- to- head comparisons of hydrochlorothiazide with indapamideand chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015;65(5):1041-1046. RxFiles. Antibiotics and common infections [Internet], 2016 October [cited 2021 June). Available from:https://www.nrfiles.ca /rxliles/uploads /documents/abx-newsletter -2016- complele.pdf. RxFiles. Pharyngitis - Management Considerations [Internet ]. 2021 June [cited 2021 June]. Available from:https:/ /www.rxfiles.ca /rxfiles/uploads /documents/ ABX -Pharyngitis.pdf. Sabaline MS. Pocket medicine: the Massachusetts General Hospital handbook of internal medicine 4th ed lippmcotl WilliamsiWilkins Philadelphia 2011 Sacnc A, Fernandez Esteban I Malaix A. et al. Metformin monotherapy lor type 2 diabetes metlilus. Cochrane DB Syst Rev 2005:3. Schiller IR. Chronic diarrhea. Curr Treat Options Gastroenterol 2005;8:259 -266. Shaw E OandasanI,Fowler N, eds. CanMEDS- FM 2017: A competency framework for family physicians across the conbnuum. Mississauga, ON: The College of Family Physicians of Canada; 2017. Shroeder SA. What to do with a patient who smoked. JAMA 2005:294:482- 487. Smith Bi ndman R Aubin C Bailitz J. et al. Ultrasound vs. computed tomography for suspected nephrolithiasis. NEJM 2014;371:1100 -1110. Society of Obstetricians and Gynecologists ol Canada Canadian Consensus Guidelines on human papillomavirus J0GC 2007:29(8, suppl 3):S 29 Soccn T Ozisik L, Basaran NC. An overview and management ol osteoporosis. Eur J Rheumatol. 2017:4(1):46 56. Spinar J, Spinarova L. Vitovec J.IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVt -ll). Vnitr Lek 2014; 60(12|:1095 -1101. Sport Concussion Assessment Tool, 5th edition (SCAT5). Br J Sports Med 2017:0:1- 8. Stead LF. Buitrago D.Preciado N. etal.Physician advice for smoking cessation.Cochrane DB Syst Rev 2008:2. Stead LF, Perera R, Bui ten C, et al. Nicotine replacement therapy for smoking cessation. Cochrane DB Syst Rev 2008:1. Swinson RP, Antony MM Bleau P et al. Clinical practiceguidelines: management of anxiety disorders. Can J Psychiatry 2006;51:Supplcment 2. Sykes EA , Wu V Bcyea MM, et al Pharyngitis: approach to diagnosis and treatment. Can Fam Physician 2020:66 (4): 251- 257 Taylor RB. Family medicine: principles and practice, 6th ed. New York: Springer - Vertag. 2003. The College of Family Physicians of Canada. Vision, Mission. Values, and Goals.2020.Available from: https://www.cTpc.ca/ en/aboul us/ Yision missionptindplesJ/four. The Hub - Family Medicine. Department of Family and Community Medicine The University of Toronto. Available from:http:// thehub.utoronto.ca/family/. World Health Organization. Palliative care [Internet], Unknown [cited 2021 June]. Available from:hltps://www.who.inl/heallh- topics/palliative - care. Toward Optimized Practice Program. Guideline lor assessment lodiagnosis of adult insomnia. 2006 ( 2010 update). lowardOptlmizcd Practice Program. Assessment to managementof adult insomnia. 2015. Toward Optimized Practice Program.Guideline for the management of acute bronchitis. 2000 (2008 update). Toward Optimized Practice Program.Guideline (or the treatment of Helicobacter pylori infection in adults. 2000 (2009 update). Toward Optimized Practice Program.Guideline for the management of low back pain. 2009 (2011 update). Toward Optimized Practice Program. Use of PSA and the early diagnosis of prostale cancer. 2006 ( 2009 update). Walhcn CN. MacMillan HI Interventions for violence against women. JAMA 2003:289:589 599. Weber PC Evaluation ol hearing loss in adulls. Rose BD (editor ) Waltham: UploDale. 2013. Wharton S, LawOCW. Vailis M, etal. Obesity in adults: a clinical practice guideline.CMAJ 2020;192:E875- E891. Wren BG. The benehts of oestrogen following menopause:why hormone replacement therapyshould be offered to postmenopausal women. Med J Aust 2009:190:321-325. YuehB, Collins MP.Souza PE etal. Screening for auditory impairment: Which hearing aid testsTArandomized clinical trial.Department of Veterans Affairs. Seattle. WA 2001. 2altzman A. Dubey V Iglar K. Update to the Preventive Care Checklist Focm . Can Fam Physician 2020:66 (4]:270 -2 Zink T, Chaffin J.Herbal "health"products: what family physicians need to know. Am Fam Physician 1998:58:1133 -1140.

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Gastroenterology Sahibjot Grewal , Anna Lee, and Andrew Royal.sky, chapter editors Karolina Gaebe and Alvssa Li, associate editors Camilla Giovino and Wei Fang Dai, LBM editors Dr. Maria Cino, Dr. Piero 'l'artaro, and Dr. Flavio Habal, staff editors Acronyms

G2

Anatomy Review. Overview of Gastrointestinal Tract Visualizing the Gastrointestinal Tract

G2

Differential Diagnosis of Common Complaints

G4

Esophagus Gastroesophageal Reflux Disease Barrett’s Esophagus Dysphagia Esophageal Motor Disorders Esophageal Diverticula Peptic Stricture (from Esophagitis) Esophageal Carcinoma Webs and Rings Infectious Esophagitis

G6

Stomach and Duodenum

G42

G45 Biliary Tract Jaundice Gilbert 's Syndrome Primary Sclerosing Cholangitis Primary Biliary Cholangitis (formerly Primary Biliary Cirrhosis) Biliary Colic, Cholecystitis Ascending Cholangitis

Pancreas Pancreatic Enzyme Abnormalities Acute Pancreatitis Chronic Pancreatitis Autoimmune Pancreatitis G10

Dyspepsia Stomach Gastritis Peptic Ulcer Disease H. pylori-lnduced Peptic Ulceration NSAID- Induced Ulceration Stress-Induced Ulceration Gastric Carcinoma Small and Large Bowel Classification of Diarrhea Acute Diarrhea Traveller's Diarrhea

Liver Transplantation Portal Hypertension Hepatic Encephalopathy Ascites

,

Clinical Nutrition Determination of Nutritional Status

G 48

G 51

Enteral Nutrition Parenteral Nutrition Common Medications

G53

Landmark Gastroenterology Trials

G 56

References

G57

G14

Chronic Diarrhea Maldigestion and Malabsorption Celiac Disease (Gluten Enteropathy/Sprue) Inflammatory Bowel Disease Crohn's Disease Ulcerative Colitis Irritable Bowel Syndrome Constipation Upper Gastrointestinal Bleeding Esophageal Varices Mallory-WeissTear Lower Gastrointestinal Bleeding Diverticular Bleeding Infectious Colitis

Colorectal Carcinoma Colorectal Polyps Familial Colon Cancer Syndromes Benign Anorectal Disease

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Liver Investigations of Hepatobiliary Disease Acute Viral Hepatitis (General) Hepatitis A Virus Hepatitis B Virus Hepatitis D Virus Hepatitis C Virus Autoimmune Liver Disease Drug - Induced Liver Disease Wilson 's Disease Hemochromatosis

G32

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Alcoholic Liver Disease Non- Alcoholic Fatty Liver Disease Acute Liver Failure (formerly Fulminant Hepatic Failure)

Cirrhosis Hepatocellular Carcinoma

Gl Gastroenterology

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G2 Gastroenterology

Acronyms Acronyms acute liver failure ALF Barrett 's esophagus BE biologic therapy BT cholccystokinin CCK Crohn's disease CD cytomegalovirus CMV CNS central nervous system DGP deamidated gliadin peptides diffuse esophageal spasm DES EpsteinBarr virus EBV EIM extraintestinal manifestation enteral nutrition EN enteropathogenic E coli EPEC endoscopic retrograde ERCP cholangiopancreatography

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ETEC EUS EVL GE

GERD Gl HAV HBV HCC HCV HRS

HSV HUS HVPG IBD

enterotoxigenic E. coli endoscopic ultrasound endoscopic variceal ligation gastroesophageal gastroesophageal reflux disease gastrointestinal hepatitis A virus hepatitis B virus hepatocellular carcinoma hepatitis C virus hepatorenal syndrome herpes simplex virus hemolytic uremic syndrome hepatic venous pressure gradient inflammatory bowel disease

IBS ICP

irritable bov/ el syndrome intracranial pressure isoniazid INH LES lower esophageal sphincter LGIB lower gastrointestinal bleed MRCP magnetic resonance cholangiopancreatography multiple sclerosis MS NAC N-acetylcysteine NAFLD non alcoholic fatty liver disease non erosive reflux disease NERD neuroleptic malignant syndrome NMS oesophagogastroduodenoscopy OGD ova and parasites O& P primary biliary cirrhosis PBC parenteral nutrition PN

primary sclerosing cholangitis PSC percutaneous transhepatic PTC cholangiography ''“ “ PUD peptic ulcer disease RA rheumatoid arthritis right lower quadrant RIO right upper quadrant RUO spontaneous bacterial SBP peritonitis TIPS transjugular Intrahepatic portosystemic shunt tumour necrosis factor TNF TPN total parenteral nutrition TTG tissue transglutaminase ulcerative colitis UC upper gastrointestinal bleed UGIB

Anatomy Review Overview of Gastrointestinal Tract • the Gl tract runs from mouth to anus ( “gum to hum")

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Toronto Notes 2023

G3 Gastroenterology

Table 1. Summary of Gl Tract Structure and Function Organ

Function

Blood Supply

Innervation

Histology and Structural Features

Esophagus

Muscular tube appronimately 40 cm long with a diameter of 2 cm blends from the pharynx to the stomach

Arterial: left gastric artery and left inferior phrenic artery Venous: left gastric vein » portal

Parasympathetic innervation via anterior and posterior gastric nerves (vagal trunks) Sympathetic innervation via thoracic trunks of the greater splanchnic nerves

Mucosa: stratified squamous epithelium Submucosa: connective tissue lymphocytes, plasma cells,nerve cells Muscularis propria (muscularis externa): inner circular, outer longitudinal muscle Upper 1/3: striated muscle Middle 1/3: transition zone lower 1/ 3: smooth muscle

Parasympathetic innervation via vagus nerve Sympathetic innervation via celiac plexus (from TG-T9)

5 parts Cardia Fundus Body Antrum Pylorus

Parasympathetic innervation via vagus nerve Sympathetic innervation via greater and lesser splanchnic nerves

4 parts

venous system

Esophageal veins » azygos vein » inferior vena cava (systemic) Stomach

Delivers food to intestine for digestion and lesser curvature absorption Right and left gastric arteries ( from Secretes acid,probably to reduce enteric celiac trunk) infectionspneumoma: facilitates digestion Greater curvature of protein and absorption of iron/Bu Right and left gastro- omental (gastroepiploic) arteries ( from Secretes intrinsic factor (If) to facilitate BT2 absorption gastroduodenal and splenic arteries Minor contribution to initial protein respectively) Fundus: short and posterior gastric d.gestion ».a pepsin arteries ( from the splenic artery)

Duodenum

Modulates enteral pH via secretin » decreased gastric acid secretion increased bicarbonate secretion Secretes CCK to stimulate gallbladder contraction Site of iron absorption

.

-

Branches of celiac artery and superior mesenteric artery

.

Superior ( 5 cm) Descending ( 7 -10 cm ) Horizontal (6 - 8 cm) Ascending (5 cm) 1st part is intraperitoneal: rest is retroperitoneal

Jejunum

Absorption of sodium, water, and nutrients Superior mesenteric artery (protein,carbohydrates, fat folic acid, and vitamin A. B.C. D.E.K )

Parasympathetic innervation via fibres of the posterior vagal trunk Sympathetic innervation via fibres of T8-T10

Deep red colour 2 -4 cm in thickness Thick and heavy wall Plicae circulates are large, tall, and closely packed Has long vasa recta Scant fat in mesentery Scant Peyer 's patches

Ileum

Absorption of sodium,water, nutrients, soluble vitamins ( only site of vitamin Bu absorption),andbile salts (entero-hepatic circulation)

Superior mesenteric artery

Same as jejunum

When compared to jejunum: Paler pink colour 2-3 cm in thickness Thin and lightwalls Plicae circulars are small and sparse Contains more mesenteric fat Many Peyer's patches

Large Bowel

Absorption of water (5-10% of total water ) Bacteria: further digestion of chyme and metabofism of undigested carbohydrate to short chain fatty acids Formation and storage of feces

Branches of superior and inferior mesenteric arteries Rectal blood supply: sigmoid, right pudendal, and rectal arteries

Parasympathetic innervation via vagus nerve Sympathetic innervation via greater and lesser splanchnic nerves

Consists of cecum, colon (ascending, transverse, descending, and sigmoid), rectum and anal canal Features include teniae coli haustra and omental appendices

2 sources

Parasympathetic innervation via fibres of the anterior and posterior vagal trunks Sympathetic innervation via fibres ol the celiac plexus

largest internal organ Composed of 4 lobes (left, right, caudate quadrate), and divided into 8 segments

Parasympathetic innervation via vagus

Consists of the hepatic ducts (intrahepatic. left,right and common), gallbladder, cystic duct, common bile duct, and ampulla of Vater

liver

.

Glucose homeostasis Plasma protein synthesis lipid and lipoprotein synthesis Bile acid synthesis and secretion Vitamin A D E K. Bti storage Biotransformation, detoxification Excretion of compounds

Portal vein ( 75- 80%)

Hepatic artery ( 20 - 25%)

...

Biliary Tract

Gallbladder stores and releases bile that is produced in the liver Bile emulsifies fat and is composed of cholesterol,lecithin, bile acids, and bilirubin

Cystic artery

nerve Sympathetic and visceral innervation via celiac nerve plexus Somatic afferent fibres via right phrenic nerve

CCK stimulates gallbladder emptying while trypsin and chymotrypsin inhibit

.

.

.

bde release Pancreas

Endocrine function:islets of Langerhans produce glucagon,insulin, and somatostatin (from the a , 8 and 6 cells, respectively) Eiocnne function:digestive enzymes, including amylase,lipase, trypsin, chymotrypsin and carboxypeptidase are produced

.

.

.

Anterior superior pancreaticoduodenal artery (from the celiac trunk) Anterior inferior pancreaticoduodenal artery (from the superior mesenteric artery) Dorsal pancreatic artery (from the splenic artery) Pancreatic veins drain into the portal, splenic, and superior mesenteric veins

Parasympathetic innervation via vagus nerve Sympathetic innervation via abdominopelwe splanchnic nerves

4 parts of pancreas: head (includes uncinate process), neck, body, and tail (Major ) pancreatic duct connecting to common bile duct prior to ampulla of Vater Accessory pancreatic duct connected directly to duodenum

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Toronto Notes 2023

G l Gastroenterology

Visualizing the Gastrointestinal Tract • see Medical Imaging, M 116

Esophagus, Stomach, Duodenum • OGD: best visualization of mucosa; also allows for therapeutic intervention (e.g. banding varices,

thermal therapy /clipping / injecting bleeding ulcers, and dilatation for the treatment of esophageal strictures)

consider barium swallow first if dysphagia, decreased level of consciousness ( increases risk of aspiration ), inability' to cooperate ( increases risk of pharyngeal trauma during intubation ), possibility of fistulae • endotracheal intubation first if massive UG1B, acidemia, or inability to protect airway Small Bowel • most difficult to visualize, especially if mucosal detail is needed

• O' enterography more accurate than small bowel follow - through , but both have low sensitivity • MRI small bowel imaging increasingly available, especially useful if radiation exposure is an issue (e.g. young patient, multiple radiological images already done) note: MRI enteroclysis, luminal contrast is administered by nasojejunal ( N ) ) tube to dilate the small bowel - disliked by both radiologist and patient, but may improve sensitivity • “ double balloon ” enteroscopy (enteroscope with proximal and distal balloons to propel endoscope into jejunum from mouth or into jejunum /ileum from anus ) may be most sensitive but currently available only in selected centres; technically demanding • wireless endoscopy capsule ( 26 x 11 mm capsule is swallowed, transmits images to a computer; contraindicated in bowel obstruction, known strictures) is also accurate in diagnosis but does not provide any therapeutic intervention Colon and Terminal Ileum

colonoscopy, with biopsy if required; contraindicated in perforation, acute diverticulitis, and severe colitis ( increased risk of perforation ) • CT colonography ( “virtual colonoscopy ” ) more accurate in diagnosing diverticulosis, extrinsic pressure on colon (e.g. ovarian cancer compressing sigmoid colon ), and fistulae; increasing evidence for use in colorectal cancer screening, especially for assessment of right side of colon in cases where colonoscopy is less sensitive most often used when optical endoscopic colonoscopy is risky (e.g. frail elderly) or unsuccessful (e.g. stricture ) Pancreatic /Biliary Duct • MRCP almost as sensitive as ERCP in determining if bile duct obstruction present, but less accurate in determining cause of obstruction (tumour, stone, stricture) • ERCP if therapeutic intervention likely to be required (strong suspicion of stone, obstruction requiring stenting, or if tissue sampling required ) • EUS can provide detailed anatomy of biliary tree and pancreas with potential for sampling/ intervention (e.g. cyst drainage)

Differential Diagnosis of Common Complaints Table 2. Differential Diagnosis of Common Presenting Complaints

PUD Biliary colic IBD Chronic pancreatitis

Neoplastic/ Vascular

Toxin

Other

Gastric cancer Recurrent bowel obstruction Mesenteric ischemia Sickle cell anemia

Lead poisoning

Mittelschmerz Endometriosis Porphyria I-

Radiculopathy Diverticular disease Anterior cutaneous nerve entrapment syndrome ACUTE DIARRHEA

Inflammatory

"Causes of bloody

Bacterial Shigella' Salmonella' Campylobacter' Yersinia' £. co/rjEHEC 0157:H7 )"

diarrhea

Noninflammatory Protozoal f. histolytica' (amoebiasis)

Strongyloides Others NSAIDs IBD " Ischemia "

Bacterial S. aureus C. per /ringens B. cereus [ . co/r (enterotoxigenic, enteropathogenic ) Salmonella enlerilidis Vibrio cholera Protozoal Ciardia lomblia

aneurysm)

s G

• see General Surgery and lhoracic Surgery, GS4

CHRONIC /RECURRENT Inflammatory ABDOMINAL PAIN

G

Acute Upper Abdominal Pain Remember to rule out thoracic sources (e.g. Ml , pneumonia, dissecting

Viral Rolavirus Norwalk CM V Drugs ABx Colchicine Laxatives Antacids ( magnesium )

Obscure but Treatable Causes of Abdominal Pain • Acute Intermittent Porphyria • Hereditary Angioedema • Familial Mediterranean Fever • Vasculitis (e.g. polyarteritis nodosa )

G

Inflammatory Diarrhea: Occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein rich fluids and a decreased ability to absorb these lost fluids. Diarrhea may be profuse or very small in volume. Often associated with abdominal pain ± fever and chills. Stool may be positive for white blood cells

-

-

Non lnflammatory Diarrhea: No damage to the mucosal lining. Nausea/ vomiting may be present Fever, chills, blood in the stool, severe abdominal pain , or tenderness are not present. Stool is negative for white blood cells

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Toronto Notes 2023

G5 Gastroenterology

Table 2. Differential Diagnosis of Common Presenting Complaints Gastric cancer

CHRONIC DIARRHEA

Organic

'Causes of bloody

Inflammatory

Secretory

Steatorrhea

Osmotic

IBD' Infectious (IB CMV HSV ) Ischemic bowel' Radiation colitis Neoplasia

Stimulant laxatives Postileal resection/ cholecystectomy (bilesalts) Bacterial toxins Vasculitis Neoplasia' (colon cancer, carcinoid, vasoactive intestinal peptide tumour (i.e. VlPoma)) Addison's disease Congenital syndromes

Giardio lamblia Celiac sprue Chconic pancreatitis

Osmotic laxatives Lactose intolerance Chewing gum (sorbitol, mannitol)

diarrhea

. .

C. dilhcilerarely causes bleeding

Chronic cholestasis

IBS Constipation (overflow diarrhea) Anal sphincter dysfunction

Commonly Forgotten Causes of Vomiting • Drugs

CONSIIPA1ION: if no associated rectal bleeding / weight loss, etc., usually no cause found (and dysmotility assumed)

NAUSEA VOMITING

DYSPEPSIA

.•

Uremia CNS disease • Pregnancy • Cannabis (cannabinoid hyperemesis)

. .

Medications (narcotics, antidepressants, calcium channel blockers) Metabolic (DM thyroid, hypercalcemia )

Collagen vascular disease |sclcioderma dcimalomyositis)

Relieved by Vomiting

Not Relieved by Vomiting

Hoadache /Oiliincss

No Other Symptoms

Gastric outlet obstruction

Gallbladder disease

Small bowel obstruction GIRD (regurgitation more common)

Pancreatitis

Cerebral tumour Migraine Vestibular disease Increased ICP

Drugs Uremia Pregnancy Metabolic (e g hypercalcemia) Gastroparesis (e.g. DM) Ketoacidosis

Common

Uncommon

Rare

Functional dyspepsia Drug side effect Peptic ulcer

Angina CD Cancer (stomach, pancreas, liver ) Gallstones

Giardia lamblia Malabsorption (celiac sprue) Pancreatitis

Colorectal cancer Stricture Extrinsic compression Anal disease

Rectoccle With AbdominalPain

.

Neurologic (Parkinson 's MS stroke)

.

Without Abdominal Pain

Ml Hepatitis Infectious Gastroenteritis

GtRD (esophagitis)

..

Uncommon

Rare

Tumours Arteriovenous malformation Dieulafoy's lesion (arterial) Gastric antral vascular ectasia (GAVE) Portal hypertensive gastropalhy Uncommon

Aorto enteric fistulae Hemobilia

Diverticulosis Ischemia Angiodysplasia (elderly) Infectious Anorectal (hemorrhoids, fissure, ulcer)

UGIB (brisk) Post -polypectomy Radiation colitis IBD

Intussusception Vasculitides Stercoral ulcer Coagulopathies

Mechanical (Solids)

Motility (Solidsand Liquids) Other

Peptic stricture/cancer Eosinophilic esophagitis Extrinsic compression

Achalasia DES Scleroderma

Foreign body Eosinophilic esophagitis

Common

. NSAIDsI

Ulcers \ H. pylori, ASA Esophageal varices Mallory - Werss tears Erosive esophagitis Erosive gastritis

LOWER Gl BLEED

DYSPHAGIA

Common

Differcntioting Between Dysphagia and Odynophagia • Dysphagia: Difficulty swallowing due to mechanical obstruction or dysmotility of the esophagus or pharynx • Odynophagia: Pain when swallowing due to ulceration or inflammation (e g. Candida esophagitis) In the esophagus or pharynx

.

Differential Diagnosis of Abdominal Distension

Aeiophagia

UPPERGlBLEED

IBD is a common cause of bloody diarrhea but can be diagnosed only if mimkhers are excluded: such as infection, ischemia, and medication induced

6Fs Fat Feces Fetus Flatus Fluid Fatal growth

Rare

Schatzki ring esophageal web Zenker 's diverticulum

'

ODYNOPHAGIA

ABDOMINAL DISTENSION

Infection

Inflammation/Ulceration

Drugs

Other

Candida HSV CMV (common in those who are immunosuppressed)

Caustic damage Eosinophilic esophagitis

Ouinidine Iron Vitamin C ABx (e.g. tetracycline) Bisphosphonates

Radiation

Fluid ( Ascites)

Flatulence

Feces

Other

Functional bowel disease leg. IBS) Fibre Lactose intolerance Chewing gum ( e.g sorbitol, mannitol)

Constipation Colonic obstruction Dysmotility

Pregnancy ( fetus) Obesity ( fat)

Portal HTN

Normal Portal Pressure

Cirrhosis Cancer Cardiac failure (especially ovarian) Hepatic vein Pancreatitis thrombosis IB

.

L

1

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ri

LJ

;d

Large tumours ( fatal growth)

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Toronto Notes 2023

( 6 Gastroenterology

Table 2. Differential Diagnosis of Common Presenting Complaints JAUNDICE (UKCONJUGATED BILIRUBIN)

Decreased Hepatic Intake

Overproduction

Hemolysis Ineffective erythropoiesis (e.g. megaloblastic anemias) JAUNDICE

Decreased Conjugation

Drug inhibition (e.g. chloramphenicol) Crigler - Najjar syndromes type I and II Gilbert 's syndrome Neonatal jaundice

Gilbert ' s syndrome Drugs (e.g. rifampin)

.

.

Common

Uncommon

Hepatocellular disease

Intraductal obstruction Gallstones Biliary stricture Parasites Malignancy (cholangiocarcinoma) Sclerosing cholangitis Extiaductal obstruction Malignancy ( e.g pancreatic cancer, lymphoma) Mctaslases in periportal nodes Inflammation (e g pancreatitis)

( CONJUGATED BILIRUBIN)

Drugs Cirrhosis (any cause) Inflammation (hepatitis, any cause) Infiltrative (e.g. hemochromatosis) Familial disorders (e.g. Rotor syndrome, Dubin-Johnson syndrome cholestasis of pregnancy) PBC PSC Sepsis Posloperativc/TPH

.

Ischemic Colitis The splenic flexure and rectosigmoid junction are watershed areas and are susceptible to ischemia History and symptoms include acute onset crampy left abdominal pain, rectal bleeding, In addition to possible abdominal tenderness on exam Risk factors include atherosclerotic risk factors, vasoconstricting medications, and histocy of low flow state

Dyspepsia - postprandial fullness, early satiety, epigastric pain or burning

.

..

Foods/Substances that May Aggravate GERD Symptoms (but diet does not change the underlying disease) EtOH • Caffeine • Tobacco • Fatty/fried foods • Chocolate • Peppermint • Spicy foods • Citrus fruit juices

.

Esophagus Gastroesophageal Reflux Disease Definition

•a condition which develops when the reflux of gastric content causes troublesome symptoms or complications Etiology • inappropriate transient relaxations of LES - most common cause •low basal LES tone (especially in scleroderma ) •contributing factors include: delayed esophageal clearance, delayed gastric emptying, obesity, pregnancy, acid hypersecretion ( rare ) from Zollinger- Ellison syndrome ( gastrin -secreting tumour ) • hiatus hernia worsens reflux, does not cause it ( see General Surgery and Thoracic Surgery GS23)

.

Clinical Features • “ heartburn" ( pyrosis ) and regurgitation ( together are 80% sensitive and specific for reflux ); less sensitive and less specific: water brash, sensation of a lump in the throat ( globus sensation ), and

frequent belching non - esophageal symptoms are increasingly recognized as being poor predictors of reflux

GERD Gastroscopy T

Non- erosi ve reflux disease (NERD) Normal esophagus Aim for symptom relief only;

PPIPRN

Esophagitis Esophageal inflammation

Aim to heal inflammation; PPI indefinitely or surgical lundoplication

Figure 2. Classification and gastroscopic findings of GERD

GERD signs/symptoms

1

I

I

Noil-respiratory Sore throat Hoarseness Dental erosions

Wheezing Aspiration pneumonia

• Only some (C. difficile diarrhea,

Esophageal

!

Respiratory Chronic cough

Side Effects of Long-Term Use of PPIs

I

Non - esophageal

1

Typical Heartburn Acid regurgitation

I Atypical

Chest pain Dysphagia (late ) Odynophagia (rare)

Figure 3. Signs and symptoms of GERD

Investigations

• usually, a clinical diagnosis is sufficient based on symptom history and relief following a trial of pharmacotherapy ( PPI: symptom relief 80% sensitive for rellux ) • however, response to anti secretory agents such as PPI is not a requirement for GERD diagnosis • gastroscopy indications • absolute indications heartburn accompanied by red - flags ( bleeding, weight loss, dysphagia, persistent vomiting, family history of G1 cancer, etc.) persistent reflux symptoms or prior severe erosive esophagitis after therapeutic trial of 4-8 wk of PPI BID history suggests esophageal stricture especially dysphagia high - risk for BE ( male, ages > 50, obese, white, tobacco use, long history of symptoms) • repeat endoscopy after 6 8 wk of PPI therapy indicated if severe esophagitis because it can mask BE or

-

symptoms

hypomagnesemia, vitamin Bn deficiency, small bowel bacterial overgrowth) seem to be related to suppressing gastric acid whereas others (pneumonia, fractures, chronic kidney disease, dementia) have no apparent pathophysiological relationship

• Stopping PPIs can increase gastric acid above baseline by a "rebound effect" causing heartburn even in healthy volunteers

• May increase the risk of IBO with prolonged regular use

• These associations do not preclude

long term use of PPIs In patients with esophagitis or peptic ulcer, or those needing gastric protection when taking NSAIDs or anti-platelet drugs, but do emphasize the importance of being as definitive as possible when making these diagnoses and accurately assessing risk-benefit ratios (as is true for all drugs)

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Toronto Notes 2023

G7 Gastroenterology

•esophageal manometry (study of esophageal motility ): indicated in patients wh o have non -cardiac chest pain and/or dysphagia with normal gastroscopy

• done to diagnose abnormalities of peristalsis and /or decreased LES tone, but cannot detect

presence of reflux; indicated before surgical fundoplication to ensure intact esophageal function ; exclude alternative diagnoses like scleroderma and achalasia • surgical fundoplication ( wrapping of gastric fundus around the lower end of the esophagus ) more likely to alleviate symptoms if lower esophageal pressure is diminished ; less likely to be successful if abnormal peristalsis • 24 h pH monitoring: most accurate test for reflux, but not required or performed in most cases most useful if PPIs do not improve symptoms

Up to 25% of patients with BE do not report symptoms of GERD

Treatment

• PPIs are the most effective therapy and usually need to be continued as maintenance therapy •empiric 8 wk trial of PP1 in patients with classic GERD symptoms; PPIs are the most effective therapy and sometimes usually need to be continued as maintenance therapy •discontinuation of PPIs after 8 wk in recovered patients without Barrett's esophagus or erosive esophagitis; symptoms may recur if therapy is discontinued •on -demand: antacids ( Mg (OH ) 2, Al(OH ) j), alginate, H2-blockers, or PPIs can be used for non -erosive esophagitis ( NERD) •diet helps symptoms, not the disease; avoid EtOH, coffee, spices, tomatoes, and citrus juices •only beneficial lifestyle changes are weight loss (if obese) and elevating the head of bed (if nocturnal symptoms) •symptoms may recur if therapy is discontinued

Complications •esophageal stricture disease - scarring can lead to dysphagia (solids ) •esophagitis (e.g. ulceration, bleeding) • BE and esophageal adenocarcinoma gastroscopy is recommended for patients with chronic GERD or symptoms suggestive of complicated disease (e.g. anorexia, weight loss, bleeding, dysphagia )

-

Barrett ’s Esophagus

Screening for Esophageal Adenocarcinoma in Patients with Chronic Gastroesophageal Reflux

Disease CMAJ 202O:192(27f:E768 E 777 Though Barren's esophagus increases the incidence of esophageal adenocarcinoma , the Canadian lash Force on Preventive Health Core currently does not recommend routine screening lor esophageal adenocarcinom and precursor conditions, including Barren's esophagus In adults vrrlh chronic GERD without red flag features (e.g. dysphagia, odynophagia , weight loss, anemia , gastrointestinal Weeding ). In this systematic review, no clinically significant survival benefits were identified in patients undergoing screening This

-

.

Definition

• metaplasia of normal squamous esophageal epithelium to intestinal columnar epithelium Etiology

• thought to be acquired via long-standing GERD and consequent damage to squamous epithelium Clinical Features

• prominent GERD symptoms Epidemiology • in North America and Western Europe, 0.5-20% of adults are thought to have BE • up to 10% of GERD patients will have already developed BE by the time they seek medical attention • more common in males, ages > 50, White individuals, smokers, overweight, hiatus hernia, and long history of reflux symptoms Pathophysiology • endoscopy shows salmon pink mucosa in distal esophagus; diagnosis of BE relies on biopsy demonstrating the presence of specialized intestinal epithelium of any length within the esophagus • BE predisposes the esophageal lining to premalignant changes characterized as low or high-grade dysplasia, which then progresses to adenocarcinoma

.

systematic review repoited that patients receiving screenng may he unnecessarily exposed to harm, ranging from pre- procedural anxiety lo endoscopic injury. Strikingly, the presence of risk factorsfor esophageal adenocarcinoma , including age male sea.and family history, is not suffidentto warrant screening endoscopy in patients with chronic GERD. On the othei hand, patients with known Garrett's esophagus should be referred to a Gastroenterologist for endoscopy.

.

CllnicalGuidelinesUpdate onthe Diagnosisand Management of Barrett's Esophagus Fora report reviewing the US and International guidelines on the diagnosisand management of 8E,

-

Significance

please refer to: Dig Dis So 2018:63:2122 2128

• rate of malignant transformation is approximately 0.12% per yr for all BE patients prior to dysplasia • risk of malignant transformation in high -grade dysplasia is significantly higher; studies have reported a 32 59% transformation rate over 5-8 yr of surveillance

-

Treatment

-

• acid suppressive therapy with high dose PPI indefinitely ( or surgical fundoplication ) may reduce the transformation of BE to dysplasia • surveillance gastroscopy every 3 5 yr if no dysplasia • high grade dysplasia: regular and frequent surveillance with intensive biopsy, endoscopic ablation / resection, or esophagectomy produce similar outcomes however, evidence increasingly favouring endoscopic ablation with mucosal resection or radiofrequency ablation • if low grade dysplasia, both surveillance (every 6 mo for 1 yr then annually ) and endoscopic ablation / resection are satisfactory options

-

.

Randomized Trial of Medical vs Surgical Treatment lor Refractory Heartburn NEJM 2019:381:1513 1523 Patients with PN ielractory and icllun related heartburn (n*TB) wore randomly assigned to surgical treatmenl (laparoscopic Nissen fundoplication ) octree medical treatment (omepraiole plus badolen , and desipramlne pen), or control medical treatment (omepraiole plus placebo) The Intrdenceol treatment success in the surgical treatment group (67%) was significantly greater than that in the active medical treatment gioup ( 28%: P 0.007 ) or control medical treatment group (12%; P«0.001).

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Toronto Notes 2023

G 8 Gastroenterology

Dysphagia Definition •

difficulty swallowing

Remember

Dysphagia - Difficulty in swallowing Odynophagia ~ Pain on swallowing

Dysphagia

_

£

Oropharyngeal

Esophageal

( difficulty initialing swallowing, choking, coughing, nasal regurgitation)

(inability to move food down esophagus)

I

Neurological *

Cortical Bulbar Peripheral

; Solid food only

Muscular Structural Muscular dystrophy Zenker's diverticulum Polymyositis Myasthenia gravis Cricopharyngeal

Thyromegaly Cervical spur

•

the act of swallowing? • Associated symptoms? (regurgitation,

Y

MMM>I I MMM

Mechanical obstruction

I Y

Progressive Y

i

Y

4 Carcinoma*

i

• • • •

Y

Reflux

chest pain, change in voice pitch, weight loss) Solids, liquids, or both? Intermittent or progressive? History of heartburn? Change in eating habits/diet?

.

symptoms

I ^ IES Scleroderma

Peptic stricture*

.

-

Prcg essr e

Intermittent Intermittent

Age >50 Heartburn Lower Diffuse (weight loss) esophageal esophageal

’Most common

Key Questions in Dysphagia Abnormal features when initiating

Solid foods and liquids

*

Figure 4. Approach to dysphagia (eosinophilic esophagitis omitted)

•

Esophageal Motor Disorders Clinical Features • •

dysphagia with solids and liquids chest pain ( in some disorders ) Endoscopic or Surgical Myotomy in Patients with Idiopathic Achalasia

Diagnosis • •

motility study (esophageal manometry) barium swallow sometimes helpful

IDM 2019;381:2219-2229

Causes • • •

idiopathic achalasia scleroderma

•

DM

-

Table 3. Esophageal Motor Disorders

____-___ .

Achalasia

Scleroderma

Diffuse Esophageal Spasm

Definition

Failure of smooth muscle relaxation at IES

See BheL ato : ~ i ItH14 Systemic disease charactered by vasculopathy and tissue fibrosis (especially skin thickening)

Normal peristalsis interspersed with frequent, repetitive, spontaneous, high pressure, non -peristaltic waves ( tertiary peristalsis)

Increased LES pressure Progressive loss of peristaltic function

Pathophysiology

Diagnosis

.

-

Disorder

.

Usually idiopathic 2° or pseudo -achalasia e.g malignancy Chagas disease (trypanosoma cruci)

Idiopathic Involves autoimmune, genetic hormonal, and environmental factors Dysphagia: caused by reflux, dysmotility or both

Inflammatory degeneration of Auerbach's plexus * increase in LES pressure, incomplete relaxation ol LES with swallowing, aperistal sis

Blood vessel damage « intramural neuronal dysfunction distal esophageal muscle weakening apevistalsis and loss of IES tone reflux » stnetute * dysphagia

.

.

.

• DKS: rare and can be difficult to diagnose due to intermittent presentation

Etiology

Purpose Tommpare peroral endoscopic myotpoiy (POEM) to laparoscopic Heller 's myotomy (LMH|in he treatment of achalasia. Methods: Patients nidi Symptomatic acialasa i“221|oare randomly assigned to either POEM or LMH.the p nary endpoint was clinical success, wh.le secondary endpo.nts included adverse evens, f nction Gastro nrasdna Ouality of Life esophageal . (GOoL) score andgastroesopliagealrefkji|GEt). Results 33.0% of patients in the POEM group and 81.7% of patens in Ce LNM group acnieied c -n cal success at 2 yr (P 0.007 for nonmferionly ].There wasno difference in m jroemen!of esophageal function or G Ool score between groups.Serious adverse events were observed in 2.7% and 73% of patents a tbe POEM and WM groups,respectively. St 12 oo.44% of patens m the POEM groupand 29 % of patens a tbe LHM group tad ie9ui esophagitis.

.

.

-

--

CXR: no air in stomach, dilated esophagus Clinical features of scleroderma Manometry: decreased pressure in Barium studies: esophagus terminates in LES decreased peristalsis n body of narrowing at IES ( "bird's beak ") Endoscopy:normal mucosa esophagus Manometry: definitive diagnosis Isigns listed

.

Conclnsions POEMwasnonxifetoralHMinthe

treatsent of symptomatic achalasia. GER was more common among patens who were treated wrtb POEM Ban ttose heated with IHM.

Potential mechanismsinclude impaired inhibitory innervation to esophageal body,malfunction in endogenoos nitric oxide synthesis

Barrum x -ray "Corkscrew pattern" Manometry.>20% premature contractions Endoscopy:normal mucosa

rT iJ

above)

Treatment

Pneumatic dilation. 5% risk of perforation Injection of botulinum toxin into LES ( temporary) Surgical myotomy POEM (peroral endoscopic myotomy)

Medical: aggressive GERO therapy (PPIs BID)

Beassuraxe that symptoms are not due to cardiac pain

Medical:nitrates,calcium channel blockers anticholinergics have variable benefit

+

,

Surgical:long esophageal myotomy if unresponsive to above treatment (rarely helpful),balloon dilatation

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Toronto Notes 2023

G9 Gastroenterology

Esophageal Diverticula Definition

• outpouching* of one or more layers of the esophageal tract Clinical Features

• commonly associated with motility disorders • dysphagia, regurgitation, retrosternal pain, intermittent vomiting, may be asymptomatic Classification

• pharyngoesophageal ( Zenker’s) diverticulum most common form of esophageal diverticulum posterior pharyngeal outpouching most often on the left side, above cricopharyngeal muscle and below the inferior pharyngeal constrictor muscle symptoms: dysphagia, regurgitation of undigested food, halitosis ( bad breath ) treatment: small and asymptomatic: no treatment required, large and symptomatic: endoscopic or surgical myotomy of cricopharyngeal muscle ± surgical excision of sac

Peptic Stricture (from Esophagitis) Definition

• a smooth, concentric narrowing most commonly seen in the lower esophagus Clinical Features

• presents as dysphagia alongside a long history of reflux symptoms, but reflux symptoms may disappear as stricture develops Diagnosis

• diagnosed with endoscopy or barium study if endoscopy contraindicated or unavailable Treatment • endoscopic dilatation and indefinite PP1

Esophageal Carcinoma • see General Surgery and Thoracic Surgery. GS21

Webs and Rings Definition • web = partial occlusion (upper esophagus) • ring = circumferential narrowing ( lower esophagus) Clinical Features • asymptomatic with lumen diameter >12 mm, provided peristalsis is normal • dysphagia with large food boluses • Schatzki ring mucosal ring at squamo- columnar junction causes intermittent dysphagia with solids treatment involves disrupting ring with endoscopic dilation

Infectious Esophagitis Definition

• severe mucosal inflammation and ulceration as a result of a viral or fungal infection

.Risk DM chemotherapeutic agents Factors

•

• immunocompromised states Clinical Features

• characteristically odynophagia, less often dysphagia Appearance • Candida (most common ): whitish- yellow plaques without visible ulceration or inflammation • HSV (second most common ), CM V: focal ulcers

Investigations • diagnosis via endoscopic visualization and biopsy

-

Plummer Vinson Syndrome Triad

• Iron deficiency anemia • Dysphagia Esophageal webs • Rare (prevalence 60 (and if ages £5 yr with comorbidities

• immunocompromised (chemotherapy, HIV ) • diarrhea >7 d in duration • exposure to suspicious foods or untreated water • sexual contacts: men who have sex with men (MSMI NO

YES Investigations

Treat Symptoms

Roubne Tests: Stool for fecal leukocytes Stool C&Sfor Campylobacter, Salmonella, and Shigella

Rehydration Antidiarrheal agents • bismuth subsalicylate • loperamide

Special Tests Stool C& S for EHEC, stool lor Shiga toxin

Indication Blood in stool

Stool for C. 65 yrwith comorbidities Immunocompromised

A and B

Stool O & P for Giardia, Cryptosporidium, £. histolytica

Diarrhea >7 d Exposure to untreated watei HIV

MSM

4

f

Illness persists

]

(

Illness resolves

Indications lor Antimicrobial Therapy Absolute Indications: • infection with S. typhi, Shigella, C. difficile, Cryptosporidium, t. histolytica • immunocompromised patients Relative Indications: • infection with V. cholerae non typhoid Salmonella, Campylobacter, Yersinia, Giardia, ETEC • decision to treat is determined by severity of illness ( see Tables 9, 10, and 11 for information on common pathogens)

. -

Figure 7. Approach to acute diarrhea

Note: S. typhi has a rose spot rash (transient moculopapular rash on anterior thorax, upper abdomen), and a prodrome ol high fover, bradycardia, headache, and abdominal pain. Diarrhea Is not the Initial presentation

r -i LJ

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G 17 Gastroenterology

Table 9. Bacteria in Infectious Diarrhea Source or Mode ot Transmission

Pathogen

Incubation

Clinical Features Fever

.

B cereus - TypeA (emetic)

Ricedishes

1- 6 h

B cereus - TypeB

Meats, vegetables, dried beans, cereals

8 -16 h

(diarrheal)

Campylobacter jejuni

Uncooked meat, especially poultry

2-10 d

.

Bloody Stool

Abdo Pain

Duration

Antimicrobial Therapy

Notes

1 wk bloody diarrhea, or immunocompromised

Most common bacterial cause of diarrhea in Canada Associated with Guillain Barre syndrome

Slop culprit anlibiolic therapy if possible Supportive therapy (IV fluids) Empiric Ireatmenlwrlh either vancomycin or fidaxomlcin II access lo empiric treatment is limited then metronidarole may be used

Usually follows antibiotic treatment (especially clindamycin, fluoroquinolones, penicillins, cephalosporins) Can develop pseudomembranous

< 24 h

None

Clostridium spores are heal resistant Secondary enterotoxin Enteroinvasive

7-10 d

None

Relatively uncommon Enterotoxigenic

3d

Fluoroquinolone or azithromycin for moderate to severe symptoms

Most common cause of traveller ’s diarrhea Heat - labile and heat - stable toxins

None: ABx increase risk ol HUS

Shiga toxin production Monitor renal lunction:10%

2 y) short- term travellers who are high- risk (e.g. chronic illness) and have an increased risk of serious consequences of traveller's diarrhea (e.g. chronic renal failure, CHI , T1 DM , IBD ) '

» immunosuppression

history of repeat traveller’s diarrhea travellers to cholera endemic countries at increased risk of exposure • two vaccines against Salmonella lyphi are available and their effectiveness is estimated to be 50-70%

Chronic Diarrhea

K

Definition • passage of frequent unformed stool for > 4 wk (compared to persistent diarrhea lasting 14-30 d )

Etiology /Classification

• majority of cases are non - infectious • see Differential Diagnosis of Common Complaints, G’5 Investigations

• guided by history

• stool analysis for: C. difficile toxin , C&S, O& P ± fecal fat, WBC, fecal calprotectin • blood for: CBC, electrolytes, C-reactive protein ( CRP) , T'SH, celiac serology ( IgA anti-tTG; ask for

serum protein electrophoresis or immunoglobulin quantitation to rule out IgA deficiency, which has an increased frequency in celiac disease) • colonoscopy and ileoscopy with biopsy • upper G1 endoscopy with duodenal biopsy • wireless small bowel endoscopy capsule ( low yield ) • trial of lactose free diet • caveat: may delay diagnosis of IBD and celiac disease Treatment

• approach is similar to that of acute diarrhea

Maldigestion and Malabsorption Definition • maldigestion: inability to break down large molecules in the lumen of the intestine into their

component small molecules

• malabsorption: inability to transport molecules across the intestinal mucosa into circulation Etiology

• maldigestion

• inadequate mixing of food with enzymes (e.g. post -gastrectomy ) • pancreatic exocrine deficiency ( • primary diseases of the pancreas e.g. cystic fibrosis (CF) ( remember CF can result in pancreatic

exocrine insufficiency as well ), pancreatitis, cancer) bile salt deficiency terminal ileal disease (impaired enterohepatic recycling in view of loss greater than synthesis), bacterial overgrowth (deconjugation of bile salts), rarely liver disease (cholestatic, e.g. PBC ) specific enzyme deficiencies (e.g. lactase) • malabsorption inadequate absorptive surface infections/ infestations (e.g. Whipple’s disease, ( iiardia ) immunologic (e.g. celiac disease ) infiltration (e.g. lymphoma, amyloidosis) fibrosis (e.g. systemic sclerosis, radiation enteritis): can lead to loss of surface area but also areas of stricture formation resulting in stasis with small bowel overgrowth small bowel resection ( length, site, location, presence/absence of ileocecal valve, and integrity of colon are important) congenital (e.g. short bowel syndrome) inflammatory': extensive ileal CD ( pivotal number is 100 cm as 100 cm = fatty diarrhea or steatorrhea )

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G20 Gastroenterology

• drug- induced

cholestyramine, ethanol, neomycin, tetracycline, and other ABx endocrine DM (complex pathogenesis)

Clinical Features • symptoms usually vague unless disease is severe • weight loss, diarrhea, steatorrhea, weakness, fatigue • manifestations of malabsorption / deficiency

Fat Soluble Vitamins: ADEK vitamin A. vitamin D. vitamin E. vitamin

K

Table 12 . Absorption of Nutrients and Fat Soluble Vitamins Deficiency

Absorption

Clinical Disease and /or Features

Investigations

Iron

Duodenum , upper jejunum

Hypochromic, microcytic anemia , glossitis, koilonychia ( spoon nails), pica

« Hb, serum Fe, a serum ferritin

Calcium

Duodenum , upper jejunum ( binds lo Cat' binding protein in cells: levels increased by vitamin D)

Metabolic bone disease, may get tetany a Serum Cat ', a serum Mg / , and and paresthesias if serum calcium tails* t ALP (see Endocrinology, E42) Evaluate for a bone mineralization radiographically ( dual energy x ray absorptiometry OEXA )

-

-

-

.

Folic Acid

Jejunum

Megaloblastic anemia, glossitis, a red cell folate (may see t lolic acid with

a Serum folic acid

Vitamin Biz

B12 ingested and bound to fi proteins mainly Irom salivary glands: stomach secretes IF in acidic medium: in basic medium , proteases Irom the pancreas cteave R protein and EU - IF complex forms, protecting Bu Irom further protease attack: B12 absorbed in ileum and binds to Itanscobalamin (IC) Complex polysaccharides hydrolyzed lo oligosaccharides and disaccharides by salivary and pancreatic enzymes Monosaccharides absorbed in duodenum! jejunum

Subacute combined degeneration of thespinal cord , peripheral / optic neuropathy, dementia , megaloblastic anemia , glossitis

Differentiate causes by nuclear Schilling test ( when available) Positive anti intrinsic factor antibodies and atrophic gastritis point toward perniciousanemia (see Hematology. H 25)

Generalized malnutrition , weight loss, flatus, and diairhca

Hydrogen breath test trial of carbohydrate restricted diet 0 xylose test

Digestion at stomach , brush border, and

General malnutrition and weight loss, amenorrhea , and a libido it severe

a Serum albumin ( lowsensitivity )

bacterial overgrowth )

Carbohydrate

Protein

inside cell

-

-

-

Absorption occurs primarily in the jejunum

Fat

Lipase, colipase, phospholipase A Generalized malnutrition, weight loss (pancreatic enzymes), and bile salts needed and diarrhea lor digestion Foul smelling lcccs * gas

-

Products ol lipolysis form micelles which solubilize fatand aid in absorption Absorption occurs primarily in the jejunum Fatty acids diffuse into cell cytoplasm

Steatorrhea

Vitamin A

Dietary sources (e.g . milk , eggs , liver, carrots, sweet potatoes)

flight blindness Dry skin Keratomalacia

Vitamin D

Skin (via UV light) or diet (e.g . eggs, fish oil fortified milk )

Vitamin E

Dietary sources (e .g. vegetable oils nuts leafy green vegetables)

Retinopathy, neurological problems

Vitamin K

Synthesized by intesbnal flora t risk of deficiency after prolonged use of broad spectrum ABx and /or starvation

Prolonged INR may cause bleeding

.

. .

' Calcium malabsorption

.

Small bowel biopsy MRCP. ERCP, pancreatic function tests ( not routinely available) Quantitative stool tat lest (72 h ) May start with qualitative stool fat test (Sudan stain of stool) C- triolein breath test (not routinely available)

Osteomalacia in adults Rickets in children

more commonly causes decreased bone density rather than hypocalcemia because serum calcium levels are protected by

leaching calcium Iromlhe bone

Investigations • tTG-lg /\ antibody serology/immunoglobulin A quantitation and abdominal imaging are most useful because celiac disease and chronic pancreatitis are the two most common causes of steatorrhea • 72 h stool collection ( weight, fat content ) documents steatorrhea ( gold standard ) • fecal elastase to screen for pancreatic insufficiency and / or consider empiric trial of pancreatic enzymes based on clinical context • serum carotene ( precursor to vitamin A ) , folate, Ca J +, Mg 2 t , vitamin Bt 2, albumin , ferritin, serum iron solution , international normalized ratio/ partial thromboplastin time (1 NR / PTT ) • stool fat globules on fecal smear stained with Sudan ( used as an initial qualitative screening tool ) • other tests specific for etiology ( e.g. Cl' scan / MRl to visualize pancreas)

rn LJ

Treatment

• dependent on underlying etiology

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G21 Gastroenterology

Celiac Disease (Gluten Enteropathy/Sprue) Definition

• abnormal small intestine mucosa due to intestinal reaction to gluten , a protein found in wheat, barley,

-

rye, and possibly oats (certified gluten free oats may be acceptable in a subgroup of patients)

Etiology

• unique autoimmune disease because the genetics ( HLA - DQ2/8), the auto -antigen (tTG), and the environmental trigger ( gluten ) are all known • associated with other autoimmune diseases, especially Sjogren’s, T1DM, thyroid disease • gluten is broken down to gliadin, which is the toxic protein • HLA - DQ2 (chromosome 6 ) found in 80-90% of patients compared to 20% of the general population; celiac also associated with HLA DQ8 • HLA DQ2 /Q8 are necessary permissive genes, but their presence docs not confer a diagnosis of celiac disease ( note: up to 40% of White individuals carry the HLA alleles, but will never develop celiac disease)

-

-

Epidemiology

• more common in women • prevalence: 1 first degree relative: 10%; 2 first degree relatives: 20% • may present any time in life, with peak presentation in infancy ( when cereals introduced )

hodomited Clinical Trial JAMA Pedralr 2020:114:1 ? Purpose: Determine whether introdactlon of high dose gluten lowers celiac disease prevalence at 3 yr of age Methods: l fa nts were random ued to consume 6 allergenic foods In addition to breast milk from age 4 mo (early introduction), or to avoid allergenic foods and follow exclusive breastfeeding guidelines (standard introduction) . Evaluation of celiac d scare was an a priori secondary outcoureoithe EAT trial, tested at age 3 with anh transglutaminase 2 anti bodies. Results:1.4% of infants in thestandard introduction group had a celiac disease diagnosisconfirmed versus 0% of infants in theearly introduction group. Cone lotion:Introduction of gluten from age 4 mo was associated with a reduction in the prevalence of celiacdrsease.

-

Clinical Features • classic presentation: diarrhea, weight loss, anemia, symptoms of vitamin / mineral deficiency, failure to thrive; more common current presentation: bloating, gas, iron deficiency, or asymptomatic ( patient at risk )

Early Gluten Introduction and Celiac Disease in the MI Study: A Prespecified Analysis of the MI

-

• improves with gluten free diet , deteriorates when gluten reintroduced • disease is usually most severe in proximal bowel

iron, calcium, and folic acid deficiency (absorbed in proximal small bow'el) more common than vitamin B 12 deficiency (absorbed in distal small bowel or ileum ) • gluten enteropathy may be associated with dermatitis herpetiformis skin eruption , epilepsy, myopathy, depression , paranoia , infertility, bone fractures/ metabolic bone disease

Investigations

-

.

• serological tests

• serum anti- tTG antibody, IgA, is 90 -98% sensitive, 94-97% specific • patients with selective IgA deficiency have false- negative anti- tTG

therefore, measure serum IgA concomitantly (via serum immunoglobulin quantitation ) • incorporate serum testing tTG and /or DGP IgG in IgA deficiencies • small bowel mucosal biopsy ( usually duodenum ) is diagnostic: lymphocytes (earliest pathologic finding) • increased intraepithelial • crypt hyperplasia ( next stage of pathophysiology) villous atrophy (last stage of pathophysiology) note: there is a wide differential diagnosis for villous atrophy, including, but not limited to, small bowel overgrowth, CD, lymphoma , Giardia, HIV • improvement with a gluten free diet, but should not be started in adults before serological tests and

biopsy

-

• consider CT enterography to visualize small bowel to rule out lymphoma • evidence of malabsorption ( localized or generalized ) • steatorrhea low levels of ferritin/iron saturation, Ca 2 \ Fe, albumin, cholesterol, carotene, Bi:absorption • quantitative fecal fat >7% Treatment

• dietary counselling

• gluten free diet; avoid barley, rye, wheat (as these grains are related and have toxic proteins,

similar to gliadin) oats allowed if not contaminated by other grains ( grown in soil without cross -contamination ) • rice and corn flour are acceptable • iron , folate supplementation ( with supplementation of other vitamins as needed ) • if poor response to diet change, consider • alternate diagnosis » non -adherence to gluten - free diet ( advertent or inadvertent ) concurrent disease (e.g microscopic colitis, pancreatic insufficiency) • development of intestinal ( enteropathy associated T cell ) lymphoma (abdominal pain, weight loss, palpable mass) development of diffuse intestinal ulceration, characterized by aberrant intraepithelial T cell population ( precursor to lymphoma )

.

-

8 yr is indicated • toxic megacolon ( transverse colon diameter > 6 cm on abdominal x ray ) with immediate danger of perforation ( see General Surgery and Ihoracic Surgery. GS45)

-

Prognosis

• chronic relapsing pattern in most patients • 10-15% chronic continuous pattern • >1 attack in almost all patients more colonic involvement in the 1st yr correlates with increased severity of attacks and increased colectomy rate • colectomy rate 1% for all patients after the 1 st yr; 20 25% eventually undergo colectomy • normal life expectancy • if proctitis only, usually benign course, lifetime risk of extension is 15% • fecal calprotectin increasingly recognized as a marker of bowel mucosal inflammation , reported to be especially useful in monitoring the activity of 1 BD, but accuracy is still controversial

-

-

=

When Considering Complications of ISO Think:

.

ULCERATIVE COLITIS Urinary calculi Liver problems

Cholelithiasis Epithelial problems Retardation of growth/ sexual maturation Arthralgias Thrombophlebitis Iatrogenic complications Vitamin deficiencies Eyes Colorectal cancer Obstruction Leakage (perforation) Iron deficiency Toxic megacolon Inanition (wasting)

Strictures

s

Irritable Bowel Syndrome Definition

• a form of functional bowel disease, now also known as disorder of gut - brain interaction; more than just a label for G1 symptoms unexplained after normal investigations

Epidemiology

• 11% worldwide prevalence

• onset of symptoms usually in young adulthood • F>M Clinical Features

• Rome IV Criteria are used for diagnosis • diagnosis is based chiefly on history; no specific diagnostic test available Emerging Biologic Treatments for Ulcerative Colitis

Pathophysiology

• associated with either abnormal perception of intestinal activity or abnormal intestinal motility • abnormal motility ; multiple abnormalities described; unclear if associated or causative • psychological: stress may increase IBS symptoms but probably does not cause IBS • 4 main types of IBS 1 BS- D: IBS with predominant diarrhea • IBS C: IBS with predominant constipation • IBS M: IBS mixed with both diarrhea and constipation ( each > 25% of all abnormal bowel

--

-

movements) IBS untyped: insufficient abnormalities to be IBS-C, D, or M

Diagnosis

Generic Name

Brand Name

Major Study

Ustekinumab

Stelara '

NEJM 2019; 381:1201

Vedolirumab

Entyvio '

Adalimumab

Humira '

1214 HUM 2019 ; 381:1215 1226 HUM 2019; 381:1215 1226

-

-

Table 16. Rome IV Criteria for Diagnosing Irritable Bowel Syndrome IBS Rome IV Criteria

.

Recurrent abdominal pain lor more than 6 mo , at least 1 d /wk in the last 3 mo associated with 2 or more of the following: 1. Related to defecation 2. Associated vrlth a change In frequency ol stool 3. Associated with a change in form (appearance) of stool Symptom onset at least 6 mo before diagnosis and criteria present during the last 3 mo Ihe Mowing are supportive , but not essential to the diagnosis: Abnormal stool frequency ( >3/ d or « 3/ wk ) Abnormal stool lorm flumpy /hard/ loose/watery ) >114 of defecations Abnormal stool passage (straining, urgency, feeling of incomplete evacuation) >1/4 of defecations Passage of mucus »1/4 of defecations 8loating

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Diagnosis ol IBS less likely in Presence of " Red Flag" Features Weight loss

Fever Hodurnal defecation

Anemia Blood ori pus in stool , gross findings on flexible sigmoidoscopy Abnorm al

+

Hormal Physical fxam

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G 27 Gastroenterology

Investigations

• if history consistent with Rome IV criteria, no alarm symptoms, and no family history' of 1BD or colorectal cancer, limited investigations required • aim is to rule out diseases which mimic IBS, particularly celiac disease and 1 BD • investigations can be limited to CBC and celiac serology • if available, fecal calprotectin is likely more reliable test to rule out IBD • consider1SH, stool cultures depending on clinical circumstances • consider colonoscopy (e.g. if alarm features present, family history of IBD, or ages >50 ) Treatment

• education: reassurance, explanation , support, aim for realistic goals • relaxation therapy, biofeedback, hypnosis, stress reduction , cognitive behavioural therapy, probably exercise

-

• dietary: low l:01)MAH ( fermentable Qllgo , Pi - , Monosaccharides And Polyols ) diet for pain, bloating, gas, irregular bowel movements ( BMs) • no therapeutic agent consistently effective, pain most difficult to control, no drug changes natural

history so the drug should be “ wanted, since it is not needed ” symptom • -guided treatment pain predominant antispasmodic medication before meals (e.g. hyoscine, pinaverium, trimebutine - low level of

evidence )

antidepressants ( TCA ), selective serotonin reuptake inhibitors (SSKI ) • tricyclic level of evidence • 1BS-D

•

moderate

increase fibre ( bran or psyllium ) to increase stool consistency but may worsen abdominal gas

(controversial)

•

loperamide ( Imodium*) (continuous use advised against ) diphenoxylate ( Lomotil* ) cluxadoline rifaximin IBS C increase fibre in diet linaclotide, plecanatide, tenapanor osmotic or other laxatives ( help more with the constipation than the pain )

-

Prognosis

IBS Mimickers

• Enteric infections e.g. Giardia • Lactose Intolcranco/other dlsaccharidase deficiency CO • Celiac sprue

.

• Drug-induced diarrhea • Diet- induced (excess tea, coffee, colas)

Rilaxiniin therapy for Patients with Irritable Bowel Syndrome withont Constipation NEJM 2011:364:22-32 Purpose: Previous evidence suggests that gut flora may play an important role in the pathophysiology of ISS. Ihis study evaluated nfatimin, a minimally absorbed antibiotic, in beating IBS without constipation. Methods: two phase 3. double blind, placebo controlled trials ( IMMI 1and IMCil | 2 12(0 patients who had I8S without constipation were randomly assigned to rifanmin (5(0 mg dose) or placebo, 110 for 2 wk with a follow up of 10 wk.The primary endpoint was adequate self -reported relief of global IBS symptoms. Results: Significantly more patents in the rifanmin group had adequate self reported relief of global IBS symptoms compared to the placebo groupduring the first 4 wk after treatment (40.831 vs 31, 2V respectively!. Also, more patients In the rifaximln group had adequate relief of bloating compared to the placebogroup (39.5 vs. 28.7V respectively ). Conclusions: Rifaiinnim therapy for 2 wk provided significant relief of symptoms, bloating, abdominal pain, and stool consistency associated with IBS without constipation.

-

.

.

-

-

.

*

• 80 % improve over time • most have intermittent episodes • normal life expectancy

s

Constipation Definition

• passage of infrequent / hard stools and /or difficult stool evacuation (e.g. straining, sensation of anorectal blockage ) Epidemiology

• increasing prevalence with age; F> M • rare in Africa and India where stool weight is 3-4x greater than in Western countries Etiology • most common: functional, idiopathic attributed to colon dysmotility but this is difficult to measure • organic causes: likely only if there are symptoms other than constipation • medication side effects (e g narcotics, antidepressants) are the most common • intestinal obstruction, left sided colon cancer (consider in older patients ), and fecal impaction

..

Causes of Constipation DOPED

Drugs Obstruction Pain Endocrine dysfunction Depression

• metabolic •

DM hypothyroidism hypercalcemia, hypokalemia, uremia neurologic intestinal pseudo obstruction Parkinson's disease MS collagen vascular disease (e.g. scleroderma ) painful anal conditions (e.g. fissures)

-

Clinical Features

+

• overlaps with IBS with constipation ( IBS- C ) but labeled as IBS- C when pain is a predominant feature • stool firm, difficult to expel, passed with straining, abdominal pain relieved by defecation, flatulence, overflow diarrhea, tenesmus, abdominal distension , infrequent BMs (50 • if refractory to treatment, consider classification based on colon transit time; can measure colonic transit time with radio opaque (Sitz) markers that are ingested and followed with a series of plain film abdominal x-rays ( normal: elimination of markers within 70 h)

-

1. normal = misperception of normal defecation ( IBS) 2. prolonged throughout “colonic inertia” (infrequent bowel movements with gas / bloating, tends to occur in youth ) 3 outlet obstruction inability to coordinate pelvic floor muscles to empty rectum , straining, stool in rectum on digital exam , tends to occur in old age • combination of 1 and 3 common

=

.

Treatment (in order of increasing potency)

• dietary fibre useful if mild or moderate constipation, but not if severe aim for 30 g daily, increase dose slowly

• surface-acting (soften and lubricate) docusate salts (likely limited efficacy based on evidence), mineral oils • osmotic agents (effective in 2-3 d ) • polyethylene glycol 3350, lactulose, sorbitol, magnesium salts (e.g. magnesium hydroxide, i.e. milk of magnesia ), lactitol ( (3- galactosido - sorhitol ) • cathartics/stimulants (effective in 24 h ) senna, bisacodyl • enemas and suppositories (e.g. saline enema, phosphate enema, glycerin suppository, bisacodyl suppository) • prokinetic agents (e.g. prucalopride ) • secretagogues: linaclotide, plecanatide (increases water secretion into the intestinal lumen ) • NHE3 inhibitors: tenapanor

Upper Gastrointestinal Bleeding Definition • bleeding proximal to the ligament of Treitz, see Overview of Gastrointestinal Tract , G2 (75% of Gl

bleeds)

ligament of Treitz: suspensory ligament where fourth portion of the duodenum transitions to jejunum

Always ask about NSAID/Aspirin ' or anticoagulant therapy in Gl bleed

Aortoenteric Fistula is a rare and lethal cause of Gl bleed, most common in patients with a history ot aortic graft surgery. Therefore, perform emergency endoscopy if suspected, emergency surgery if diagnosed Note: The window of opportunity is narrow. Suspect if history of aortic graft, abdominal pain associated with bleeding

Etiology • above the GE junction

epistaxis

-

Traasfusaon Strategies for Acute Upper Gastrointestinal Bleeding

esophageal varices (10 30%)

esophagitis

-

St JM 2013:368:11 21

• esophageal cancer Mallory- Weisstear (10%)

-

Study: Prospective, unblmded. RCI, follow up up

toASd .

stomach gastric ulcer (20%) (see Peptic Ulcer Disease, Gl I ) * erosive gastritis (e.g. from EtOH or post surgery ) (20% )

-

gastric cancer gastric antral vascular ectasia ( rare, associated with cirrhosis and connective tissue disease ) Dieulafoy’s lesion (very rare) • duodenum ulcer in bulb ( 25%) aortoenteric fistula: usually only if previous aortic graft (see sidebar ) • coagulopathy (drugs, renal disease, liver disease) • vascular malformation ( Dieulafoy’s lesion, arteriovenous malformation ) Clinical Features • in order of decreasing severity of the bleed: hematochezia (brisk UG1B) > hematemesis > melena > coffee ground emesis > occult blood in stool

Population: 921 patients with hematemesis, bloody nasogastric aspirate, melena or both. Exclusion criteria inebded massive Meed , acute coronary syndrome, strohel transient ischemic attack or

.

transfusion within previous 90 d:rece nt traum af surgery; lower Gl Weed . Intervention: Patients randomized to restrictive («20 gl) or liberal|«90 gfl) transfusion. Outcome: Mortality, further bleeding, adverse events. lesults: fewer patients in the restrictive group required transfusion (51% vs.15%; P *0.001) Ihe hazard ratio loi death for restrictive compared to tbera I transfusion was 0.55:05% Cl 0.33 0.92; P^O.02. Further bleeding occurred in 10 % vs.16% (P-0.01) of patients, while adverse effects occurred in 40% vs. 48% ( P - 0.02) of patients in the restrictive and liberal strategies, respectively. The restrictive strategy had a better survival rate in patients with bleeding associated with cirrhosis Child Pugh class A or 6 (HR: 0.30 ; 95% Cl 0.11 0.85), but not in cirrhosis Child -Pugh class C ( HR:1.04:05% Cl 0.45 2.37) or a peptic ulcer (HR: 0.70; 05% 0 0.2( 125). Conclusions: Transfusing patients with anacute UGIB at Hb of 0.5 cc /min • CT enterography if wireless endoscopy capsule/double balloon endoscopy not available

Management ol Monvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations from tbelnternational Consensus Group Ann Intern Med 2019:171:805822 Pro Endoscopic Management In patients without cardiovascular disease, the suggested Kb threshold lor blood transfusion is CD )) Hemorrhoids/ fissure Angiodysplasia Neoplasm Diverticular disease

Neoplasm • cancer •

polyps

• inflammation colitis ( ulcerative, infectious, radiation, ischemic) (see Ulcerative Colitis , G25 ) • post- polypectomy

Clinical Features • hematochezia • anemia • occult blood in stool • occasionally melena due to slow small bowel or right-colonic course Treatment • ifblood per rectum with hemodynamic instability, stabilize patient ( 1 2 large bore lVs, IV fluids, monitor) and rule out upper G! source with endoscopy (OGD) • send blood forCBC, cross and type, INR / PTT, electrolytes, BUN , Gr, LITs • initial examination of choice is colonoscopy to determine source of the bleeding • if bleeding is severe or ongoing, consider radionuclide imaging or angiography (see Medical Imaging, M l 16)

-

c

+

• treat underlying cause majority of cases will stop bleeding spontaneously

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G31 Gastroenterology

1. Assess hemodynamic stability

*

2. Resuscitate (IV fluids * blood transfusion)

I i 4. Determine site ol bleeding

3. Assess coagulation status ICBC. INR/PTT)

Always exclude upper Gl lesion before localizing the site of the bleeding to the lower Gl tract

i T

Massive bleeding'llemodynamically unstable? Clinical suspicion of UGIB based on risk factors? ( increased possibility of UGI source)

Hemodynamically stable, no UGIB risk factors? ( decreased possibility of UGI source)

i Colonoscopy and OGD

(or

Colonoscopy only flexible sigmoidoscopy)

I •For SLOW bleeding (0.5 ml/min): angiography ± embolization

Figure 11. Approach to hematochezia

Diverticular Bleeding Etiology • herniation of diverticula exposes vasa recta, increasing susceptibility to

disruption

• bleeding most common from the right colon (thinner walled), although diverticula often develop

throughout colon Clinical Features • painless hematochezia, acute onset • stool can range from bright red to dark maroon; gelatinous clots often mixed in

Management • often resolves spontaneously

• if colonoscopy identifies source ( rare), hemostatic therapy can be applied • if ongoing, can consider embolization or surgery

Infectious Colitis Etiology • variety of pathogens; often due to Campylobacter, • consider travel history, food exposures

Entamoeba histolytica . Salmonella , E . coli , Shigella

Clinical Features • bloody diarrhea, fever, abdominal pain

Management •

stool cultures to determine pathogen and guide management Acute Diarrhea , U 15

• see

SIS

Colorectal Carcinoma • see General Surgerv and lhoracic Surgery, GS43

Colorectal Polyps • see General Surgerv and lhoracic Surgerv. GS 41

Familial Colon Cancer Syndromes .

• see Genera! Surgerv and lhoracic Surgerv GS42

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G 32 Gastroenterology

Benign Anorectal Disease •

see General Surgery and Thoracic Surgery, GS47

Quids Reference Diagnostic Tests for Common Liver Conditions

.

Liver

Disease

Diagnostic Tests

Viral Hepatitis

Ant HAVIgM, HBsAg, anti- HCV

Investigations of Hepatobiliary Disease

Aitoamnune Hepatitis ANA SMA, LKM, Ig levels

.

toon's Disease

A. Tests of Liver Function

biopsy

Hemochromatosis

Iron saturation, ferritin HFE genetic testing

nVAnbtrypsm Deficiency

1-antitrypsin levels, liver biopsy

Druganduced liver

Careful medication history, liver biopsy

Hereditary

Table 17. Liver Function Tests Test

What Do Levels Correlate With?

Increased by

Prothrombin Time (PTorlMR)

Hepatic protein synthesis All coagulation factors except VIII

Hepatocellular dysfunction PT/INR will promptly correct if vitamin K is administered, so Vitamin K deficiency (due to malnutrition,malabsorption, etc.) increased PTi'INR in absence of vitamin K deficiency is a reliable marker of hepatocellular

Howto Interpret

dysfunction Serum Albumin

Hepatocellular dysfunction Hepatic protein synthesis (and other causes listed in next column) Malnutrition Renal or fit losses Significant inflammation Malignancy

Rule out potential causes other than hepatocellular dysfunction

Serum Direct Bilirubin’

Hepatic excretion from hepatocyte to biliary system

Conjugation is pteserved even in end stage liver failure, thus increased direct bilirubin indicates liver dysfunction

liver dysfunction

’Serum Bilirubin ‘ canaliculus breaXUowr product of hemoglobin: metabolized in the reticuloendothelial system ol liver, transported through biliary system, excreted via gut •direct bilirubin = conjugated; indirect bilirubin = unconjugated

B. Tests of Liver Injury Table 18. Liver Enzyme Profile Profile

Liver Enzyme Change

Hepatocellular

t

Cholestatic

AST

•ALT » AlP

» GGT

Ceruloplasmin, liver

Notes

ALT more specific to liver AST from multiple sources (especially muscle) Elevation of both highly suggestive of liver injury Mosl common cause of elevated AIT is fatty Ever

Cholestasis " stasis of bile flow If AlP is elevated alone,rule out bone disease by fractionating AlP and/ or checking GGT If ALP elevation out of proportion to ALT,' AST elevation,consider: Obstruction ol common bile duct (e.g. extraturmnal - pancreatic cancer, lymphoma: intraluminal stones, cholangiocarcinoma.sclerosing cholangitis,helminths) Predominant rise in hepatocellular enzyme possible in acute biliary obstruction secondary to a stone due to the sudden impairment in bile flow and because ALP is an inducible enzyme which takes time to rise Destruction of microscopic ducts (e.g. PBC) Bile acid transporter defects (e.g. drugs, intrahepatrccholestasis of pregnancy) Infiltration of the liver (e.g.liver metastases.lymphoma granulomas, amyloid)

k>MY

NAFUVNonalcoholic Steatohepafitis

.

U/S, metabolic testing, liver biopsy

(HASH) UU = wtkaxtea antibody; SMA = smoothmuxde mttodf.LXM = hw-lidrey mkimonial-1antibody;

DDx for Hepatomegaly • Congestive (right heart failure BuddChiari syndrome) • Infiltrative Malignant (primary, secondary lymphoproliferative. leukemia) • Benign (fatty liver, cysts, hemochromatosis, extramedullary hematopoiesis, amyloid) • Proliferative • Infectious (viral,tuberculosis, abscess, echinococcus) • Inflammatory (granulomas (sarcoid), histiocytosis X)

.

.

All clotting factors except factor VIII and von Willebrand factor are exclusively synthesized in the Irvet Factor VIII is also produced in the endothelium. In cirrhosis, risk of bleeding does not correlate closely with elevations in INR/ PTT since so many of the proteins in the coagulation cascade are affected

,

ALT > AST most causes of hepatitis AST > ALT = alcoholic liver disease or other causes of hepatitis (ie. non-alcoholic liver disease) that have progressed to advanced cirrhosis -

Acute Viral Hepatitis (General) Definition •

viral hepatitis lasting 1000 due to Viral hepatitis Drugs/ toxins Autoimmune hepatitis Hepatic ischemia Less often, common bile duct stone

• • • • •

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Toronto Notes 2023

G33 Gastroenterology

Investigations • AST and ALT ( >10-20 x normal in hepatocellular necrosis) • ALP minimally elevated • viral serology, particularly lgM antibody directed to the virus

Treatment • supportive ( hydration , diet ) • usually resolves spontaneously, but if severe HBY infection, treatment with antiviral agent such as tenofovir or entecavir can be considered; in acute hepatitis C, antiviral treatment should be considered (see Hepatitis C Virus, G34 ) • indications for hospitalization: encephalopathy, coagulopathy, severe vomiting, hypoglycemia Prognosis poor prognostic indicators: comorbidities, persistently high bilirubin ( >340 mmol; 20 mg/dL), increased 1 NR, decreased albumin , hypoglycemia

•

Complications • cholestasis ( most commonly associated with HAV infection ) • hepatocellular necrosis: AST, ALT > 10-20x normal , ALP and bilirubin minimally increased , increased cholestasis

Hepatitis A Virus • RNA virus • fecal-oral transmission; incubation period 4-6 wk • diagnosed by elevated transaminases, positive anti- HAV lgM • in children: characteristically asymptomatic • in adults: fatigue , nausea , arthralgia, fever, jaundice, hepatomegaly • can cause ALL and subsequent death (< l 5%) • can relapse ( rarely ), but never becomes chronic • treatment is supportive ( no specific treatments available, disease is often self-limiting )

-

Hepatitis B Virus

Alcoholic Hepatitis: history ot chronic EtOH use (possibly with recent increased consumption, although often patient may have stopped drinking in the days- weeks prior to presentation due to symptoms). RUO abdominal pain. AST/ ALT >2. AST usually 20000 lU / mL), HBeAg positive, but normal ALT/AST; due to little immune control and minimal immune- mediated liver damage; characteristic of perinatal infection (or ‘incubation period’ in adult with newly-acquired HBV ) 2. immune clearance (or immunoactive): HBV- DNA levels ( >20000 lU / mL), HBeAg positive; due to immune attack on the virus and immune mediated liver damage; characterized by progressive disease without treatment and increasing liver fibrosis (sometimes progressing to cirrhosis and /or HCC ); likely to benefit from treatment 3 inactive carrier ( immune control): lower HBV DNA (< 2000 lU / mL ), HBeAg negative, anti HBe positive, ALT/AST normal; due to immune control without immune - mediated liver damage; risk of reactivation to phase 2 (clinically resembles acute hepatitis B), especially with immunosuppression e.g. corticosteroids or chemotherapy 4. HBeAg- negative chronic hepatitis ( immune escape) ( “core or precore mutant ” ): elevated HBV-DNA (>2000 lU / mL), HBeAg negative because of pre-core or core promoter gene mutation, anti-HBe positive, ALT/AST high; characterized by progressive disease without treatment and increasing liver fibrosis (sometimes progressing to cirrhosis and/or HCC ); likely to benefit from treatment

-

.

-

-

Treatment

• counselling: 40% of men and 10% of women with perinatal infection without treatment will die from

-

HBV related complications

-

.

In acute hepatitis B HDV coinfection increases severity of hepatitis but does not increase risk of progression to chronic hepatitis. However in the conte xt of chronic hepatitis B superinfection with HDV increases progression to cirrhosis

.

Causes of Elevated Serum Transaminases In Chronic Hepatitis B

•

.

Active hepatitis (either immune HBeAg positive f1*? **5Phase f HBeA9 ne9atlve ac1lve

'

hepatfths)

'"

-

'

Reactivation (e.g. due to immunosuppression)

• Hepatitis D *

°

^^ ^ iJ J

,

,

,

rt ylive ' E 0H'

• HCC screening with U / Sq6 mo, especially if high serum HBV DNA levels, cirrhosis, men , (ages > 40 in

RlSy *n t°s

• contexts to consider pharmacological therapy: 1. HBeAg positive and HBV-DNA >20000 IU / mL and elevated ALT 2. HBeAg negative and HBV-DNA >2000 IU /mL and elevated ALT with or without stage >2 fibrosis on liver biopsy 3. to prevent flare when placed on immunosuppressive therapy such as prednisone, chemotherapy, biologies, etc • treatment goal: reduce serum HBV-DNA to undetectable level • prolonged immune mediated damage leads to higher risk of liver fibrosis • treatment options: tenofovir, entecavir, lamivudine ( not preferred due to high rate of developing resistance) • vaccinate against HAV if serology negative ( to prevent further liver damage) • follow blood and sexual precautions • vaccinate household contacts

• Unprotected sexual intercourse

.

(

^^ 7 ^ ! dB to hepah

B nfecti.

(especially if multiple partners)

• Needle sharing (e.g. injection drug users) • Travel to endemic regions • Exposure to human blood, semen , and other bodily fluids

-

Hepatitis D Virus • defective RNA virus requiring HBsAg for entry into hepatocyte, therefore infects only patients with HBV; causes more aggressive disease than HBV alone • coinfection: acquire HDV and HBV at the same time • HDV can present as ALT and /or accelerate progression to cirrhosis • treatment: low dose interferon ( 20% response) and liver transplant for end stage disease

-

Clinical Features of Hepatitis B • Many patients are asymptomatic, both in the acute and chronic phases • Acute hepatitis can manifest as jaundice, nausea , arthritis, or constitutional symptoms • Patients with chronic hepatitis can be asymptomatic, experience exacerbations, develop extrahepatic complications (e.g. glomerular disease), or develop cirrhosis

-

Hepatitis C Virus • RNA virus (7 genotypes; genotype 1 is most common in North America ) •blood-borne transmission; sexual transmission is “inefficient” • major risk factor: injection drug use • other risk factors: blood transfusion received before 1992 (or received in developing world), tattoos, intranasal cocaine use • acute hepatitis C occurs 2-6 mo after transmission • symptoms mild and vague (fatigue, malaise, nausea ) therefore not commonly diagnosed in acute stage almost 30% of cases of acute hepatitis C are cleared spontaneously without therapy Diagnosis • suspected on basis of elevated ALT/AST' and positive serum anti HCV • diagnosis established by detectable HC V- RNA in serum • normal hepatocellular enzymes does not rule out active disease or presence of advanced fibrosis • abdominal U /S and transient elastography (TibroScan*) to assess the staging of the disease and the degree of fibrosis

-

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Toronto Notes 2023

G 35 Gastroenterology

Treatment

blood - borne precautions; vaccinate for hepatitis A and B if serology negative; avoid HtOH clearest indication for treatment is in subgroups likely to develop clinically significant liver disease , i.e. persistently elevated transaminases, liver biopsy showing moderate - advanced fibrosis/ cirrhosis, and at least moderately severe necrosis/ inflammation • now that a safe, effective cure is available , the risk / benefit ratio favours treating everyone with chronic hepatitis G • choice and duration of treatment depends mostly on whether patient is cirrhotic ( and if so, whether decompensated or not ), prior treatment history, and possibly genotype ( but less so with availability of pan - genotypic therapies ) • direct acting antiviral ( DAA ) tablets ( Maviret*, a combination of glecaprevir and pibrentasvir, and Epdusa’, a combination of velpatasvir and sofosbuvir) are the most commonly used • other oral interferon - free regimens ( for all genotypes ) (e .g . sofosbuvir/ ledipasvir, ombitasvir/ paritaprevir /ritonavir t dasabuvir, or elbasvir/grazoprevir, and sofosbuvir/ velpatasvir) are also available but used less frequently • it is important to check for hepatitis B prior to therapy as direct acting antivirals may lead to reactivation of hepatitis B • •

Prognosis 80% of acute hepatitis C cases become chronic (of these, 20% evolve to cirrhosis within 20 years of exposure) • risk of HCC increases if cirrhotic • can cause cryoglobulinemia ; associated with membranoproliferative glomerulonephritis, lymphoma •

Table 20 . Characteristics of the Viral Hepatitides Virus Family

HAV

HBV

HCV

HDV

HEV

CMV

EBV

Yellow Fever

Picomotiridoe

Hepadnavmdae

Flamiridoe ENA

Delloviiidae

Caliciuridae

Herpesviridoe

Herpesviridoe

Flavivirus

RNA

RNA

DNA

RNA

Yes Parentcral/sexual llianslusion IV drug user, sexual (- HBV )) 40% have no known lisk factors

Yes Non parenteral ( close contact in endem ic areas) Parenteral (blood products IV drug user ) sexual transmission is

No

Yes

Yes

Fecal- oral ( en demic : Africa, Asia, central America India Pakistan)

Close contacts,

Saliva - oral

RNA Yes Vector (mosquito)

2 -8 wk Usually abrupt Unknown

20 - 60 d Variable Variable dormant or persistent

Genome

SNA

DNA

Envelope Transmission

No

Yes Parenteral/ sexual or equivalent Veitical

Fecal- oral

4 - 6 wk Usually abrupt Onset Communicability 2- 3 wkin lateincuba lion to early clinical phase Aculc hepatitis in most adults 10% of children Chronicity None, although can

Incubation

-

.

.

2 - 26 wk

6 wk 6 mo Usually insidious

Insidious

HBsAg* state highly communicable Increased during third trimester or early

Communicable prior to overt symptoms and throughout chronic illness

.

-

inefficient 3 -13 wk

5% adults, 90% infants

80 %, 20% ol which develop cirrhosis HCV- RNA Anli-HCV ( IgGi'IgM)

5%

None

Anti-HOV (IgGflgM)

HBsAq

Anti -HEV (IgGf IgM)

Anti - CMV IlgMI gG)

No

No

No

Serology

Anli - HAV (IgM)

See Table 19, 633

Vaccine

Havrix - , 2 dosesq 6 mo, combined with Twinrix - at 0, 7, and 21d

Recombivax; HBTM ages 11-15.2 doses q6 mo

No

Management

General hygiene Treat close contacts (anti - HAV Ig) Prophylaxis for high risk groups (HAV vaccine * HAV Ig)

Prevention;HBVvaccine and/or hepatitis B Ig (HBIg) for needlestick sexual contact, infants of infected mothers (unless already immune) Rx; oral antivirals vs. interferon ifindications

0.10.3%

0.5 - 2%

Prevention: no Prevention: HBVvaccine vaccine Rx: interferon ribaviriniprotease inhibitor; although all oral antiviral (IFNfree) therapies now available are highly efficacious 2-20% coinfection with 1% H 8V 30% superinlection Predisposes HBV carriers to mote severe hepatitis and faster progression to cirrhosis Yes Yes Leukocylodastic HCC In 2 - 5% of vasculitis, membranous cirrhosis per yr, , cryoglobulinemia glomerulonephfopathy 8 cell non - Hodgkin

.

.

met

Acute Mortality

Oncogenicity

No

Complications

Can causeAIFand subsequent death (*TS%|

.

Yes HCCsecondary to cirrhosis, serum sickness like syndrome, glomerulonephritis cryoglobulinemia lymphoma polyarteritis nodosa, porphyria cutanea tarda

-

..

fluids

30 - 50 d Variable Highly communicable during year after primary infection but nevercero Common; latent Common; latent

Usually abrupt Infectious only in presence ofH 8V ( HBsAg required for replication)

post partum

relapse

unless immune

. .

most body

-

Monospot; anti-EBV IgM/ IgG, EBV -DNA quantitation No

-

Supportive Prevention:gen- In high risk eral hygiene, no transplant treatment patients: CMV post -infection vaccine Ig and antivirals ( ganciclovir, valgancidovir)

.

1- 2% overall 10 - 20% in pregnancy

No Mild, except in third trimester (10 - 20% AIF)

Rareinimmu

-

3-6 d Usually abrupt Variable, vector - dependent

Infection confers lifelong immunity Anti- YF (IgM/IgG)

-

Yf -VAX ,1dose booster qTOyr Prevention Supportive treatment post infection

Rare

20 - 60% in devel oping countries

Yes

No Can cause a recurrent toxic phase with liver damage Gl bleeding, and high mortality rates

nocompctent

-

adults

No

5% of newborns Associated with Burkitt ' s handicaps lymphoma and nasopharyngeal Immunocom promised carcinoma (rare patients at risk in Western ofCMV-induced world) hepatitis, retinitis, colitis, esophagitis, pneumonitis with multiple

c.

.

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Toronto Notes 2023

G 36 Gastroenterology

Autoimmune Liver Disease • diagnosis of exclusion: rule out viruses, drugs/ EtOH, metabolic, or genetic causes • can be severe: 40 % mortality at 6 mo without treatment • extrahepatic manifestations sicca, Raynaud’s, thyroiditis, Sjogren’s, arthralgias hypergammaglobulinemia ( particularly elevated IgG ) typical auto antibodies: ANA and /or anti smooth muscle antibody infrequently may see anti LKM elevation ( liver kidney microtome), especially in children • can have false positive viral serology (especially anti HCV ) biopsy periportal ( zone I ) and interface inflammation and necrosis • treatment: corticosteroids (80 % respond ) ± azathioprine (without this, most will relapse as corticosteroids are withdrawn )

-

-

-

-

-

Drug- Induced Liver Disease Table 21. Classification of Hepatotoxins Predictable

Idiosyncratic

Acetaminophen , CCI 4

Phenytoln lNH

Dose Dependence

Usual

Unusual

latent Period Host Factors

Hours days Not important

trample

-

.

-

-

Weeks months Very important

• many different patterns of liver injury' (i.e. hepatocellular, cholestatic, mixed, granulomatous, ALE ) can be seen in drug-induced liver injury and thus this requires a high index of suspicion • see: LiverTox for Information regarding drug-specific risks and patterns of hepatotoxicity ( http:// livertox nih.gov )

.

Hy’s Law: drug-induced hepatocellular jaundice indicates a mortality of at least 10%

Specific Drugs

• acetaminophen

• metabolized by( hepatic cytochrome P450 system can cause ALE transaminases >1000 U / L followed by jaundice and encephalopathy ) » requires 10-15 g in healthy individuals, 4-6 g in alcoholics /anticonvulsant users mechanism: high acetaminophen dose saturates glucuronidation and sulfation elimination pathways -» reactive metabolite ( NAEQ1 ( n -acetyl-p-benzoquinone imine)) is formed -> covalently binds to hepatocyte membrane presentation first 24 h: nausea and vomiting ( usually within 4 -12 h of overdose ) 24 48 h : asymptomatic, but ongoing hepatic necrosis resulting in increased transaminases > 48 h: continued hepatic necrosis possibly complicated with ALE or resolution note: potential delay in presentation in sustained release products blood levels of acetaminophen correlate with the severity of hepatic injury, particularly if time of

-

-

ingestion known therapy gastric lavage/emesis ( if ages >40, elevated liver enzymes, or ferritin >1000 ng/ mL considered if compound heterozygote and potential other cause of liver injury (e.g. NAl ' LD, excess LtOH , hepatitis) if C282 Y/C282Y and no markers of advanced fibrosis, then biopsy generally not needed • HCC screening if cirrhosis

-

Treatment

• phlebotomy: weekly or q2 wk then lifelong maintenance phlebotomies q2-6 mo, generally aiming for ferritin of 50 -100 ng / mL • deferoxamine if phlebotomy contraindicated (e.g. cardiomyopathy, anemia ) • primary hemochromatosis responds well to phlebotomy • secondary hemochromatosis usually requires chelation therapy (administration of agents that bind and sequester iron, and then excreted ) Prognosis

• normal life expectancy if treated before the development of cirrhosis or DM

Alcoholic Liver Disease Definition • spectrum of diseases, ranging from: fatty liver (common amongst individuals with EtOH use disorder): reversible if EtOH stopped • alcoholic hepatitis (35% of individuals with EtOH use disorder): usually reversible if EtOH

stopped cirrhosis (10-15% of individuals with EtOH use disorder): potentially irreversible

Pathophysiology • several mechanisms, poorly understood • ethanol oxidation to acetaldehyde reduces NAD + to NADH; increased NADH decreases ATP supply to liver, impairing lipolysis so fatty acids and triglycerides accumulate in liver binds to hepatocytes evoking an immune reaction • EtOH increases gut permeability leading to increased bacterial translocation • EtOH metabolism causes: relative hypoxia in liver zone 111 ( near central veins; poorly oxygenated ) > zone 1 (around portal tracts, where oxygenated blood enters) necrosis and hepatic vein sclerosis

• histology of alcoholic hepatitis ballooned (swollen ) hepatocytes often containing Mallory bodies, characteristically surrounded by neutrophils • large fat globules fibrosis: space of Disse and perivenular

Standard Drink Equivalent 1 standard drink = 14 g EtOH - 12 oz beer (5% alcohol ) - 5 oz wine (12 17%) 3 oz fortified wine (17 22%) - 1.5 oz liquor (40%) Tip: percentage EtOH multiplied by oz in 1 standard drink roughly equals 60

-

-

-

Biopsy + Histology of Alcoholic Hepatitis (triad) • Hepatocyte necrosis with surrounding inflammation in zone ID • Mallory bodies (intracellular eosinophilic aggregates of cytokeratins) • Chicken wire fibrosis (network of intralobular connective tissue surrounding cells and venules)

n

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G39 Gastroenterology

Toronto Notes 2023

Clinical Features

• >2-3 standard drinks/d in females and >3-6 standard drinks/d in men for >10 yr leads to cirrhosis, but only in about 10-20% of those who consume this amount daily on a continuous basis; cirrhosis risk increases with amount of EtOH consumed above threshold • clinical findings do not accurately predict type of liver involvement

• fatty liver

mildly tender hepatomegaly; jaundice rare mildly increased transaminases 2:1 ( both usually < 300)

.•

Ascites HCC

CBC: increased mean corpuscular volume ( MCV ), increased W BC often seen with alcoholic hepatitis but not necessarily in other alcohol- related liver injury increased GGT

Treatment

.

• alcohol cessation (see Psychiatry PS28) • Alcoholics Anonymous ( or similar programs), disulfiram , naltrexone, acamprosate • multivitamin supplements (especially thiamine) • caution with drugs metabolized by the liver

• prednisolone if severe alcoholic hepatitis based on Maddrey’s discriminant function or Model for End Stage Liver Disease ( MELD) score as described in Prognosis pentoxifylline less used since most definitive trial did not demonstrate efficacy Prognosis

• Maddrey’s discriminant function ( based on PT and bilirubin ) and MELD predict mortality and guide treatment (consideration of corticosteroids for severe disease based on Maddrey < 32 or MELD S21) • bilirubin response at day 7 of corticosteroids ( Lille model ) also factors into prognosis and decision on whether to continue full course of corticosteroids if started • fatty liver: complete resolution with cessation of EtOH intake • alcoholic hepatitis mortality immediate: 30%-60% in the first 6 mo if severe with continued EtOH: 70% in 5 yr • with cessation: 30% in 5 yr

.

Non- Alcoholic Fatty Liver Disease Definition

• spectrum of disorders characterized by macrovesicular hepatic steatosis, sometimes with inflammation and/or fibrosis • most common cause of liver disease in North America Etiology

• pathogenesis not well elucidated ; insulin resistance implicated as key mechanism , leading to hepatic steatosis

• histological changes indistinguishable from those of alcoholic hepatitis despite negligible history of EtOH consumption

Risk Factors

• component of the metabolic syndrome along with obesity, T2DM, HTN , hypertriglyceridemia • other less common causes such as medications (e.g. tamoxifen, corticosteroids, MTX), Wilson’s, TPN , rapid weight loss, and others Clinical Features

• often asymptomatic • may present with fatigue, malaise, and vague RUQ discomfort

r LJ

Investigations • elevated serum AST, ALT ± ALP; AST/ALT < 1 • presents as echogenic liver texture on U /S • non -invasive testing of fibrosis: E1B4, NAFLD fibrosis score, PibroTest", EibroScan * • liver biopsy cannot distinguish fatty liver from alcoholic vs. non -alcoholic, but considered when investigating alternative etiologies or assessing for level of fibrosis

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Toronto Notes 2023

G 10 Gastroenterology

Treatment

• mainstay is gradual weight loss (0.5-1 kg/ wk) as rapid weight loss can worsen liver disease ideally, aim to lose at least 7-10% of body weight • evidence for the use of pharmacologic agents such as pioglitazone and liraglutide, but potential benefits must be balanced with associated adverse effects (e.g. weight gain and CHI' with pioglitazone ) some evidence for vitamin E (800 IU daily ) if there is hepatic inflammation in non diabetic, non • cirrhotic patients • some evidence for benefits of coffee drinking ( 3 cups/d ) and vitamin D • consideration for bariatric surgery

-

Prognosis

-

-

-

• main causes of death, particularly in non cirrhotic group, are cardiovascular disease and malignancy • better prognosis than alcoholic hepatitis » < 25% progress to cirrhosis over a 7 10 yr period • risk of progression increases if inflammation or scarring occurs alongside fat infiltration ( non alcoholic steatohepatitis) • other clinical indicators of unfavourable prognosis: obesity, T2DM, age, metabolic syndrome, higher levels of fibrosis

-

-

Acute Liver Failure (formerly Fulminant Hepatic Failure) Definition

• severe decline in liver function characterized by coagulation abnormality ( INK >1.5) and encephalopathy

• in setting of previously normal liver • rapid (< 26 wk duration )

Etiology

-

• drugs (especially acetaminophen ), hepatitis B ( measure anti HBc, IgM fraction because sometimes HBV - DNA and even HBsAg rapidly become negative), hepatitis A, hepatitis C ( rare ), ischemic, idiopathic

Figure 13. Progression of liver dysfunction based on liver function tests - the “W"

Treatment • correct hypoglycemia, monitor level of consciousness, prevent G1 bleed with PP1, monitor for infection and multiorgan failure (usually requires ICU ) • consider liver biopsy before INK becomes too high • chief value of biopsy is to exclude chronic disease, less helpful for prognosis • liver transplant ( King 's College criteria can be used as prognostic indicator ): consider early, especially if time from jaundice to encephalopathy >7 d (e.g not extremely rapid ), ages < 10 or > 40, cause is drug or unknown, bilirubin > 300 pmol/ L, INK >3.5, creatinine >200 prnol / L

.

Cirrhosis Definition

• liver damage characterized by diffuse distortion of the basic architecture with fibrosis and formation

of regenerative nodules • biopsy gold standard for diagnosis • compensated cirrhosis = absence of complications, can last for 10-20 yr with almost normal life

expectancy • decompensated cirrhosis = development of complications such as ascites ( most common ), variceal

bleeding, encephalopathy

Etiology

• fatly liver (alcoholic or NAI LD) '

• chronic viral hepatitis ( B, B + D, C; not A or E) • autoimmune hepatitis • drugs (e.g. chronic MTX or amiodarone use) • hereditary hemochromatosis • PBC • chronic hepatic congestion

cardiac cirrhosis (chronic right heart failure, constrictive pericarditis ) hepatic vein thrombosis ( Budd Chiari ) • cryptogenic ( i.e. no identifiable cause, although many of these patients may represent “ burnt-out non alcoholic steatohepatitis ( NASH )")

-

-

-

MELD Na ( Model for End Stage Liver Disease) • Predicts 3 mo survival and used to stratify patients on transplant list • Based on creatinine, INR, total bilirubin, and serum sodium concentration MELD 3.0 • Updated score that Includes new variables such as female sex and serum albumin

• rare: Wilson’s disease, Gaucher’s disease, al -antitrypsin deficiency

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Toronto Notes 2023

G ll Gastroenterology Investigations

• definitive diagnosis is histologic (liver biopsy) • other tests may be suggestive blood work fall in platelet count < 150 is the earliest finding in late stages of cirrhosis, rise in 1NR, fall in albumin, rise in bilirubin elevated bilirubin is usually seen in more advanced disease or in the setting of a concurrent insult in very advanced cirrhosis ( pre terminal event ), may also see hypoglycemia but this is more often a feature seen in severe AL1 I'ibroTestcombination of various clinical and biochemical markers that can predict degree of fibrosis imaging U /S is the primary imaging modality but only finds advanced cirrhosis CT to look for varices, nodular liver texture, splenomegaly, ascites transient elastography ( TibroScan * ): noil invasive tool using elastography for measuring liver

-

•

-

Cirrhosis Complications

VARICES Varices Ascitcs/Anemia Renal laiturc ( HRS) Infection Coagulopathy Encephalopathy Sepsis

-

compliance (variable availability ) rapidly replacing liver biopsy to determine extent of liver fibrosis and make the diagnosis of cirrhosis • gastroscopy: varices or portal hypertensive gastropathy

-

Treatment

• treat underlying disorder • decrease insults (e.g. EtOH cessation , hepatotoxic drugs, immunize for hepatitis A and B if non immunc)

• follow patient for complications (esophageal varices, ascites, HCC) • prognosis: Child -Pugh Score and MELD score • liver transplantation for end-stage disease; use MELD score (e.g. MELD >15) Table 22. Child- Pugh Score and Interpretation Classification

1

2

Serum bilirubin (|iinol/L) Serum albumin (g/L)

04

34 - 51

>

>35

28- 35


30% HVPG >10 mmHg is the strongest predictor of variceal development treatment: resuscitation, antibiotic prophylaxis, vasoactive drugs (e.g. octreotide IV ) combined with endoscopic band ligation or sclerotherapy, TIPS • renal failure in cirrhosis

classifications

-

pre renal (usually due to overdiuresis) acute tubular necrosis HRS - type 1: sudden and acute renal failure (rapid doubling of creatinine over 2 wk) type II: gradual increase in creatinine with worsening liver function (creatinine doubling over years ) HRS can occur at any time in severe liver disease, especially after: - overdiuresis or dehydration, such as diarrhea, vomiting, etc. - Gi bleed - sepsis

-

.

-

Hepatorenal Syndrome vs Pre Renal

-

Failure Difficult to Differentiate • Similar blood and urine findings Urine sodium: very low in hepatorenal: low in pre renal • IV fluid challenge: giving volume expanders improves pre renal failure, but not HRS

.

-

-

Hepatopulmonary Syndrome

Clinical Triad

• Liver disease

-

• Increased alveolar arterial gradient while breathing room air • Evidence for intrapulmonary vascular abnormalities

o

Fibrosis may regress and disappear if cause of liver injury is treated or resolves

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Toronto Notes 2023

G42 Gastroenterology

-

treatment for HRS ( generally unsuccessful at improving long term survival ) for type I HRS: octreotide + midodrine t albumin (increases renal blood flow by increasing systemic vascular resistance ) - definitive treatment is liver transplant • hepatopulmonary syndrome majority of cases due to cirrhosis, though may be due to other chronic liver diseases, such as noncirrhotic portal HTN thought to arise from: ventilation - perfusion mismatch ( intrapulmonary shunting and limitation of oxygen diffusion ) failure of damaged liver to clear circulating pulmonary vasodilators and /or increased production of vasodilators by liver

-

• clinical features

* hyperdynamic circulation with cardiac output >7 L / min at rest and decreased pulmonary + systemic resistance (intrapulmonary shunting) , platypnea ( increase in dyspnea in upright position, improved by recumbency ), and dyspnea • orthodeoxia (desaturation in the upright position, improved by recumbency ) diagnosis via contrast-enhanced echocardiography: inject air bubbles into peripheral vein; air bubbles appear in left ventricle after third heartbeat ( normal = no air bubbles; in ventricular septal defect, air bubbles seen melena •Splenomegaly •Caput medusa, umbilical henna •Gastric varix

•Ascites

•Hemorrhoids

Muscle wasting

Bleeding tendency (bruising)

Loss of sexual hair,testicular atrophy Ankle edema Palmar erythema Dupuytren's contracture,asterixis anemia v Leuckonychia, Terry s nails, clubbing

I 7 /

i

j

I I C3 -

J

.

Figure 14 Clinical features of liver disease

Hepatocellular Carcinoma • see General Suruerv and thoracic Suruerv , GS53 '

Liver Transplantation • see General Surgery and Thoracic Surgery, GS54

Portal Hypertension Definition

s

• pressure gradient between hepatic vein pressure and wedged hepatic vein pressure (corrected sinusoidal pressure) > 5 mmHg Pathophysiology

• 3 sites of increased resistance ( remember pressure = flow x resistance)

• pre-sinusoidal (e.g. portal vein thrombosis, schistosomiasis, sarcoidosis) sinusoidal (e.g. cirrhosis, alcoholic hepatitis) • post-sinusoidal (e.g. right-sided heart failure, hepatic vein thrombosis, veno-oedusive disease, constrictive pericarditis)

Complications

• G1 bleeding from varices in esophagus, less commonly in stomach, even less frequently from portal hypertensive gastropathy • ascites • hepatic encephalopathy

Portal Hypertension Signs

• Esophageal varices • Melena • Splenomegaly • Ascites • Hemorrhoids Management

.

-

• (3 blockers Nitrates • Shunts (e.g. TIPS)

• thrombocytopenia • renal dysfunction • sepsis • arterial hypoxemia

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Toronto Notes 2023

G 13 Gastroenterology Treatment

• non -selective (3- blockers ( propranolol, nadolol, carvedilol ) decrease risk of bleeding from varices; PKEDESCI trial ( Lancet 2019;393:1597 1608 ) showed that non selective (3 blockers in cirrhotic patients with portal hypertension lowers risk of decompensation ( particularly ascites)

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• TIPS: to decrease portal venous pressure

• •

radiologically inserted stent between portal and hepatic vein via transjugular vein catheterization and percutaneous puncture of portal vein can be used to stop acute bleeding or prevent rebleeding or treat ascites complications: hepatic encephalopathy, deterioration of hepatic function contraindicated with severe liver dysfunction , uncontrolled hepatic encephalopathy, and congestive heart failure most commonly used as a “ bridge" to liver transplant

Hepatic Encephalopathy Definition

• spectrum of potentially reversible neuropsychiatric syndromes secondary to hepatic insufficiency

and /or portosystemic shunting, diagnosed after ruling out other causes for symptoms (e.g. structural/ metabolic)

Pathophysiology

• portosystemic shunt around hepatocytes and decreased hepatocellular function increase level of systemic toxins ( believed to be ammonia from gut , mercaptans, fatty acids, amino acids) which go to tne brain

Precipitating Factors • nitrogen load (Gl bleed, protein load from food intake, renal failure, constipation ) • drugs ( narcotics, CNS depressants) • electrolyte disturbance ( hypokalemia, alkalosis, hypoxia, hypovolemia) • infection ( SBP ) • deterioration in hepatic function or superimposed liver disease • spontaneous portosystemic shunts (e.g. splenorenal shunts) or intentional portosystemic shunts (e.g.

TIPS) Stages A. minimal hepatic encephalopathy (diagnosed with specialized cognitive testing ) B. overt hepatic encephalopathy ( stages 1 to IV ) I: apathy, restlessness, reversal of sleep wake cycle, slowed intellect, Impaired computational

-

abilities, impaired handwriting II: asterixis, lethargy, drowsiness, disorientation 111: stupor ( reusable ), hyperactive reflexes, extensor plantar response ( positive Babinski sign ) IV: coma ( response to painful stimuli only )

Investigations

• clinical diagnosis: supported by laboratory findings and exclusion of other neuropsychiatric diseases • rule out:

-

non liver- related neuropsychiatric disease in a patient with liver problems (e.g. EtOH withdrawal or intoxication, sedatives, subdural hematoma, metabolic encephalopathy) » causes of metabolic encephalopathy (e.g. renal failure, respiratory failure, severe hyponatremia, hypoglycemia) • characteristic EEG findings: diffuse ( non focal ), slow, high amplitude waves • scrum ammonia levels increased , but not often necessary to measure in routine clinical use

-

Treatment

• treat underlying precipitating factors • decrease generation of nitrogenous compounds routine protein restriction is no longer recommended given patients generally have concurrent malnutrition and muscle wasting; however, vegetable protein ( as opposed to animal protein ) may help reduce risk of encephalopathy lactulose or lactitol: titrated to achieve 2 3 soft stools/d prevents diffusion of NHJ ( ammonia ) from the colon into blood by lowering pH and forming non-diffusible NHt +(ammonium ) serves as a substrate for incorporation of ammonia by bacteria, promotes growth in bowel lumen of bacteria which produce minimal ammonia also acts as a laxative to eliminate nitrogen producing bacteria from colon • oral rifaximin for both acute treatment and maintenance therapy has high level evidence for efficacy • best acute treatment in patients who cannot take medication orally is lactulose or lactitol enemas

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Precipitating Factors for Hepatic Encephalopathy

HEPATICS Hemorrhage in Gl tract/Hypokalemia

Excess dietary protein Paracentesis Alkalosis/Anemia Trauma Infection Colon surgery Sedatives

A Randomized . Double - Blind. Controlled Trial Comparing BHaximin plus Lactulose with lactulose Alone in Treatment of Overt Hepatic Encephalopathy American j Ustioenterol 2013:103:1498 U63 Study: Prospettnre double blinded Kl. Purpose: Efficacy and safety ol illenmin plus lactulose n. lactulose alone lor treatment of

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overt HE. Results: Of trie patients 48 (76%) in group A 0actulose plus rifaximin 1200 mg/d ir63|compared with 29 (S0.n|in group B ( lactulose plus placebo irST|bad complete reversal ol HE ( P'0.004) Th ere was a significant decrease in mortality alter treatment until lactulose plus ilfaumin vs. lactulose plus placebo (23JH vs. 49.1V P«0.05). Ihere were significantly more deaths m group B because ol sepsis (group A vs.group B: 7:17, P'0.01), whereas there were as differences because ol Gl Weed (group Avs. group B:4:4, nonsignificant ( NS)|and HRS (group A us. group B:4:7 P HS), Patients in the lactulose plus rilasmin group had shoitor hospital stay (5.8 34 vs 8Je4.Sd.MI.001l. Conclusion: Combination ol lactulose plus idaiimin is moceeffettive than lactulose alone in the treatment ol overt HE.

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G44 Gastroenterology

Toronto Notes 2023

Ascites Definition

• accumulation of excess fluid in the peritoneal cavity Etiology

Table 23. Serum - Ascites Albumin Gradient in the Evaluation of Ascites

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Serum [Alb] Ascitic [Alb] >11 g / L (1.1 g /dl) Portal Hypertension Related

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Serum [Alb] Ascitic [Alb] 90% 1 yr survival; mean follow up time from diagnosis to need for transplant is 10 yr) • ursodiol : previously recommended , but studies suggest that it increases mortality if taken in high doses

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Prognosis

• unfavourable regardless of treatment • mean survival after diagnosis remains 4 10 yr

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G‘I 7 Gastroenterology

Primary Biliary Cholangitis (formerly Primary Biliary Cirrhosis)

O

Definition • chronic inflammation and fibrous obliteration of intrahcpatic bile ductules

Etiology/Epidemiology likely autoimmune (associated with Sjogren’s syndrome, scleroderma, CREST syndrome (calcinosis , Raynaud ’s phenomenon , esophageal dysfunction , sclerodactyly, telangiectasia ), RA, thyroiditis) • affects mainly middle- aged women ( M:l '= l :9)

MRCP/ERCP • Absence of narrowing in PBC • Narrowing of intra - and extrahepatic ducts in PSC

Signs and Symptoms

• often asymptomatic

-

initial symptoms: pruritus, fatigue • chronic: jaundice and melanosis (darkening skin ) and other signs of cholestasis • end -stage: hepatocellular failure, portal HTN, ascites

• high incidence of osteoporosis Investigations

• increased ALP, GGT; bilirubin rises in later stage • positive anti mitochondrial antibodies ( AM A; 95% specificity and sensitivity)

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• elevated IgM • increased serum cholesterol ( mild increase in LDL, larger increase in HDL ) • may have: xanthelasmas, xanthomas • liver biopsy confirms diagnosis and stages severity • normal bile duct on MRCP rules out bile duct obstruction which can mimic PBC • “overlap” syndromes with autoimmune cholangitis, autoimmune hepatitis, sclerosing cholangitis are

possible Treatment

drugs that treat the underlying disease: • ursodiol ( usual first line treatment ) obeticholic acid ( particularly if inadequate response to ursodiol ) • cholestyramine ( for pruritus and hypercholesterolemia ) • calcium and vitamin D for low bone density; bisphosphonates if osteoporosis severe • repeated monitoring of U 'l's (q 3 6 mo), TSH (annually ), and BMD ( q 2 1 y r ) • ensure vaccines are updated ( notably HAV & HBV ); avoid EtOH , smoking • liver transplant if disease severe, progressive

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Endoscopic or Surgical Step Up Approach for Infected Necrolising Pancreatitis: A Multicentre fendomised trial luxe! 2018.381:51 58 Purpose: lo compute the outcomes ol endoscope is. the standard surgical removal of infected necrotising pancreatitis. Study: RCT. Population: 08 patients with pancreatic or eitrapancreatic neuosis were randomiied to either endoscopic removal or surgical lemoval of the infected necrosis. Outcomes: Uwjor complications and death atimo follow - up. Results: the primary endpoints of mortality and major com pi cations were the same in the two groups, hut the endoscopic group had shortened hospital stays and less pancreatic fistutae. Conclusions: Ir ree points are worth emphasizing: (1) necrotising pancreatibsis a severe disease: about 15% m each group died: (2) it is best to wail at least 4 wi alter the necrosis has developed to alow it to he encapsulated: (3) the management of severe acute pancreatitis should include eiperts shil led in therapeutic endoscopy.

Prognosis

• can be fatal, although not all asymptomatic patients show progression Table 24 . Primary Sclerosing Cholangitis vs. Primary Biliary Cholangitis Primary Sclerosing Cholangitis

Primary Biliary Cholangitis

PredominantGender

Male

Female

Associated Comorbidities

IBD. especially UC Both intra - and oilraltepalic ERCP/ MRCP ( narrowing and dilatations of ducts

Other autoimmune disorders (Sjogren 's CREST. RA)

Affected Ducts Investigations

visualized )

.

Intrahcpatic only

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Anti mitochondrial antibodies. IgM. increased lipids, liver biopsy (absence of duct narrowing on ERCP)

Biliary Colic, Cholecystitis • see ( icncral Surttcrv and thoracic Suruerv , GS56 ’

Ascending Cholangitis • see General Surgery and thoracic Surgery, Acute Cholangitis , GS58

Definition • infection of the biliary tree

Etiology • stasis in the biliary tract due to obstruction or stricture

m

Charcot' s Triad • RUOpain • Fever

• Jaundice

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• bacteria

E. coli , Klebsiella , Enterobacter, Enterococcus coinfection with Bacteroides and Clostridia can occur

Signs and Symptoms •Charcot’s triad: fever, RUQ pain, jaundice ( 50- 70%) • Reynolds’ pentad in patients with suppurative cholangitis: fever, RUQ pain, jaundice, hypotension ,

Reynolds' Pentad • Charcot's triad • Hypotension • Altered mental status

+

altered mental status

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Toronto Notes 2023

G48 Gastroenterology

Investigations

• evidence of systemic inflammation (increased WBC, increased CUP)

• usually increased ALP and bilirubin, ALT variably elevated (can be markedly increased if acute obstruction from common bile duct (CBD) stone) • blood culture • abdominal U /S: CBD dilation, stricture, stones Treatment • most important is drainage, ideally via HRCP; perform by percutaneous biliary or by surgical routes (least often ) if ERCP not possible • antibiotic therapy: broad spectrum to cover Gram negatives, Enterococcus, and anaerobes (especially ifCBD manipulation )! no clear consensus on antibiotic choice but consider: • ampicillin + sulbactam or piperacillin / tazobactam metronidazole + 3rd generation cephalosporin (e.g. ceftriaxone) or fluoroquinolone (e.g. ciprofloxacin orlevofloxacin) carbapenem monotherapy (e.g. imipenem or meropenem )

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Prognosis • good with effective drainage and ABx in mild to moderate cases • high mortality ( 50%) in patients with Reynolds’ pentad

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Pancreas Pancreatic Enzyme Abnormalities Causes of Increased Serum Amylase

• pancreatic disease

•

pancreatitis, pancreatic duct obstruction (e.g. ampullary cancer), pseudocyst, abscess, ascites, trauma, cancer non - pancreatic abdominal disease

biliary tract disease, bowel obstruction /ischcmia , perforated or penetrating ulcer, ruptured ectopic pregnancy, aneurysm, chronic liver disease, peritonitis • non-abdominal disease cancer (lung, ovary, esophagus, etc.), salivary gland lesions, bulimia, renal transplant / insufficiency, burns, ketoacidosis • macroamylascmia Causes of Increased Serum Lipase • pancreatic disease: same as above • non - pancreatic abdominal disease ( mild elevations only): same as above

I

( ) Pancreatic Enzymes

TALC Trypsin Amylase Lipase Chymotrypsin

When serum amylase >5x normal, the cause is almost always pancreatitis or renal disease

• non- abdominal disease • macrolipasemia

•

renal failure

Acute Pancreatitis Etiology ( most common are alcohol and gallstones ) • Idiopathic: thought to be hypertensive sphincter or microlithiasis • Gallstones (45%) • Ethanol (35%) • Tumours: pancreas, ampulla , choledochocele

• Scorpion stings • Microbiological

bacterial: Mycoplasma , Campylobacter, TB, M . avium intracellulare, Legionella, Leptospira viral: mumps, rubella, varicella, viral hepatitis, CMV, EBV, HIV, Coxsackievirus, echovirus,

s (£) When thinking about the causes of acute pancreatitis remember: I GET SMASHED, but vast majority due to gallstones or ethanol

adenovirus , echinococcosis • parasites: ascariasis, clonurchiasis , ,

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• Autoimmune:!gG 4 related disease SLE polyarteritis nodosa ( PAN ), CD • Surgery/ trauma manipulation of sphincter of Oddi (e.g. ERCP), post-cardiac surgery, blunt trauma to abdomen , penetrating peptic ulcer • Hyperlipidemia ( TG > 11.3 mmol / L; > 1000 mg /dL), hypercalcemia, hypothermia • Emboli or ischemia • Drugs/ toxins azathioprine, mercaptopurine, furosemide, estrogens, methyldopa, Ht -blockers, valproic acid, ABx, acetaminophen, salicylates, methanol, organophosphates, steroids (controversial )

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Toronto Notes 2023

G'I9 Gastroenterology Pathophysiology

• activation of proteolytic enzymes within pancreatic cells, starting with trypsin, leading to local and systemic inflammatory response • in gallstone pancreatitis, this is due to mechanical obstruction of the pancreatic duct by stones • in ethanol- related pancreatitis, pathogenesis is unknown • in rare genetic diseases, mutations prevent the physiological breakdown of trypsin required normally to stop proteolysis (e.g. mutant trypsin in hereditary pancreatitis or mutation in SPINK 1 gene, which normally inhibits activated trypsin ); may be model for ethanol related pancreatitis

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Pathology

• mild (interstitial)

peri-pancreatic fat necrosis interstitial edema • severe ( necrotic) • extensive peri-pancreatic and intra- pancreatic fat necrosis parenchymal necrosis and hemorrhage -> infection in 60% • release of toxic factors into systemic circulation and peritoneal space (causes multi organ failure) • severity of clinical features may not always correlate with pathology • 3 phases • local inflammation + necrosis -> hypovolemia • systemic inflammation in multiple organs, especially in lungs, usually after IV fluids given -> pulmonary edema local complications >2 wk after presentation -> fluid collection ( pseudocyst ) or tissue collection (necrosis), sterile or infected

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o

Cullen's Sign

• Sensitive, not specific for acute pancreatitis

’s Sign -Turner .GreyFlank ecchymosis

Signs and Symptoms

• jaundice: compression or obstruction of bile duct • pain: epigastric, noncolicky, constant • can radiate to hack • Cullen's/Grey Turner’s signs • may improve when leaning forward ( Ingleflnger's sign ) • tetany: transient hypocalcemia • tender rigid abdomen; guarding • hypovolemic shock: can lead to renal failure

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.

N/ V • abdominal distention from paralytic ileus • fever: chemical, not due to infection

• acute respiratory distress syndrome • coma

Increased Amylase

• Sensitive, not specific for acute pancreatitis

Increased Lipase

• Higher sensitivity and specificity • Stays elevated longer

Investigations

• increased serum pancreatic enzymes: amylase, lipase ( more specific) • ALT >150 specific for biliary cause • increased WBC, glucose, low calcium • imaging: CT most useful for diagnosis and prognosis • x- ray: "sentinel loop" (dilated proximal jejunum ), calcification , and “colon cut -off sign" (colonic spasm )

• U /S: useful for evaluating biliary tree (67% sensitivity, 100% specificity) CT scan with IV contrast: most useful when done >1 d after presentation, helpful for diagnosis and prognosis because contrast seen only in viable pancreatic tissue, non-viable areas can be biopsied percutaneously to differentiate sterile from infected necrosis ERCP or MRCP if cause uncertain, assess for duct stone, pancreatic or ampullary tumour,

pancreas divisum Classification

• interstitial edematous vs. necrotizing • mild , moderate, severe Prognosis • usually a benign , self-limiting course, single or recurrent • occasionally severe leading to:

• shock • pulmonary edema

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multi organ dysfunction syndrome

• (il ulceration due to stress • death

numerous scales to describe severity: probably most useful is proportion of pancreas not taking up contrast on CT done 48 h after presentation ( necrotic pancreas does not take up the contrast dye) presence of organ failure, particularly organ failure that persists > 48 h, is associated with

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worse outcomes Table 25. Collections in Pancreatitis (Revised 2012 Atlanta Classification) Liquid

Solid

Acute

Acute petlpancrcalic fluid collection |APfC )

Acute necrolic collection ( ANC)

Chronic

Pancreatic pseudocyst

Walled- off necrosis ( WON)

+

All of these collections ate classified as inlecled ot not infected

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Toronto Notes 2023

G50 Gastroenterology

Treatment • goals (only supportive therapy available)

1. hemodynamic stability 2. analgesia 3. oxygen 4. stop progression of damage (difficult) 5 treat local and systemic complications • antibiotic use in infection (cephalosporins, imipenem ), not indicated to prevent infection , although without aspiration / biopsy can be difficult to distinguish infection from non - infected inflammation • aspirate necrotic areas of pancreas to diagnose infection; drain if infected • IV fluids (crystalloid or colloid ) beware third spacing of fluid, monitor urine output carefully • NG suction (lets pancreas rest) if vomiting, stomach very dilated • endoscopic sphincterotomy if severe gallstone pancreatitis ( i.e. cholangitis or ongoing obstruction ) • nutritional support: N ) feeding tube or TPN if cannot tolerate enteric feeds recent evidence supports NG enteral (or oral if feasible ) feeds • no benefit: glucagon, atropine, aprotinin, H ’-blockers, peritoneal lavage • follow clinically and CT or U /S to exclude complications • chief role of invasive intervention is to drain fluid collection, excise necrotic tissue ( necrosectomy), especially indicated if pseudocyst or walled off necrosis is infected , try to delay for >2 wk to allow demarcation between viable and necrotic tissue, better done endoscopically or radiologically, rather than surgically if technically possible

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Late Complications

• pseudocysts: follow if asymptomatic, drain if symptomatic or growing

drain preferably: endoscopic, percutaneous under radiological guidance, surgical if less invasive methods fail • infected necrosis/abscesses: ABx + percutaneous drainage, endoscopic preferable to surgical • bleeding: ( 1) gastric varices if splenic vein thrombosis, ( 2) pseudoaneurysm of vessels in areas of necrosis, especially splenic artery, (3) duodenal ulcer related to compression of duodenum by enlarged pancreas • splenic and portal vein thrombosis: no effective therapy described , anticoagulation not proven,

hazardous • rare: DM, pancreatic duct damage

Chronic Pancreatitis Definition • irreversible damage to pancreas characterized by 1 pancreatic cell loss ( from necrosis)

.

2. inflammation 3. fibrosis

Etiology /Pathophysiology

• Toxic- metabolic

EtOH ( most common ) causes a larger proportion ( >90%) of chronic pancreatitis than acute pancreatitis changes composition of pancreatic juice ( e.g. increase viscosity) decreases pancreatic secretion of pancreatic stone protein ( lithostathine ), which normally

solubilizes calcium salts

- precipitation of calcium within pancreatic duct results in duct and gland destruction toxic effect on acinar and duct cells - directly or via increasing free radicals « acinar cell injury leads to cytokine release, which stimulates pancreatic stellate cells to form collagen ( leading to fibrosis) varying degrees of ductular dilatation, strictures, protein plugs, calcification no satisfactory theory to explain why only a minority of individuals with EtOH use disorder develop pancreatitis

• smoking

hypercalcemia hypertriglyceridemia

• medications

• Idiopathic • Genetic • Autoimmune pancreatitis /steroid - responsive pancreatitis (e.g. IgG4- related disease) • Recurrent acute pancreatitis/severe acute pancreatitis • Obstructive (e.g. pancreas divisum , ampullary stenosis) Signs and Symptoms

• early stages recurrent attacks of severe abdominal pain ( upper abdomen and back ) chronic painless pancreatitis: 10% • late stages: occurs in 15% of patients steatorrhea ( maldigestion ) when >90% of function is lost diabetes, calcification, jaundice, weight loss, pseudocyst, ascites, GI bleed

Gallstones only cause acute pancreatitis (not chronic pancreatitis)

Symptoms of Chronic Pancreatitis

• Abdominal pain • Diabetes • Steatorrhea Etiology = Almost Ahways Alcohol

Treatment

• EtOH abstinence • Pancreatic enzyme replacement • Analgesics • Pancreatic resection if ductular blockage

When toCall the Surgeon In Acute Pancreatitis? Endoscopic Transgastric vs. Surgical Necrosectomy ter

Infected Necrotizing Pancreatitis: A Random ired Trial JAMA 2012:307:1053 1061 Once it was recognized that severe acute (necrotizing) pancreatitis had a terrible prognosis because ol an enubeiant inflammatory response leading to multkirgai) failure, pancreatectocny was attempted. However, contrary to the expected favourable results, clinical eiperieuce has shown that surgical pancreatectomy is usually nol helpful, perhaps because oncethe inflammatory coscadestirts it persists as a self perpetuating cycle. Ihe problems caused by acute pancreatitis can be thought of as widespread burn initiated by inDarn matron in the pancreas, hut haring little to do with ongoing problems within the pancreas itself. Studies suggest that the only compellmg indication tor surgery is infected necrotizing pancreatitis not responding to ABi. As predicted, without removal of sudi infected pancreatic tissue , death is likely from sepsis. In this recent randomized trial, transgastric neaosectomy, an endoscopic lech nigue that also removes infected necrotic pancreatic tissue, reduced both a composite endpoint of major pancreatitis complications (especially new onset organ failure) and the pro inflammatory response (as measured by serum IL S levels) to a greater extent than surgical necrosectomy. Of course, not all necrotic collections are in areas amenable to endoscopic intervention, andthe advice olan eipeiienccd surgeon should always he welcomed in severe acute pancreatitis, hut the role ol surgery in this previously considered surgical disease is rapidly diminishing.

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G51 Gastroenterology

Investigations

• laboratory

• increase in serum glucose

increase in serum ALP, less commonly bilirubin ( jaundice) serum amylase and lipase usually normal • stool elastase is low in steatorrhea • abdominal x ray: pancreatic calcifications • U /S or CT: calcification, dilated pancreatic ducts, pseudocyst • MRCP or ERCP: abnormalities of pancreatic ducts- narrowing and dilatation • LUN: abnormalities of pancreatic parenchyma and pancreatic ducts, most sensitive test • 72 h fecal fat test: measures exocrine function , fecal elastase preferable • secretin test: gold standard, measures exocrine function but difficult to perform, unpleasant for patient, expensive

-

Treatment

• most common problem is pain, difficult to control • general management • complete abstinence from EtOH • enzyme replacement may help pain by resting pancreas via negative feedback analgesics celiac ganglion blocks • time: pain decreases with time as pancreas " burns out" • endoscopy: sphincterotomy, stent if duct is dilated , remove stones from pancreatic duct • surgery: drain pancreatic duct ( pancreaticojejunostomy) if duct is dilated ( more effective than endoscopy); resect pancreas if duct is contracted

• steatorrhea

pancreatic enzyme replacement neither endoscopy nor surgery' can improve pancreatic function

Autoimmune Pancreatitis • most commonly presents as a mimicker of pancreatic cancer ( pancreatic mass detected because of jaundice ± abdominal pain ) Investigations • histology: lymphocyte and plasma cell infiltration of pancreas

• imaging: focal or diffuse enlargement of pancreas on CT or MRI , sausage -shaped , low density rim

around pancreas •serology: increased serum lgG4 in type 1 • other organ involvement: sialadenitis, retroperitoneal fibrosis, biliary duct narrowing, nephritis Treatment

• responds to prednisone • for refractory patients, consider immunomodulators (azathioprine, mycophenolate mofetil, methotrexate ) or rituximab

Clinical Nutrition Determination of Nutritional Status Challenging to Differentiate Markers of Malnutrition from Markers of Disease • most important feature in assessing the need for nutritional support is weight loss (expressed as change in body mass index ( kg/ m -)) • Subjective Global Assessment divides nutritional status into A ) adequately nourished, B ) mild or moderate malnutrition, and C ) severe malnutrition in order to identify those who will benefit from

nutritional support • includes weight change in past 6 mo, weight change in past 2 wk, dietary intake change, current dietary intake, G1 symptoms, functional capacity, effect of disease on nutritional requirements and physical examination, including loss of subcutaneous fat / musdes wasting /edema /ascites n L J

Table 26. Small Bowel Nutrient Absorption Fe »’

CHO

Proteins, Lipids Na' HiO

.

Bile Acids

Vitamin Bn

Duodenum

+

Jejunum Ileum

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G52 Gastroenterology Determining Nutritional Requirements • calories: total energy expenditure (THE) = resting energy' expenditure ( REE) x stress factor (e.g. 1.7 for burns) usually works out to be 25-35 keal / kg depending on how disease affects metabolism, with IV nutrition delivered as about 60% carbohydrate, 40% fat. Current trend is to provide fewer calories ( “ permissive underfeeding"), especially in 1CU , to prevent hyperglycemia • protein: 1 2 g / kg/d , depending on effect of disease on protein metabolism In disease, a greater proportion of energy expenditure comes from protein than in health • electrolytes, minerals, and vitamins also required

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Indications for Aggressive Nutritional Support:

• inability to meet nutritional needs; logical, but convincing evidence from literature not available for 1CU and other acute illnesses • evidence that nutritional support improves outcome available for ( I ) short bowel syndrome ( home TEN ), ( 2) before major abdominal or thoracic surgery if there is substantial malnutrition , ( 3) before therapy for cancer of esophagus, head , and neck , (4 ) decompensated alcoholic liver disease, (5) pancreatitis (acute and chronic). May be helpful for other indications also, but insufficient data • nutritional support at best prevents protein loss but usually no gain

Enteral Nutrition Definition

• EN ( tube feeding ) is a way of providing food through a tube placed in the stomach or the small

intestine support required for brief time; percutaneous • nasogastric ( NG), or nasojejunal ( N|) if nutritional endoscopic gastrostomy ( “G-tube” or “PEG tube") /percutaneous endoscopic jejunostomy ( J -tube) if nutritional support required for more than 1 mo • tubes can be placed endoscopically, radiologically, or surgically

Most Common Indications for Artificial Nutrition Support • Preexisting nutritional deprivation • Anticipated or actual inadequate energy intake by mouth • Significant multiorgan system disease

Indications

• oral feeding inadequate nr contraindicated Feeds

• polymeric feeds contain whole protein, carbohydrates, fat as a liquid, and may or may not have fibre

added

• elemental feeds contain protein (as amino acids), carbohydrates (as simple sugars), and are low in fat content (are therefore high in osmolarity) • specific diets: low carbohydrate/ high fat solution for ventilated patients (carbohydrate has a high respiratory quotient so minimizes carbon dioxide production ), high energy, low electrolyte solutions

for dialysis patients Relative Contraindications • non functioning gut (e.g. intestinal obstruction , enteroenteral or enterocutaneous fistulae ) • uncontrolled diarrhea • GI bleeding

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.

Whenever possible EN is ALWAYS preferable over PN

Complications

• aspiration

• diarrhea

• refeeding syndrome ( rare): carbohydrate can stimulate excessive insulin release, leading to cellular uptake and low serum levels of phosphate, magnesium, potassium

• overfeeding syndrome ( rare ): hypertonic dehydration, hyperglycemia, hypercapnia, azotemia (from excess protein )

Parenteral Nutrition Definition

• PN is the practice of feeding a person intravenously, bypassing the usual process of eating and digestion

Indications

• short-term (15% ofpre morbid weight, serum albumin < 28 g / L or < 2.8 g/dL ), and only if given for > 2 wk renal failure: PN shown to increase rate of recovery; no increase in survival liver disease: branched chain amino acids may shorten duration of encephalopathy; no increase in survival IBD: PN closes fistulae and heals acute exacerbations of mucosal inflammation, but effect is transient ( EN is equally effective)

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Toronto Notes 2023

G53 Gastroenterology

• some evidence for efficacy, but convincing data not available for:

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radiation /chemotherapy induced enteritis AIDS with wasting diarrhea severe acute pancreatitis • long- term ( > 1 mo): can be given at home

Hypomagnesemia may be an initial sign of short bowel syndrome in patients who have undergone surgical bowel

• severe untreatable small bowel disease ( e.g. radiation enteritis , extensive GD, high output (istulae ) • following surgical resection of >70% of small bowel (e.g. small bowel infarction )

resection

severe motility diseases ( e.g. scleroderma affecting bowel )

Relative Contraindications

• functional G1 tract available for EN • active infection; at least until appropriate antibiotic coverage

• inadequate venous access; triple- lumen central venous lines usually prevent this problem

Complications of PN • sepsis: most serious of the common complications

Enteral »s. Parenteral Nutrition lor Acute Pancreatitis Coch rane DB Syst Ber 2010:1:C 00 02837 Purpose: Compare EN vs. IPN m mortality, morbidity, and hospital stay in patients with

• mechanical pneumothorax from insertion of central line, catheter migration and thrombosis, air embolus • metabolic: congestive heart failure, hyperglycemia, gallstones, cholestasis, electrolyte abnormalities, micronutrient deficiency

Enteral Nutrition Preferable to Parenteral Nutrition • fewer serious complications (especially sepsis ) • nutritional requirements better understood • can supply gut -specific fuels such as glutamine and short chain fatty acids with EN • nutrients in the intestinal lumen have a trophic effect ( prevent atrophy of the gut and pancreas)

pancreatitis.

Study Selection PCIsoflPNvs. EN in pancreatitis . Results: E gut trials (n- 348) were included. EH decreases RR of death (0.50), multiple organ failure (0.55), infection |0.39), and Otter local complications (0.?0|. It also decreased hospital stay by 2.3? d . Conclusion: EN reduces mortality, organfiilure infections, and length ol hospital stay m patients with pancreatitis.

.

• prevents gallstones by stimulating gallbladder motility • much less expensive

Common Medications Table 27. Common Drugs Prescribed in Gastroenterology Class

Generic Drug Name

Trade Name

Dosing

Proton Pump

omeprazole

Losec / Prilosec '

20 mg PO once daily

lansoprazole or dexlansoprazole

Prevacid ' Dexilanl

pantoprazole

PantolocT Protonix :

Oral therapy : lansoprazole 15 - 30 mg once daily (before breakfast ), dexlansopra role 30- 60 mg once daily (does not need to be taken before breakfast ) 40 mg PO once daily for UGIB:80 mg IV bolus then 8 mg /h infusion

rabeprarolc

Pariet ' / Aciphex ' Nexium ' Zantac *

Inhibitors ( If / K ATPasc inhibitors)

-

csomepraiolc

Histamine Hz Receptor Antagonists

ranitidine* 'ranitidine drugs recalled in 2019 due to impurity

-

-

famotidine

Stool Softener

docusate sodium

Indications

Contraindications

Side Effects

Hypersensitivity lodrug

Dizziness , headache, flatulence, abdominal pain, nausea rash , increased risk of osteoporotic fracture (secondary to impaired calcium absorption)

Same as above

Duodenal ulcer, gastric ulcer, HSAIO associated gastric and duodenal ulcers , reflux esophagitis , symptomatic OERO, dyspepsia. Zollinger Ellison syndrome, eradication ofH. pylori (combined with ABi) Same as above

Same as above

Same as above

Same as above

SameasaboveandUGIB

Same as above

Same as above

40 mg PO once daily

Same as above

Same as above

Same as above

Same as above

20 - 40 mg P0 once daily 300 mg PO once daily or 1S0 mg 8ID IV therapy: 50 mg q 3

Same as above Same as above Inhibits gastric Duodenal ulcer, gastric histamine H 2 receptors ulcer, HSAID - associated gastric and duodenal ulcers, ulcer prophylaxis, reflux esophagitis , symptomatic GERD; not useful lor acute Gl bleeds Same as above Same as above

Same as above Hypersensitivity to drug

Same as above Confusion, dizziness, headache, arrhythmias, constipation, nausea, agranulocytosis,

h ( but tachyphylaxis a problem)

concerns

Pepcid !

Colace

Mechanism of Action Inhibits gastric enzymes H'/ K'- ATPase (proton pump)

Oral therapy: duodenal/ gastric ulcers: 40 mg qhs GERD: 20 mg BIO IV therapy: 20 mg BID 100 400 mg PO once Promotes daily, divided in 1- 4 doses incorporation of water into stool

.

pancytopenia,

depression

Same as above

Same as above

r Rebel of constipation

-t

.

Presence of abdominal pain, throat irritation lever. N / V abdominal cramps, rashes

+

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G54 Gastroenterology

Toronto Notes 2023

Table 27. Common Drugs Prescribed in Gastroenterology Class Osmotic Laxatives

Generic Drug Name lactulose

Trade Name

Dosing

lactulose Constulose

Constipation: 15 30 ml POonce daily to BIO

'

Encephalopathy: 15 -30 ml BID to OID

lax -a - day 5 RestoralAX Golytelyr

or liquid POonce daily

magnesium hydroxide

Milk of Magnesia / Pedia - Lax !

Constipation (adult): 400 mg/ 5 mL:30- 60 mL POqhs

senna

Senokot 5

Tablets:1- 4 POqhs Syrup:10 -15 ml POqhs

bisacodyl

Bisacodyl!

PEG 3350

Stimulant laxatives

Constipation: 17 g powder dissolved in 4 - 8

5-30 mg PO once daily

(start at 10 mg for bowel preparation)

Bulk Laxatives

psyllium

Metamucil 5

Start at one heaping tablespoon daily

Guanylate Cyclase C Agonist

linadotide

Constella 1

75-145 pg once daily

Antidiarrheal

loperamide

Imodium ®

Acute diarrhea: 4 mg PO initially, followed by 2 mg after each unformed stool

diphenoxylate/

Lomotil -

5 mg PO TID to OID

Agents

atropine

Mechanism of Action Poorly absorbed in Cl trad and is broken down by colonic bacteria into lactic acid in the colon , increases osmotic colonic contents, increases stool volume Osmotic agent causes water retention in stool and promotes frequency of stool Osmotic retention of fluid which distends the colon and increases peristaltic activity Induce peristalsis in lower colon

Enteric nerve stimulation and local contact -induced secretory effects Colonic movements Increases stool bulk •water retention in stool Opens water channels

-

Indications

Contraindications

Side Effects

Chronic constipation, prevention, and treatment of portal-systemic encephalopathy

Patients who require a low galactose diet

Flatulence, intestinal cramps,nausea, diarrhea if excessive dosage

Relief of constipation Colonoscopy prep

Hypersensitivity to drug

Relief of constipation

Patients with myasthenia gravis or other neuromuscular disease

Constipation

Patients with acute abdomen

Constipation Preparation of bowel for procedure

G! obstruction Gastroenteritis

Constipation

Hypersensitivity to drug Gl obstruction

Antiemetics

dimenhydrinate

Gravol -

Children

Adjunctive therapy for acute non- specific diarrhea, chronicdiarrhea associated with IBD and for reducing the volume of discharge for ileostomies, colostomies, and other intestinal resections

Children «2 yr,known hypersensitivity to drug, acute dysentery characterized by blood in stools and fever, acute UC or pseudomembranous colitis associated with broadspectrum ABx

Abdominal pain or discomfort,drowsiness or dizziness, tiredness, dry mouth , N/ V, hypersensitivity reaction

Inhibits Gl propulsion via direct action

Adjunctive therapy for diarrhea, as above

Hypersensitivity to

Dizziness, drowsiness, insomnia, headache, N/ V, cramps,allergic reaction

Pancreatic disease, excess EtOH , gallstonesor other biliary disease Hypersensitivity to drug

Pancreaticobiliary pain including sphincter of Oddi dysfunction Xerostomia,sedation

Postoperative N /V, antipsychotic, anxiety

Hypersensitivity to drug

Dystonia, extrapyramidal symptoms |EPS ), seizure, NMS (rarely)

GERO, diabetic gastroparesis postoperative and chemotherapy induced N / V, migraines, constipation

Hypersensitivity to drug Gl obstruction, perforation, hemorrhage pheochromocytoma seizures, and EPS

Restlessness, drowsiness, dizziness, fatigue, EPS, some rareseriousside effects include NMS, agranulocytosis

75 -100 mg BID

Bowel opioid modulator

IBS Diarrhea

25 - 50 mg PO /IV/IM

Competitive Hr receptor antagonist in Gl tract, blood vessels, and respiratory tract, Blocks chemoreceptor trigger zone Diminishes vestibular simulation and disrupts labyrinthine function through central anticholinergic action 01, DLeceptor antagonist in chemoreceptor trigger zone and o- adrenergic and anticholinergic

Motion sickness, radiation sickness, postoperative vomiting, and druginduced N /V

-

q4 6 h PRN

prochlorperazine

metoclopramide

Stemetil 5

Maxeran

-

5 -10 mg PO/IV /IM BID TID PRN

-

10 mg IV /TM q2 3 h pm, 10 -15 mg P 0 OID ( 30 min before meals and qhs)

Abdominal cramps, discolouration of breast milk,urine,feces, melanosis coli and atonic colon from prolonged use (controversial) Abdominal colic, abdominal discomfort, proctitis (with suppository use), diarrhea Gl obstruction, diarrhea, constipation, abdominal cramps Diarrhea

Chronic constipation IBS - constipation

in peristaltic action and increase in transit lime Viberzil -

.

nausea, rigor, tonicclonic seizures (rare) Renal impairment Abdominal pain, vomiting, diarrhea

in bowel epithelial cells to add water to stool Acts as antidiarrheal via cholinergic, noncholingeric, opiate,and non- opiate receptor-medicated mechanisms; decreases activity of myenteric plexus

on smooth muscle, resulting in a decrease

eluxadoline

Abdominal distension,

pain, anal pain thirst,

effects Depresses reticular activating system (RAS) affecting emesis Dopamine and 5 HI receptor antagonist in chemoreceptor trigger zone. Enhances response to ACh in upper Gl tract , enhancing motility and gastric emptying. Increases IES tone

-

.

diphenoxylate or atropine, jaundice, pseudomembranous enterocolitis, diarrhea caused byenterotoxin producing bacteria

.

.

.

ri LJ

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G55 Gastroenterology

Table 27. Common Drugs Prescribed in Gastroenterology Class

Generic Drug

Trade Name

Dosing

Zofran

Depends on procedure. generally 8 -16 mg PO

Name

ondanselton

'

Mechanism of Action Selective 5 - HT 3 receptor antagonist in central chemoreceptor trigger zone and peripherally on vagus

Prokinetic

1 mg PO BID (for nausea from chemotherapy/

granisetron

Kylril -

domperidone

Motilium

Agents

nerve Same as above

radiation) Gl motility disorder (e.g. peripherally acting gastroparesis): 10 mg TID D2 receptor blocker. main effect in the

upper Gl tract (i.e. increased esophageal peristalsis, gastric motility), antiemetic properties

prucalopride

Resotran' Motegrity:

high affinity S-HK agonist, main effect in the lower Gl tract (i.e.increased colonic peristalsis,

2 mg POOD

Indications

Contraindications

Morphine, hypersensitivity AT caused by cancer chemotherapy and to drug radiation therapy; multiple off label uses,including gastroenteritis N /V

Same as above

upper Gl motility disorders

hypersensitivity to domperidone, prolonged 0T interval, prolactinoma. electrolyte disturbances. CYP3A 4 inhibitors, mechanical Gl obstruction or perforation, Gl hemorrhage, severe hepatic dysfunction children dPO

Same as above

Same as above

Induction of remission for acute exacerbations: 20 - 40 mg P0 once daily: taper 2.5 - 5 mg / wk until

Anti-inflammatory

Symptomatic moderate to severe CD and UC

Hypersensitivity to prednisone, systemic fungal infections

Hyperglycemia, insomnia, osteoporosis, weight gain, increased risk of infections

prednisone

Monoclonal antibody toTNFo

Medically refractory CD

Heart failure, moderate to severe,doses »5 mg/kg

Reported cases of reactivated TB PCP fymphoma, other infections Other THFo share similar serious sideeffects Headaches, skin rashes, upper respiratory tract infection

discontinued

Biologies

infliximab

Remicade '

5-10 mg /kg IV over 2 h

adalimumab

Humira!

CD in du ction: four 40 mg Monoclonal antibody SC on day 1 then 80 mg 2 to TNFa wk later (day 15) CD maintenance: 40 mg

.

every other wk beginn ing day 29

gotimumab

vedohzumab

Simponi:

Entyvio:

RA: 2 mg/kgatwkO. 4. and then every 8 wk thereafter (use with methotrexate) UC induction: 200 mg SC at wkO, then 100 mg at wk 2 UC maintenance: 50 mg every 4 wk CD /UC: 300 mg at 0.2.6 wkand then every 8 wk

thereafter ustekinumab

Same as above

'

Stelara -

Induction: single IV weight - based dose on day 1 Maintenance: 90 mg subcutaneous injection every 8 wk

Monoclonal antibody to TNFa

Monoclonal antibody to o4fl7 integrin Monoclonal antibody to IgGIK inhibits signals by 11-12 and 11-23

.

Medically refractory CD or Hypersensitivity to poor response to infliximab adalimumab Severe infection Moderate-to-severe heart failure Active ankylosing spondylitis Psoriatic arthritis Moderate- to - severe active RA (combined with methotrexate) UC: medically relractory UC

Medically refractory CD UC. including other TNFa inhibitors and corticosteroids Moderate to severe CD

andUC

. .

Hypersensitivity to gol mumab or latex

Severe infection

- -severe heart

Mpderate to

failure

Hypersensitivity to vedolizumab Hypersensitivity to ustekinumab

Infections, liver injury, and progressive multifocal leukoencephalopathy Infections, headaches, joint pain fever , H / V

rm j

.

+

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Toronto Notes 2023

G56 Gastroenterology

Table 27. Common Drugs Prescribed in Gastroenterology Trade Name

Dosing

Small Molecules

Generic Drug Name tofacitinib

Xeljanc

S 10 mg BID

Antibiotics

rifaximin

Zaxine '

Class

'

SSO mg BIO or TID

Mechanism of Action JAK inhibitor

Indications

Contraindications

Side Effects

UC

IB, hepatitis B

Infections, macro ' cardiac events, thrombosis (e g. PE, DVI )

Nonabsorbable antibiotic, affects dysbiosis of microbiome

Hepatic encephalopathy Non - constipation IBS Traveller 's diarrhea

Nil

Nil

Landmark Gastroenterology Trials Trial Name

Clinical Trial Details

Reference

PEPTIC ULCER DISEASE

FAMOUS

-

Lanccl 2009;374:119 25

.

.

Title: Famotidine for the Prevention of Peptic Ulcers and Oesophagitis in Patients Taking low - dose Aspirin ( FAMOUS) : A Phase III Randomised Double -blind Placebo- controlled Trial Purpose: Evaluate the efficacy ol famotidine in the prevention of peptic ulcers and erosive esophagitis In patients receiving low dose aspirin. Methods: Patients without erosions or ulcers on upper endoscopy, currently on low dose aspirin, were randomited to lamolidine 20 mg 610 or placebo, (he primary endpoint was development of new stomach ulcers. Results: At 12 wk, gastric ulcers occurred in 3.4% of famotidine patients and 15% of placebo - matched patients ( OR 0.20: 95% Cl 0.09 to 0.47; P'0.0002). Duodenal ulcers developed in 0.5% of famotidine patients and 8.5% of placebo patients (OR 0.05: 95% Cl 0.01 to 0.40: P ~0.0045). Conclusions: Famotidine is effective in the prevention of gastric and duodenal ulcers, and erosive esophagitis in patients taking low- dose

.

.

-

aspirin.

INFLAMMATORY BOWEL DISEASE SONIC

NEJM 2010:362:1383- 95

.

Title:Infliximab Azathioprine, or Combination Therapy for Crohn’s Disease Purpose: Compare the efficacy and safety of infliximab and azathioprine therapy alone or in combination, in patients with CD. Methods: CD patients who had not undergone previous biologic or immunosuppressive therapy were randomized to infliximab 5 mg/kg IY infusion or 2.5 mgoral azathioprine or combination therapy of both drugs. Results: Among patients receiving combination therapy 56.8% were in steroid- free remission, compared with 44.4% of patients receiving infliximab monotherapy, and 30% receiving azathioprine monotherapy (P Dartos muscle/ fascia • Scarpa's fascia ( membranous ) > Colles' superficial perineal fascia 3. muscle ( see figure 2 and figure 3) • external oblique > inguinal ligament > external spermatic fascia • internal oblique > cremasteric muscle/fascia • transversus abdominis > posterior inguinal wall 4. transversalis fascia > internal spermatic fascia 5. preperitoneal fat 6. peritoneum > tunica vaginalis Midline Abdominal Wall Layers ( superficial to deep ) 1 skin

.

2. superficial fascia 3. rectus abdominis muscle: in rectus sheath , divided by linea alba (see figure 3) • above arcuate line ( midway between symphysis pubis and umbilicus ) anterior rectus sheath = external oblique aponeurosis and anterior leaf of internal oblique

ri

LJ

aponeurosis posterior rectus sheath = posterior leaf of internal oblique aponeurosis and transversus abdominis aponeurosis • below arcuate line aponeuroses of external oblique, internal oblique, and transversus abdominis all pass in front of rectus abdominis

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GS3 General and Thoracic Surgery

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4 . arteries: superior epigastric ( branch of internal thoracic ), inferior epigastric ( branch of external iliac ); both arteries anastomose and lie behind the rectus muscle ( superficial to posterior rectus sheath above arcuate line ) 5. transversalis fascia 6. peritoneum Transversus abdominis muscle Internal oblique muscle

I

I

Peritoneum

i

I

IC artery

epigastric -Inferior vein

_—

^ “ 5

Transversalis fascia Deep inguinal nng

-External oblique muscle

Membranous layer

-Internal oblique muscle -Aponeurosis of internal

of superficial fascia (Scarpa's fascial

oblique muscle

-Aponeurosis of external

Fatty layer of superficial fascia ( Camper 's fascial Superficial inguinal nng Tunica vaginalis

oblique muscle ( cut edge)

Cremaster muscle

-Spermatic cord

Tesos Internal spermatic fascia Cremaster muscle

External spermatic fascia Code's superficial penneal fascia Dartos muscle Skin of scrotum

Figure 2. Continuity of the abdominal wall with layers of the scrotum and spermatic cord Above arcuate line

Skin Superficial fascia ( Camper's + Scarpa’s fascial

Rectus abdominis

External oblique Internal oblique Transversus abdominis Transversalis fascia Preperitoneal fat Peritoneum Below arcuate line

)

Inferior epigastric artery

Skin Superficial fascia

External oblique Internal oblique Transversus abdominis Transversalis fascia Preperitoneal fat Peritoneum

5

J

S

1

V

Figure 3. Midline cross- section of abdominal wall

Organ

Arterial Blood Supply

liver

Lell and right hepatic

Spleen

Splenic

(branches of hepatic proper)

Gallbladder

Cystic (branch of right hepatic)

Stomach

1. Lesser curvature:right and left gastric 2. Greater curvature:right (branch of gastroduodenal) and left (branch of splenic) gastroepiploic 3. Fundus: short gastnes (branches of splenic)

Duodenum

1 Gastroduodenal

Celiac trunk (1)

i) Common hepatic artery (2) •Hepatic proper (3) - left hepatic artery (4) - Right hepatic artery ( 5) •Right gastric artery (7 ) •Gastroduodenal artery (81 ii) left gastric artery ( 6) iii) Splenic artery (9)

(superior branch of

gastroduodenal, inferior branch of superior

Superior mesenteric artery (10) i) Middle colic artery (11) ii) Right colic artery (121

mesenteric) Pancreas

iii) Ileocolic artery ( 13)

1. Pancreabc branches of splenic

iv) Ileal and jejunal branches 114) Inferior mesenteric artery (15) il Left colic artery ( 16) iilSigmoid arteries ( 17) ii) Superior rectal artery (181

.

2. Pancreaticoduodenal

2. Pancreabcoduodenai5

5

-

,Z

Small intestine

Superior mesenteric branches: jejunal,ileal, ileocolic

Large

1. Superior mesenteric branches:right colic, middle colic

intestine

2. Inferior mesenteric branches: left colic,

+

sigmoid, superior rectal

Figure 4. Arterial blood supply to the Gl tract

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GS4 General and Thoracic Surgery

Venous Flow Portal vein ( II

Superior mesenteric vein (7) i) Ileal and jejunal veins (131 ill Ileocolic vein ( 141 iiil Right colic vein (121 hr ) Middle colic vein ( II ) v) Pancreaticoduodenal vein (8) vi) Right gastroepiploic vein (9) Splenic vein (51 i) I nferior mesenteric vein (10) ( superior rectal vein until crossing common iliac vessels ) •Left colic veins (15) •Sigmoid veins (16 ) •Superior rectal veins (17 ) ii ) Pancreatic veins ml Left gastroepiploic vein hr ) Short gastric veins (6) Left gastric ( coronary ) vein (2) Right gastric vein (3) Cystic vein ( 4)

aa | -

-

Paraumbilical vein (within round ligament , not shown )

? 69 yr and no risk factors Note: Choosing Wisely does not recommend routine preoperative blood work for ambulatory/elective surgery

.

.

Appendicitis" Crohn's disease Tuberculosis of the ileocecal junction

Cecal tumour Intussusception Mesenteric lymphadenitis (Yersinia )

Cecal diverticulitis Cecal volvulus' Hernia:femoral, inguinal obstruction. Amyand's (and resulting cecal distention ) Gynaecological

See 'suprapubic'

Types of Peritonitis • Primary peritonitis: spontaneous without dear etiology • Secondary peritonitis: due to a perforated vise us • Tertiary peritonitis: recurrent secondary peritonitis more often with resistant organisms

Genitourinary

See 'suprapubic' Extraperitoneal Abdominal wall hematoma, abscess Psoas abscess

Localization of Pain • Most digestive tract pain is perceived in the midline because of bilaterally symmetric innervation: kidney, ureter, ovary, or somatically innervated structures are more likely to cause lateralized pain • Parietal peritoneum: supplied by somatic sensory nerves of body wall. Pain is sharp and well-localized • Visceral peritoneum: supplied by autonomic sensory fibres. Pain is colicky and poorly localized

rT iJ

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Table 1. Differential Diagnosis of Acute Abdominal Pain Left Upper Quadrant (LUO)

Left Lower Quadrant (LLO)

Pancreatic Pancreatitis (acute »s. chronic) Pancreatic pseudocyst Pancreatic tumours' Gastrointestinal

Gastrointestinal Diverticulitis *

Diverticulosis Colorsigmod rectal cancer fecal impaction Proctitis (e.g.UC. infectious: i.e. gonococcus or Cbbmydio ) Sigmoid votvulus* Hernia (mcarceraledslrangulaled*)

Gastritis PUD Splenic flexure pathology (e.g.CRC.ischemia) Splenic Splenic infarcllabscess*

Gynaecological See 'suprapubic' Genitourinary

Splenomegaly

See 'suprapubic' Extraperitoneal Abdominal wall hematoma /abscess' Psoas abscess

Splenic rupture' Splenic artery aneurysm Cardiopulmonary (see RUOand Epigastric ) Genitourinary (see DUO)

SeeG » nae:: CTi. Urslinv. Respiroloav, and Cardiology and Cardiac Surgery for further details regarding respective etiologies of acute abdominal pain .

EPIGASTRIC

SUPRAPUBIC

DIFFUSE

Cardiac Aortic dissechonruplured AAA'

Gastrointestinal (see RL0/LL0) Acute appendicitis* IBO Gynaecological Ectopic pregnancy * Pelvic inflammatory disease

Gastrointestinal

Ml

Pericarditis Gastrointestinal Gastritis GERD esopha;; s

Peritonitis* Early appendicitis,perforated appendicitis* Mesenteric ischemia*

Gasboenteritisi'colitis

.

scapula

Renal coSc to groin • Appendicitis: periumbilical to RLQ • Pancreatitis: to back • Ruptured AAA: to back or flank • Perforated ulcer to RLO (right paracolic gutter) • Hip pain: to groin • Ovarian torsion: to flank or groin

Most Common Presentations of Surgical Pain • Sudden onset with rigid abdomen “ perforated visors • Pain out of proportion to physical findings - ischemic bowel • Vague pain that subsequently localizes ~ appendicitis or other intraabdominal process that imitates the parietal peritoneum • Waves of colicky pain - bowel obstruction

Constipation Bowel obstruction* Pancreatitis

Endometriosis Threatened/incomplete abortion* Hydrosalpinx /salpingitis Ovarian torsion* Hemorrhagic fibroid Tubo-ovarian abscess Gynaecological lumours Genitourinary Cystitis (infectious, hemorrhagic) Hydroureter /urinary colic Epididymitis Testicular torsion* Acute urinary retention Extraperitoneal Rectus sheath hematoma

PUD Pancreabtrs Malloty-Weiss tear

Referred Pain

• Biliary colic to right shoulder or

IBD Irritable bowel syndrome Ogilvie's syndrome Cardiovascular, Hematological Aortic dissection* Ruptured AAA* Sidde cellcrisis Genitourinary Gynaecological Perforated ectopic pregnancy* Pehric inflammatory disease Acute urinary retention Endocrinological Carcinoid syndrome* Diabetic ketoacidosis Addisonian crisis Hypercalcemia Other lead poisoning Tertiary syphilis

.

Acute Abdominal Pain Mnemonic

ABDOMINAL Appendicitis Biliary tract disease Diverticulitis Ovarian disease Malignancy Intestinal obstruction Nephritic disorders Acute pancreatitis Liquor /ethanol

’indicated need tor urgent surgical evaluation

Abdominal Mass Table 2. Differential Diagnosis of Abdominal Mass RUO

Upper Midline

LUO

Gallbladder:cholecystitis, cholangiocarcinoma,peri-ampullary

Pancreas: pancreaticadenocarcinoma,other pancreatic neoplasms, pseudocyst Abdominal aorta: AAA (pulsatile) Gl: gastric tumour (adenocarcinoma, gaslrointestinal stromal tumour,carcinoid tumour ) MALT lymphoma

Spleeo: splenomegaly, tumour, abscess, subcapsular splenic hemorrhage, can also present as RLO mass if extreme splenomegaly Stomach:tumour

malignancy, cholelithiasis

Biliary tract Klatskin tumour Liver:hepatomegaly, hepatitis, abscess tumour (hepatocellular carcinoma, metastatic tumour, etc.)

.

.

Lower Midline

RLO

.

Intestine: stool, tumour (CRC) mesenteric adenitis, appendicitis, appendiceal phlegmon or other abscess, typhlitis, intussusception. Crohn's inflammation Ovary: ectopic pregnancy, cyst (physiological vs.pathological),tumour (serous,mucinous,struma ovarii,germ cell.Krukenberg) Fallopian tube:ectopic pregnancy, tubo- ovarian abscess,hydrosalpinx, tumour

Pancreatitis can look like a surgical abdomen, but is rarely an indication for immediate surgical intervention

LLO

.

Uterus: pregnancy, leiomyoma ( fibroid) uterine cancer, pyometra hematometra GU: bladder dislention, tumour

.

Intestine: stool, tumour, abscess ( see RLO) Ovary: see RLO Fallopian tube:see RLO

rt lJ

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GS6 General and Thoracic Surgery

Gastrointestinal Bleeding • see Gastroenterology. G 28 and G30 Indications for Surgery

• failure of medical management ( after at least 2 endoscopic attempts at management ) • exsanguinating hemorrhage: hemodynamic instability despite vigorous resuscitation • recurrent hemorrhage with up to two attempts of endoscopic hemostasis • prolonged bleeding with transfusion requirement >3 units • bleeding at rate >1 unit /8h

.

Indications for Urgent Operation IHOP I sc hernia Hemorrhage Obstruction Perforation

Surgical Management of Gl Bleeding

• UC IB bleeding from a source proximal to the ligament of I reitz often presents with hematemesis and rnelena unless very brisk ( then can present with hematochezia ), may present with anemia, hypovolemic shock initial management with PPls and endoscopy; if fails, then consider surgical management appropriate to etiology • PUD accounts for approximately 55% of severe UCilB LG IB bleeding from a source distal to the ligament of T'reitz often presents with BRBPR unless proximal to transverse colon, rarely rnelena ( right-sided colonic bleeding) initial management with colonoscopy to detect and potentially stop source of bleeding 75% of patients will spontaneously stop bleeding, however if bleeding continues, barium enema should NOT be performed angiography or RBC scan to determine source as indicated surgery indicated if bleeding is persistent aimed at resection of area containing source of bleeding for obscure bleed conduct wireless capsule endoscopy, may require blind total colectomy if the

.

Overt Bleeding: obvious hematemesis. hematochezia or rnelena per rectum (i.e. visible to naked eye) Occult Bleeding: bleeding per rectum is not obvious to naked eye (c.g. positive guaiac FOBT) Obscure Bleeding: bleeding with no identifiable source after colonoscopy and endoscopy (source usually in small bowel). Can be either overt or occult

'

-

source is not found diverticular bleeding is the most common cause of LG1B (accounting for 40% of cases)

Table 3. Differential Diagnosis of Gl Bleeding Anatomical Source

Etiology

Hematological

Excess anticoagulation ( warfarin , heparin , etc.) Excess antiplatelet (dopidogrel. ASA )

Nose

Epistaxis

Esophagus

Esophageal varices Mallory Weiss tear Esophagitis

Aorto esophageal fistula (generally postendovascular aortic repair)* Esophageal cancer

Stomach

Gastritis Castric varices Dieulaloy’s lesion

Castric ulcer Gastric cancer *

Duodenum

Duodenal ulcer Perforated duodenal ulcer*

Duodenal cancer’

Jejunum

Tumours'

-

DIC Congenital bleeding disorders

-

BloodworkforGI Bleeds CBC (including platelet count), serum chemistries (electrolytes. BUN, LFTs, etc,), coagulation studies (INR , PT, PTT), blood type and crossmatch if anticipate transfusion

Polyps Ileum and Ileocecal

Junction large Intestine

Ulcers Meckel 's diverticulum Small bowel obstruction

Colorectal cancer * Mesenteric tlrrombosis/isthemic bowel* UC’(subtotal colectomy if failure of medical management)

Crohn 's disease* Tuberculosis of ileocecal junction Crohn’s disease (less frequently presents with bleeding )’ Pancolitis (infectious, chemotherapy, or radiation induced )

-

Bleeding post gastrointestinal anastomosis

Angiodysplasia Diverticulosis (’if bleeding is persistent)

not amenable tocolonoscopic polypectomy )

Sigmoid

Diverhculosis ('if bleeding is persistent ) Sigmoid cancer * Bleeding postpolypcclomy

Polyps ('if

Rectum and Anus

Hemorrhoids Fissures Pedal cancer* Anal varices

Pa ypsj'il nolamenable tocolonoscopic polypectomy ) Crohn’s orUC* Solitary rectal ulcer syndrome

’Managed surgically in most cases

Biochemical Signs for Differentiating Jaundice Hepatocellular Elevated bilirubin + elevated ALT/AST Cholestatic: Elevated bilirubin + elevated ALP/GGT t duct dilatation upon

rn LJ

biliary UfS

Jaundice

Hemolysis: haptoglobin t LDH

*

+

• see Gastroenterology, G45 Note: cholestatic jaundice is often surgical

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GS7 General and Thoracic Surgery

Preoperative Preparations Considerations • informed consent (see Ethical, Legal, and Organizational Medicine ELOM 11 ) • screening questionnaire to determine risk factors e.g. age, exercise capacity, medication use, allergies, exposure to people with infection (i.e. COVID-19) • consider preoperative anesthesia, medicine consult as indicated to optimize patient status

.

• IV - balanced crystalloid at maintenance rate ( 4:2:1 rule for paediatrics, roughly 100-125 cc / h for

adults): NS or RL ( RL most common ); bolus to catch up on estimated losses including losses from bowel prep appropriate use of fluids perioperatively decreases risk of cardiorespiratory complications • patients can take their regular medications except for hypoglycemic agents, diuretics, and ACEis • patients with primary adrenal insufficiency (e.g. Addison's disease ) or secondary adrenal insufficiency (e.g. glucocorticoid use) may reuuire additional glucocorticoid stress dose coverage • anticoagulation /antiplatelet medication must be managed to decrease surgical bleeding but not put patient at risk for increased thrombotic events (e.g. Bridging: switching from warfarin to LMWH, easier to start/stop as needed ) • prophylactic antibiotics depending on wound class ( immediately/within 1 h prior to incision): cefazolin (skin flora coverage ) ± metronidazole (Gl flora coverage ) for contaminated cases • role of MBP: Current evidence suggests that use of MBP preoperatively has no impact on postoperative complications, and therefore, routine use of MBP for non LAK elective colorectal surgery is not recommended MBP is indicated in open or laparoscopic anterior resection i.e. rectal resection where

m

Bilirubin Levels

Prchepatic

bitra hepatic

Posthepatic

Serum Bilirubin

Indited Owed

t

»

N

N

t

t

t

t

t

e

Urine Urobilinogen Bilirubin Fecal

Urobilinogen

m

In patients with liver disease and an acute abdomen, spontaneous bacterial peritonitis must be ruled out

-

anastomosis is at or below sacral promontory; given with antibiotics • assess risk for postoperative V I E prior to surgery based on procedure- and patient - related factors;

tools such as Caprini Score can be used only hold VT'E prophylaxis if epidural is expected • smoking cessation and weight loss preoperatively can significantly decrease postoperative complications • infection: delay elective surgery until infection managed, including respiratory infection ( particularly in asthma patients) • when scheduling elective surgeries following a COVID 19 diagnosis, consider the severity of COVID 19 illness, the risks of complications, and risks of delaying surgery

Table 4. Recommendations for Timing of Surgery following Recovery from COVID-19 with Consideration of Individual Risk /Benefits

-

Clinical Severity of COVID 19 Infection

Mild

Moderate

Severe

Critically ill

Mild (suspected or confirmed) COVID - 19 and/ or asymptomatic and/or upper respiratory tract infection

Moderalc symptomatic COVID 19 not requiring hospitalization and/ or persistent symptoms

Lung involvement requiring hospilalnalion and/ or significant comorbidities and/or immunocompromised

Severe C 0VID -19 wrlh ICU admission and/or meet criteria lor severe

Do case urgently/ emergently

«7 wk post

infection consider non operative oplionsil sale and available

infection consider non operative options if sale and available

7 wk post infection

7 wk post inlection

12 wk post infection

Urgent or Emergent «2 wk Do case urgently/ ACATS and PCATS Urgent emergently within 3,7 or 14 days Urgent (28 or 42 days) 2-SwkACATS/PCATS

Allergies

Medications fast medical/surgical history (including anesthesia and bleeding disorders) Last meal

Events - HPI

-

-

Priority of Surgical Procedure

Surgical Emergencies: Take an AMPLE History

-

4 7 wk post infection

-

-

-

Best Practice In General Surgery (BPIGS) http:/ / www.bpigs.ca / Best Practice in Surgery is a resource from the quality improvement program at the University of Toronto Department of Surgery. Since its inception, it has expanded beyond general surgery best practices and provides EBM guidelines for a variety of fields and procedures

disease and/or severely immunocompromised 69 and no risk factors • P-hCG testing in all women of reproductive age • for patients undergoing low- risk surgery without systemic disease ( ASA 1 or II ), routine preoperative chest x rays, CBC, 1 NR, and PTT should be avoided

Mechanical Bowel Preparation Strategies: A Clinkal Practice Guideline developed bylbe University ol Toronto's lest Practice in Surgery Informed by: Can J Surg 2010:53:385 -395 14 ICIs (5071 participants) 8 meta-analyses 1. All open,'laparoscopic colorectal procedures (excluding LAfts t diverting stoma) • l, a MBP • Ho dietary restrictions before IPO • fleet enema lor left cotononastomows with bansrectal stapling 2. Open/laparoscopicIAR divertingstoma MBP • Ho dietary restrictions before MBP;cleat fluids after MBP complete

.

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Toronto Notes 2023

GS8 General and Thoracic Surgery

.

Drains NG tube

• indications: gastric decompression, analysis of gastric contents, irrigation /dilution of gastric

contents, feeding, and /or administration of medications, if necessary 2 types: NG tube ( for drainage or feeding ) and Dobhoff ( for feeding only) insertion should be done in stages with x -ray protocol to avoid injury • contraindications: suspected basal skull fracture, obstruction of nasal passages, esophageal stricture, esophageal varices • Foley catheter with urometer indications: to accurately monitor urine output , decompression of bladder, relieve obstruction, rapidly expanding suprapubic mass contraindications: suspected urethral injury and difficult insertion of catheter

Drain Sire Measured by the unit French: French ~ diameter (mm) x 3

Surgical Complications • general principles in preventing complications during the postoperative period Include:

• frequent examination of the patient (daily or more) and their wound • removal of surgical tubes as soon as possible (e.g. Foley catheters and surgical drains) •

early mobilization monitor fluid balance and electrolytes analgesia - enough to adequately address pain ( minimize opioids through routine use of anti inflammatories and acetaminophen )

Postoperative Fever • postoperative fever is considered a temperature higher than 38C on two consecutive postoperative days or higher than 39 C on any postoperative day • fever does not necessarily imply infection, particularly in the first 24 48 h postoperative!)' • fever may not be present or may be blunted if patient is receiving chemotherapy, glucocorticoids, or other immunosuppressive agents • timing of fever may help identify cause • hours after surgery - POD #1 inflammatory reaction in response to physiological stress from surgery; most common cause of fever on POD #1-3 and unlikely to be infectious (unless necrotizing fasciitis or another severe infection ) reaction to blood products received during surgery malignant hyperthermia • POD #1 2 (acute) atelectasis early necrotizing fasciitis wound infection (especially Clostridium perfringens, (5-hemolytic Group A Streptococcus ), feel for crepitus and look for “dishwater" drainage • aspiration pneumonitis • other: acute adrenal insufficiency, thyroid storm, and transfusion reaction POD # 3 7: likely infectious UT1, surgical site infection, IV site/ line infection (commonly with Staphylococcus ) , septic thrombophlebitis, and leakage at bowel anastomosis (tachycardia, hypotension, oliguria, and abdominal pain) POD #8+ intra -abdominal abscess, DVT/ PE (can be anytime postoperative, most commonly POD #810, may occur earlier but recognition is often delayed ), and drug fever other: URT’I, infected scroma / hiloma / hcmatoma , C difficile colitis, and endocarditis

-

-

-

-

Treatment

• resuscitation then treat primary cause

Wound /Incisional Complications WOUND CARE (see Plastic Surgery, PL 8)

• can shower POD # 2-3 after epithelialization of wound (or earlier depending on dressing) • most dressings can be removed POD # 2 and left uncovered if dry • Steri strips or dermabond glue should be left on for up to 2 wk • examine wound for wet dressing, signs of infection (fever, tachycardia, and pain ) • skin sutures and staples can be removed POD # 7-10 exceptions: incision crosses crease ( groin ), closed under tension , in extremities ( hand ) or patient factors (elderly, corticosteroid use, or immunosuppressed ) removed POD # 14 or earlier if there are

n

LJ

+

signs of infection • negative pressure dressings consist of foam and suction, promote granulation ideal for large (grafted sites) or non- healing wounds ( irradiated skin or ulcer)

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Toronto Notes 2023

GS9 General and Thoracic Surgery DRAINS • drains may be placed selectively at the time of surgery to prevent fluid accumulation ( blood , pus, serum, bile, and urine) can be used to assess quantity of third space fluid accumulation postoperativelv • potential route of infection; to decrease risk of wound infection bring out through separate incision ( vs. operative wound ) and remove as soon as possible

• types of drains • open (e.g. Penrose ), higher risk of infection closed: 1 ) gravity drainage (e.g. Foley catheter ); 2) underwater-seal drainage system ( e.g. chest tube); 3) suction drainage (e.g. lackson - Pratt ) sump (e.g. NG tube) • monitor drain outputs daily • drains should be removed once drainage is minimal ( usually 25, PO’ 30 pack-yr smoking Hx • Current smoker or quit within last 15 yr Annual screening low-dose CT up to 3 yr ONLY in centres with expertise in diagnosis and treatment of lung cancer

.

53% limited stage 5% extensive stage

.

US Mortality Files National Center tor Health Statistics CDC

Risk Factors • cigarette smoking: the relative risk of developing lung cancer is 10-30 times higher for smokers than for nonsmokers • risk of lung cancer increases with number of cigarettes smoked per day ( linear) and duration of smoking (exponential ) • other risk factors: cigar smoking, pipe smoking, second-hand smoke, asbestos without smoking ( relative risk is 5), asbestos with smoking ( relative risk is 92), metals (e.g. chromium, arsenic, nickel ), radon gas, ionizing radiation, and genetics Clinical Features may be due to primary lesion, metastasis, or paraneoplastic syndrome • primary lesion cough (75%); beware of chronic cough that changes in character dyspnea (60% ) chest pain ( 45%) hemoptysis (35%) other pain ( 25%) clubbing (21% ) constitutional symptoms: anorexia, weight loss, fever, and fatigue • metastasis • lung, hilum , mediastinum , pleura: pleural effusion, atelectasis, wheezing, post-obstructive pneumonia pericardium: pericardial effusion, pericardial tamponade esophageal compression: dysphagia • phrenic nerve: paralyzed diaphragm, dyspnea • recurrent laryngeal nerve: hoarseness superior vena cava syndrome obstruction of SVC causing neck and facial swelling other symptoms: dyspnea, cough, hoarseness, tongue swelling, epistaxis, and hemoptysis physical findings: dilated neck veins, increased number of collateral veins covering the anterior chest wall, cyanosis, edema of the face, arms, and chest, Pemberton's sign ( facial flushing, cyanosis, and distension of neck veins upon raising both arms above head ) milder symptoms if obstruction is above the azygos vein • lung apex ( Pancoast tumour ): Horner’s syndrome, brachial plexus palsy ( most commonly C8 and T1 nerve roots) • rib and vertebrae: erosion, pain • distant metastasis to brain, bone, liver, and adrenals • paraneoplastic syndromes • most often associated with SCLC •

©

Malignant lung tumours are the most common cause of cancer mortality in both men and women worldwide

Endobronchial Ultrasound ( EBUS) • Allows visualization of peri bronchial structures and lung lesions • Allows for guided biopsies of lymph nodes and tumours • Used for diagnosis and staging

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“»

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Toronio Notes 2023

Table 10. Paraneoplastic Syndromes System

Clinical Features

Associated Malignancy

Skeletal

Clubbing, hypertrophic pulmonary osteoarthropathy ( HPOA) Acanthosis nigricans Oermatomyosltis Hypercalcemia (osteolysis or PIHrP) Hypophosphatemia Hypoglycemia Cushing's syndrome ( ACIH ) Carcinoid syndrome

Non small cell lung cancer ( NSCLC) Lung cancer

Dermatologic

Endocrine

-

SCC

SCC

Saicoma Small cell lung cancer (SCLC) Bronchial carcinoid SCLC SCLC

SIADH Heuromyopathic

Vascular /Hematologic

lambert - Eatonsyndrome Polymyositis Subacute cerebellar degeneration Spinocerebellar degeneration Peripheral neuropathy Nonbacterial endocarditis trousseau's syndrome ( migratory thrombophlebitis) QIC

Renal

2/3 of primary lung cancer is found in the upper lung: 2/3 of metastases occur in the lower lung (hematogenous spread secondary to increased blood flow to the base of the lung)

Lung cancer NSCLC Lung carcinoma

Nephrotic syndiome

Investigations

• initial diagnosis

imaging: CXR, CT chest + abdomen, PET scan biopsy: bronchoscopy, EBUS, CT-guided percutaneous needle biopsy • staging workup TNM staging system : T - primary tumour (size ); N - regional lymph nodes; M - distant metastasis blood work: electrolytes, Ll Ts, calcium , ALP • imaging: CXR, CT thorax and abdomen , PET ' scan , bone scan ( in confirmed stage I cancer ), neuroimaging ( MRI Brain ) • invasive: bronchoscopy ( EBUS), mediastinoscopy, VATS '

-

Prevention • Smoking cessation • Avoidance of exposures • Early detection

Terminology • "Nodule" 3 cm

Table 11. SCLC vs. NSCLC SCLC

Stage

Definition

Treatment

Median Survival

Limited stage

Confined lo single radiation port (one hemithorax and regional lymph nodes) Extension beyond a single radiation port

Radiation t chemotherapy i prophylactic to brain

1 2 yr (12 vvk without treatment)

Chemotherapy

6 mo (5 wk without treatment )

Stage

TNM

0

IIA

TisNOMO TtaNOMO TlbNOMO TkNOMO T 2 aN 0 M 0 T 2 bH 0 M0

5 Yr Survival ( % ) • Treatment 1st line iscomplete surgical resection (VAIS or open thoracotomy ) with possible 90 92 postoperative adjuvant chemotherapy 83-85 77 80 with stage IB and stage It: radiotherapy for non surgical candidates 68 -73 60 65

IIB

T3 N0 M 0 or T1H 1M 0 or T 2 N1M 0

53 56

IMA

36 - 41

IIIB

T 4 N0 M 0 or T 4 H1M0 or I 3M 1N 0 or T1N 2 M 0 Combined modality appioach (chemo t radiation, and sometimes surgical or T 2 N 2 M 0 resection ) T 3 N 2 M0 or I 4 M 2 N0 or T1 N 3 M 0 or I 2 N 3 M 0

IIC

f 3N 3 M 0 or I 4 N 3 M 0

IVA

T1 4N 0- 3M1a 1b

IVB

T1-4H 0 -3M1C

Extensive stage

HSCLC

IA1 IA 2 IA3

IB

-

-

-

-

-

24 26

1213 Systemic therapy or molecularly targeted 10 therapy or symptom - based palliative management (radiation ): isolated 0 metastasis may be resected

.

' Depends on clinical vs. pathologic stage Reler to AJCC Cancel Staging Manual 8th ed. 2017 lor complete TNM classification

Mutations in endothelial growth factor receptor are more common in nonsmoking patients with adenocarcinoma

Corona Radiata Sign on Chest CT

• Fine striations that extend linearly

from a nodule in a spicutated fashion • Highly associated with malignancy

Carcinoids • Early onset (40- 60 yr) • Most are central and can produce symptoms and signs of bronchial

obstruction

-

• Hemoptysis is present in 50% of cases • Assuming adequate pulmonary function, surgical resection (i.e. segmentedomy. wedge resections, and lobectomy ) is the preferred treatment approach

Treatment

• options include surgery, radiotherapy, ablation , chemotherapy, and palliative care lor end -stage

disease • surgery not usually performed for SCLC since it is generally non -curable • contraindications for surgery spread to contralateral mediastinal lymph nodes or distant sites patients with potentially resectable disease must undergo mediastinal node sampling since CT thorax is not accurate in 20 - 40% of cases poor pulmonary status (e.g. unable to tolerate resection of lung ) postoperative estimated l ' HVi and DLCO must be at least 40% of predicted to tolerate surgery ( used in combination with other treatments ) chemotherapy • • common agents: cisplatin vinorelbine ( standard of care ), etoposide, ifosfamide, vincristine, anthracyclines, paclitaxel irinotecan , gefitinib ( an endothelial growth factor receptor inhibitor) • pembrolizumab, a HD- 1 monoclonal antibody is used in those with tumour PD - l. l levels > 50%; for those with PD - L 1 levels 24 h duration )

• abscess, phlegmon

• sepsis

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Toronto Notes 2023

GS36 General and Tlioracic Surgery

Investigations • laboratory

mild leukocytosis with left shift ( may have normal WBC counts) higher leukocyte count with perforation p-hCG to rule out ectopic pregnancy

-

urinalysis

• imaging

•

-

U /S: may visualize appendix, but also helps rule out gynaecological causes overall accuracy 90 94 %, can rule in but CANNOT rule out appendicitis ( if >6 mm , SENS/SEEC/ NEV/ PFV 98% ) CT scan: thick wall, enlarged ( > 6 mm ), wall enhancement , appendicolith , and inflammatory changes overall accuracy 94 100%, optimal investigation

-

Antibiotics versus Appendectomy for Acnte Appendicitis Longer Term Ontcomes N Engl J Ued 202 T;38S|25|:2395. Epub 2021 Oct 25 Purpose: Compare Ibe efficacy of antibiotics is. an appendectomy for acute appendicitis wild respect to long term outcomes Method: Pe domned trial comparing antibiotic treatment mth appendectomy in patients with

-

-

Treatment • hydrate, correct electrolyte abnormalities • appendectomy (gold standard ) laparoscopic is standard complications: intra abdominal abscess, appendiceal stump leak perioperative antibiotics: cefazolin + metronidazole, if uncomplicated perioperative dose is

-

adequate • consider treatment with postoperative antibiotics for perforated appendicitis • for patients who present with an abscess ( palpable mass or phlegmon on imaging and often delayed

-

.

-

'

appendicitis.

Results: he 30 - day general health status of patients treated with antibiotics was comparable to the appendectomy group.However, 29 percent of medially-treated patients required appendectomy by 90 days, longer term data from this trial now confirm h gi rates of subsequent appendectomy after indial medical therapy: 40 percent at one year, 46 percental two years, and 49 percent at three and foot years. Conclusions: Sutgery should continue to be recommended foi uncomplicated appendicrtisand antibiotic therapy should be reserved for those who are medially unfit for or decline surgery.

-

-

diagnosis with symptoms for > 4 5 d ), consider radiologic drainage + antibiotics xl 4 d ± interval appendectomy once inflammation has resolved = (controversial ) • medical management with antibiotic therapy should be reserved for those who are unfit for or refuse surgery • colonoscopy in those >50 yr to rule out concurrent etiology ( neoplasm ) Prognosis

-

• mortality rate: 0.09 0.24%

Inflammatory Bowel Disease • see Gastroenterology', G 22 Principles of Surgical Management

• medical management remains first line, but surgery can alleviate symptoms, address complications, and improve quality of life • conserve bowel: resect as little as possible to avoid short gut syndrome • perioperative management optimize medical status: may require TEN (especially if >7 d NEC)) and bowel rest hold immunosuppressive therapy preoperative, provide preoperative stress dose of corticosteroid; if patient had recent steroid therapy, taper steroids postoperative VTE prophylaxis: LMWH or heparin ( IBD patients at increased risk of thromboembolic events)

Crohn’s Disease

m

•see Gastroenterology. G 23 Treatment

-

•surgery is for symptom management; it is NOT curative, but over lifetime 70% of Crohn 's patients will have surgery • indications for surgical management failure of medical management SBO (due to stricture/inflammation ): indication in 50% of surgical cases abscess, fistula (enterocolic, vesicular, vaginal, cutaneous abscess), quality of life, perforation, hemorrhage, chronic disability, failure to thrive (children ), and perianal disease

•surgical procedures resection and anastomosis/stoma if active or subacute inflammation , perforation, or fistula • surgery should be attempted in the elective setting ideally off steroids • resection margin only has to be free of gross disease ( microscopic disease irrelevant to prognosis) stricturoplasty widens lumen in chronically scarred bowel: relieves obstruction without resecting bowel (contraindicated in acute inflammation )

-

Complications of Treatment •anastomotic leak •dehydration •short gut syndrome (diarrhea, steatorrhea, malnutrition )

Crohn's 3 Major Patterns • Ileocecal 40% (RIO pain, fever, weight loss) • Small intestine 30% (especially terminal ileum) Colon 25% (diarrhea)

.

Findings in Crohn’s • "Cobblestoning” on mucosal surface due to edema and linear ulcerations • “Skip lesions": normal mucosa in between

• "Creeping fat": mesentery infiltrated

•

by fat Granulomas: 25 30%

r -t LJ

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+

•fistulas •gallstones ( if terminal ileum resected , decreased bile salt resorption > increased cholesterol precipitation )

• kidney stones ( loss of calcium in diarrhea -> increased oxalate absorption and hyperoxaluria > stones)

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GS37 General and Thoracic Surgery

Toronto Notes 2023

Prognosis

• recurrence rate at 10 yr: ileocolic (25-50%), small bowel (50%), colonic (40-50%) • re-operation at 5 yr: primary resection ( 20%), bypass (50%), strictureplasty (10% at 1 yr ) • 80 85% of patients who need surgery lead normal lives mortality: 15% at 30 yr

.

-

Ulcerative Colitis •see Gastroenterology. G25 Treatment

• indications for surgical management

failure of medical management ( including inability to taper steroids ) complications: hemorrhage, obstruction , perforation , toxic megacolon (emergency), failure to thrive (children ) reduce cancer risk (1-2% risk per yr after 10 yr of disease) •surgical procedures proctocolectomy and ileal pouch-anal anastomosis (1PAA ) ± rectal mucosectomy (operation of choice) proctocolectomy with permanent end ileostomy (if not a candidate for ileoanal procedures) colectomy and 1FAA ± rectal mucosectomy in emergency: total colectomy and ileostomy with Hartmann closure of the rectum , rectal preservation Complications of Treatment •early: bowel obstruction, transient urinary dysfunction, dehydration ( high stoma output ), anastomotic leak •late: stricture, anal fistula/abscess, pouchitis, poor anorectal function , reduced fertility

Prognosis • mortality: 5% over 10 yr

• total proctocolectomy will eliminate risk of cancer

• perforation of the colon is the leading cause of death from UC

LARGE INTESTINE Large Bowel Obstruction Mechanical Large Bowel Obstruction Etiology Top 3 Causes of LBO (in order) • Cancer ( >60%)

Table 18. Common Causes of LBO Intraluminal

Intramural Adenocarcinoma Diverticulitis (edema, stricture) IBD stricture Radiation stricture

Constipation Foreign bodies

Extramural Volvulus

..

-

Volvulus (10 15%) Diverticulitis (10%)

Adhesions Hernias (sigmoid colon in a large groin hernia)

Clinical Features (unique to LBO ) • open loop ( 10 20% ) • incompetent ileocecal valve allows relief of colonic pressure as contents reflux into ileum , therefore clinical features similar to SBO • closed loop (80-90%) (dangerous) competent ileocecal valve, resulting in proximal and distal occlusions massive colonic distention -» increased pressure in cecum -» bowel wall ischemia -> necrosis ->

-

In a patient with a clinical LBO consider impending perforation when: • Cecum i12 cm in diameter • Tendern ess present over cecum

perforation

n L

Investigations

• GBG with differential , BUN , electrolyte panel, creatinine, CEA if patient is suspected to have

malignancy, and lactate for level of ischemia • imaging: AXK and CT scan

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GSM General and Thoracic Surgery Treatment

• supportive management: IV fluids, gastrointestinal decompression • surgical intervention (75% of cases) volvulus: initial decompression with flexible sigmoidoscopy, operative reduction or sigmoid resection dependent on severity colorectal obstruction: ostomy alone (fecal diversion ), colectomy with primary anastomosis, or Hartmann procedure • may pursue stenting as a bridge to surgery or palliation Prognosis • overall mortality: 10%

• cecal perforation t feculent peritonitis: 20% mortality Table 19. Bowel Obstruction vs. Paralytic Ileus SBO

LBO

Paralytic Ileus

N /V

Early, may be bilious

Present

Abdominal Pain

Colicky (pros SBO) ** (distal SBO)

Late, may be feculent Colicky

Normal, increased (borborygmi) Absent il secondary ileus (delayed presentation)

Decreased absent

Minimal or absent

.

Abdominal Distention Constipation

.

Bowel Sounds

Normal Increased Absent if secondary ileus (delayed presentation)

AXR Findings

Ait fluid lewis “ ladder" pattern ( plicae

-

circulares) Proximal distention ( >3 cm)

no colonic gas

-

Air fluid levels “ Picture frame" appearance Proximal distention distal decompression No small bowel air if competent ileocecal valve Coffee bean sign ( sigmoid volvulus)

.

Air throughout small bowel and colon

Functional Large Bowel Obstruction: Colonic PseudoObstruction (Ogilvie’s Syndrome) Definition

• acute pseudo -obstruction • distention of colon without mechanical obstruction in distal colon • exact mechanism unknown, likely autonomic motor dysrcgulation

Associations

• most common: trauma, infection , and cardiac ( MI, CHI ) • disability ( long- term debilitation, chronic disease, bed - bound nursing home patients, and '

paraplegia ), drugs ( narcotic use, laxative abuse, and polypharmacy), and other ( recent orthopaedic or neurosurgery, post partum , electrolyte abnormalities including hypokalemia, retroperitoneal hematoma , and diffuse carcinomatosis )

-

Clinical Features

-

• classically presents with abdominal distention (acute or gradual over 3 7 d ) • abdominal pain, N / V, constipation or diarrhea • watch out for fever, leukocytosis, and presence of peritoneal signs (suggestive of colonic ischemia or perforation ) Investigations

• AXR: cecal dilatation ( if diameter £ 12 cm , increased risk of perforation ) Treatment

• treat underlying cause • NFC), NG tube • decompression: rectal tube, colonoscopy, neostigmine (cholinergic drug), or surgical (ostomy/ resection )

• surgery (extremely rare): if perforation, ischemia , or failure of conservative management r -i

Prognosis • most resolve with conservative management

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GS39 General and Thoracic Surgery

Diverticular Disease Definitions

• diverticulum: abnormal outpouching from the wall of a hollow organ • diverticulosis: presence of multiple diverticula • diverticulitis: inflammation of diverticula • true (congenital ) diverticuli: contain all layers of colonic wall, often right-sided • false (acquired ) diverticuli: contain mucosa and submucosa , often left sided

-

FALSE DIVERTICULUM , (mucosal herniations) V

TRUE DIVERTICULUM (full wall thickness)

Y

,11

x— Antimesentenc tenia /

Mucosa ' Circular muscle

I

Mesocolon-

Mesenteric tenia -

SBR I

Figure 13. Diverticular disease - cross- sections of true and false diverticula

Diverticulosis Epidemiology • 5-50 % of Western population, lower incidence in non-Western countries, M=F • prevalence is age dependent: inflammation and focal necrosis -> micro or macroscopic perforation • usually mild inflammation with perforation walled offby pericolic fat and mesentery; abscess, fistula , or obstruction can ensue • poor containment results in free perforation and peritonitis

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GS 10 General and Thoracic Surgery

Clinical Features • depend on severity of inflammation and whether or not complications are present; hence ranges from asymptomatic to generalized peritonitis • LLQ pain / tenderness ( 2 /3 of patients ) often for several days before admission • constipation, diarrhea, N / V, and urinary symptoms ( with adjacent inflammation) • low-grade fever, mild leukocytosis, and occult or gross blood in stool rarely coexist with acute

diverticulitis

• complications ( 25% of cases)

• abscess: palpable, tender abdominal mass

fistula: colovesical ( most common ), coloenteric, colovaginal, and colocutaneous colonic obstruction: due to scarring from repeated inflammation perforation: generalized peritonitis (feculent vs. purulent ) • recurrent attacks rarely lead to peritonitis Investigations

• CT scan ( test of choice)

Efficacy and Safety of Monantibiotic Outpatient Treatment in M lid Acute Diverticulitis ( DINAMO study ) : A Multicentre, landomised , Open label Noninferiority Trial Ann Surg 2021;274(5):e435. Background: In recent years, it has shown no benefit olantrkotntjAl!) in the treatrnentof uncomptcated AD mhospitalited patients. Methods: Prospective, nnlticentre open-label,

-

.

.

noninferiority, randomized controlled trial. Desalts: Differences in hospitaliiation rates, revisits, and poor par n control at 2 days follow up were within the non inferiority margin. Conclusions lit of mild AD is safe and effectne and is not inferior to current standard treatment

-

-

very useful for assessment of severity and prognosis (97% sensitive, 99% specific)

• usually done with rectal contrast

.

-

increased soft tissue density within pericolic fat secondary to inflammation, diverticula secondary to inflammation, bowel wall thickening, soft tissue mass ( pericolic fluid, abscesses), and fistula 10% of diverticulitis cannot be distinguished from carcinoma AXR, upright CXR • localized diverticulitis (ileus, thickened wall, SBO, and partial colonic obstruction ) free air may be seen in 30% with perforation and generalized peritonitis

• colonoscopy or barium enema and flexible sigmoidoscopy (elective evaluation )

establish extent of disease and rule out other diagnoses ( polyps and malignancy ) AFTER resolution of acute episode

Treatment

• uncomplicated: conservative management

• outpatient: clear fluids only until improvement. Avoid treatment with antibiotics for those with uncomplicated acute diverticulitis • hospitalize: if severe presentation, inability to tolerate oral intake, significant comorbidities, or fail to improve with outpatient management treat with NPO, IV fluids, and IV antibiotics (e.g. IV ceftriaxone + metronidazole ) • image-guided (CT) percutaneous drainage of abscesses reduces the urgency of surgical resection in

diverticulitis and inflammation

most patients

• surgery:

indications:

Colostomy

unstable patient with peritonitis Hinchey stage 3-4 (see Table 19) after 1 attack if immunosuppressed consider if recurrent episodes of diverticulitis (S3); recent trend is toward conservative management of recurrent mild/ moderate attacks

Resection of diseasedarea and closure of distal rectal stump

• procedures:

•

•

Hartmann resection ( for unstable or complex cases) colon resection + colostomy and rectal stump > colostomy reversal in 3 6 mo • for more stable patients with Hinchey stage 3 and 4 acute diverticulitis: colonic resection , primary

-

anastomosis + diverting loop ileostomy is becoming more common, with benefits for mortality and morbidity for Hinchey stage 3: laparoscopic peritoneal lavage with drain placement near the affected colon, in addition to 4 antibiotics ( NO resection ), has been proposed complications: perforation, abscess, fistula, obstruction, hemorrhage, inability to rule out colon cancer on endoscopy, or failure of medical management

Anastomosis in approximately

3 mo

-

s :„-

Figure 14. Hartmann procedure

Prognosis • mortality rates: 6% for purulent peritonitis, 35% for feculent peritonitis • recurrence rates: 13-30% after first attack, 30-50% after second attack Table 20. Hinchey Staging and Treatment for Diverticulitis Hinchey Stage

Description

Acute Treatment

1

Phlegmonfsmall pericolic abscess

Medical

2 3

large abscess/ fistula

Medical, abscess drainage t resection with primary anastomosis

Purulent peritonitis ( ruptured abscess) Feculent peritonitis

Resection or Hartmann procedure Hartmann procedure

4

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GS41 General and Thoracic Surgery

Toronto Notes 2023

Colorectal Neoplasms Colorectal Polyps Definition Bowel lumen

• polyp: protuberance into the lumen of normally Hat colonic mucosa

- Bowel wall

sessile (flat ) or pedunculated (on a stalk ) v

Epidemiology • 30% of the population have polyps by age 50, 40% by age 60, 50% by age 70; M >F

Clinical Features • 50% in the rectosigmoid region , 50% are multiple • usually asymptomatic, do not typically bleed , tenesmus, intestinal obstruction , and mucus • usually detected during routine endoscopy or familial /high -risk screening Pathology

• non-neoplastic/ non-adenomatous hyperplastic: most common non neoplastic polyp mucosal polyps: small < 5 mm, no clinical significance hamartomas: juvenile polyps (large bowel ), Peutz| - egher syndrome (small bowel ) malignant risk due to associated adenomas ( large bowel ) low malignant potential -> most spontaneously regress or autoamputate inflammatory pseudopolyps: associated with IBD, no malignant potential • submucosal polyps: lymphoid aggregates, lipomas, leiomyomas, and carcinoids • neoplastic/adenomatous adenomas: premalignant, considered carcinoma in situ if high - grade dysplasia may contain invasive carcinoma ( “ malignant polyp” 3 9%): invasion into submucosa malignant potential related to histological type: villous > tubulovillous > tubular

-

O Janlea Wong 2003

J

Figure 15. Sessile and pedunculated polyps

--

Table 21. Characteristics of Tubular vs. Villous Polyps Tubular

Villous

Incidence

Com raon (60- 80%)

less common (10%)

Size

Small (2 cm)

Attachment

Pedunculated

Sessile

Malignant Potential

Lower

Higher

Distribution

(ven

tell sided predominance

Investigations

• colonoscopy with biopsy/resection ( gold standard )

• CT colonography: increasing in availability; patients still require bowel prep and will require colonoscopy if polyps are identified • other: flexible sigmoidoscopy ( if polyps are detected, proceed to colonoscopy for examination of entire bosvel and biopsy)

Treatment • indications: symptoms, malignancy or risk of malignancy (i.e. adenomatous polyps) • endoscopic removal of entire growth • indications for segmental resection for malignant polyps: 1) lymphovascular invasion; 2 ) tumour budding; 3) positive resection margin ; 4 ) poorly differentiated cells; 5) evidence of regional or distant

metastases on staging most of these cases are usually discussed at multi-disciplinary’ tumour boards • follow up endoscopy: • every 5 yr: if low risk polyp ( 10 mm tubular or serrated polyp, adenoma with villous features or high grade dysplasia, or sessile serrated with dysplasia )

-

-

-

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i. J

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GSI2 General and Thoracic Surgery

Familial Colon Cancer Syndromes FAMILIAL ADENOMATOUS POLYPOSIS

Epidemiology • accounts for 100 colorectal adenomas) • To provide pre symptomatic testing for individuals at risk for FAP (1st degree relatives who are >10 yr) • To confirm the diagnosis of attenuated FAP ( in patients with >20 colorectal adenomas)

-

small bowel congenital hypertrophy of retinal pigment epithelium presents early in life in 2 /3 of patients; 97% sensitivity

• variants

Gardner’s syndrome: FAP + extra - intestinal lesions (sebaceous cysts, osteomas, desmoid tumours ) • Turcot syndrome: FAP f CNS tumours (childhood cerebellar medulloblastoma )

Investigations

• genetic testing ( 80 -95% sensitive, 99-100% specific ) • if no polyposis found : annual flexible sigmoidoscopy from puberty to age 50, then routine screening • if polyposis or APC gene mutation found: annual colonoscopy, consider surgery, and consider upper endoscopy to evaluate for periampullary tumours Treatment • surgery indicated by ages 17-20

• total proctocolectomy with ileostomy or total colectomy with ileorectal anastomosis • doxorubicin - based chemotherapy • NSAIDs for intra abdominal desmoids

-

HEREDITARY NON - POLYPOSIS COLORECTAL CANCER - LYNCH SYNDROME

Revised Bethesda Criteria for HNPCC and Microsatellite Instability ( MSI ) T umours from individuals should be tested for MSI in the following situations: • Colorectal cancer diagnosed in a patient who is high rates of extracolonic tumours ( endometrial , ovarian , hepatobiliary, small bowel, adrenal )

-

Diagnosis

-

--

• Amsterdam Criteria (“3 2 1 rule") • 3 or more relatives with verified Lynch syndrome associated cancers , and I must be 1 st degree relative of the other 2 • 2 or more generations involved • I case must be diagnosed before 50 yr • FAP is excluded • genetic testing ( 80% sensitive ) • refer individuals for genetic screening if they fulfill either the Amsterdam Criteria or the revised Bethesda Criteria • colonoscopy ( starting age 20 ) annually • surveillance for extracolonic lesions

APR removes distal sigmoid colon , rectum, and anus: permanent end colostomy required LAR removes distal sigmoid and rectum with anastomosis of distal colon to distal roctum /anus j

Treatment

+

• total colectomy and ileorectal anastomosis with annual proctoscopy

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Toronto Notes 2023

IRemoved

Colorectal Carcinoma Epidemiology • 3rd most common cancer ( lung > breast >colon ), 2 nd most common cause of cancer death Risk Factors most patients have no specific risk factors ages > 50 (dominant risk factor in sporadic cases), mean age is 70 genetic: FAP, HNPCC, or family history of CRC colonic conditions adenomatous polyps (especially if >1 cm , villous, multiple) • IBD (especially UC: risk is 1-2%/ yr if UC >10 yr ) previous colorectal, gonadal, or breast cancer • diet ( increased fat, red meat , decreased fibre) and smoking • DM and acromegaly (insulin and IGF-1 are growth factors for colonic mucosal cells )

• • • •

Pathogenesis • adenoma-carcinoma sequence; rarely arise de novo Clinical Features • often asymptomatic • hematochezia / melena, abdominal pain, and change in bowel habits • others: weakness, anemia, weight loss, palpable mass, and obstruction • 20% patients have distant metastatic disease at time of presentation • spread direct extension, lymphatic, and hematogenous ( liver most common, lung, bone, and brain; tumour of distal rectum -> I VC -> lungs ) • peritoneal seeding: ovary and Blumer’s shelf ( pelvic cul- de -sac)

Table 22. Clinical Features of CRC Right Colon

Left Colon

Rectum

Frequency

25%

35%

30 %

Pathology

Exophytic lesions with occult bleeding

Annular , invasive lesions

Ulcerating

Symptoms

Weight loss, weakness, rarely obstruction

Constipation ± overflow (alternating bowel patterns), abdominal pain, decreased stool calibre, rectal bleeding

Obstruction, tenesmus, rectal bleeding

Signs

Fe- deficiency anemia, RLQ mass (10%)

BRBPR . LBO

Palpable mass on ONE. BRBPR

Investigations • colonoscopy ( gold standard ): look for synchronous lesions (3-5% of patients) if a patient is FOB!positive, has microcytic anemia, or has a change in bowel habits -»

-

colonoscopy

alternative: air contrast barium enema ( “apple core" lesion ) + sigmoidoscopy • laboratory: CBC, U /A, LFTs, CEA ( preoperative for baseline, >5 ng/ mL have worse prognosis ) • staging: CT chest /abdomen / pelvis; bone scan and CT head only if lesions suspected • rectal cancer: pelvic MRI or endorectal U / S to determine T and N stage Table 23. TNM Classification System for Staging of Colorectal Carcinoma ( AJCC/ UICC 8th

edition) Primary Tumour ( T)

Regional Lymph Nodes ( N)

Tx

Primary tumour cannothe assessed

Nx

Regional nodes cannot be assessed

M0

No distant metastasis

TO

No primary tumour found

NO

No regional node metastasisand no tumour deposits

M1a

Distant metastasis to 1 organ or site and no peritoneal metastasis

Tis

Carcinoma vns/fer , limited to intraepitbelial or invasive lamina propria

N1a

Metastasis In 1 regional node

M 1b

Distant metastasis to >1 (2 or more organs sites) and no peritoneal metastasis

Mic

Metastasis to peritoneal surface

T1

Invasion inlosubmucosa

N1b

Metastasis in 2- 3 regional nodes

12

Invasion into muscularis propria

H1c

No regional node metastasis: tumour deposits were submucosal, mesangial or peritoneum- covered para - colorectal tissue

T3

Invasion through muscularis propria and intopericolorectal tissues

N2 a

Metastasis in 4 - 6 regional nodes

T4 a

Invasion through visceral peritoneum

N2b

Metastasis in > 7 regional nodes

T4b

Invasion or adhorenl to other organs or structures

Distant Metastasis (M )

Figure 16. APR vs. LAR

5 Year Survival Rates for CRC >65 yr 20-64 yr Stage 95.2% 89.1% I 89.6% 84.4% IIA 67.6% IIB 55% IIIA 91.3% 851% 64.6% IIIB 76.9% 61.8% 45.5% INC IV 14.2% 7.4%

.

Preoperative vs Postoperative Chemoradiotberapyior Locally Advanced Rectal Cancer:Results of tbeCerman CAQ AR0 A1094 RandamiiedPhase III Trial after a Median Follow-Up of TIFr J Clin OncDl 2012;30:1925-1933 Background: fhe CAO ARO AI0-94 trial (pub listed 2004) recommeried preoperative chemoradiofieiapy (CR1) as standard treatment for localcy advanced rectal cancer.Hnwever,no survival benefit was shown after median follow -upoUEno and this study reports long -term effects. Methods: Patients with stage II to ill recal cancer (n-799) were ran do miy assigned tu preoperative (r 404|or postoperative CRI|n-395) with ftuorouracil |FU| rada’Jon and adjuvant FU chemotherapy,in addition to total mesorectel excision surgery,follow -up was designed to assess long-term overall sumalas the primary an dp omt and emulative incidence of localand distant relapses as well as disease-free survival as secondary endpoints. Results: ‘0 yr incidence of local relapse was significantly lower in the preoperative CRI group than in the postoperative group (11% vs.10.1% R*0.048). Overall survival at 10 yr was similar a: ruts preoperatve or “60% for patents treated postoperative CRI (P*0.85|. Disease-free sovival rates at 10 yr was similar a: 68 % for paten tineared with preoperatve or postoperative CRT (P'0.54).No significant difference was detected for 10 yr incidence of distant metastases (preoperatve CRI 29.8 % is. postoperative CRI 29.6% R'0.9). Conclusion laereis long- term reduction in local recunence of stage I! to IN rectal cancel wits pieoperatve chemotherapy, hut no improvement in overall survival or distant recunence of disease.

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Toronto Notes 2023

GS44 General and Thoracic Surgery Treatment • colon cancer • wide surgical resection of lesion according to vascular distribution and regional lymphatic drainage; usually colectomy with primary anastomosis curative: wide resection of lesion (5 cm margins) with nodes ( > 12) and mesentery care is taken to not spread tumour by unnecessary palpation adjuvant chemotherapy (oxaliplatin - based ) for stage 111 and is considered in select stage II

patients

palliative: if distant spread, local control for hemorrhage or obstruction • metastatic lesions confined to the liver can be resected with curative intent • rectal cancer • choice of operation depends on individual case LAR: curative procedure of choice if adequate distal margins ( ~2 cm ); uses technique of total mesorectal excision APR: if adequate distal margins cannot be obtained; involves the removal of distal sigmoid colon, rectum, and anus permanent end colostomy required transanal minimally invasive surgery ( TAM1S)- local excision for select T1 lesions only palliative procedures involve proximal diversion with an ostomy for obstruction and radiation for bleeding or pain combined neoadjuvant chemoradiation therapy followed by postoperative adjuvant chemotherapy for stages 11 and 111

-

Follow-Up

• stage 1: mixed recommendations; either routine colonoscopy or screening like stage 11 & ill • stage 11 & 111: regular follow-up q3-6 mo for 3 yr, then q6 mo until 5 yr, with regular measurement of serum (.'HA for at least 3 yr; annual CT chest/abdo/ pelvis for at least 3 yr; colonoscopy at 1, 3, and 5 yr • stage IV: no data on surveillance strategy

Other Conditions of the Large Intestine Angiodysplasia Definition • vascular malformation: focal submucosal venous dilatation and tortuosity

Clinical Features • most frequently in right colon of patients >60 yr • predisposition in end-stage renal disease, and VWD, and aortic stenosis • bleeding typically intermittent, rarely massive, and not usually hypotensive ( melena, anemia, and occult blood positive stools) • >90% of cases cease bleeding spontaneously Investigations

• colonoscopy: cherry red spots, branching pattern from central vessel • angiography: early filling vein, vascular tuft, and delayed emptying vein; rarely active bleeding • RBC technetium -99 scan • barium enema is contraindicated (obscures other x rays, i.e. angiogram )

-

-

Treatment • none if asymptomatic

• cautery, embolization, vasopressin infusion, sclerotherapy, band ligation, laser, octreotide, and rarely segmental resection if other treatments fail

Volvulus Definition • rotation of segment of bowel about its mesenteric axis • sigmoid (65%), cecum (30%), transverse colon (3%), and splenic flexure (2%) elderly >70 yr ( sigmoid ), adult 40 60 yr (cecal), and neonates and infants ( midgut) • 5 10% of large bowel obstructions; 25% of intestinal obstructions during pregnancy

-

-

Risk Factors • age (50% of patients >70 yr: stretching /elongation of bowel with age) • high fibre diet (can cause elongated/ redundant colon ), chronic constipation, laxative abuse, pregnancy, bedridden, and institutionalization (less frequent evacuation of bowels) • megacolon • intestinal bands/adhesions

Cecal Volvulus AXR: Central cleft of “coffee bean" sign points to RLO

-

r
3 cm , perineural invasion ( invasion of tumour into microscopic nerves of pancreas ) • overall 5 yr survival for all patients with pancreas cancer is 1%; following surgical resection 5 yr survival is 20% • median survival for unresectable disease: 3 6 mo if metastatic, 8 12 mo if locally advanced at presentation

-

-

Table 27. TNM Classification System for Exocrine Tumours of the Pancreas ( AJCC 8 th edition ) Primary Tumour ( T )

Regional Lymph Nodes ( N )

Distant Metastasis ( M )

TX

Primary tumour cannot be assessed

NX

Regional lymph nodes cannot be assessed

M0

TO Tis

No evidence ol primary tumour Carcinoma in situ

NO

No regional lymph node metastasis Metastasis in one to three regional lymph nodes

Ml

T1

Tumour :2 cm in greatest dimension

N2

Metastasis in four or more regional lymph nodes Tumour » 2 cm and s 4 cm in greatest dimension

T2

-

T3

Tumour > 4 cm in greatest dimension

T4

Tumour involves celiac axis SMA. or common hepatic artery

.

N1

No distant metastasis Distant metastasis

Steps of a Whipple Resection ( Pancreaticoduodenectomy ) 1. Assessment of metastatic disease ( all peritoneal surfaces) 2. Mobilization of the hepatic flexure of the colon 3. Mobilization of the duodenum ( Kochcr maneuver ) and head of the pancreas 4. Identification of the superior mesenteric vein and mobilization of the pancreatic neck 5. Mobilization of the stomach: dissection of the hepatoduodenal ligament and cholecystectomy 6. Division of the stomach , proximal jejunum, and CBD 7 Transection of the pancreatic neck and dissection of the uncinate process from the retroperitoneum 8. Restoration of gastrointestinal continuity: construction of a pancreaticojejunostomy, hepaticojejunostomy, gastrojejunostomy using a neoduodenum Remove

.

.

CBD • Gallbladder • Duodenum • Pancreatic head • Distal stomach (sometimes)

Oncological Benefits of Neoadjuvant Chemoradiation with Gemcitabine vs . Upfront S urgery in Patients with Borderline Resectable Pancreatic Cancer: t Prospective, Randomised, Open label Mullicenler Phase 2 /3 Trial Ann Surg 2018:268:215 222 Purpose: lo deter r e whether neoadjinant treatment increases survival in patients with borderline resectable pancreatic cancer ( BRPC ). Methods: A total of SO patients were randomized to neoadjuvant gemutabine- based chemoradiotherapy or upfront surgery. Results: Ihe 2 yr survival rate|2YSR|and median survival of patients tieated with ncoadiuvant chemoradiation was significantly improved ( 40.7% 2 YSR 21 mo median suivival ) compared to upfront surgery (26.1% 2YSR.12 mo median survival).Ihe RO resection rate was also significantly increased in the neoadjuvant chemoradiation group. Conclusion: Neoadjuvant chemoradiation provides survival and surgical benefits in patients with BRPC.

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GS63 General and Thoracic Surgery

Table 28. Staging and Treatment of Pancreatic Cancer 5 Yr Survival

Treatment Surgical resection t chemotherapy

.

m

13, NO. MO T1- 3, N1. M 0

12% 7% 5% 3%

Same as above Same as above Same as above

Stage 0

Classification

IA

11, NO MO 12 , NO. MO

Tis, NO. MO

IB

IIA I IB

. .

III

11-3 N2 MO 14, any N, MO

IV

anyI anyN M1

.

.

Same as above Borderline resectable, trial ol chemotherapy and radiation

-

1%

Mon resectable, palliative treatments

Lett and right hepatic ducts ontmon hepatic

duct

Stomach Liver

Gastrojejunostomy

Gallbladder

-Tail of pancreas

Cystic duct

Pancreas

CBD Ampulla of Vater

Pancreatic duct

Hepaticojejunostomy

Pancreaticojejunostomy

Duodenum Jejunum

Resected portion

.

© Natalie Comiier 2015 after Caitlin O'Connell

Figure 26. Schematic of Whipple resection showing the resected components

Spleen Splenic Trauma Clinical Features

-

• most common intra abdominal organ injury in blunt trauma (especially can occur in people with

splenomegaly ) • may have Kenr’s sign

-

patients may be hemodynamically unstable with altered mental status • initial presentation may be masked by other injuries and contained ruptures may have few symptoms

Kehr’s Sign Left shoulder pain due to diaphragmatic irritation from splenic rupture, worsens with inspiration

Investigations

• FAST' (used in trauma with hemodynamically unstable patients)

-

• CT with oral or IV contrast (once stable or when l'AST negative)

Treatment

-in stable patients: extended bed rest with serial hematocrit levels, close monitoring for 3-5 d;

• non operative

paediatric guidelines for days of bed rest is grade plus 1 (i.e. grade 3 splenic laceration requires 4 d of bed rest )

hemostatic control

• splenic artery embolization if patient stable and one of: active contrast extravasation , splenic pseudoaneurysm, hemoperitoneum

• operative

•

hemodynamically unstable patients with positive FAST will undergo emergent operative surgical exploration splenorrhaphy (suture of spleen ) ± splenic wrapping with hemostatic mesh ( if patient is

•

splenectomy if patient unstable or high-grade injury or ongoing bleeding with hemodynamic instability packing the spleen with temporary abdominal closure and relook laparotomy in 48 h

+

hemodynamically stable)

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Toronto Notes 2023

GSM General and Thoracic Surgery

Splenectomy Indications

• splenic trauma ( most common reason for splenectomy ), hereditary spherocytosis, primary hypersplenism, chronic immune thrombocytopenic purpura (1TP), splenic vein thrombosis causing esophageal varices, splenic abscess, thrombotic thrombocytopenic purpura ( TI P), and sickle cell disease • does not benefit all thrombocytopenic states (e.g. infection, most malignancies involving the bone marrow, drugs/toxins) • probability of cure of IIP by splenectomy is 60 70%, maybe predicted by response to 1VIG

-

Complications

• short- term

injury to surrounding structures (e.g. gastric wall, tail of pancreas) and their vascular supply postoperative thrombocytosis, leukocytosis thrombosis of portal, splenic, or mesenteric veins

Indication of Splenectomy SHIRTS Splenic abscess/splenomegaly Hereditary spherocytosis Immune thrombocytopenic purpura Rupture of spleen Thrombotic thrombocytopenic purpura Splenic vein thrombosis

subphrenic abscess

• long- term post-splenectomy sepsis (encapsulated organisms ): 4% of splenectomized patients ( highest risk < 16 yr ) splenosis: intra-abdominal “seeding" of splenic tissue during removal increased risk of malignancy, DVT, and PH

• 50% mortality

Prophylaxis

-

• vaccinations, ideally 2 wk pre or postoperative ( pneumococcal, H. influenzae, and meningococcus) • liberal use of penicillin especially in children 30 yr, menarche 55 yr decreased risk with lactation , early menopause, and early childbirth >5 yrHRTuse, > IOyrOCPuse breast density high • • radiation exposure (e.g. mantle radiation for Hodgkin’s disease) • BRCA 1 and BKCA 2 gene mutations • alcohol use, obesity, and sedentary lifestyle Male Breast Cancer (1 cm and low nuclear grade Mastectomy * » SLMB 8CS * axillary node dissection •radiotherapy Mastectomy * ’axillary node dissection / SIN 6

Consider postoperative tamosilen lor ER * Iraslurumab lor HER 2 *

.

I IA: T1 MO MO IB: 11, N1 ml , MO

. .

BCS > axillary node dissection * radiotherapy Mastectomy * axillary node dissection /SLNB

II

A:10. N1. M 0 11. N1, MO 12 NO MO 8: 12 N1, MO 13 NO MO III A:10. N 2. M 0 11. N 2, MO 12 N 2 M 0 13 N1 M 0 13 N 2. MO 6: 14, NO , MO 14 N1 M 0 I4 N 2 M 0

. . . . . . . . . .

-

likely mastectomy axillary node dissection + radiotherapy after chemotherapy ( neoadjuvanl)

. .

-

.

May not be needed ; discuss rislrs / benelits of chemotherapy and tamoxifen Chemotherapy lor premenopausal women or postmenopausal and ER negative, followed by tamoxifen if ER

-

Neoadjuvant therapy should be considered ( i.e. preoperative) especially if not resectable chemotherapy and/or hormone therapy. Adjuvant radiation and chemotherapy may also be appropriate ( i .e. postoperative)

. .

Mastectomy * axillary node dissection radiotherapy Surgery as appropriate lor local control

Inflammatory

IV any 1, any N Ml

-

.

Neoadjuvant therapy

Primary treatment Is systemic therapy ( i.e. chemotherapy ) and / or hormone therapy

BCS breast conserving surgery : SLNB •sentinel lymph node biopsy 'll no reason to select mastectomy, the choice betwvcn BCS •radiotherapy and mastectomy can be made according to paUenl s preference since choice ol local treatment does not significantly affect survival If local control Is achieved

PRIMARY SURGICAL TREATMENT Breast Conservation Surgery ( BCS) • lumpectomy must be combined with radiation for survival equivalent to mastectomy

• contraindications include • high - risk of local recurrence ( e.g. extensive malignant - type calcifications on mammogram ), and multifocal primary tumours failure to obtain tumour-free margins after re-excision not suitable for radiation therapy ( pregnancy, previous radiation, and collagen vascular disease ) • large tumour size relative to breast

BCS can be offered to most women with stage I/ll disease

There is no survival benefit of mastectomy over lumpectomy plus radiation for stage I and II disease

Mastectomy

• radical mastectomy ( rare ): removes all breast tissue, skin, pectoralis muscle, and axillary nodes • modified radical mastectomy ( MRM ): removes all breast tissue, skin, and axillary nodes • simple mastectomy: removes all breast tissue and skin • see Plastic Surgery. PL38 for breast reconstruction Sentinel Lymph Node Biopsy (SLNB ) • performed in women with clinically node- negative invasive breast cancer and those with extensive

DGIS who are undergoing mastectomy • patients with clinically suspicious nodes should get U /S i I NA prior to decision to proceed with SLNB • technetium 99 ± blue dye injected at tumour site prior to surgery to identify sentinel node( s) • intraoperative frozen section evaluated can be considered • proceed with A 1.N 1) if >3 positive nodes, with 1 3 nodes whole breast radiation therapy maybe an '

-

alternative • 5% false negative rate

-

Axillary Lymph Node Dissection ( ALND) • perform in patients with: locally advanced (T4a, b, c) or inflammatory breast cancer clinically node- positive axilla, confirmed by IN A or core biopsy, in a patient for whom neoadjuvant chemotherapy is not planned • several other specific cases (sentinel or axillary nodes, which remain positive after neoadjuvant chemotherapy, axillary recurrence following previous breast cancer treatment, among others) • side effects: risk of arm lymphedema (10 -15%), especially if getting radiation therapy, decreased arm sensation , and shoulder pain

Effect of Radiotherapy after Mastectomy and Axillary Surgery on 10 Tear Rccurience aad 20 Yeai Breast Cancer Mortality: Meta Analysis ol Individual Patient Data for 8135 Women in 22 Randomised Trials EBCICG ( Early Breast Cancel lilalists' Collaborative Group) lancet 2014; 383|993S|: 2127 - 2135 Study: Assessed the elied of radiotherapy lungs > pleura > liver > brain • treatment is palliative: hormone therapy, chemotherapy, radiation • overall survival of metastatic breast cancer is 36 - 60 mo

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GS71 Genera! and Ihorack Surgery

Toronto Notes 2023

Surgical Endocrinology Thyroid and Parathyroid • see Endocrinology. E24

Thyroidectomy • indications: some thyroid cancers or suspicious thyroid nodules, metastases to thyroid, large (substernal ) or symptomatic thyroid goitre , toxic nodules , or some patients with Graves’ disease ( not candidates for RA1) • preoperative workup: thyroid U /S for thyroid nodules, ENA for nodules > 1 cm with suspicious U /S features or for most nodules > 1.5 cm with low suspicion U /S features, and Cl' neck for preoperative staging when advanced disease is suspected • complications

• lobectomy: recurrent laryngeal nerve palsy ( hoarseness or swallowing issues ), neck hematoma total thyroidectomy: same as above plus hypoparathyroidism /hypocalcemia, bilateral RLN palsy ( requiring tracheostomy ) 20-75% of patients need thyroxine after lobectomy and 100% need thyroxine after total

thyroidectomy Parathyroidectomy • elevated calcium found for any reason as an outpatient ( but also incidental finding as inpatient ) is

likely primary hyperparathyroidism and should be investigated further • indications: symptomatic primary hyperparathyroidism (osteoporosis/stones), asymptomatic primary hyperparathyroidism with specific laboratory criteria ( profoundly elevated serum Ca 2+, hypercalciuria/asymptomatic kidney stones, Cr clearance < 30% normal, metastases to adrenal (22%) » cyst carcinoma pheochromocvtoma, ,

neuroblastoma •metastasis to adrenal gland from: lung > breast, colon, lymphoma , melanoma, and kidney •peak incidence of carcinoma: females ages 50 -60, risk decreases with increasing age and male gender

Investigations •CT: size >4-6 cm is best predictor of primary adrenal carcinoma (92% are >6 cm), MRI is not as good as CT and does NOT need to be done after CT •functional studies pheochromocvtoma: plasma metanephrines ( highly specific and sensitive). If not available, 24 h

urine catecholamines Cushing’s: 24 h urine cortisol or 1 mg overnight dexamethasone suppression test • aldosteronoma: electrolytes, AM aldosterone, AM plasma renin activity level, ARR ( AldosteroneRenin - Ratio). If inconclusive, saline suppression test if appropriate not routinely - only if clinical suspicion: adrenal androgens: 17-OH progesterone and dehydroepiandrosterone ( DHEAS ) • ENA biopsy: NO T APPROPRIATE in most cases. Diagnostic adrenalectomy by high volume endocrine surgeon ideal if diagnostic uncertainty

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Treatment

• functional tumour: resect • non-functional tumour > 4 cm: consider resection • 1 cm enlargement genetic testing important for ALL Pheochromocytoma/ paragangliomas as >30% are related to genetic syndrome

-

Pancreas INSULINOMA

• tumour that secretes insulin

• most common pancreatic endocrine neoplasm; 10% associated with MENI syndrome Clinical Features

• Whipple's triad

• palpitations, trembling, diaphoresis, confusion, seizure, and personality changes Investigations • blood work: decreased scrum glucose and increased serum insulin and (.' peptide, pro insulin • CT, HUS, MKI: insulinomas evenly distributed throughout head, body, tail of pancreas

-

-

o

Whipple's Triad • Symptomatic fasting hypoglycemia • Serum glucose 2 cm located close to the pancreatic duct may require pancreatectomy or pancreaticoduodenectomy GASTRINOMA • tumour secreting gastrin; cause of Zollinger-Ellison syndrome, associated with MEN1

Clinical Features • abdominal pain, PUD, severe esophagitis • multiple ulcers in atypical locations refractory to antacid therapy Investigations • blood work: serum gastrin levels (usually >1000 pg/ mL), secretin stimulation test • endoscopy: 90% of patients develop peptic ulcers • CT, EUS, MRI: 70-90% found in Passaro’s triangle ( head of pancreas medially, 2 nd portion of duodenum inferiorly, and the confluence of the cystic and CBD superiorly) • somatostatin receptor scintigraphy scan

Relief of symptoms when glucose is administered

-

Zollinger Ellison Syndrome Characterized by gastric acid hypersecretion caused by secretion of gastrin from gastrinomas: patient experiences diarrhea and abdominal pain, as well as peptic disease and reflux disease

Hypertrophic Pyloric Stenosis Non bilious emesis in infants is the classic presentation

-

Treatment

• 50% are malignant • surgical resection of tumour dependent on location • non - surgical treatment: high dose PPI, octreotide ( somatostatin analogs) • radiation therapy may be considered for nonsurgical candidates VASOACTIVE INTESTINAL PEPTIDE- SECRETING TUMOUR

• tumour secreting VIP; commonly located in the distal pancreas and most are malignant when diagnosed Clinical Features

• severe watery diarrhea causing dehydration , anorexia , weakness, and electrolyte imbalance ( hypokalemia )

Rule of 2s for Meckel's Diverticulum • 2% of the population • 2:1 male-tofemale ratio • Symptomatic in 2% of cases

.

-

Found within 2 feet (10 90 cm) of the ileocecal (1C) valve • 2 inches in length • 2 inches in diameter • 2 types of tissue (ileal or ectopic gastric, pancreatic) • Often present by 2 y/o

Investigations

.

• blood work: serum VIP levels CT, MRI, EUS Treatment

• repletion of fluid and electrolytes • somatostatin analogues • surgical resection/ palliative debulking

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GS73 General and Thoracic Surgery

Toronto Notes 2023

Paediatric Surgery Condition

Epidemiology and Pathophysiology Risk Factors

Clinical Features and History

Hydrocele

t-2%of live bvths

Painless scrotaI mass Communicating hydroceles increase in sire with standing or valsalva,may be absent in the morning and large in the evening

. U32)

(seetl'ology

Majority resolve spontaneous bylyr

MF-61

Prematurity

Hypertrophic Pyloric Stenosis

0.031.Che of live births Can present at I 20 wk most commonly at 6 8 wk M: F -4:1 Early erythromytin exposure (*13 d old)

.

Communicating hydroceles: processus vaginalis connects peritoneumwithtunica vaginalis, so peritoneal fluid flows freety between the two with potential for abdominal contents to enter groin (Le. inguinal hernia) Noncommunicating hydroceles: processus vaginalis isclosed and more fluid produced than absorbed in tunica vaginalis: in older children, may be secondary to testicular pathology (e.g.reactors hydrocele)

Physical Exam Investigations

Treatment

Prognosis

Transiilummalion

U/ S if suspect pathology

Most resolve spontaneously bylyr Surgical repair if: Persistence »2 yr Pain Fluctuating in sire which suggests communication Cosmetic reasons Infection

*2% recurrence

Electrolytes (assess hypochloremia. dehydration) U/S shows pyloric length 17 mm musde thickness >4 mm UpperGI series

Fluid resuscitate with NS correct electrolyte and acid,1 base abnormalities with OS V 2MS * 20 mEqil KCI at

Prenatal USMRI ABO CXR (bowel loopsin hemithorax. shifted heart) Echocardiography Genetic consultation if warranted

Intubatei'ventilate

AXR Meckel scan:scan for ectopic gastric mucosa with technetium Tc99m pertechnctate IV (sensitivity 85% specificity 95%)

Stabilize, resection by

AXR: obstruction

tv antibiotics Fluid resuscitation EMERGENUAPAROfOMYLadd procedure:counterclockwise reduction of midgut volvulus, division of Ladd's bands, division of peritoneal

suggests hydrocele

Silk glovesign: gently pupating hydroceiesac overpubic tubercle feels like rubbing silk on silk

Acquired pyloric circular Projectile non-bilious Smooth oblong muscle hypertrophy results in vomiting T2 cm “olive" gastric outlet obstruction Vomiting 30 - 60 min mass palpable Hypovolemia caused by emesis after feeds above umbilicus ol gastric contents causes Hungry after vomiting intheSUQ hypochloremic, hypokalemic Dehydration ( variable Visible left toseverity) metabolic alkalosis right gastric Electrolyte exchange based contraction volume retention in kidneys “waves" after results In paradoxical acitfciria feeding

.

Congenital Diaphragmatic Hernias 3 types: Posterolateral (Bochdalek) Left-sided (85%) Right -sided (13%) Bilateral, rare, often fatal

1 in 2000 to 5000 live Combinations of smal bowel births large bowel, stomach,and Presents vnthn hours solid viscera (spleen,liver) may of life although some herniate into thorax cases of delayed presentation Varying de grees of puhnonary M-F hypoplasia and pulmonary »10 are associated hypertension possible = with other congenital

Anterior IMorgagm)

common

Early respiratory

Decreasedair

distress Cyanosis Scaphoid abdomen Prenatal diagnosis

entry r bowel sounds in the

BRBPR (heterotopic gastric mucosa in Meckel'scausing mucosal ulceration and bleeding in adjacent small bowel mucosa) Abdominal sepsis (Meckel’s diverticulitis ± perforation)

Tenderness and distension (lower abdomen) near umbilicus

chest (hsp acedheart ’ sounds

.

anomalies Prenatal diagnosis

1-3% of population M:F 3:1 Present most frequently during first 5 yr of kfe Symptomatic m 2%

-

of cases

Failure of vitelline duetto regress 5 -7 wkrncrfero: 50% contain heterotopic tissue (e.g. gastric mucosa ectopic pancreas): other associated anomalies include omphalomesenteric fistula umbilical sinus,umbilical cyst and fibrous band

.

.

Pytoromyotomy curative

.

maintenance rate

NG lube decompression unnecessary (necessary only when Pyloromyotomy, open U/S is unavailable or (Ramstedt vs. tiansumbilical or laparoscopic approach) isthe non-diagnostic) will definitive treatment show “string sip" Alternative therapies such as IPR wait or atropine impractical due to long time course of effect

Hiatus

Meckel's Diverticulum Most common remnant ol vitelline duct that connects yolk sac with primitive midgut

.

Orogastric suction Period of respiratory stabilization due to associated pulmonary hypoplasia (may

Better outcomes in later presentations Neurodevelopmental impairment

Hearing defrat (40%) require extracorporeal Assocated GERD MSKdefects chest wall membrane oxygenation) andscoliotic defects as Scxgical repair after stable by hernia reduction and closure ol potenbal complications diaphragmatic defect open vs. of thoracotomy thoracoscopic vs. laparoscopic long- term surveillance for potential recurrence nth or without prosthetic or Fibre to thrive muscular patch depending on sice of defect Chronic lung disease if severe hypoplasia

Resection curative

laparotomy or laparoscopy t incidental appendectomy

.

Small bowel volvulus around fibrous band Intestinal obstruction symptoms

Matrotation

1:500 live txrttis 1/ 3 present by Ink ofage. 34 by 1mo of age.90% bylyr of age M:F-1:1

failure of gut lo normally rotate around SMA with associated abnormal intestinal attachments and anatom positions Represent a spectrum of rotational abnormalities Higher incidence among patients with including complete noncardiac anomalies or rotation (which Is not at heterotaxy syndromes high risk (or volvulus)

*

-

Cardinal sign: bilious emesis (especially rlabdomen nondistended) If bilious emesis with distended abdomen consider surgical

.

exploration to rale out volvulus Rectal bleed (late/ ominous signs)

Intermittent symptoms

Bilious drainage from NG tube Tachycatdic.pale

Diaphoretic

Flat abdomen Tenderness

.

of proximal S80 double-bubble

sign, intestinal wall thickened Immediate UGt dilated duodenum, duodenojejunal segment (Ligament of Treitz) right of midline and not fixed posteriorly over spinal column, “corkscrew" sign indicating volvulus U/S: “whirlpool" sign, abnormal SMA SMV relationship indicates UGI to rule out rotational anomalies

attachments between cecum

Mortality related to length of bowel loss: W% necrosis 100% survival rale.75% necrosis 35% survival rate Recurrence 2 6%

-

and abdominal wall that obstruct duodenum, broadening of themesentery (open folded mesentery likea book and dhnde congenital adhesions),r appendectomy Positioning the bowel into nonrotation (SB0 in right abdomen. LS0 in left abdomen)

rm

u J

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Toronto Notes 2023

Condition

Epidemiology and Pathophysiology Risk Factors

Clinical Features and History

Physical Exam Investigations

Treatment

Prognosis

Gastroschisis

1:2000 live births Antenatal diagnosis

Hot associated with genetic syndromes

Hollow viscera Prenatal U/S |slomach small Elevated MS AFP and large bowels)

NG lube decompression IV fluids IVanlibiotics Keep viscera moist and protected until surgical

>90% survival rale

common

Increased risk with younger maternal age andassodated with IUGR Rate slightly higher in male infants Smoking

Omphalocele

Delect of abdominal wall near umbilicus, with free extrusion of intestine intoamniotic cavity No specific environmental factor identified Defect in embryogenesis unclear

Defect of abdominal wall and 1:5000 live births umbilical ring, with extrusion Antenatal diagnosis of sac-covered viscera (amnion, common Lower gestational age Wharton’s jelly,peritoneum) through the umbilical ring Increased maternal Duhamel's theory failure of III MF -1 5 :1 body wall morphogenesis

Commonly associated with rotational abnormalities of the intestine Umbilical Hernias

Incidence 2-14% Increases with prematurity Decreases with Increasing age

Cryptorchidism

to cord (usually

associated with short bowel syndrome due to antenatal volvulus andnecrosisof herniated bowel

right) Bowel may be inflamed, thickened mailed, foreshortened Defect siie variable

reduction with primary abdominal closure or staged closure with silo May have bowel dysmotility requiring motility medications

30 - 70% associated with genetic syndromes (e.g. Pentalogy of Cantrell, congenital heart disease, Beckwith Wiedemann syndrome, fnsomy 18) Associated pulmonary hypoplasia

Hollow viscera Prenatal Ur’S (stomach,small Elevated MS AFP and large bowels, often liver) Sac present with cord attached

NG tube decompression IV fluids,IVanlibiotics Small defect [4 cm) defects: silver sulfadianne coupled with compression dressing (toallow eptlhelialitation and gradual reduction) or Silon Silo Pouch, followed by future repair tmesh

40 - 70% survival rate Higher survival rales most likely related to antenatal mortality of fetuses with giant omphaloceles

Repair if not spontaneously closed by age 5 Earlier repair of large “ptoboscoid" hernias with extensive skin stretching may be warranted lor cosmetic

Rarely become incarcerated Low risk of recurrence

.

determines chances ol spontaneous closure

Incidence 2 -14%

Duodenal failure ol bowel to

Gastric distension

May be antenatally diagnosed by dilated bowelloopsor ‘‘double-bubble" sign on x- ray for duodenal

recanabre after endodermal epithelium proliferation (wk 8-10) Jejunal/ileal acquired as a result of vascular disruption » ischemic necrosis * resorption of necrotic tissue •blind distal and proximal ends Colonic mechanism unknown, Ihoughl lobe similar to small bowel atresia

and vomiting (usually bilious) Duodenal maybe associated with other anomalies (tracheoesophageal fistula, cardiac renal, and vertebral anomalies) 24- 28% have Down syndrome Jejunal/ileal within 2 d of birth,may be associated with CF Colonic within 3 d of birth

atresia Decreased with increasing age

Congenital Aganglionic Meirschsprung's Disease

Delect lateral

Protrusion from None if uncomplicated umbilicus Different from spontaneously resolve less common by age 4 abdominal wall Incarccralionpriorlo herniasthaldo ageSveryrarc not spontaneously Mostsymptomsoccur resolve (e.g. in late adolescence or epigastric hernias) adulthood Most defects >1.5 cm in infancy will not dose spontaneously

Incomplete closure of peritoneal and fascial layers within umbilicus by 4 yr Hernia is peritoneum lined and skin - covered

-

Sire of fascial defect

Intestinal Atresia

10% with intestinal atresia Some cases

.

-

Majority asymptomatic Majority (95%)

.

.

Complete physical Conlrasl enema $ Special attention UGI with small bowel follow through (S8FI) to abdominal exam,perineum Group and screen andanus INR and PIT if for Include evaluation surgery of respiratory distressand signs ol volume depiction Congenital anomalies Jaundice

.

Deled in migration of neurocrcst cells to intestine resulting in aganghomc bowel that (ails to perislalseand internal sphincter that fails to relax (internal anal sphincter bowel as well achalasia) causing functional Familial and partial mechanical Hirschsprung's in 1yr ) For incarcerated hernia: repair where exam can be immediately (emergency) difficult) Herniorrhaphy (laparoscopic or open) definitive treatment by reduction of herniated contents and high ligation of sac for indirect hernias

..

Risk of recurrence after surgical reduction 80 yr) •in the elderly, chronic constipation may present as fecal impaction and overflow diarrhea Etiology

• neurological: dementia • metabolic: hypercalcemia, hypothyroidism , hypokalemia • nutritional: low dietary fibre, dehydration •drugs association with constipation:

• OiC

opioids psychotropics (e.g. antipsychotics, TCAs ) anticholinergics (e.g. dimenhydrinate, diphenhydramine, TCAs, antimuscarinics for urinary incontinence)

calcium channel blockers diuretics supplements (e.g. iron, calcium ) Pathophysiology

• impaired rectal sensation ( increased rectal distention required to stimulate the urge to defecate)

•colorectal dysmotility Alarm Symptoms

•fever •blood in stool •severe nausea / vomiting, severe abdominal pain

•abdominal/rectal mass • unintentional weight loss •obstipation • new changes in bowel habits when age >50 yr • unexplained anemia or iron deficiency on blood work Treatment • non - pharmacological bowel training » increase fibre intake ( note: bulking agents, e.g. psyllium, Metamucil*, may worsen constipation in some)

• ensure adequate fluid intake • increase physical activity • pharmacological

• see f igure I • discourage chronic laxative use

review medication regime, reduce dosages or substitute •see Common Medications, GM 17

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GM5 Geriatric Medicine

Chronic Constipation

{

NO

j

.

Fecal Impaction

YES

4 Remove constipating medications (if possible) Increase fluid intake Increase activity or exercise 4 Increase fibre intake ( 20-30 gfd) Start Urned toilet training

Perform manual disimpaction Use enemas and/ or suppositories Start bowel regimen to prevent recurrence

Milk of magnesia Lactulose Peg Lyte Senna compounds Bisacodyl

-

-

YES

i

Continue regimen

^

4 Continue regimen

.

NO

Effective

i

polyethylene glycol (PEG3350 high dose)

j

YES

Effective

j n

’

Lubiprotone

A Double - Blind Placebo- Controlled Study of Prucaloprido in ildorly Patients with Chronic Constipation Neurogastioenteiol Hotil 2010:22(91991 98 Purpose: lo assess the efficacy, safety, and tolerability of prucalopride in chronically constipated elder ty patients. lesults / Conclusions Ire prucalopnde dose range tested (1-4 mg duly) is effective at promoting bowel movements, nunmiiiing constipation - associated symptoms,and nptonng quality of life. It Is safe and well tolerated in elderly patients wtb chronic constipation.

NO

I Biofeedback therapy Idyssynergic defecation)

the Effect of Probiotics as a Treatment for Constipation in the Elderly: ASystematic Review

Arch GerontolGeriatr 2017:71:142 49 Purpose : Evaluate the effectiveness of probiotxs m treating elderly constipation, as an alternative to traditional dug based tieatments. Results Conclusions Analysis of placebo controlled RCIs suggested that administration ol probiotics significantly impioved constipation in the elderly by 10 AO1i compared to placebo further trialsare requited to elucidate optimalprotocols of probiotic treatment regimens. ,

Alvimopan Methylnaltrexone opioid-induced constipahon)

Figure 1 Treatment algorithm for the management of chronic constipation in older adults

-

Adapted from: Clin Interv Aging 2010:5:163 171

Delirium • see Psychiatry. PS23 and Neurology. N 21 Definition • acute and potentially reversible disturbance in cognition, attention, or level of consciousness

Epidemiology • delirium is especially common among patients in the 1CU setting, postsurgical setting, and general medical setting • up to 25% of patients after elective surgery 50% of patients after high - risk procedures (e.g. cardiac surgery, hip-fracture repair ) up to 75% of mechanically ventilated patients in the 1CU • can affect all ages but is especially common in hospitalized older adults one- third of general medical patients >70 yr have delirium

Screening/ Diagnostic Tools • screened using the Confusion Assessment Method: delirium likely if 1 + 2 and either 3 or 4 are present 1 . acute onset and fluctuating course 2. inattention 3. disorganized thinking 4. altered level of consciousness •classified as: hyperactive, hvpoactive, or mixed

Differential Diagnosis •3 Ds ( dementia , delirium, depression ) can present with overlapping cognitive changes

Delirium in Older Persons: Advances in Diagnosis and treatment JAMA 2017:318(12):1161-74 Purpose: To provide overview of current state of diagnosis and treatment of delirium and identify prom sing areas for future research Methods:Controlled vocabulary and keyword terms were sea abed in Ovid MEDLINE Embase and the

Cochrane Library with focus cn studies conducted In elderly populations. Results:127 articles met inclusion criteria.High sensitnrity and specificity brief screening tools and measures of delirium sererity contribute to ability fo if agnose.Heat risk stratify, and prognosticate patents. Honphatmacologic approaches are effective for delirium prevention and retommeeded for dehriumtreatment. Pharmacologic treatment (antipsycbotics other sedatives) for agitation should only be used if the patient is at safety risk fo thniselns oi others or is impeding medical treatment oltbe underlying cause. Condusioa: Better screening and diagnosis of dehrium leads to bettei nsk stratification. Nonphamucotogic approaches of delirium prevention are effect re whereas pharmacological management o!delmum is controversial.

.

..

An Approach to Delirium: “ DIMS- R ” • D: drugs (consider prescribed, over the counter, overdose, intoxication, and withdrawal ) •I: infection (consider urinary tract, lungs, skin, bacteremia ) •M: metabolic disturbances ( consider fluid imbalances, electrolyte abnormalities, nutritional deficiencies) •S: structural insults ( cardiovascular, CNS, pulmonary, Gl ) • R : retention ( urinary retention, constipation )

Work-Up

+

• work - up is not universal and depends on possible causes based on history and physical exam : drugs, toxins, withdrawal: medication review, substance use history • infection, infarction, inflammation: CBC, urinalysis, urine culture, blood culture, CXR, EGG, troponin, creatinine kinase

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GM6 Geriatric Medicine

Toronto Notes 2023

metabolic: basic and extended electrolytes, vitamin Bt ’, TSH , LI T, toxicology screen, glucose, arterial blood gas / venous blood gas , creatinine structural: neurologic exam, CT head Delirium Prevention in Older Adults •ensure optimal vision and hearing to support orientation (e.g. appropriate eyewear and hearing aids ) • frequent reorientation techniques • family visitation

• maintaining a routine in prolonged hospital stays •ensure adequate dentition •adequate pain management • provide adequate nutrition and hydration (up in chair to eat and drink whenever feasible ) •encourage regular mobilization to build and maintain strength, balance , and endurance • avoid unnecessary medications and monitor for drug interactions •avoid bladder catheterization

•ensure adequate sleep at night and wakefulness during the day

Table 2. Differentiating the Three Ds of Cognitive Impairment Depression

Dementia

Delirium

Onset Duration

Gradual or step - wise decline

Aculc (hours todays)

Subacule ( weeks to months)

Months to years

Days to weeks

Variable

Natural History

Progressive , usually irreversible

Fluctuating, reversible High morbidily/morlalityin very old

Recurrent, usually reversible

Level of Consciousness

Normal

Fluctuating

Normal

Attention

Intact initially

Impaired , difficulty concentrating

Orientation

Intact initially

Impaired, fluctuating

Intact

Behaviour

Oisinhibition. loss of ADlitADLs. personality change

Severe agitation/retardation

Importuning, self - harm/suicide

Psychomotor

Normal

Fluctuates between eitremcs

Slowing

Sleep - Wake Cycle

Fragmented sleep at night

Reversed sleep - wake cycle

Early morning awakening

Mood and Affect

Labile, flattened , apathetic

Anxious, irritable, fluctuating

Depressed. stable

Cognition

Chronic , gradually progressive

Fluctuation preceded by mood

Impdired concentration

decline in cognilion Domains impacted depend on dementia subtype

changes Inattention

Memory Loss

Short term memory impairment

May have impaired short - term

Possible impairment in episodic

is predominate in Alzheimer 's dementia

memory

memory

Evidence on Management of Delirium: see “Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review” • see “ Delirium in Older Persons: Advances in Diagnosis and Treatment" •

Elder Abuse Definition includes physical abuse, sexual abuse, emotional / psychological abuse , financial exploitation, and neglect • elder abuse is a criminal offence under the Criminal Code of Canada and in most EJ . S. states

Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review A nn Intern Med 2019 :1)1:435-95 Purpose Eviluile willi current literature the risks and benefits of antipsyctiotics in delirium management hosp . tal zed adults. Study Selection: KIs of antipsychoticvs. placebo 01 another antipsychotic , is well as prospective observational studies that report barms, ate selected through searches on PuSMed. Embase, CENlltAl, CINAHL. and PsytIHFO from inceptron to July 2019. the review selected 16 RCtsard 10 observat onal studies ofhospitalired adults. Data Synthesis: No significant difference m sedation, delirium, hospital length-of-stay. or mortality between haloperidol and second- generation antipsychotics vs. placebo. No difference In modality m direct comparisons between second- generation antipsychotics. While shortterm use ofantipsychotics lor delirium managementdoes not appear to pose neiiiotogicalhatm , it posesa risk of 01 protongalion. Conclusion . Ire current evidence does not suppoit the routine use ol haloper dot or second-generation antipsychotics in delirium management for adult inpatients.

tldcr Abuse Prevalence inCommunity Settings: A Systematic Review and Meta - Analysis lancet Glob Health 2017:5:117- 56 Purpose: Snce quantitative syntheses of elder abuse prevalence are raie. the study aimed to quantity and understand prevalence variation at global and regional levels. Methods: A comprehensive search strategy from M databases was employed to identity elder abuse prevalence studies in the community, published from inception to June 2015. Subgroupana lysis and meta regression were used to eiptore heterogeneity. Results: 52 of the 38544 in t ally identified studies were eligble loi inclusion, all of wh ich were geographically diverse (28 countries). The pooled prevalence estimates werelt.6% for psychological abuse. 6.8 % for financial abuse. 4.2 % lor neglect. 2.6% lor physical abose. and 0.9% lorseiual abuse. Significant heterogeneity was found in associations with overall prevalence estimates, including sample size, income classification , and method of data collection, but not with gender. Conclusion tldei abuse isa neglected pubk health priority, especially compared with other types of violence. Elcder abuse seems to affect 1in 6 older adults worldwide, a figure totaling 141 million people .

•

Epidemiology • in Canada in 2019, almost 4518 seniors were victims of police - reported family violence • the perpetrators of family violence against seniors were identified to be their grown child ( 34% of cases) and their spouses ( 26% of the cases ) • in older adults > 60 yr, elder abuse is estimated to occur in 10% of patients • insufficient evidence to include/ exclude screening in the Periodic Health Exam Risk Factors Table 3. Risk Factors for Elder Abuse Situational Factors

Social

Victim Characteristics

Physical or emotional dependenceon caregiver

lack of close family lies History ol family violence Dementia or recent deterioration in health Perpetrator Characteristics

Related to victim Dependency on older adult (e .g. financial dependency )

Elder Abuse Screening tools: A Systematic Review J Adult Prot 2017:19:368 )9 C ontext and Purpose: Wrth high rates of morbidity and mortality, along with deleterbos psychological harms, elder abuse is often difficult to detect this study seeks to review currently available elder abuse screening tools. Results: 11 of 34 full text studies met inclusion criteria and weie included « the final analysis. 01 these, three studies reported sensitivity and specificity while the remainder reported validty and reliability testing. Ultimately, the dinical environment will dictate the choice ol screening tool , limitations Ydiiatior.s n tool qualitiesand characteristics led to challenges in data synthesis. A further challenge was the lack of a gold standard screen ing tool (or elder abuse, for evaluation of heterogeneity. Conclusion Research on screening tools remains hard-pressed in distinguishing those assessing suspected or actual elder abuseard those assessing risk lactorsfor abuse. Allhough screening tools cany inherent Imitations, they can be used to guide luithei assessments lor an object,- diagnosis. ,

+

*

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GM 7 Geriatric Medicine Screening Tools

• Elder Abuse Suspicion Index © ( EASI©): a six-item questionnaire to raise a physicians level of

suspicion for elder abuse and promote referral of possible victims for further assessment by social

services

Management • assess patient’s decision

EASI For each of the 6 Items below, indicate “yes " “no " or “did not answer." A response of “yes" on 1+ of questions 2-6 is concerning for elder abuse 010.S asked of patient; 0.6 answered by doctor (Within the last 12 months)

. .

- making capacity regarding any proposed intervention

• address imminent safety

• consider referral to local resources ( home care, respite agencies, shelters, legal services, police

services, government-supported elder abuse consultants) • create emergency safety plan • offer assistance with reporting abuse • in Ontario, reporting elder abuse is mandatory when an older adult resides in a Long term Care Home or a Retirement Home

-

Falls Definition

• an event resulting in a person coming to rest inadvertently on a lower level, other than as a consequence of sudden paralysis, epileptic seizure, or overwhelming external force

Epidemiology

• approximately 20-30% of older adults >65 yr fall each year in Canada, prevalence increases with age falls resulting in injury (e.g. broken / fractured bones, sprain /strain , concussion ) were more likely to occur in women than men 25% associated with serious and 1 / 3 of hospitalizations were associated with hip fractures more than 1/3 of older adults are admitted to long-term care after hospitalization Etiology • intrinsic factors

-

age related changes and diseases associated with aging: MSK (arthritis, muscle weakness), sensory ( visual, proprioceptive, vestibular), cognitive (depression , dementia, delirium, anxiety ),

cardiovascular ( CAD, arrhythmia, Ml, low BP), neurologic (stroke, decreased LOC, gait disturbances/ataxia ), and metabolic (glucose, electrolytes) orthostatic/syncopal acute illness, exacerbation of chronic illness • extrinsic factors environmental ( e.g. home layout, slippery surfaces, overcrowding, new environments) side effects of medications, polypharmacy (>4 medications), and substance misuse (e.g. alcohol misuse)

• situational factors activities (e.g. rushing to the toilet , walking while distracted ) History and Physical Exam • falls history: pre-fall symptoms (chest pain, syncope, presyncope, palpitations), infectious symptoms, mechanisms, loss of consciousness, head trauma, neck/cervical spine trauma, post-fall ( how long were they on the ground , who helped them up, post-fall confusion or amnesia) • extended history: previous falls and /or gait instability, intrinsic, extrinsic and situational factors, associated symptoms, medication and alcohol use, change in medications have a witness present, if possible, for interview • • physical exam: orthostatic BP, injury screen , cardiac, visual acuity, examination of feet and footwear, gait assessment, Timed Up-and-Go Test, MSK, neurologic

1 Have you relied on people for any of the following: bathing, dressing, shopping, banking, or meals? 2 Has anyone prevented you from getting food , clothes, medication, glasses, hearing aids or medical care, or from being with people you wanted to be with? 3 Have you been upset because someone talked to you in a way that made you feel shamed or threatened? 4 Has anyone tried to force you to sign papers or to use your money against your will? 6 Has anyone made you afraid, touched you in ways that you did not want, or hurt you physically? 6 Doctor; Elder abuse may be associated with findings such as: poor eye contact, withdrawn nature, malnourishment hygiene issues, cuts, bruises, inappropriate clothing, or medication compliance issues. Did you notice any of

.

these today or in the last 12 months?

.

.

.

Mk HJ Nlun C URiwick M eU. fcwkprent and nMdioo ol a tool to assist ptry cats' ajenbliuljon ol elder abuse Tie Elder torse Suspicion tnta (EIS! ;|. J Elder Abuse «ed O8:2O(3i:276 3O0. , Mips '«ww.rricgill.tJiTjmlyir« 4 re» ch projettslelder

*

»

' *

o

Additional Canadian Resources for Management of Suspected Elder Abuse Older A dults Safety Line: 24/7 confidential phone line providing Information and referrals for older adults experiencing abuse Advocacy Centre for the Elderly Canadian Network for Prevention of Elder Abuse

Key Clinical History Findings in Falls Evaluation SPLATT

Symptoms Previous falls Location of falls Activity at the time of fal I Time of fall Trauma

Investigations

• CGA to identify potential causes

• investigations should be tailored based on history and physical examination. Ihey might consist of:

CBC, electrolytes, BUN, creatinine, glucose, Ca 2+, TSH, vitamin B12, urinalysis, cardiac enzymes, ECG, CT head (as directed by history and physical), coagulation profile • bone densitometry (dual-energy X- ray absorptiometry) for osteoporosis screening in all women and men >65 yr

Interventions • interventions depend on the identified intrinsic and extrinsic risk factors. First address any acute illness that precipitated the fall and treat any injuries or complications • muscle strengthening, balance retraining (e.g. Tai Chi ) with appropriate assistive devices, and group exercise programs • hip protectors

Impact of Medication Classes on Falls Risk in Geriatrics (Odds Ratios) • Antidepressants (1.68) • Neuroleptics/antipsychotics (1.59) • Benzodiazepines (1.57) • Sedatives/hypnotics (1.47) Antihypertensive agents (1.24) NSAIDs (1.21) Diuretics (1.07) fl blockers (1.01)

.. . .

MeManalpk ol the impact 49 oaSutrai

n LJ

< clam on Mlt in eWerly persons.Inti Mem Med 20O9:l69f2t):t952 1960

-

+

• fitted gait aid

• multidisciplinary, multifactorial, health and environmental risk factor assessment, and intervention programs in the community

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GM8 Geriatric Medicine • home hazard assessment and modification with potential for collaboration with occupational therapy (e g remove loose rugs and tripping hazards, add shower bars and stair railing, improve lighting ) • prescription of vitamin D 1000 1 U daily if vitamin D stores are low • optimization of calcium in diet with 1200 mg of supplemental calcium advised if osteoporosis is a risk

..

• tapering or gradual discontinuation of psychotropic medication • postural hypotension , heart rate , and rhythm abnormalities management • eyesight (cataract surgery ) and footwear optimization • compression socks if venous stasis edema

Frailty

Dulhousie University Clinical Frailty Scale

i

domains: oitliostatic hypotenvon , visual impairment , impairment of gait or balance, medication use limitations in DDLs or UDls. and cognitive impairment. Ihe estimated pretest probebilitr ol falling at least once in any g .ven yr lor individuals »6 b yr was 2J% (95% Cl 19 -36% ). Patients who have fallen m the past year are more likely to falI aga n (182.3 • 2.8). Best predictors of future falls were dislorbances n gait or balarce|lR 1.7-2.4). while visual impairment impaired cognition, and medication were not reliable predittors. Conclusions Screening for nsk ot fallingdliragthe cluneal examination begins with determining if the patient has fa lien in the past yr. For patents who have not previously fallen , screening consists of an assessment of g ai t and balance. Patients who have fallen or who have a gaitor balance problem are at higher risk of future falls.

.

Definition • frailty: clinicallv- recognizable state of decreased reserve in older adults with increased vulnerability to acute stressors resulting from functional decline across multiple physiologic systems • functional decline: progressive limitation in the ability to carry out basic functional activities • frailty is associated with higher risk of in - hospital death, adverse events, length of stay, hospital readmission , and newly dependent at discharge following critical illness

1

Will My Patient Fall ? JAMA 2007;197:77-86 P urpoic Ip identify the prognostic Hint of mk farlors lor future falls amoirqolder patients. Study Selection : Meta anaiysisot prnspectnae cohort studies of list factors lor falls. Results It studies were included . Clin calif identiliable risk factors were identified across 6

Very Fit

4

People who are robust, active,

.

enorgotlc and inotnrotod. They tend to exorclso regularly and are among the fittest for their ege.

Very Mild Fraility

Severe Frailty

Previously "vulnerable ' Eoily

Completely dependent on others for personol cine, from whatever cause Iphysical or cognitive I. Even so. they seem stable and

transition from complete

Independence. While not dependent on others for dally help, often symptoms limit activities- A common

not at high risk of dying (within

-6 mol

complaint is being "slowed up" onCkor bump bred during the day

5

Fit People who have no active disoaso symptoms, but are less fit than category 1. Ofton, they exercise or are very active occasionally (e g. seasonally ).

A

Mild Frailty More evident slowing and need help with high ordoi lADLs ( finances, transportation, heavy

Very Severe Frailly Completely dependent for personal cato and approaching tho end of fafo. Typically, they could not recover even from a minor

). Mild frailty J / A housework PfW ssivaly impairs shopping

4 walking^ alone outside, moal prop. ,

illness

,

medications and bogins 1o restrict light housework.

(

Moderate Frailty Need help with all outsido activities and housekeeping. Ofton have problems with stairs, need help bathing , and might need minimal assistance with dressing ( cuing.

Managing Well

Poople whoso medical problems aie well controlled, ovoti if occasionally symptomatic, but are not regularly active beyond routine walking

Terminally III Approaching tho end ol life Poople w ill a life expectancy ol 3 criteria; at risk or pre frail 1 or 2 criteria 1. shrinking: unintentional weight loss ( baseline: >10 lbs or 5% total body weight lost in prior

-

-

=

yr ) 2. weakness: grip strength in lowest 20% ( by gender, BMl ) 3. poor endurance: as indicated by self- report of exhaustion 4. slowness: walking time/ 15 feet in slowest 20% ( by gender, height ) 5. low activity: keals / wk in lowest 20% ( males: < 383 keals/ wk, females: < 270 keals/ wk ) Cumulative Deficit Approach (Rockwood et al.)

• balance between assets ( e.g. health, attitudes, resources, caregiver ) and deficits (e.g. illness, disability, dependence, caregiver burden ) that determines whether a person can maintain independence in the

ri LJ

community •frailty index : number of deficits present / number of deficits possible

+

Etiology • multifactorial: dvsregulated immune, endocrine, stress, and energy response systems lead to

development of clinical frailty

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GM9 Geriatric Medicine Table 4. Etiologies of Frailty Etiology

Physiologic Changes with Aging

Immune System

Endocrine System

Mechanism Saicopenia (age related loss of skeletal muscle and strength), decreased mass and increased stiffness of organs, decreased reserve capacity of systems

-

- -

Elevated levels of circulating interleukin 6, C readive protein, white blood cells and monocytes associated with skeletal muscle decline Elevaled dotting markers (factor VIII , fibrinogen, D dimer ) upregulates dolling cascade Chronic inflammation

.

-

Sarcopenia via: Decreased growth hormone and IGF 1 Increased cortisol levels Decreased 0 HEAS Decreased 25 (OH ) vitamin D

-

Stress dysregulation of autonomic nervous system Age- related changes in renin - angiotensin system and mitochondria likely impact sarcopenia and inflammation

-based Approach to the Frail Older Patient .Evidence CGA

history, medications, allergies, social history, function, and geriatric • includes: past medical , , , , , , , , (

review of systems cognition mood sleep pain nutrition falls continence vision / hearing skin, and safety) • physical exam investigations: CBC, electrolytes, TSH, vitamin Bi’, vitamin D, LFTs, extended electrolytes • management CGA to tailor management of geriatric syndromes (e.g. falls, cognitive impairment , incontinence) • physical activity programs, nutritional optimization, multicomponent interventions interdisciplinary primary care referral to Acute Care for Elders ( ACE) unit for inpatients who are living with frailty • medication optimization • caregiver support

Immobility Definition

• limitation in independent and voluntary physical movement of the body or one or more lower extremities • associated with disability, increased frailty and risk of falls, decreased quality of life Etiology and Risk Factors

• multifactorial; functional assessment in addition to comprehensive history - taking and

interdisciplinary approach to care is crucial • psychological • fear of falling, motivation , depression • physical changes MSK disorders: history of hip or leg fractures, osteoporosis, arthritis • neurologic disorders: stroke, Parkinson's disease, severe dementia, neuropathies • cardiovascular : CHE, angina secondary to CAD, claudication secondary to PVD • sensory: poor vision, decreased peripheral sensation /proprioception • interpersonal / social factors • environmental changes • iatrogenic ( healthcare facilities) deconditioning secondary to prolonged bed rest inadequate mobility aids • poorly controlled chronic and acute pain Complications

• cardiovascular: orthostatic hypotension , venous thrombosis, embolism • respiratory: decreased ventilation, atelectasis, pneumonia

• gastrointestinal: anorexia, constipation, incontinence, dehydration, malnutrition • genitourinary: infection, urinary retention, bladder calculi, incontinence • MSK: atrophy, contractures , bone loss • skin: pressure injuries • psychological: sensory deprivation, delirium, depression

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Incontinence Fecal Incontinence

Definition

• involuntary or inappropriate passing of feces that impacts social functioning or hygiene

• severity can range from unintentional flatus to the complete evacuation of bowel contents • there are three subtypes:

1. passive incontinence: involuntary discharge of stool or gas without awareness 2. urge incontinence: discharge of fecal matter in spite of active attempts to retain bowel contents 3. fecal seepage: leakage of stool following otherwise normal evacuation

Epidemiology

• the incidence of fecal incontinence differs by setting: community (17-36%), hospital (16%), and nursing home (33 65%) • risk factors: constipation, age >80 yr, female sex, UJ , impaired mobility, dementia , neurologic disease

-

Etiology

• physiological changes with age >80 yr (e.g. decreased external sphincter strength , decreased resting tone of internal sphincter, weakened anal squeeze, increased rectal compliance, and impaired anal sensation )

• trauma (e.g. vaginal delivery, pudendal nerve damage, cauda equina ) • iatrogenic

• surgical (e.g. anorectal surgery, lateral internal sphincterotomy, hemorrhoidectomy, colorectal resection )

• radiation (e.g. pelvic radiation ) • neurogenic ( e.g. neuropathy, stroke, MS, diabetic neuropathy ) • anorectal /colorectal diseases (e.g. rectal prolapse, hemorrhoids, 1BD, rectocele, cancer) • medication (e.g. laxative, anticholinergics, antidep ressants, caffeine, muscle relaxants ) • cognitive (e.g. dementia , willful soiling with psychosis) • constipation / fecal impaction Investigations (if cause not apparent from history and physical) • differentiate true incontinence from frequency and urgency

• stool studies • endorectal ultrasound • colonoscopy, sigmoidoscopy, anoscopy

• anorectal manometry/ functional testing Management

• physiological changes with age: medication management (antimotility agents (e.g. loperamide), diet / bulking agents forloose stool ), increase fluid intake, biofeedback , retraining of pelvic floor muscles, surgery • trauma: direct surgical repair or augmentation of the sphincters • iatrogenic: surgical repair, artificial sphincters • neurogenic: medication management, abdominal massage, digital stimulation for dysfunction , biofeedback and behavioural training, prevent autonomic dysreflexia in spinal injury • anorectal /colorectal diseases: treat underlying cause ( optimize IBD medications ), surgical (e.g. mass

removal, prolapse repair, hemorrhoid removal, colostomy) • medication-related causes: stop laxatives, lower dose, or discontinue any other offending agents cognitive: regular defecation program in patients with dementia, psychiatric consult (optimize medications and cognitive function ) / fecal impaction: disimpaction , prevent impaction, enema , or rectal irrigation constipation • • safety assessment: assess bathroom distance, fall prevention strategies, need for a bedside commode, liaise with occupational therapy if necessary

.

Urinary Incontinence Urology, U 6

• see

Definition

• complaint of any involuntary loss of urine • there are 4 subtypes: 1. stress incontinence: leakage associated with physical strain 2. urge incontinence: leakage associated with strong urge to urinate 3. overflow incontinence: leakage associated with poor bladder emptying 4. functional incontinence: leakage due to illness or disability not related to the urinary tract Epidemiology • 15 30% prevalence dwelling in community and at least 50% of institutionalized older adults • morbidity: cellulitis, pressure injuries, urinary tract infections, falls with fractures, sleep deprivation, social withdrawal, depression, sexual dysfunction

-

Transient Causes of Incontinence

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DIAPERS De lirium Infection Atrophic urethritis/vaginitis Pharmaceuticals Excessive urine output Restricted mobility Stool impaction

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GM 11 Geriatric Medicine

• not associated with increased mortality

• risk factors: impaired mobility, falls, medications, depression , TIA /stroke, dementia, CHI ', obesity Etiology • physiologic changes with age: ( e.g. decreased bladder capacity) • genitourinary diseases (e.g. cystitis, urethritis, BPH ) • neurogenic (e.g. cauda equina syndrome, stroke, MS) • iatrogenic: (e.g. prostate surgery) • trauma: (e.g. pelvic trauma , traumatic spinal cord injury) • drugs (e.g. alcohol , loop diuretics, sedative hypnotics, GABAergic agents ) • cognitive (e.g. dementia, depression ) • functional impairment (e.g. arthritis, poor vision ) Investigations

• laboratory tests: urinalysis and urine culture, serum creatinine, BUN • imaging: post void residual, renal ultrasound • other: voiding diary, pad test

-

Management • lifestyle modification: avoid excessive fluid intake and alcohol • pharmacologic: (J - adrenergic agonists to reduce involuntary bladder contractions • physiologic changes with age: pelvic muscle exercises, bladder training, biofeedback • genitourinary diseases: treat underlying cause (empiric antimicrobial treatment for cystitis, a blockers/5 a reductase inhibitors for BPH ) • functional impairment: incontinence pads, environmental modification, personal assistance • cognitive: referral to incontinence program if needed • safety assessment: assess bathroom distance, fall prevention strategies, need for a bedside commode,

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liaise with occupational therapy if necessary

Malnutrition Definition

• no uniformly accepted definition of malnutrition in older adults. One definition provided by the 2018 Global Leadership Initiative on Malnutrition requires a combination of one phenotypic and one etiologic finding: • phenotype involuntary weight loss (community: > 2% over 1 mo, >10 lbs over 6 mo, or >4% over 1 yr; nursing home: >5% over 1 mo, >10% over 180 d ) loss of muscle mass low BM 1

-

• etiology

• decreased food intake /absorption inflammation

• chronic disease

• other definitions include: hypocholesterolemia ( 24 h

.

First, single, unprovoked: nodliving for 3 mo until complete neurologic assessment EES. Cl head

Seizures

-

.

Epilepsy: can drive it seizure free lor 6 mo on medication that docs not impair ability to drive, and physician has insight into patient compliance (Ontario guideline)

If patient is believed to be at risk due to a symptomatic sleep disorder but refuses investigation with a sleep study or refuses appropriate treatment, the patient should notdrive Visual acuity : contraindicated to drive if '20/ 50 with both eyes examined simultaneously

Sleep Disorders

Visual Impairment

Visual field: contraindicated to drive if 60% of older adults reported using >5 medications • hospitalized older adults are given an average of 10 medications during admission

New medications: Start Low, Go Slow! Avoid starting 2 drugs at the same time.

Risk Factors for Polypharmacy

• patient-level risk factors: age, female sex, cognitive impairment, frailty, mental health conditions, multiple chronic conditions, lack of primary care physician , residing in LTC, multiple pharmacies systems -level risk factors: multiple prescribers, poor documentation systems, automated refill • systems, lack of systematic medication review Risk Factors for Non-Compliance • greater number of medications (compliance with 1 medication is 80% , but drops to 25% with £6 medications) • increased dosing frequency, complicated container design , financial constraints, and cognitive

impairment Adverse Drug Reactions (ADRs)

• any noxious or unintended response to a drug that occurs at doses used for prophylaxis or therapy • risk factors in older adults intrinsic: comorbidities (>5), age >85, low BM1, age-related changes in pharmacokinetics and pharmacodynamics, CrCl 9 medications, >12 doses/d), multiple prescribers, unreliable drug history, prior ADR • prescribing cascade: process whereby an ADR is misinterpreted as a new medical condition, and a subsequent drug is prescribed to treat the initial drug-induced event. Providers should ask themselves: is the new drug being prescribed to address an adverse event from a previously prescribed drug therapy? • is the initial drug therapy really needed, especially if leading to a drug cascade? do the benefits of the initial drug therapy outweigh the harms?

Adverse drug reactions In older adults may present as delirium , falls, fractures, urinary incontinence/retention , or fecal incontinence/impaction.

Preventing Polypharmacy

• consider drug: safer side effect profiles, convenient dosing schedules, convenient route, efficacy • consider patient: other medications, clinical indications, medical comorbidities • consider patient drug interaction risk factors for ADRs • review drug list regularly to eliminate medications with no clinical indication or with evidence of

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toxicity • avoid treating an ADR with another medication

Inappropriate Prescribing in Older Adults

Principles for Prescribing in Older Adults

CARED Caution /Compliance Age (adjust dosage for age) Review regimen regularly Educate Discontinue unnecessary medications

.

Geriatric Peals. PMadelpMa FA Dans Company 1999

Epidemiology • the estimated prevalence of potentially inappropriate prescribing ranges from 12 -40% Beers Criteria

• a list of medications to avoid in adults >65 yr due to safety concerns • 2019 update lists drugs that are inappropriate in most older adults, those that should typically be avoided with certain conditions, drugs to use with caution, drug- drug interactions, and drug dose adjustment based on kidney function • examples include long acting benzodiazepines, strong anticholinergics, high dose sedatives • older adults are often under treated ( ACEI ASA, p blockers, thrombolytic*, oral anticoagulants)

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.

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STOPP /START Criteria

• another screening tool for potentially inappropriate prescribing in older adults • STOPP: Screening Tool of Older Persons Prescriptions • systems - based list of medications contraindicated in adults £65 yr in the context of their diagnoses

• START: Screening Tool to Alert physicians to Right T reatment

systems-based list of medications indicated in adults >65 yr in the context of their diagnoses

Inappropriate prescribing in older persons: A systematic review of medications availablein d ifferenl criteria Arcli Gerontol Geriatr 2017:68:55 61 Purpose: Comprehensive review ol all potentially inappropriate medications for older persons, included ! : trla of the last decade. Results: Iron 118 ankles, 14 criteria were minded in l he boil analysis, including a total ol J 28 med iation classes among all analyted criteria. Dratepam was included In all 14 criteria , followed by amitriptyline in 13 criteria and donepin In 12 criteria. Seniodiaiepmes antihistamines, and antipsyclrolics wrerethe moot common drugs reported as potenlially inappropriate for older adults, among final criteria . Cone lesion: Seniodiaiepmes, HSAIDs. antihistamines, and antipsycholics were the most common drugs reported as potentially inappropriate for older persons.

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GM17 Geriatric Medicine

Common Medications Table 10. Common Medications Drug Name

Brand Name

Dosing Schedule Indications

Contraindications

Side Effects

Mechanism of Action

5 -10 mg PO once

Known hypersensitivity, caution in untreated obstructive airway disease, cardiac conduction abnormalities, active PUD or occult Gl bleed, seizure disorder,syncope NYD

N/ V, diarrhea, an oreiia. insomnia, fatigue,muscle cramps, syncope, bradycardia (uncommon), heart block (uncommon)

Reversible inhibition of acetylcholinesterase

HIV diarrhea, anorexia, weight loss, headache, dizziness, syncope, heart block (rare), seizure (rare), delirium (rate)

Reversible inhibition of acetylcholinesterase

Cognitive Enhancers donepezil

AricepG

Moderate to severe dementia of Alzheimer 's

daily

type

galantamine

RemmyP

rhrastigniine

Exelon '

memantine

8-12 mg PO BID

Mild to moderate dementia of Alzheimer 's type

Known hypersensitivity, caution in untreated obstructive airway disease, cardiac conduction abnormalities, active PUD or occult Gl bleed, seizure disorder, syncope NYD

1.5 mg POBID (starting) up to 6-12

Mild to moderate dementia ol Alzheimer 's

mg POBID

type

Known hypersensitivity, severe hepatic disease, caution m untreated obstructive auway disease, cardiac

Ebixa " He men da ' 5 mg PO once daily Mild to moderate (Can) /|U.S.) (starting) up to 10 mg dementia of Alzheimer 's type POBID

. .

.

Acetylcholinesterase inhibition N / V diarrhea, headache dizziness, anorezia. insomnia, (reversible but very slow) weight loss, delirium,heart conduction abnormalities,active PUD block (rare) or occult Gl bleed,seizure disorder, syncope NYD

Known hypersensitivity, conditions that alkalinize urine, caution in renal failure, seizures

Dizziness, headache, hypertension, constipation confusion, hallucinations

NMDA-receptor antagonist

.

Laxatives bran

All -Bran 1

1cup PO once daily

Constipation

Bloating, flatus

Bulk - forming laxative

psyllium

Metamucil1 Prodiem' Plain ®

3.4 gPO once daily totID

Constipation, hypercholesterolemia

N'V abdominal pain, obstruction if another medication is taken within 2 h

Bloating, flatus

Bulk - forming laxative

lactulose

Chronulac' Cephulac Krislalose 1 ( U.S ) Acilac;: Apo-

15 -30 ccPO once daily 'BID and 5-10 ml POBID for 2-4 wk for bowel evacuation after barium

Constipation,hepatic encephalopathy, bowel evacuation following barium exam

Patients on low galactose diets, abdominal pam NY

Flatus, cramps, nausea, diarrhea

Osmotic laiatrve

17 gPO once daily ( 1 Constipation, bowel prep Known/suspected bowel obstruction heaping tablespoon) (different dosing schedule) known hypersensitivity,renal impairment dissolved in1cup (250 ml) of beverage

.

Abdominal cramps, bloating of the stomach, diarrhea, flatulence,nausea

Osmotic laxative

2 -4 tablets P0 once daily or 10 -15 ml syrup once dahy BID. Dosing should be the smallest required to pass soft stool

Constipation

Known / suspected bowel obstruction or abnormal constriction, atonic bowel. IBD. abdominal pain NYD. rectal bleeding NYD.severe

Abdominal cramps. N/V. diarrhea, urine and / or fecal discolouration

Stimulant laxative

5-15 mg P0 (10 mg PR)

Constipation

Abdominal cramps, pain, diarrhea, dehydration, dizziness, N/ V

Stimulant laxative

.

Lactulose s; Laxilose '; PMSLactulose ' (Can)

PEG 3350 (polyethylene glycol)

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lax- A Day ®, Restora LAX Pegalax ( Can) -

Gavilax ®,

Healthylax -' (U.S.)

senna

bisacodyl

SenokoG /Ex - lax"

Dulcolax ®

..

.

-

dehydration

.

Acute Gl diseases (e.g.appendicitis diarrhea),ileus, obstruction, abdominal pain HY severe dehydration, and ulcerative proctitis and.or anal fissures if PR

. .

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Parkinsonian Agents - see Neurology, table 26 N57 Note Docusate has been shown to be ineffective for the prevention treatment of constipation in older adults

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GM18 Geriatric Medicine

Landmark Geriatric Medicine Trials Trial Name

Reference

Clinical Trial Details

JAMA 2011;305:50 - 58

Title: Gail Speed and Survival in Older Adults Purpose: Evaluate the relationship between gait speed and survival. Methods: Pooled analysis ol 9 cohort studies of adults > 65 yr with baseline gait speed data, followed up for 6 - 21 yr The main outcomes weic survival and life expectancy Results: lire overall 5 - yt survival was 84.8% and 10 yr survival was 59.7%. Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1m/s. 0.88; 95% Cl 0.87 to 0.90: P‘0.001). Survival increased across the range of gait speeds with significant increments at 0.1 mis. Conclusions: Gait speed was associated with 10 - yr survival in all studies, with considerable variability in predicted 10 - yr survival across the range of gait speeds, at 75 yr.

FRAILTY

Gail Speed and Survival in Older Adults Studenskietal. 2011

.

.

frailty in Older Adults: Evidence for a Phenotype Fried elal 2001

.

.

J Gerontol A Biol Sci Med Sci 2001:56 ( 3): M146 56

NEJM 2021:385:203 - 216

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Title: frailty in Oldei Adults: Evidence for a Phenotype Purpose: Develop phenotype of frailty as a clinical syndrome Methods: Saselme and annual follow up for outcomes of incident disease, hospitalization, falls, disability, and mortality in an oiiginal cohort of 4735 participants and later- recruited cohort of 582 African American participants. All participant data from the prospective observational Cardiovascular Health Study. Results: Frailty may be defined as the presence of three or more of: unintentional weight loss (10 lbs in pastyr ) self reported exhaustion, weakness (grip strength ) slow walking speed, low physical activity, frailty is associated with increased risk of comorbidity and disability Conclusions: frailly m community dwelling older adults may be defined as above While comorbidity is a risk factor for Irailty and disability is an outcome of frailly, frailty itself does nol equal comoibidily or disability Assessment loi frailly is vital in identifying patients at increased risk for comorbidity and disability.

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REHAB - AF

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Title: Physical Rehabilitation for Older Patients Hospitalized for Heart Failure Purpose: Investigate interventions to address physical frailly in older patients hospitalized for acute decompensated heart failure. Methods: Multicentci randomized,controlled trial to evaluate transitional, tailored, progressive rehabilitation inlervention including four physical function domains initiated dunng or soon after heart failure hospitalization and continued post discharge for 36 sessions Piimary outcome was Short Physical Performance Battery score, and secondary outcome was 6 month ichospitalizalion rale. Results: Older adults hospitalized for acute decompensated heait failure produce improved clinical outcomes when treated

.

.

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with this rehabilitation intervention program. DELIRIUM

Delirium is a Strong Risk Factor Brain 2012:135|9):2809 16 loi Dementia in the Oldest Old: A Population Based Cohort Study, Oavis etal. 2012

Title: Delirium is a Strong Risk Factor lor Dementia in the Oldest - Old: A Population - Based Cohort Study Purpose: Use a Irue population sample to determine if delirium is an incident risk factor for incident dementia and cognitive

decline. Methods: 553 individuals aged *85 yr were used to assess associations between delirium and incident dementia, as well as decline in MMSE scores. The relationship between dementia common neuropathological maikers was modelled and

stratified. Results: Delirium increased the risk of incident dementia (OR 8.7; 95 % Cl 2.1 to 35) worsened dementia severity (OR 3.1; 95% Cl 1.S to 6.3) and deterioration in global function score|0 R 2.8; 95% Cl 1.4 to 5.5). Delirium was associated with a loss of 1.0 more MMSE points per yr (95% Cl 0.11 to 1.89 ) than those with no history of delirium. Conclusions: Delirium is a stiong risk faclor for incident dementia and cognitive decline in elderly patients

.

A Multicomponent Intervention to Prevent Oelirium in Hospitalized Older Patients Inouye etal. 1999

HEJM 1999:340:669 676

.

Title: A Multicomponent Inlervention to Prevent Delirium in Hospitalized Older Patients Purpose: Evaluate the effectiveness of a multicomponent strategy foi delirium prevention among older inpatients Methods: A total of 852 inpatients >70 yr were included in the study. In lieu of randomization,prospective individual matching was used to compare patients admitted to an intervention unit vs.one of two usual care units. In the intervention unit, the multicomponent approach sought to address cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. Results : Delirium developed in 9.9% of patients in the intervention unit vs 15% in the usual care unit |95% Cl 0.39 to 0.92) Iota ! number of days with delirium (105 d vs 161 d P '0.02! and tolal number of delirium episodes (62 vs 90 P'0.03) were both lower in the inteivention unit. Conclusions: A multicomponent intervention model aimed ataddressing risk factors for delirium in hospitalized older adults is effective at reducing delirium incidenceand delirium duration.

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.

.

.

.

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FALLS

PR0 FET

lancet 1999:353:93 97

Title: Prevention ol falls in the Elderly Irial fProlct): A Randomised Controlled Trial Purpose: Assess the benclit ol a structured interdisciplinary assessment ol people who have fallen Methods: Patients >65 yr presenting to ED with a fall were randomized to Ihc intervention group (detailed medical and OT -lherapy assessment with referral if indicated) or to a control group (usual care only). Results: Ihe risk of falling was significantly lower in the intervention group compared to the control group (OR 0.39; 95% Cl 0.23 ID 0.66) as was the risk of fall recurrence (OR 0.33:95% Cl 0.16 to 0.68). Conclusions:Demonstrates that an interdisciplinary approach to elderly adults with a previous history of falls can significantly decrease the risk of further falls and limit functional impairment.

HEJM 2012:366:893 903

Title: Doncpezil andMemantine for Moderate - to - Severe Alzheimer 's Disease Purpose: Assess the benefits of cholinesterase inhibitorsfor the long- term treatment ol moderate - severe Alzheimer 's

.

NEUR0 C 0GNITIVE DISORDERS

Donepezil and Memantine for Moderate to Severe Alzheimer 's Disease. Howard etal. 2012

-

disease. Methods: 295 community - dwelling patients with moderate-severe Alzheimer's disease treated with donepezilwere randomized to either continue donepezil discontinue donepezil and start memantine, or continue donepezil and start memantine.Ihe piimary outcomes were SMMSE scores and Bristol Activities of Daily living (BADLS) scores. Results : Patients assigned to continue donepezil compared to those who discontinued, had a 1.9 higher average SMMSE score 195% Cl 1.3 to 2.5) Ihc score on Ihc 8 ADLS was lower (less impairment) by 3.0 points (95% Cl 1.8 lo 4.3) IP 0.001 for both comparisons). Patients who received memantine, compaied with placebo, had a 1.2 higher average SMMSE score ( 95% Cl 0.6 to 1.8 P 40 risk factors for or history of endometrial cancer failure of medical treatment

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significant intermenstrual bleeding consider in women with infrequent menses suggesting anovulatory cycles

Hysterectomy Indications

• uterine fibroids • endometriosis, adenomyosis • uterine prolapse

• pelvic pain • AUB • cancer (endometrium, ovaries, fallopian tubes, cervix) Complications

• general anesthetic • bleeding • infection • injury to other organs (ureter, bladder, rectum ) • loss of ovarian function ( if ovaries removed, iatrogenic menopause) • venous thromboembolism

. -

No 377 Hysterectomy for Benig n Gyoaecological Indications J Obstet Cyraecol Can 2019:41|4|:543-SS7 Summary: 1. Hysterectomy should be approached by either vaginal, laparoscopic, oc open routes. 2 Correction of preoperatiieaaemia ( hemi>globhi (Hb 6 mo or 3 cycles after documented menarche

Most Common Causes of Primary Amenorrhea 1 Gonadal dysgenesis (e.g. Turner's Syndrome) 2. Functional hypothalamic amenorrhea 3 Mullerian agenesis

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Table 3. Differential Diagnosis of Secondary Amenorrhea With Hyperandrogenism

Without Hyperandrogenism

PCOS Autonomous hyperandrogenism (androgen secretion independent of the HPO axis) Ovarian: tumour, hypcilhccosis Adrenal androgen secreting tumour Late onset or mild congenital adrenal hyperplasia (rare)

Pregnancy Hypergonadotropic hypogonadism (i.e. primary ovarian insufficiency: high FSH, low estradiol) Idiopathic Autoimmune: type 1 DM, autoimmune thyroid disease Addison's disease, celiac disease Iatrogenic:cyclophosphamide drugs,radiation Hyperprolactinemia Endocrinopathies: most commonly hyper or hypothyroidism Hypogonadotropic hypogonadism (low ESH): Pituitary compression or dcslrudron: pituitary adenoma, craniopharyngioma, lymphocytic hypophysitis, infiltration (sarcoidosis),head injury, Sheehan'ssyndrome Functional hypothalamic amenorrhea (often related to stress, excessive exercise and/or anorexia)

Functional hypothalamic amenorrhea is the most common cause of secondary amenorrhea

.

-

Amenorrhea

i

History and Physical Exam

I

; 1' Amenorrhea

2 ' Amenorrhea

I (3- hCG

I

2 sexual characteristics Yes

XX

I

l

^

No

Negative

^

Karotypc

FSH/IH

Prolactin

1

1

t

Imperforate hymen

Transverse vaginal septum Cervical agenesis MOIIcrian agenesis

|XY AIS

^

High

Hypergonadotropic • Gonadal agenesis/ dysgenesis

Normal

Lots

* HPO axis abnormality

.

Withdrawal bleed

i

Abnormal

High

PCOS - hyperandrogenism

No withdrawal bleed

1

Primary ovarian insufficiency

LH/FSH

I

Pregnancy

Progesbn challenge

Hypogonadotropic

• Constitutional delay

i

1Positive Prolactin t ( normal 100 ng/dl • TSHtoscroon hypothyroidism for

Uterine defect Normal/ Low Asherman’s syndrome or HPO axis dysfunction HPO axis dysfunction •MRI hypothalamus, pituitary •Measure other pituitary hormones •Common etiology: • Weight loss • Excessive exercise • Systemic diseases

J

Figure 6. Diagnostic approach to amenorrhea

Investigations • P-hCG, hormonal workup (1SH, prolactin , FSH, LH, androgens, estradiol) • progesterone challenge to assess estrogen status • medroxyprogesterone acetate ( Provera*) 10 mg PO once daily for 10- 14 d • any uterine bleed within 2 7 d after completion of Frovera* is considered to be a positive W / L> test • W / D bleed suggests presence of adequate estrogen to thicken the endometrium; thus W / D of progesterone results in bleeding if no bleeding occurs, this may be secondary to inadequate estrogen ( hypoestrogenism ), excessive androgens or progesterones (decidualization ), pregnancy, obstructive causes (e.g. cervical stenosis ), or structural causes (e.g. uterine adhesions) • karyotype: indicated if primary ovarian insufficiency or absent puberty • U /S to confirm normal anatomy, identify PCOS ( in adult population only )

-

Prolactinoma Symptoms Galactorrhea, visual changes, headache

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Treatment

Table 4 . Management of Amenorrhea Management

Etiology

1° AMENORRHEA

AIS

Gonadal resection alter puberty Psychological counselling

Creation ol neo - vagina with dilation Anatomical Imperforate hymen

Surgical management

Transverse vaginal septum Cervical agenesis

Suppression and ultimately hysterectomy

Mullerian dysgenesis [ MRKH syndrome)

Surgical management Psychological counselling

Creation of neo vagina with dilation Diagnostic study to confirm normal urinary system and spine

2« AMENORRHEA HPO axis dysfunction

Identify modifiable underlying cause Combined OCP to decrease risk ol osteoporosis, maintain normal vaginal and breast development ( NOT proven to work )

MRI /CT head to rule out lesion

Hyperprolactinemia

If no demonstrable lesions by MRI:

2° amenorrhea is pregnancy until proven otherwise

Bromocriptine , cabergoline if fertility desired

Combined OCPs il no fertility desired Polycystic ovarian syndrome

Demonstrable lesions by MRI : surgical management See Polycystic Ovarian Syndiome, CY 24

Premature ovarian failure

Screen foi DM , hypothyroidism, hypoparathyroidism , hypocortisolism

Uterine defect

Hormonal therapy with estrogen and progestin to decrease risk of osteoporosis: can use OCP after induction of puberty Evaluation with hysterosalpingography or sonohysterography

Asherman 's syndrome

Hysteroscopy: excision ofsynechiae

Abnormal Uterine Bleeding AUB

i T Irregular

Regular ( predictable cycle )

( unpredictable cycle)

Heavy

Intermenstrual Bleeding

AUB and/or unpredictable AUB

AUB- A AUB-Uv AUB- C AUB-E

AUB -P

AUB-0 AUB-M

Figure 7. Diagnostic approach to abnormal uterine bleeding

Approach • menstrual bleeding should be evaluated by ascertaining: frequency / regularity of menses, duration , volume of flow , impact on quality of life, and timing ( inter - or premenstrual, or breakthrough ) • is it regular? regular: cycle to cycle variability of BID x 2 d -> once daily ( more commonly used ) after (a) or ( b), maintain patient on monophasic OCP for next several months or consider

-

-

•

alternative medical treatment medical (can also consider ): - high dose progestins - danazol ( Danocrine*) - GnRH agonists (e.g. Lupron * ) with add -back if taken for >6 mo ulipristal acetate

-

-

l

• surgical polypectomy myomectomy *

•

rm

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+

uterine artery embolization endometrial ablation • if finished childbearing • repeat procedure may be required if symptoms recur, especially If < 40 yr hysterectomy: definitive treatment

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GY11 Gynaecology

Dysmenorrhea Etiology • primary/idiopathic • secondary (acquired )

• endometriosis

Primary Dysmenorrhea Recurrent, crampy lower abdominal pain during menses in the absence of

adenomyosis uterine polyps

uterine anomalies (e.g. non - communicating uterine horn )

demonstrable disease

leiomyoma

• • •

Secondary Dysmenorrhea Pain during menses that can be attributed to an underlying disorder (i.e. endometriosis, adenomyosis. fibroids)

intrauterine synechiae ovarian cysts cervical stenosis imperforate hymen, transverse vaginal septum

rlD IUD (copper ) foreign body Table 6. Comparison of Primary and Secondary Dysmenorrhea Features

Primary Dysmenorrhea

Secondary Dysmenorrhea

Recurrent, crampy lower abdominal pain that occurs during menses in the absence ol demonstrable disease

Similar features as primary dysmenorrhea but with an underlying disorder that can account for the symptoms such as endometriosis, adenomyosis or uterine fibroids

.

.

.

Signs and Symptoms

Colicky pain in abdomen, radiating to the lower back labia, and inner thighs beginning hours before onset of bleeding and persisting for hours or days (48 - 72 h) Associated symptoms: N /V, altered bowel habits, headaches, fatigue (prostaglandin -associated)

Same symptoms as primary dysmenorrhea Associated symptoms: dyspareunia, abnormal bleeding infertilily

Diagnosis

Assess for associated dyspareunia abnormal bleeding. infertility (signs of 2’dysmenorrhea) Buie out underlying pelvic pathology and confirm cyclic nature of pain Pelvic examination not required; indicated for patients not responding to therapy or with signsof organic

Bimanual exam: uterine or adnexal tenderness, fixed uterine retroflexion,uterosacral nodularity, pelvic mass. or enlargedirregular uterus (findings are rare in women < 20 yr ) U / S laparoscopy, end hysleroscopy may be necessary to establish the diagnosis Vaginal and cervical cultures may be required

.

pathology Regular exercise,local heat NSAIDs: should be started before onset of pain CHCs with continuous or extended use: suppress ovulation/reduce menstrual flow

Treatment

.

.

Treatunderlying cause

Endometriosis Definition • the presence of endometrial tissue ( glands and stroma ) outside of the uterine cavity • chronic condition, resolving only with menopause

Etiology

• not fully understood ; proposed mechanisms include (combination likely involved ): • retrograde menstruation (Sampson’s theory ) immunologic: decreased N K cell activity limiting clearance of transplanted endometrial cells from pelvic cavity ( may be due to decreased N K cell activity) metaplasia of coelomic epithelium • extra pelvic disease may he due to aberrant vascular or lymphatic dissemination of cells • e.g. ovarian endometriosis may be due to direct lymphatic flow from uterus to ovaries

-

Epidemiology • incidence: 15- 30% of premenopausal women • mean age at presentation: 25 30 yr

• regresses after menopause

-

Risk Factors • family history (7-10x increased risk if affected 1 st degree relative) • obstructive anomalies of the genital tract (earlier onset ) - resolves with treatment of anomaly

• nulliparity • age >25 yr • early menarche (< 11-13 years old ), shorter menstrual cycles (defined as < 27 days )

Differential Diagnoses

• Chronic PID, recurrent acute

.•

salpingitis Hemorrhagic corpus luteum Bcnign/malignant ovarian neoplasm • Ectopic pregnancy

4 “Dys" of Endometriosis

• Dysmenorrhea

• Dyspareunia (cul-de-sac, uterosacral ligament) • Dyschezia (uterosacral ligament culde sac rectosigmoid attachment) • Dysuria (bladder involvement)

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GY 12 Gynaecology

Toronto Notes 2023

Sites of Occurrence • ovaries: 60 % of patients have ovarian involvement • broad ligament, vesicoperitoneal fold • peritoneal surface of the cul -de -sac, uterosacral ligaments • rectosigmoid colon, appendix • rarely may occur in sites outside abdomen / pelvis, including lungs and diaphragm Clinical Features • may be asymptomatic and can occur with one of 3 presentations I . pain (80%) • menstrual symptoms cyclic symptoms due to growth and bleeding of ectopic endometrium , usually precede menses ( 24 48 h ) and continue throughout and after flow

-

secondary dysmenorrhea sacral backache with menses pain may eventually become chronic, worsening perimenstrually deep dyspareunia

Long- Term Outcomes of Elagolix in Women with Endometriosis: Results from Two Extension Studies Obstet Gynecol 2018:132.147-160 Purpose: An evaluation of the safety and efficacy of elagolix (a GnRH agonist) orer 12 mo in women wdh endometriosis associated pain. Methods A repwlof 2. double - blind Phase III placebo controlled Mis to evaluate ( wo doses ol elagolix over 12 mo of continuous treatment m patients with moderate lo severe endometriosis associated pain Results: In the lint trial. S2.1l ol women receiving ISO mg elagot ionce daily had a dincal response with regards lo dysmenorrhea and 67.8% had a response with regards lo coo- menstrual pelvic pain. In tine h gher dose group (200 mg q12 h), the response rate was 78.1% and 69.1%. respectively, these response rateswere comparable in the second trial. Women who received elagb ix had higher rates of hot flushes, higher serum I puts, and deueases in hone mineral density. Conclusion : Both h gb and low doses of elagolix were effective m improving dysmenorrhea and non menstrual pelvic pain in women with endometriosis associated pain .

-

.

-

.

-

.

'

bowel and bladder symptoms frequency, dysuria, hematuria cyclic diarrhea /constipation , hematochezia, dyschezia (suggestive of deeply infiltrating

disease) 2. infertility ( 25%) 30 40% of patients with endometriosis will be infertile • 15 30% of those who are infertile will have endometriosis 3. mass (endometrioma ) ( 20% ) • endometrioma: an endometriotic cyst encompassing ovary ovarian mass can present with any of above symptoms or be asymptomatic physical examination: tender nodularity of uterine ligaments and cul-de-sac felt on rectovaginal exam fixed retroversion of uterus

-

-

-

firm , fixed adnexal mass Investigations

• definitive diagnosis can be made based on : direct visualization of lesions typical of endometriosis at laparoscopy ( gold standard ) • biopsy and histologic exam of specimens 2 or more of: endometrial epithelium , glands, stroma , hemosiderin -laden macrophages

• laparoscopy mulberry spots: dark blue or brownish - black implants on the uterosacral ligaments, cul- de-sac, or anywhere in the pelvis endometrioma: “chocolate" cysts on the ovaries “ powder-burn" lesions on the peritoneal surface early white lesions and clear blebs peritoneal “ pockets" • CA-125 maybe elevated in patients with endometriosis but should NOT be used as a diagnostic test

-

Endometriosis Take Home Points

• Suggestive history even with a negative exam should be considered adequate for a presumptive diagnosis Pelvic pain that is not primary dysmenorrhea should be considered endometriosis until proven otherwise • Medical management is the mainstay of endometriosis

•

Suspocted Endometriosis V

’

First Line

CHC therapy ( ideally continuous! Progestin alone ( oral. IM, SC ) Failure of first line therapy

I

;

T

Laparoscopy for diagnosis and treatment

u. Failure of surgical or medical therapy

Second Line 1 . GnRH agonist with addback 2. Progestin IUS

r1

-

i

1. Reconsider diagnosis additional testing and / or non gynaecologic referrals 2. Chronic pain management and multidisciplinary support

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Figure 8. Society of Obstetricians and Gynaecologists of Canada (SOGC) guidelines for treatment of endometriosis

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Toronto Notes 2023

GY13 Gynaecology

Treatment • surgical confirmation of disease is NOT required prior to starting medical management. Asymptomatic endometriosis does not require treatment. Management depends on certainty of the diagnosis, severity of symptoms, extent of disease, desire for future fertility, and impact to Gl /GU systems (e.g. intestinal obstruction) • medical NSAlDs (e.g. naproxen sodium - Anaprox*). Avoid selective COX-2 inhibitors (celecoxib, rofecoxib, valdecoxib) in those who are attempting conception as some studies indicate these drugs can prevent or delay ovulation • 1st line cyclic/continuous estrogen- progestin (OCP) progestin (1M medroxyprogesterone ( Depo- Provera*) or oral dienogest ( Visanne’)) Mirena' lUS • 2nd line GnRH agonist (e.g. leuprolide ( Lupron*)): suppresses pituitary glands - side effects: hot flashes, vaginal dryness, reduced libido - use >6 mo: include add -back progestin or estrogen to prevent decreased BMD, reduce vasomotor side effects danazol ( Danocrine*): weak androgen - side effects: weight gain, fluid retention, acne, hirsutism, voice change ( not commonly used due to side effects) • surgical conservative laparoscopy using laser, electrocautery ± laparotomy ablation / resection of implants, lysis of adhesions, ovarian cystectomy of endometriomas definitive: hysterectomy ± bilateral salpingo - oophorectomy best time to become pregnant is immediately after conservative surgery if patient is not planning to become pregnant postoperatively, suppress ovulation medically to prevent recurrence ( not proven ) • above treatments are for the pain , not for the infertility associated with endometriosis, which usually involves surgery + assisted reproductive technologies. Also, management for endometriomas is surgical for symptomatic and expanding masses, but this can decrease ovarian reserve, so if it is asymptomatic and small (35 y/o; found in 20 -40% of hysterectomy specimens • mean age at presentation: 40-50 y/o (older age group than seen in endometriosis) • adenomyosis is a common histologic finding in asymptomatic patients

Adenomyosis Extension of areas of endometrial glands and stroma into the myometrium

Clinical Features • often asymptomatic • heavy menstrual bleeding, secondary dysmenorrhea, pelvic discomfort • dyspareunia , dyschezia • uterus symmetrically bulky, usually < 14 cm • Halban’s sign: tender, softened uterus on premenstrual bimanual exam Investigations

• clinical diagnosis

Final diagnosis of adenomyosis is based

• endometrial sampling to rule out other pathology

on pathologic findings, but predictably identified on MRI

• U /S or MR 1 can be helpful Treatment

• medical

•

.

iron supplements for anemia

• analgesics, NSAlDs Mirena' 1 US

* ) limited evidence for efficacy • CHC, medroxyprogesterone ( Depo- Provera • GnRH agonists (e.g. leuprolide ( Lupron * ))

-

danazol 100 200 mg PO once daily (trial x 4 mo)

• surgical

rn

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definitive: hysterectomy treatment of choice in women who have completed childbearing

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AL GRAWANY

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Toronto Notes 2023

GYM Gynaecology

Fibroids Epidemiology • diagnosed in approximately 40 50% of premenopausal women >35 yr • more common in Black women, where they are also larger and occur at earlier age • common indication for major surgery in females • minimal malignant potential (1 in 1000) • typically regress after menopause

-

Pathogenesis • estrogen stimulates monoclonal smooth muscle proliferation • progesterone stimulates production of proteins that inhibit apoptosis • degenerative changes (occur when tumour outgrows blood supply) fibroids can painfully degenerate, become calcified, develop sarcomatous component, or obtain parasitic blood supply

Classification • intramural: most common, grow within the muscular wall of the uterus • submucosal: grow within myometrium , can grow into endometrial cavity • subscrosal: grow from the serosa • fibroids can also grow in the cervix and vagina Clinical Features • majority asymptomatic ( 60%), often discovered as incidental finding on pelvic exam or U /S (occur in 50% of ALL women ) • abnormal uterine bleeding (30%): dysmenorrhea, heavy menstrual bleeding • pressure/ bulk symptoms ( 20-50%) pelvic pressure/heaviness • increased abdominal girth urinary' frequency and urgency constipation, bloating ( rare) acute urinary retention (extremely rare, but surgical emergency!) • acute pelvic pain

fibroid degeneration fibroid torsion ( if pedunculated subserosal ) • infertility, recurrent pregnancy loss • pregnancy complications ( potential enlargement and Increased pain , obstructed labour, malprcsentation , difficult cesarean delivery )

Leiomyomata/Fibroids Benign smooth muscle tumour ol the uterus (most common gynaecological tumour)

Submucosal leiomyomata are most symptomatic (bleeding, infertility)

Large fibroids can cause distressing bulk symptoms

The effect of pregnancy on fibroid siie is variable

'Pedunculated bubskir usdl

iubserosal

Intramura '

Cervical

Pedunculated submucosal g) Camilla Matuk

.

Figure 9 Possible anatomic locations of uterine leiomyomata

^

Investigations

• bimanual exam: uterus asymmetrically enlarged, usually mobile • CBC: anemia ( only found if associated with AUB/ heavy menstrual bleeding ) • pelvic and /or transvaginal U / S: to confirm diagnosis and assess location of fibroids • sonohvsterogram: useful for differentiating endometrial polyps from submucosal fibroids, for assessing intracavitary growth or for assessing potential risks with fertility associated with the fibroid (submucosal only) • endometrial biopsy to rule out uterine cancer for abnormal uterine bleeding (especially if age > 40 yr) • occasionally MRI is used for preoperative planning (e.g. before myomectomy) Treatment

• only if symptomatic (heavy menstrual bleeding, bulk symptoms), rapidly enlarging or intracavitary • treat anemia if present • conservative approach ( watch and wait ) if: • symptoms absent or minimal fibroids 99% with perfect use) • may be less effective in women > 90 kg Contraceptive Ring (Nuva Ring ; ) • thin flexible plastic ring that is inserted into the vagina by the patient and left there for 3 wk then removed for a week to allow for menstruation; releases etonogestrel 120 pg /d and estradiol 15 pg /d • as effective as (KIP in preventing pregnancy ( 98%) • side effects: vaginal infections/irritation, vaginal discharge

• associated with less breakthrough bleeding than other methods

Starting Hormonal Contraceptives • thorough history and BP measurement ( post- pandemic SOGC guidelines do not require BP reading anymore to allow for virtual appointments) • pelvic exam not required as ST1 screening can be done by urine, and pap smear screening does not start until >25 yr • can start at any time during cycle but ideally within 5 d of LMP • follow-up visit 3 mo after hormonal contraceptives prescribed • generally recommended to use back- up contraception for 7 days, particularly if initiated > 5 days front LMP Table 8. Combined Estrogen and Progestin Contraceptive Methods Advantages Highly effective

Side Effects

Contraindications

-

Estrogen related Reversible Nausea Cycle regulation Breast changes (tenderness, enlargement) Decreased dysmenorrhea and heavy menslrual Fluid retention,1bloating / edema bleeding|1ess anemia) Weight gain (rare) Decreased benign breast disease and ovarian Migraine,headaches Thromboembolic events cyst development Decreased risk of ovarian and endometrial Liver adenoma (rare) cancer Breakthrough bleeding (low estradiol levels) Increased cervical mucus which may lower risk of STIs Progestin-related Decreased PMS symptoms Amenorrhea!breakthrough bleeding Less acne Headaches Osteoporosis protection (possibly) Breast tenderness Patient controlled Increased appetite Decreased libido Mood changes H1N

Acnefoilyskin* Hirsutism*

Absolute 4 wk postpartum (breastfeeding) or < 21 d postpartum (not breastfeeding) Major surgery with prolonged immobilication ttnown/suspected pregnancy Undiagnosed abnormal vaginal bleeding Prior thromboembolic events, thromboembolic disorders (FactorIf Leiden mutation;protein Cor S. or anbthrombin III deficiency), active thrombophlebitis Cerebrovascular or coronary artery disease Estrogen- dependent tumours (breast, uterus) Impaired liver function associated with acute

liver disease Congenital hypertriglyceridemia Smoker age >35 yr Migraines with focal neurological symptoms (eiduding aura) Uncontrolled HTN

Relative

'Androgenic side effects may be minimiced by prescribing formulations containing desogestrel, norgestimate drospvenone. or cyprolerone acetate

.

Migraines (non - local with aura 75 kg not recommended il >80 kg

.

Ulipristal (Ella ) 30 mg P0 within 5 d ol unprotected intercourse

.

with contraindications lo OCP

N0 N- H 0HM 0 NAI

Postcoital IUD (Copper) Insert up to 7 d postcoitus Prevents implantation 1% failure rate Can use (or short duration in higher risk individuals

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Follow-up • 3-4 \vk post treatment to confirm efficacy (confirmed by spontaneous menses or pregnancy test ) • contraception counselling

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Toronto Notes 2023

GV19 Gynaecology

Termination of Pregnancy Indications

• patient desires an end to pregnancy • may be for medical reasons ( health of mother or fetal anomaly ) or social reasons, including patient request

Legal Considerations

• no current law in Canada concerning abortion, therefore considered legal at any GA, however GA limits and access vary significantly by region • CPSO: a physician must provide a referral for abortion services regardless of personal beliefs, but not compelled to personally perform procedure Rates

• 13.1 abortions in 1000 women 15- 44 yr in Canada ( 2017 CIH 1 data )

• worldwide: 56 million induced abortions per yr; half are unsafe ( WHO data ) • maternal mortality almost zero where induced abortion is safe and legal; rises to 100 maternal deaths in 100000 live births in sub-Saharan Africa and other countries where abortion is illegal and unsafe • in Canada, 91% of induced abortions occur 24 h culture 1CSJ

-

.•

1VM

± oocyte or sperm donors ± pre-genetic screening for single gene defects in karyotype of zygote •not performed in Canada

Male Factors • see Urology. U 37 Normal Semen Analysis (WHO lower reference limits) • Must be obtained after 2-7 d of abstinence • Volume 1.5 cc • Count 15 million/cc • Vitality 58% live • Motility 32% progressive 40% total (progressive non-progressive) • Morphology 4.0% normal

Etiology • varicocele (> 40% ) • idiopathic ( >20%) • obstruction ( 15%) • cryptorchidism ( 8%) • immunologic ( 3%)

•

- exogenous androgens

.

Investigations

• semen analysis and culture

Polycystic Ovarian Syndrome Etiology Insulin

t estrogen

t

t peripheral conversion to estrogen

t

Obesity

I I

Polycystic Ovarian Syndrome - HAIR-

4 FSH secretion 11 LH secretion

Anovulation

t ovarian secretion ol androgens

Oligomenorrhea

I Hirsutism

i

AN

Hirsutism. Hyper Androgcnism , Infertility. Insulin Resistance Acanthosis Nigricans

.

I

Infertility

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Figure 12. Pathophysiology of polycystic ovarian syndrome

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Toronto Notes 2023

GY25 Gynaecology Diagnosis • Rotterdam diagnostic criteria: 2 of 3 required oligomenorrhea / irregular menses for 6 mo

PCOS may be confused with • Late onset CAH (21- hydroxylase deficiency) • Cushing's syndrome • Ovarian and adrenal neoplasms • Hyperprolactinemia • Hypothyroidism

• hyperandrogenism

clinical evidence - hirsutism or acne biochemical evidence - raised free testosterone • polycystic ovaries on U /S ( not appropriate in adolescents ) Clinical Features

-

• average age 15 35 yr at presentation • in adolescents, wait at least I - 2 yr to make diagnosis as adolescence resembles PCOS • abnormal / irregular uterine bleeding, hirsutism , infertility, obesity, virilization • acanthosis nigricans: darkening of skin folds in intertriginous zones ( indicative of insulin resistance ) • insulin resistance occurs in both lean and obese patients

• FMHxofDM

Investigations

• assess BMI , BP, and fasting lipid profile at presentation goal: identify hyperandrogenism or chronic anovulation and rule out specific pituitary or adrenal disease as the cause • laboratory prolactin , TSH , free '14 17 hydroxy progesterone, LH:1'SH >2:1 ( LH is chronically high with l 'SH mid - range or low ( low sensitivity and specificity )) • increased DHEAS, androstenedione, and free testosterone ( most sensitive) • transvagina] or transabdominal U /S: polycystic-appearing ovaries “string of pearls” - 12 small follicles 2 -9 mm or increased ovarian volume (>10 cc) for insulin resistance or glucose tolerance tests • 75 g OGTT yearly ( particularly if obese ) • consider endometrial biopsy if long standing abnormal uterine bleeding to rule out hyperplasia • rule out other causes of abnormal bleeding

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Clinical Signs of Endocrine Imbalance • Menstrual disorder/amenorrhea (80%) , Infertility (74%) • Hirsutism (69%) Obesity (49%) • Impaired glucose tolerance ( 35%) DM (10%)

. .

Long - Term Health Consequences • Hyperlipidemia • Adult onset DM • Endometrial hyperplasia • Subfertility • Obesity • Sleep apnea

-

Treatment

• cycle control • lifestyle modification (decrease BMI, increase exercise ) to decrease peripheral estrone formation • hormonal 1 US, combined hormonal contraception or cyclic Provera" to prevent endometrial hyperplasia due to unopposed estrogen oral hypoglycemic (e.g. metformin ) if T2DM or if trying to become pregnant tranexamic acid (Cyklokapron*) for menorrhagia only • infertility medical induction of ovulation : letrozole, clomiphene citrate, human menopausal gonadotropins ( HMG ( Pergonal * )), LHRH , recombinant l'SH , and metformin metformin may be used in conjunction with clomiphene citrate for ovulation induction ovarian drilling ( perforate the stroma ), wedge resection of the ovary • rarely done • bromocriptine ( ifhyperprolactinemia ) • hirsutism any OCP can be used Diane 35* (cyproterone acetate): antiandrogenic Yasmin * (drospirenone and ethinyl estradiol ): spironolactone analogue ( inhibits steroid

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Diagnostic Ctiterii for Polycystic Ovary Syndrome Pitfalls « nd Controversies JOCC 2008:8:671-679 tt prevent , there is no deaa ent definition of biochemical hyperandrogenernia, parbcularly since there is dependence on poor laboratory standards for measuring androgens in women. Clinical signs of hyperandrogenism are iB -defir.ed in women wrtti PCOS. eoddagnoss of bob) hirsutism and polycystic ovarian morphology remains subjective. There is aisothe inappropriate tendencyto assign ovulatory status solely on the basis of menstrual cycle history or poorly timed endocrine measurements, therefore it is important as clinicians to recognize the multifactorial and complet nature ol PCOS and place this in the conteit of oor present diagnostic limitations.

-

receptors)

• mechanical removal of hair • finasteride (5-a reductase inhibitor) • flutamide ( androgen reuptake inhibitor ) spironolactone ( androgen receptor inhibitor )

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Toronto Notes 2023

GY26 Gynaecology

Gynaecological Infections Physiologic Discharge

-

• clear, white, flocculent, odourless discharge; pH 3.8 4.2 • smear contains epithelial cells, Lactobacilli • increases with increased estrogen states: pregnancy, OCP, mid-cycle, PCOS, or premenarchal

• if increased in perimenopausal / postmenopausal woman, consider investigation for other effects of excess estrogen (e.g. endometrial cancer)

Non- Physiologic Discharge • etiology genital tract infection vulvovaginitis: candidiasis, trichomoniasis, BV, polymicrobial superficial infection chlamydia, gonorrhea pyosalpinx, salpingitis • genital tract inflammation ( non-infectious) local: chemical irritants, douches, sprays, foreign body, trauma , atrophic vaginitis, desquamative inflammatory vaginitis, focal vulvitis neoplasia: vulvar, vaginal, cervical, endometrial • systemic: toxic shock syndrome, Crohn’s disease, collagen vascular disease, dermatologic (e.g. lichen sclerosis) IUD, OCP (secondary to progesterone)

Vulvovaginitis PREPUBERTAL VULVOVAGINITIS

• clinical features: irritation, pruritus, discharge, vulvar erythema , vaginal bleeding (can be due to (iroup A Streptococcus and Shigella ) etiology • • non -specific vulvovaginitis is responsible for 25- 75% of vulvovaginitis in prepubertal girls • there are a number of potential factors in children that increase the risk of vulvovaginitis: lack of labial development non - estrogenized , thin mucosa more alkaline pH ( pH 7) than postmenarchal girls/ women obesity poor hygiene ( proximity of anus to vagina) foreign bodies ( most commonly toilet paper ) irritation by bubble baths, shampoos, perfumed soaps, and chemicals localized skin disorders: lichen sclerosis, condyloma acuminata trauma: accidental straddle injury, sexual abuse infectious

Vulvovaginitis Vulvar and vaginal Inflammation

Vulvar Hygiene Recommend wipe front to back, wash vulva only with water , avoid daily pantyliners. avoid douching , no need for "feminine cleansers/sprays/ powders", use gentle laundry detergents for underwear, cotton underwear, no underwear at night

pinworms

Candida (if using diapers or chronic antibiotics) Group A Streptococcus, S. aureus, and Shigella discovery of STI should raise suspicion of sexual abuse other polyps, tumour ( ovarian malignancy ) psychosomatic vaginal complaints ( specific to vaginal discharge ) endocrine abnormalities ( specific to vaginal bleeding ) blood dyscrasia ( specific to vaginal bleeding ) other systemic diseases: measles, chickenpox, scarlet fever, Hpstein Barr Virus, Mycoplasma pneumonia induced rash and mucositis, Stevens lohnson syndrome, Crohn 's disease, and Kawasaki disease have all been associated with vulvovaginal signs and symptom • investigations • vaginal swab for culture (specifically state that it is a pre pubertal specimen ) pH, wet mount, and KOH smear in prepubertal adults only • treatment enhanced hygiene and local measures ( handwashing, white cotton underwear, use sitz baths, use mild detergent , urinate with legs spread apart, no nylon tights, no tight - fitting clothes, no sleeper pajamas, avoid bubble baths, eliminate fabric softener, avoid prolonged exposure to wet bathing suits) to protect vulvar skin • infectious: treat with antibiotics for organism identified

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-

-

-

Prepubertal and Adolescent Gynaecological Infections: Legal Aspects of Confidentiality Clinicians who treat adolescents must be aware of federal, state, and provincial laws related to adolescent consent and confidentiality • Clinicians must be aware of guidelines governing funding sources for particular services and be familiar with the consent and confidentiality policies of the facility In which they practice

.

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Most common gynaecological problem in prepubertal girls is non- specific vulvovaginitis, not yeast

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Toronto Notes 2023

GY 27 Gynaecology

Table 14. Other Common Causes of Vulvovaginitis in Prepubertal Girls Pinworms

Lichen Sclerosis

Foreign Body

Diagnosis

Cellophane tape test

Area of white patches and thinning of skin (figure of 8)

Careful examination with or without sedation

treatment

empirical treatment with mchendarole [anthelmintic)

Topical steroid creams

Irrigation of vagina with saline, may require local anesthesia or an exam under anesthesia

INFECTIOUS VULVOVAGINITIS

Table 15 . Infectious Vulvovaginitis Organisms

Candidiasis

Bacterial Vaginosis (BV )

Trichomoniasis

Condida albicans (90%) Candida glabrala («5%) Condida Iropicolis (20% clue cells * squamous

Petcchiae on vagina and cervix Occasionally irritated, tender vulva Dysuria frequency, dyspareunia

.

s 4.5

epithelial

cells dotted with coccobacilli [ Cordnerella] Paucity of W 8C Paucity of Lactobacilli Positive whilf test: fishy odour with addition ol KOH to slide (due to formation ol amines)

Motile flagellated organisms Many V/ 8 C Inflammatory cells (PMNs) Can have positive whiff test

Ho treatment it non- pregnant and asymptomatic, unless scheduled for pelvic surgery or procedure Oral Metronidazole 500 mg P0 BID x 7 d * Oral treatment is best in pregnancy Vaginal Metronidazole 0.75% gel x 5 d once daily Clindamycin 2% 5 g intravaginally at bedtime lot 7 d Probiotics { loctobocillus sp ): oral or topical alone orasadjuvant

Treat even if asymptomatic Metronidazole 2 g P0 single dose or metronidazole 500 mg BID x 7 d (alternative) Symptomatic pregnant women should be treated with metronidazole 2 g once

Associated with recurrent preterm labour, preterm birth, and postpartum endometritis Routine treatment of partner (s) not recommended (not sexually transmitted)

Treat partner(s) (sexually transmitted)

.

Other

Prophylaxis for recurrent infection includes boric acid, vaginal suppositories, luteal phase fluconazole Routine treatmentof partner (s) not recommended (not sexually transmitted)

* Need to warn patients on metronidazole nottoconseme alcohol (dlsultlram.like action }

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GY 28 Gynaecology

Sexually Transmitted Infections

IS

• see Family Medicine , 1 M46

FALLOPIAN TUBE

SPECULUM EXAM

CDC Notifiable Diseases

• Chancroid

•

Chlamydia

.•

Hepatitis A, B. C

• Gonorrhea HIV

• Syphilis

Pelvic inflammatory disease ( PID ) Gonorrhea Chlamydia

LABIA MAJORA

ABIAMINURA leipes

.

«1« Syphilis 1. Chancre sore 2. Condylomatalata

I

HP V warts

Risk Factors for STIs History of previous STI Contact with infected person Sexually active individual < 25 yr Multiple partners • New partner in last 3 mo • Lack of barrier protection use • Social factors ( homelessness, drug use)

• • • •

richomomasis ( yellow-green frothy discharge )

(#)ANUS

Figure 13. Speculum exam TRICHOMONIASIS • see Infections Vulvovaginitis, GY 27 CHLAMYDIA

Etiology • Chlamydia trachomatis

Epidemiology

• most common bacterial STI in Canada • often associated with N. gonorrhoeac ( patients with chlamydia should also he tested for gonorrhea ) Clinical Features • asymptomatic ( 80% of women ) • muco- purulent endocervical discharge • urethral syndrome: dysuria, frequency, pyuria, no bacteria on culture • pelvic pain • postcoital bleeding or intermenstrual bleeding ( particularly if on OCP and prior history of good cycle control ) • symptomatic sexual partner Investigations

• cervical culture or nucleic acid amplification test (can present in pharynx , rectum ) • obligate intracellular parasite: tissue culture is the definitive standard • urine and self vaginal tests now available, which are equally or more effective than cervical culture Treatment • doxycycline 100 mg PC) BID for 7 d or azithromycin 1 g PC) in a single dose Doxycycline is contra - indicated in the 2 nd and 3rd trimesters of pregnancy • reportable disease, test and provide empiric treatment to all sexual partners of the index case within 60 d prior to symptom onset or dale of specimen collection ( if the index case is asymptomatic) • test of cure is recommended 3 wk after completion of treatment when compliance to treatment is suboptimal, an alternative treatment regimen is used, experiencing persistent symptoms, or the person is prepubertal or pregnant

Screening • during pregnancy • asymptomatic sexually active people under 25 yr • neonates born to mothers with chlamydia

• any other people with risk factors for sexually transmitted and blood- borne infections

ft STI Testing • Vaginal swab • Tests for bacterial vaginosis, trichomoniasis Candida • Cervical swab • Tests for gonorrhea and chlamydia

.

Test of cure for C. trachomatis and N. gonorrhoeae is not routinely indicated Repeat testing if symptomatic, if compliance with treatment is uncertain , or if pregnant

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GY29 Gynaecology

Toronto Notes 2023

Complications • PID: low -grade salpingitis and adhesions resulting in tubal obstruction • infertility • ectopic pregnancy • chronic pelvic pain • Fitz-Hugh -Curtis syndrome ( liver capsule inflammation ) • reactive arthritis ( male predominance , HLA - B27 associated ), conjunctivitis, urethritis • perinatal infection: conjunctivitis, pneumonia GONORRHEA Genital Warts During Pregnancy

Etiology • Neisseria gonorrhoea? • symptoms and risk factors same as chlamydia

• Condyloma tend to get larger in

pregnancy and should be treated early (consider excision ) • Removal only if obstructing birth canal or risk of extensive bleeding • Do not use imiquimod, podophyllin , or podofilox in pregnancy • Baby at risk for juvenile respiratory papillomatosis, but cone dissection does not significantly reduce the risk

Investigations • Gram stain shows Gram - negative intracellular diplococci • cervical , rectal, and throat culture ( if clinically indicated ) Treatment

• single dose of ceftriaxone 250 mg IM plus azithromycin 1 g PO if pregnant: above regimen or spectinomycin 2 g IM plus azithromycin 1 g PO (avoid quinolones) • also treat chlamydia , due to high rate of co infection • treat partners

-

• reportable disease screening as with chlamydia

HUMAN PAPILLOMAVIRUS Etiology • most common viral ST'l in Canada • >200 subtypes, of which >30 are genital subtypes • HPV types 6 and 11 are classically associated with anogenital warts/condylomata acuminata • HPV types 16 and 18 are the most oncogenic (classically associated with cervical HSIL ) • types 16, 18, 31, 33, 35, 36, 45 (and others ) associated with increased incidence of cervical and vulvar intraepithelial hyperplasia and carcinoma • HPV is readily transmissible between opposite and same sex partners through receptive and penetrative vaginal, anal and oral sex , and non penetrative sex ( digital vaginal sex and skin to skin contact ) infection with one HPV type does not appear to provide protection against infection with related

-

-

-

- -

HPV types Clinical Features • latent infection no visible lesions, asymptomatic only detected by DNA hybridization tests • subclinical infection visible lesion found during colposcopy or on Pap test • clinical infection visible wart like lesion without rnngni Acation (check pharynx too)

-

hyperkeratotic, verrucous or flat , macular lesions • vulvar edema

Human Rights in Health Equity: Cervical Cancer and HPV Vaccines Am JIdA Med 2009.3S 36S 3 B 7 While cervical cancer rates have drastically (alien In developed countries due lo effective prevention and treatment, socially disadvantaged women within these countries remain disproportionately more lively to develop and die olcervical cancer. • In most develop ng countries cervical cancer rates have risen or remained unchanged. • It must be recognized that cervical cancer disparities between race groups, urban and rural residence.and high and low socioeconomic status are attributed to dispaiate screening and vaccination coverage. • Programs are implemented without sufficient attention to conditions that lender screening less effective ov inaccessible to disadvantaged social groups including: lack ol information , undervaluing ol prevenbve care, opportunistic delivery In kmlled healthcare settings, setual health stigma , and related privacy concerns.

A 9 Valent HPV Vaccine Against Infection and Intraepithelial Neoplasia in Women NEJM 2015:372:711 723 Purpose: lo determine the efficacy and immunogen city of the qHPV ( types 6, 11, 16.18) vs. 9 vHPV (five Jddt onal types 31.33 45.52 58)

-

vaccines.

Treatment

• anogenital svarts • patient administered podofilox 0.5% solution or gel BID x 3 d in a row ( 1 d off ) then repeat x 4 wk imiquimod ( Aldara* ) 5% cream Jx / wk nightly x 16 wk sinecatechins 10% ointment 0.5 cm strand T ID x up to 16 wk , daily dose 250 mg ( need not be washed off )

-

.

-

Method itteinalio alrandonnted . double- blinded phase 28 3 study of 9vHPV va tc me i n 14215 worn eu between agesol 16-26. Participants were random it ed lo the 9rHPV vaccmegroup or the qHPIf vaccine group and each recerr ed a series of three IM inactions (d 1.2 mo and 6 mo). Swabs ol labial, valvar, perineal, perianal , endocenrical. and ectocervical tissue was obtamedend used for HPV DM A testing /Pap smear. Results: Pate ol high -grade cervical, vulvar, or va gi nal disease was14.0 per 1000 person-yr in both vaccinegroups.Tbe rate of bigh -grade cervical, vulvar, or vagnal disease related to HPV 31, 33.45 52 and 58 was 0.1 per 1000 person yr in the 9 vHPV group and 1.6 per 1000 person yr in the qHPV group (95% CI 80.9 99.81. Antibody responses to HPV 6, 11, 16. and 18 were not sign ficantly different between the two vaccine groups although adverse events related lo injection vies weie more common n the 9vHPV group. Conclusions the 9iHPV vaccine was non - inferior to qHPV vaccine in prevent ng infection and disease related to HPV- 6.11. K. and 18 and also coveved additional oncogen c types KPV- 31.33. 45.52 and 58

-

Investigations • cervical cytology by Pap test • koilocytosis: nuclear enlargement and atypia with perinuclear halo • biopsy of lesions at colposcopy • detection of HPV DNA subtype using nucleic acid probes ( not routinely done but can be done in presence of abnormal Pap test to guide treatment )

.

.

.

- -

in a susceptible popnlabon.

-

-

.

-

-

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Toronto Notes 2023

GY30 Gynaecology

provider administered cryotherapy with liquid nitrogen: repeat ql 2 wk podophyllin resin in tincture of benzoin : weekly trichloroacetic acid (TCA ) (80 90%) or bichloroacetic acid weekly x 4 6 wk; safe in pregnancy surgical removal /laser • intraepithelial lesions and cancers (See Gynaecological Oncology, GY42 )

-

-

-

Prevention

• vaccination: Gardasil‘9, Gardasil", Cervarix* (see Table 28, GY49 ) •condoms may not fully protect (areas not covered, must be used every time throughout entire sexual act)

HERPES SIMPLEX VIRUS OF VULVA

.Etiology are HSV -2, 90%

10% are HSV -1

Clinical Features

• may be asymptomatic • initial symptoms: average incubation is 4 d after exposure ( range 2- 12 d ) • prodromal symptoms: tingling, burning, and pruritus • multiple, painful, shallow ulcerations with small vesicles appear 7-10 d after Initial infection (absent in many infected persons ); lesions are infectious • inguinal lymphadenopathy, malaise, and fever often with first infection • dysuria and urinary retention if urethral mucosa affected • recurrent infections: common but less severe, less frequent, and shorter in duration ( usually only HSV 2)

-

Investigations

• viral culture preferred in patients with ulcer present; however, decreased sensitivity as lesions heal • HSVDNAPCR • cytologic smear ( Tzanck smear ) shows multinucleated giant cells, limited use due to low sensitivity and specificity • type specific serologic tests for antibodies to HSV- 1 and HSV-2 ( not routinely available in Canada ) Treatment

• first episode: acyclovir 200 mg PO five times daily x 7-10 d, famciclovir 250 mg PO T1D x 7-10 d, or

-

valacydovir 1 g PO BID x 7 10 d

• recurrent episode: acyclovir 400 mg PO TTD x 5 d, famciclovir 125 mg PO BID x 5 d , or valacydovir I g PO once daily x 5 d

• daily suppressive therapy

consider for >6 recurrences per yr or recurrence every 2 mo

• acyclovir 400 mg PO BID, famciclovir 250 mg PO BID, valacydovir 500 mg PO once daily, or

valacydovir 1 g PO once daily • severe disease: IV acyclovir 5 10 mg/ kg IV q 8 h x 2 7 d or until clinical improvement observed followed by oral antiviral therapy to complete 10 d of total therapy • education regarding transmission: avoid sexual contact from onset of prodrome until lesions have cleared, use barrier contraception

-

-

SYPHILIS

Etiology

• Treponema pallidum Classifications

Epidemiology of Genital Ulcere

• primary syphilis

HSV

7080%

painless chancre on vulva , vagina, or cervix painless inguinal lymphadenopathy • serological tests usually negative, local infection only • secondary syphilis (can resolve spontaneously ) • 2 6 mo after initial infection , in 25% of patients with untreated primary syphilis • nonspecific symptoms: malaise, anorexia , headache, and diffuse lymphadenopathy • generalized maculopapular rash: palms, soles, trunk, and limbs • condylomata lata: anogenital, broad -based , fleshy, grey lesions serological tests usually positive • latent syphills no cliinical manifestations; detected by serology only

r Syphilis

5%

Chancroid

45 yr: no testing necessary 40 -45 yr: p- hCG, prolactin, TSH 35 IU / L ) on day 3 of cycle ( if still cycling) and LH ( FSH > LH ) • FSH level not always predictive due to monthly variation; use absence of menses for 1 yr to diagnose • decreased levels of estradiol ( later )

1 i

-

Increased FSH and LH

Stromal cells continue to produce androgens as a result of increased LH stimulation

Figure 18. Menopause pathophysiology

Treatment • goal is for individual symptom management • 85% of women experience hot

Table 17. Treatment of Menopause

flashes

Urogenital Health

Osteoporosis

Instability

Vaginal Atrophy

Menopause hormonal therapy ( MHI ) as first

local estrogen:

cream ( Premarin '

lifestyle changes ( weight loss, bladder training ) , pelvic floor exercises, local estrogen replacement ,

Calcium 10001500 mg once

Vasomotor

.

line SSRI , venldlaxiiie, gabapentin propanolol , donidine,

.

.

acupuncture

behavioural modifications

or Estragyn Vaginal

Cream - ), vaginal suppository (VagiFems) ring ( Estring - )

lubricants

..

( Replens : ). intravaginal laser

surgery

Decreased

.

Mood and

Libido

Memory

Vaginal lubricants, Manage CVD counselling, risk factors androgen

Anti depressants (lirsl line ) MHI (augments elfcct ), CBT

-

daily , vitamin replacement 0800 1000 ID weight bearing testosterone exercise, smoking cream or the oral cessation. form ( Andriol 3)

-

CVD'

• 20-30% seek medical attention • 10% are unable to work

.

bisphosphonales

(e.g. alendronate).

SERMs (e.g.raloxifene (E vista 3)) HUT (second line

-

.

treatment ) 'CVD (cardiovascular disease)

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Toronto Notes 2023

GY37 Gynaecology

Menopause Hormone Therapy • see family Medicine, IM I 3 Treatment Guidelines • primary indication is treatment of menopausal symptoms ( vasomotor instability) should not be prescribed if the only objective is the prevention of chronic disease • before starting, review the benefits and risk (see Table 18 ) and contraindications with the patient • use the lowest effective dose; patients with standard dose should be advised to lower dose after a few

years • patients receiving MHT must be evaluated annually • decisions around duration of treatment should be individualized , but recommended to avoid treatment >5 yr with combination estrogen and progesterone treatment due to the duration dependent risk of breast cancer • tapering and abruptly discontinuing MH 'l have similar impact on symptom recurrence, but for patients with a history of severe baseline vasomotor symptom , gradual tapering is probably

-

preferable Benefits

Risks

Reduction of vasomotor symptoms Reduction of sleep problems Reduction of mood or anxiety problems Reduction of aches and pains Osteoporosis prevention and treatment Reversal of vulvar and vaginal atrophy (local eslrogen therapy recommended il such atrophy is the only Indication for therapy)

Ihromboemholic events

Stroke

Breast cancer (increased risk after 4- 5 yr with estrogen -progesterone regimens, noincreased risk (oral least 8 yr with estrogen- alone regimens) Coronary heart disease ( for women age >60 and those who are >10 yr after menopause) Endometrial hyperplasia and cancer ( with estrogen -only regimens)

MHT Components

• estrogen • oral or transdernial ( e.g. patch , gel ) • transdernial preferred for women overall, especially with hypertriglyceridemia or impaired hepatic function, smokers, and women who suffer from headaches associated with oral MHT, due to decrease risk of VTE low -dose ( preferred dose: Premarin' 0.3 mg / Estradot* patch 25 pg, can increase if necessary ) • progestin given in combination with estrogen for women with an intact uterus to prevent development of endometrial hyperplasia/cancer

;

No

1

Yes

Free of broast cancer endometrial cancer, venous thromboembolism, CHD, strokc/TIA and other contraindicaions to HT and interested in considering HT? No

.

No

Yes

1

Prior Hysterectomy? * Yes - Sec estrogen- only options in Table 19 • No = See combined estrogen-progestin options in Table 19

k

No

I

_

lubricants and/or moisturizers

• Consider

low -dose vaginal estrogen if response is

inadequate

lubricants and/ or moistunzers

Yes

£

low -dose

paroxetine or other

Assess CVD risk and time since menopause onset Yrsince menopause onset

sM « 5 •

10

HTOK

Avoid HT

Avoid HT HTOK (chODSC Ichoose transdermat ) transdcrmall

| Avoid HI o High l > 10: o!

Avoid HT

Avoid HT

S

well-studied

SSRIs/SNRIs Ivcnlafaxino,

cscitaloprarn, others) if no contraindications

.

.

.

Cardiovascular disease is the leading cause of death post -menopause

Increased risk of breast cancer (RR 1.3) is associated with estrogen+progesterone HRT but not with estrogen- only HRT

No

£

.

• Avoid

SSRIs/SNRIs

• Consider

gabapentin, pregabalin or clonidine if no contra

.

All women taking HRT should have periodic surveillance and counselling regarding its benefits and risks

-

indications

l ri

Adequate control of hot flashes?

Yes

LJ

No

I • Continue

low -doso

DECISION ABOUT DURATION OF USE continued moderatc -to- scvcrc symptoms; patient preference; weigh baseline nsks of breast cancer, CVD, and osteoporosis

.

.

.

Eroo of contraindications to SSRIs/SNRIs?

• Considor

• Vaginal

• Vaginal

.

Osteoporosis is the single most important health hazard associated with menopause

Yes

t Genitourinary symptoms such as vaginal dryness or pain with intercoursc/ scxual activity

f Avoid HT

.

cessatonofHT. Results: 22 studies with 43632 women included. Host studies included postmenopausal American women with at least some degree ol comorbidity, with a mean participant age oner 60 yr. Combined continuous HI:increased risk of coronary event after 1yr (from 2 /1004 to 3-7 /1000) venous thromboembolism after 1 yr (2 /1000 to 4 11/1000) stroke alter 3 yr (6 /1000 to 6 -12 /1000) breast cancer after 5.6 yr |19 1000 to 20 -30/1000) gallbladder disease after 5.6 yr (27/1000 to 38 -60 /10001, and death from lung cancer after 5.6 yr use plus 2.4 yr additional follow up (5 /1000 to 6 -13 /1000). Estrogen only HI: increased risk ol venous thromboembolism alter 1-2 yr use 12 /1000 to 2-10 /1000; alter 7 yr 16 / MOO to 16 - 28 / 1000), stroke after 7 yr (24 /1000 to 25 - 40 /1000) and galtbi adder disease after 7 yr use (27/1000 to 38 -60 /1400) but reduced the risk of breast cancer alter 7 yr ( 25 /1000 to 15 - 25 /1000 and clinical fracture alter 7 yr (141/1000 to 92 -113 /1000 ) Women >65 yr ol age taking combmed HI had shown an increase in the incidence of dementia after 4 yr use (9/1000 to 11-30/1004). for women with cardiovascular disease, use of combined conbnuous HI sigitifutilly increased the risk ol venous thromboembolism al 1 yr (3 /1000 to 3-29 /1400). Conclusions: HI may be contraindicated for some women with increased risk of cardiovascular disease, thromboembolic disease, and certain cancers socb as breast cancer in women with a uterus HI is not indicated lor pnmary or secondary prevention ol cardiovascular disease, dementia, or deterioration ol cognitive function.

(#

Moderatc - to - scvcrc hoi flashes end/or night sweats ( and inadequate response to bchavioural/lifcstyle modifications)

Froo of breast cancor, endometrial cancer, and other homronc -sensitrve cancers?

.

'

Table 18. MHT Benefits vs . Risks

Yes

tong - Tcrm Hormone Therapy for Perlmcnopausal and Postmenopausal Women Cocfcra -e DB Syst Per 2017:tt D004143 Purpose To determine tire effect of long -term HI (hormone therapy) on mortality cardiovascular outcomes, cancer, gallbladder disease, fractures, cognition, and quality ol life (001) in perimenopausal and postmenopausal women.dunngHT use andafter

paroxotino or other

SSRIs/SNRIs

• Adiustdose

+

or consider gabapentin pregabalin or clonidine

.

Figure 19. Hormone therapy in menopause

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Toronto Notes 2023

GY38 Gynaecology

Table 19. Examples of MHT Regimens MHT Regimen

Trade Names

Estrogen - only - oral

Estrace Premara : Estragyn : Patches: Estradot :. Sandoz Estradiol Derm ; Oesdia - Climara Gel : !

-

Estrogen- only transdermal

.

Estrogel Oivigel : Estrogen - only - vaginal

-Combined E -P - transdermal Combined E P oral

-

Standard Doses

-

17 8 estradiOl 0.5 -1 mg tablet dally CE 0.3 0.625 mg tablet daily Esterrfied estrogens 0-3-0-625 mg cyclic

-

. 17 fl - estradiol 25-100 pg1-2x /wk 1- 2 metered dosev'actualion daily 0.25-1 mg packets daily

Cream: Premarin 3 Estragyn ' Inserts: Vagrfem : Ring: Estr .ng :

CE 0.625 mg 'g Estrone 1 mg' g 17 p-estradiol 10 pg 17 (l-estradiol 2 mg

Actrvelle " Angeiiq -

1 mg 17 9- estradiol 0.5 mg NEA 1 mg 17 O - eshadioll mg drosprrenone

Patch: Estahs ( 2 doses available )

17 P estradiolHEA: 50140 mpg continuous 2xi'wk 50.140 mag or 50250 mpg cyclic 2*/vvk

-

-

CE*conjugated estrogen: E P - estrogen progestin: NEA - noretlrindrone acetate Current common practice Includes using trie Mrrera IUO as the progesterone component pevonorgesbel 52 mg over 5 yr . approximately 20 us d )

Side Effects of MHT • estrogen

• breast tenderness • nausea

headache • bloating • progestins

• mood alterations • breast tenderness • bloating sedation ( micronized progesterone) Contraindications to MHT •

absolute acute liver disease

undiagnosed vaginal bleeding history of breast cancer known or suspected uterine cancer / breast cancer acute vascular thrombosis, or history of severe thrombophlebitis or thromboembolic disease cardiovascular disease •

relative pre-existing uncontrolled HTN uterine fibroids and endometriosis familial hyperlipidemias migraine headaches • family history of estrogen -dependent cancer • chronic thrombophlebitis • DM ( with vascular disease )

Menopausal Hormone Therapy end Health Outcomes During the IniErreitkii and Eitended Poststopping Phases of the Women's Health Initiative Randomized Trials

JAMA 2013:310:1353-1363 Purpose: Toreport com pre’e'snt rings from the 2 Women 's Health Initiative (181) to ate therapy trials with eitended postmteneutoa f: wr up. Methods: 4 total of 27341 posr r::a sz women ages 50 - 79 were enrolled a:40 US centers la the C £ t * MPA trial. 166 33 noreLwit atadutcns. received either conti nuoascorh ed H!I ( CEE 0.625 mg MPA 2.5 rag once daily) or osteho. hr tie CEEonly trial, 10739 women, wdt pcor ysferectomy. received either CEE 0.625 -g once teiy or p aceoo. Results: Results al : reported as cases per 10000 person - yr, stratified for age (50-59.60-69.70-79 :) • CEE MPJCHD: 6 additional cases (50 591.0 additional cases 160 -69).19 sddtoat cases (70 79| • CEE MP& Invasive toast catcer: 6 Mdrtrotal cases (50-59). 7 additional cases (6069).15 additional cases (70 -79) CEE MPA Stroke: 5 addrtnral cases (50-59).11 additional cases (60-69).13 addrtnral cases (70 79| • CEE MPi PE: 6 additional cases (50-591. S additional cases (60-69).18 addtncal cases (70 ?9| CEE ^ MPA ColcrecUl cancer: T fencer case (50 S9). 8 fewer cases (60 -69). 17 fewer cases ( 70- 79) • CEE MPA Hip iractuies: 2 lews cases (50-59). 3 fewei cases (60 -691. H lews cases (79-79) CEE -only CHD: 11 lew« cases (50-59).2 fewer cases (60 -69) 7 addrtnral cases (70-791 • CEE -only Invasive breast cancer 5 fewer cases ISO59). II iewee cases (60-691.5 fewer cases (70-79) • CEtonlySlmte: lienee case (50 59).ttadSional cases (60-69).18 additional cases (70 791 • CEE only PE: 4 additional cases (50-59).7 additional cases|60-69|. 2 fewer cases (70-79) • CEE only Colorectal cancer 3 fewer cases|50 59|. 3 (ewer cases (60 -69).18 arkhbceal cases (70 79) • CEE only Hip Iraclures: 3 edtoccalcases (50 59) 7 fewei cases (60 -69). 21 fewer cases (29-79)

—

-

-

-

.

,

-

-

-

-

-

-. -

.

-

-

.

-

-

-

- .

Absolute Contraindications to MHT

ABCD Acute liver disease Undiagnosed vaginal Bleeding Cancer ( breast uterine) Cardiovascular disease DVT (thromboembolic disease)

-

.

• gallbladder disease, hypertriglyceridemia , and impaired liver function ( consider transdermal

estrogen ) • fibrocystic disease of the breasts

-

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Toronto Notes 2023

GY39 Gynaecology

Urogynaecology Sacrum

i

fr

.c 2

Small intestine

ligaments

I

5

1

Uterus Reek Vaginal Canal rlird

Rectocele

Cystocele

Uterine Prolapse

Enterocele

Figure 20. Pelvic anatomy

Pelvic Organ Prolapse Etiology • related to:

vaginal childbirth aging decreased estrogen ( post- menopause ) increased intra -abdominal pressure (obesity, chronic cough, constipation, ascites, heavy lilting ) ethnicity (greater incidence in White women > Asian or African women) connective tissue disorders Diagnosis • medical history assess symptoms specific to prolapse: pressure, bulge assess urinary, defecatory, and sexual concerns, which are often associated with pelvic organ

prolapse • physical exam (each component with patient relaxed and then while straining) » inspection in the dorsal lithotomy position evaluate for apical prolapse with a bivalve speculum exam, then evaluate for anterior and posterior prolapse with the posterior blade of the bivalve speculum use the POP-Q staging system to quantify stage of prolapse evaluate for any coexisting pelvic abnormalities with a bimanual exam test the strength of pelvic floor muscles with voluntary Kegel contractions • ancillary studies if continent with apical prolapse, consider clinical or urodynamic testing with and without reduction of prolapse to investigate for occult stress urinary incontinence if voiding symptoms, consider post-void residual volume to evaluate urinary retention if urgency or other UT1 symptoms, consider urine microscopy and culture to test for UT1 GENERAL CONSERVATIVE TREATMENT

• weight loss • pelvic floor muscle training (e.g. Kegel exercises, pelvic physiotherapy ) • local vaginal estrogen therapy • vaginal pessary ( intravaginal devices that are either supportive or space-occupying)

Pelvic Organ Prolapse A weakening in the structures of the pelvic floor resulting in descent of one or more of the pelvic structures ( bladder / rectum/smatt intestine/ uterus) into the vagina

H

-

POP Q Staging of Pelvic Organ Prolapse • 0 no prolapse • 1 most distal portion of prolapse on above level of hymen • 2 most distal portion of prolapse is between 1 cm above or below the hymen • 3 most distal portion of prolapse >1cm below level of hymen but no further than 2 cm less than the total vaginal length • 4 complete procidentia (uterus present with complete herniation of anterior, posterior, and apical compartments) or vault eversion (no uterus present with complete eversion of the anterior, posterioc and apical compartments), most distal prolapse protrudes 2 cm of total vaginal length

-

-

-

n LJ

Ihe primary clinical features of pelvic organ prolapse are vaginal bulge and pressure

+

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GY 40 Gynaecology

Table 20. Types and Management of Pelvic Organ Prolapse Type

Clinical Features

Treatment

Anterior Vaginal Wall Prolapse (previously "cystocelo") (protrusion of bladder into the anterior vaginal wall)

Frequency, urgency,nocturia Stress incontinence Incomplete bladder emptying 2 associated increased incidence olUTIs (may lead to renal impairment)

General conservative treatment (see above) Anterior colporrhaphy ( “anterior repair *) Consider additional/alternative surgical procedure if documented urinary stress incontinence

Posterior Vaginal Wall Prolapse (previously ”) (protrusion of rectum into posterior vaginal wall)

Straining/ digitation to evacuate stool Constipation

General conservative treatment (see above) Also laxatives and stool softeners Posterior colporrhaphy (“posterior repair *), plication ofendopelvic fascia and penneal muscles approximated in midline to support rectum and perineum (can result in dyspareunia)

Uterine Prolapse (protrusion of cervix and uterus mto vagina)

A type of apicalprolapse Groinfback pain (stretching of uterosacral ligaments) Feeling of heaviness pressure in the pelvis Worse with standing lifting Worse at the end of the day Relieved by lying down Ulceration/bleedng (particularly if hypoestrogenic) 2 urinary incontinence

General conservative treatment (see above)

"rectocele

,

Vault Prolapse (previously "enterocele ".protrusion of apex of vaginal vault into vagina,post- hysterectomy, often containingsmall bowel)

A type of apical prolapse Same as uterineprolapse

Vaginal hysterectomy 2 surgical prevention of vault prolapse Consider additional surgical procedures if urinary incontinence, cystocele. rectocele. and'or enterocele are present

General conservative treatment (see above) Sacralcolpopexy ( vaginal vault suspension), sacrosp nous Fixation, or uterosacral ligament

The only true hernia of the pelvis is an ENTEROCELE because peritoneum

suspension

herniates with the small bowel

Surgery: native tissue repair vs.mesh reconstruction (usually reserved for severe, recurrent prolapse)

Urinary Incontinence • see Urology, U6 STRESS INCONTINENCE

Definition • involuntary loss of urine with increased intra-abdominal pressure (cough , laugh , sneeze, walk, run ) • affects 4 - 35% of all women

Risk Factors for Stress Incontinence in Women • increased age • obesity • pregnancy/ vaginal delivery • hypoestrogenic state ( post- menopause) • smoking /chronic cough • neurological

• genetics • high impact exercise Diagnosis • history » onset, frequency', severity, and pattern of urinary' incontinence frequency, dvsuria, urgency, and nocturia pads used per 24 h • obstructive urinary symptoms ( incomplete voiding , hesitancy, straining, post void dribbling, and recurrent Ull ) • pelvic organ prolapse symptoms • neurological conditions /symptoms • obstetric history, and current menopause / hormone therapy status medications ( sedatives, diuretics, anticholinergic medications, and OTCs) lifestyle risk factors (caffeine, smoking, weight, exercise, and occupation ) urinary diary

-

• physical exam height, weight, and BM1 • abdominal exam: scars, abdominal mass, and presence of a full bladder neurological exam: S2-S4 sacral nerves ( motor, sensory, and reflexes) elderly: mini mental status exam, and observe mobility » pelvic exam: inspect vulva and urogenital epithelium, assess for signs of pelvic organ prolapse, and digital rectal exam to assess for anal sphincter tone and perineal sensation • standing stress test

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GY41 Gynaecology

• studies urinalysis: hematuria, pyuria, ghicosuria, proteinuria hematuria / irritative voiding symptoms: cytology pyuria/ bacteria; urine culture

post-void residual normal 1/3 total volume ( poor bladder contractility or bladder outlet obstruction) urodynamic testing Society of Obstetricians and Gynaecologists of Canada (SOGC): uncertain diagnosis, fails to improve with treatment, clinical trials, or surgical intervention is planned

Treatment • for conservative management, see Pelvic Organ Prolapse , GY39

• procedures: vaginal laser, urethral bulking • surgical « midurethral sling ( TVT, TOT ) urethropexy ( Burch procedure) pubovaginal sling • urethral bulking OVERACTIVE BLADDER

Definition

• symptom syndrome defined as "urgency, with or without urge urinary incontinence ( UU1), usually with frequency and nocturia”

• 16% of all women • UU1: involuntary leakage with or immediately preceded by a strong desire to void involuntary bladder contraction that overcomes the urethral sphincter mechanism OR poor bladder compliance Etiology • idiopathic: congenital and aging • medical: CHF, DM, and diuretics • neurogenic: multiple sclerosis, Parkinson s, CVD, dementia, and spinal cord injury • bladder outlet obstruction: previous bladder neck surgery and pelvic organ prolapse • gynaecologic: UT1, pregnancy, pelvic mass, and urethral diverticulum • psychosomatic: habits, anxiety, and high fluid consumption Diagnosis • see Stress Incontinence, GY40 for diagnosis

. behaviour bladder intake regular voiding schedule Treatment

modification ( reduce

water

irritants (caffeine, smoking, alcohol, acidic, spicy); adequate

)

;

• bladder training with pelvic physiotherapist • medications

anticholinergics

; patch: Oxytro!*; transdermal gel: Gelnique') • oxvbutynin ( oral: Ditropan * *

tolterodine ( Detrol )

fesoterodine ( Toviaz * ) ( Vesicare’) solifenacin • • trospium (Trosec*) * darifenacin ( Enablex ) • (J-adrenergic agonist: mirabegron ( Myrbetriq*) • procedures: sacral neuromodulation , detrusor botox injection

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GY42 Gynaecology

Gynaecological Oncology Pelvic Mass ( Pelvic Mass ]

Functional Cysts

lalways benign )

Corpus luteum cyst Follicular cyst Theca lutein cyst Hemorrhagic cyst

f

Neoplasm

v

.

[ Ovarian )

[

Benign

Imost common ) Endometrioma

[

Uterine

±

f Symmetrical )

( Asymmetrical j

PCOS Tubo-ovarian abscess Luteoma of pregnancy

Pregnancy

Hematometra'pyometra

Adenomyosis Leiomyoma Leiomyosarcoma

Malignant Epithelial cell Imost common in >40 yr) Germ cell ( most common in 50 yr • causes more deaths in North America than all other gvnaecologic malignancies combined • 4 th leading cause of cancer death in women • 85% epithelial; 15% non epithelial • 10 15% of epithelial ovarian cancers are related to hereditary predisposition

-

-

Risk Factors (for epithelial ovarian cancers ) • early menarche and /or late menopause • personal history of hreast, colon, or endometrial cancer • family history of breast, colon , endometrial, or ovarian cancer • advanced age • BUGA mutation ( serous) and Lynch syndrome ( non serous, non - mucinous )

• use of fertility drugs ( limited evidence )

-

Protective Factors ( for epithelial ovarian cancers) • OCR: likelv due to ovulation suppression ( significant reduction in risk even after 1 vr of use, 50% alter 5 yr) • pregnancy/ breastfeeding Prophylactic Measures • prophylactic BSO in high - risk women ( i.e. BRCA mutation carriers ) • prophylactic salpingectomy in high - risk women ( i.e. BRCA mutation carriers who do not want oophorectomy yet ) Screening • no effective method • routine CA -125 or U /S not recommended

Clinical Features • most women with epithelial ovarian cancer present with advanced stage disease ( i.e. stage I 11C high

grade serous histology ) • symptoms: • abdominal symptoms ( nausea , bloating, pain, dyspepsia, anorexia, early satiety ) • symptoms of mass effect increased abdominal girth ( from ascites or tumour itself ) urinary urgency and frequency

• constipation

Diagnosis of ovarian tumours requires surgical pathology

Any adnexal mass in postmenopausal women should be considered malignant until proven otherwise

Omental Cake: a term for ascites plus a fixed upper abdominal and pelvic mass; almost always signifies ovarian cancer

Screening forOvarian Cancer Updated Evidence Deport and Systematic Review for the US fteventive Services Task Force JAMA 2018:319(6):595 606 Purpose : lo systematically review evidence on benefits and harms ol ovarian cancer screening among average risk, asymptomatic women. Methods Systematic review of RCtsof ovarian cancer screening in average - risk women that reported mortality or qualrty -of lrfe outcomes. Interventions included liansvaginallFSard /ni CA -125 lesbng. Comparators were usual care or no screening. Results: Fcortrials ( n ^ 293587) »rere ircl.ded. No trial found a significant difference in ovarian cancer mortality with screening. In two bra Is screening led to surgery lor suspected ovarian cancer In 11s ol women without canter and lor transvagad tl /S with or without CA 125 screen mg m 3 V with major complications occurring wr 3% to 15V ol surgeries. Evidence ol psychological harms was fou j In cases of repeat follow - up sea ns and tests. Conclusions: Ovarian cancer mortality did not significantly differ between screened women and those with no screening or in usual care.

-

-

.

-

-

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Toronto Notes 2023

GYI5 Gynaecology

Treatment • debulking surgery including total hysterectomy, BSO, omentectomy, removal of all visible disease • many epithelial ovarian cancers (i e. serous ovarian carcinoma) are chemosensitive: treat with

.

Malignant Ovaiian Tumour Prognosis

platinum -based chemotherapy t taxol • neo adjuvant chemotherapy (if needed) to shrink down tumours prior to debulking • adjuvant chemotherapy to treat microscopic disease

-

Low Malignant Potential (also called "Borderline") Tumours • a subcategory of epithelial ovarian cancer ( 15% of all epithelial ovarian tumours) • approximately one third of tumours are identified in women < 40 yr • pregnancy and breastfeeding are protective factors • tumour cells with histologically malignant characteristics arise from the ovarian surface, but do not invade ovarian stroma • able to metastasize, but uncommon • treated primarily with surgery ( BSO/omental biopsy ± hysterectomy ) chemotherapy has limited benefit: can be treated with hormonal manipulation ( letrozole) young patients can be treated with fertility-sparing options such as cystectomy or unilateral

-

-

5 Yr Survival Stage I Stage II Stage III

75 95% 60-75% 23 - 41%

Stage IV

11%

salpingo-oophorectomy

• generally slow growing, excellent prognosis • 5 yr survival >99% recurrences tend to occur late, may be associated with low-grade serous carcinoma

Table 25 . Ovarian Tumours Type

Description

Presentation

Ultrasound/ Cytology

Treatment

Usually asymptomatic

4 -8 cm mass, unilocular, lined with granulosa cells

Symptomatic or suspicious masses warrant surgical ciploration Otherwise il 6 cm, wail 6 wk then ro - exaininc as cyst usually regresses with nest cycle OCP (ovarian suppression): will prevent development ol new cysts Treatment usually laparoscopic (cystectomy vs oophorectomy, based on fertility choice)

FUNCTIONAL TUMOURS ( ollbcnign)

Follicular Cyst

Follicle tails to rupture during ovulation

May rupture, bleed, tort , infarct, causing pain t signs ol peritoneal irritation

-

.

Corpus luteum Cyst

Corpus luteum fails to regress after 14 d, becoming cystic or hemorrhagic

More likely to cause pain than follicular cyst May delay onset of next period

Theca-Lutein Cyst

Due to atretic follicles stimulated by abnormal P - hCG levels

Associated with molar pregnancy, ovulation induction with domiphene

Endometrioma

See Endometriosis. GY11

Polycystic Ovaries

See Polycystic Ovarian Syndrome GY24

Larger (10 -15 cm) and firmer than follicular cysts

Same as for follicular cysts

Conservative Cyst will regress as p- hCG levels fall

.

BENIGN GERM CEttTUMOURS

Benign CysticTcratoma ( dermoid)

Single most common ovarian germ cell neoplasm Elements of all 3 cell lines;contains dermal appendages (sweat and sebaceous glands, hair follicles, teeth)

May rupture, twist, infarct 20 % bilateral 20% occur outside of reproductive yr

-

Smooth walled, mobile, unilocular U/S may show calcification which Is pathognomonic

Treatment usually laparoscopic cystectomy: may recur

MALIGNANTGERMCEU TUMOURS Rapidly growing 2 3% of all ovarian cancers

Usually children and young women 1* 30 yr|

Suigical resection (often conservative unilateral salpingo oophorectomy t nodes) s chemotherapy

Dysgcrminoma

10 - 15% bilateral

When diagnosed at stage IA, no adjuvant treatment is indicated If diagnosed at advanced slage vciy responsive lo chemotherapy, therefoie complete resection is not necessaiylor cure

.

General Information

Produces tOH

.

Immature Teratoma

No tumour marker identified

Almost always unilateral

When diagnosed at stage IA Grade 1, no adjuvant tieatment is indicated When diagnosed at Grade 2 3 either adjuvant

-.

chemotherapy or surgical staging is indicated If diagnosed at advanced stage, very responsive to chemotherapy, therefore complete resection is not necessary for cure Yolk Sac Tumour

Produces AFP

Ovarian Choriocarcinoma Produces 0 - hCG

Abdominal pain and pelvic mass

High grade tumour can be treated with adjuvant chemotherapy or monitor AFP levels

Precocious puberty and irregular vaginal bleeding

High grade tumour usually treated with adjuvant chemotherapy

_

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GY46 Gynaecology

Table 25 . Ovarian Tumours Description

Type

Presentation

Ultrasound/Cytology

Treatment

Varies depending on subtype

Borderline Cystectomy vs. unilateral salpingo-oopborectomy Malignant 1. Early stage (stage I): Hysterectomyi 3S0 staging (omentectomy peritoneal biopsies, washings, pelvic and para aortic lymphadenectomy). Depending on histology, may require adjuvant chemotherapy 2. Advanced stage: Upfront cytoreductive ( debulking) followed by adjuvant chemotherapy consisting of IV carboplalin/paditaxel vs.intraperitoneal chemotherapy (stage III) neoadjuvant chemotherapy with IV carboplatin/ paditaxel, followed by delayed debuDcing with further adjuvant IV chemotherapy

EPITHELIAL OVARIAN TUMOURS (malignant or borderline) General Information

Derived from mesoUielial cells lining peritoneal cavity Classified based on histologic type 80 - 85% of all ovarian neoplasms (including malignant tumours)

.

Serous

Most common ovarian tumour histology 50% of all ovarian cancers 75% of epithelial tumours 70% benign

20 -30 » bilateral

Lining similarto fallopian tube epithelium Often multilocular Histologically contain psammoma bodies (calcified concentricconcretions)

See above

Mucinous

20% ol epithelial tumours

Rarely complicated by Pseudomyioma peritonei: implants seed abdominal cavity and produce large quantities

Resembles endocervical epithelium Often multilocular May reach enormous size

Poor response to chemotherapy If mucinous, remove appendix as well to rule out possible source of primary disease

Clear Cell

10% of epithelial tumours Can be found adjacent to endometriosis More common in the Asian population

More likely to be detected at an early stage

Contains glycogen-rich cells with clear cytoplasm and hobnail cells

Poor response lo chemotherapy

Endometrioid

10% of epithelial tumours

Can beassociated with endometrial neoplasm

Typically cystic or solid, unilateral, and confined to

lend to respond well to chemotherapy

Can be found adjacent to endometriosis

'

ofmudn

the ovary

SEX CORD STROMAL OVARIAN TUMOURS

FibromaiThecoma (benign)

From mature fibroblasts in ovarian stroma Non- functioning Occasionally associated with Meig's syndrome (triad of benign ovarian tumour, ascites.and pleural effusion)

-

Granulosa Theca Cell Tumours (benign or malignant)

Tumour marker is inhibin

Sertoli-Leydig Cell

Can measure elevated androgens as

Tumour (benign or malignant)

tumour markers

Estrogen-producing: feminizing

.

effects (precocious puberty

menorrhagia, postmenopausal bleeding) Risk of endometrial cancer due to estrogen

Histologic hallmark of cancer is small groups of cells known as Call -Exner bodies

Androgen-producing:virilizing effects (hirsutism,deep voice, recession of front hairline)

Surgical resection of tumour Chemotherapy may be used for unresectable metastatic disease

Surgical resection of tumour Chemotherapy may be used for unresectable metastatic disease

METASTATIC OVARIAN TUMOURS

. .

From 61 Tract Breast, 4-8% of ovarian malignancies Endometrium Lymphoma Krukenberg tumour: metastatic ovarian tumour (usually Gl tract commonly stomach or colon, breast primary tumour )

80% bilateral

Krukenberg tumours have

“signet -ring" cells

Investigation of Suspicious Ovarian Mass • women with suspected ovarian cancer based on history, physical, or investigations should be referred to a gynaecologic oncologist bimanual examination solid, irregular, or fixed pelvic mass is suggestive of ovarian cancer RM1 ( Risk of Malignancy Index) is best tool available to assess likelihood of ovarian malignancy and need for preoperative gynaecologic oncology referral (see sidebar) • physical exam findings largely dependent on stage of disease • blood work: CBC, LF Ts, electrolytes, Cr, tumour markers as appropriate ( CIA-125, inhibin, p-hCG, LDH , AFP, androgens, CEA, Cai 9 9, estrogen ) • biopsy not recommended due to tumour spillage into peritoneum , if extensive disease, can get cytological diagnosis from paracentesis from ascites or tissue biopsy from peritoneal deposits or omental cake • radiology transvaginal U/S best to visualize ovaries CT abdomen and pelvis to look for metastatic disease bone scan or PET scan not indicated

-

Causes of Elevated CA-125

• Age influences reliability of test as a tumour marker

• 50% sensitivity in earty-stage ovarian cancer (poor), therefore not good for

screening

• Malignant • Gynaecologic ovary, uterus • Non-Gynaecologic pancreas, stomach, colon, tectum

• Non-Malignant • Gynaecologic benign ovarian

_

r

neoplasm, endometriosis, pregnancy, fibroids PID • Non-Gynaecologic cirrhosis, pancreatitis, renal failure

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Toronto Notes 2023

GY 17 Gynaecology

• try to rule out other primary source ( if suspected ), based on: occult blood per rectum: endoscopy ± barium enema • gastric symptoms: gastroscopy ± upper G1 series • abnormal vaginal bleeding: endometrial biopsy to rule out concurrent endometrial cancer; abnormal cervix: need to biopsy cervix ( not Pap smear ); breast lesion identified or risk factors present: mammogram

A Risk of Malignancy Incorporating CA-125, Ultrasound, and Menopausal Status lor the Accurate Preoperathre Diagnosis of Ovarian Cancer 6J0G 890:97:922-929 RMI U M i CA-125 Ultrasound Findings |1 pt for each) -

Table 26. FIGO Staging for Primary Carcinoma of the Ovary (Surgical Staging) ( 2014 ) Stage

Description

I

Growth limited to the ovaries

IA

t ovaiy, no ascites, no tumour on external surface, capsule intact , negative washings

IB

2 ovaries, no ascites, no tumour on external surface, capsule intact

IC

t oc 2 ovaries with any of flic following: surgical spill |IC1). capsule ruptured |IC 2), lumour on ovarian surface ( IC2 ). or malignant cells in ascites (IC 3)

II

Growth involving one or both ovaries with pelvic extension or primary peritoneal cancer

IIA

Extensioniimplants to uterus/ tubes

lie

Extension to other pelvic structures

III

Tumour involving oncor both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal nodes

IMA

Positive retroperitoneal INs and/or microscopic metastasis beyond pelvis

IIIA1

Positive retroperitoneal INs

IIIA 2

Microscopic , extrapelvic peritoneal involvement t positive retroperitoneal INs

NIB

Macroscopic peritoneal metastasis beyond pelvis 12 cm. t positive retiopenloncal INs. Includes extension to capsule ol liver / spleen

NIC

Same asabove but peritoneal metastasis »2 cm

IV

Distant metastasis beyond peritoneal cavity

IVA

Pleural effusion with positive cytology

IVB

Hepatic and/ or splenic parenchymal metastasis or metastasis lo extra - abdominal organs (inguinal INs and LNsoutside of abdominal cavity included)

FIGO = International Federation of Gynaecology and Obstetrics

Cervix MALIGNANT CERVICAL LESIONS

Epidemiology • majority are SCC (90 % ); adenocarcinomas increasing ( 10% ); rare subtypes include small cell,

adenosquamous

• 8000 deaths annually in North America • average age at presentation : 50 yr ; bimodal distribution ( increased frequency in 40s and 60s)

• Multilocular cyst Evidence ol sold areas Evidence of netattases • Presence of asdles | Mini Mm

U '1 (for UfS scores of 0 or 1) U - 4 |for IPS scoresof 2- 5) Menopausal Status • Postmenopause': V - 4 Premenopausal:Mri JfisohitE Zaire of CA -125 Serum Level • For fill| >200: gynaecoloi|icoacniogy referral is j

recommended

Optimal Primary Soigicil treatment lor Advanced Epithelial Ovaciaa Cancer Cochrane 08 Syst Ret 201l:(8|:CD00f 56S Summary During primary surgery Ini stage III or IV epithelial ovarian cancer, all attempts should be made toach.eve completecyloreduction. When this is not achievable, optimal (1 cm) was compared with optimal |* tcm) cyioreduction. Ihesurvival estimates were reduced but remained statistically in favour of the lower volume disease gruup. 2. No sign hunt difference in overall survival between subopbmal and optimal cytoreduction. 3. Borderline difference in progression- free survival when resxlual disease >2 cm and ASCUS

jr

Return to cytology screening

every Syr3

Refer to colposcopy

' Those guidelines apply to anyone with a cervix including women; prognant pooplo, transmen; non binary people; people who havo undergone a subtotal hysterectomy, and pooplo who have been

vaccinated with tho HPV vaccine visible corvicol abnormalities or abnormal symptoms must bo investigated Consider loforrol to e specialist ( e g colposcopist , gynaecologist, gynoQoncologist ) Immunocompromised people may be at olovoted risk and should recoivo annual screening J Ontario Health ( Cancer Care Ontario ) is aware that the Screening Activity Report is not yet aligned with this guidance and will be updated with HPV implementation. Criteria for preventive care bonuses may not be updated during the interim period of changeover to HPV testing. Criteria for preventive care bonuses will be updated when HPV testing is implemented in screening 1 HPV testing is not currently funded by the Ministry of Health. Primary care providers can consider HPV testing for those with ASCUS results on a patient pay basis or wtvere available ( i.e. in some hospital settings! for people ages 30 and older * Repeat cytology or colposcopy are acceptable management options after the first LSIL result Low grade abnormalities often regress on their own and may be best managed in surveillance, however colposcopy may be considered 2 Any ]

Figure 23. Decision making chart for Pap test (not applicable for adolescents) Adapted from: Ontario Cervical Screening Program . June 2020. Cervical screening guidelines unique to each province

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GY49 Gynaecology

Toronto Notes 2023

Diagnosis • colposcopy is a clinical • in colposcopy :

procedure that facilitates identification and biopsy of suspicious cells

apply acetic acid and identify acetowhite lesions, punctation, mosaicism, and abnormal blood vessels to guide cervical biopsy ECC if entire lesion is not visible or no lesion visible diagnostic excision ( LEEP ) if: unsatisfactory colposcopy ( poor visualization /access to transformation zone ) discrepancy between cytology , colposcopy , and histological findings positive findings /glandular abnormalities in endocervical curettage suspicious for adenocarcinoma in situ ( consider cold - knife conization ) recurrence of lesion post-ablation or excision inability to rule out invasive disease , i .e. large lesions ( lesions extending into endocervical canal , extending widely on cervix , or onto vaginal epithelium ) • consider cold- knife conization ( in OR ) if glandular abnormality suspected based on cytology or colposcopic findings due to concern for margin interpretation • any imaging modality or pathological findings are permitted for E1GO clinical staging Table 27. FIGO Staging Classification of Cervical Cancer ( Clinical Staging) ( 2018) Stage

Description

I

Confined lo cervix

IA

Diagnosed only by microscopy

IA1

Stromal invasion not >3 mm deep

IA2

IB

3 mm to < 5 mm deep Measured deepest invasion >5 mm (greater than stage IA ). lesion limited to cervix

IB1 IB 2

Stromal invasion >5 mm deep and > 2 cm and < 4 cm wide

IB 3

>4 cm

II IIA

Beyond uterus but not to the pelvic wall or lower 1/3 of vagina Limited to upper 2/ 3 of vagina , no obvious parametria! involvement Clinically visible lesion 4 cm wide Clinically visible lesion ;4 cm wide

Stage IV

75% 55% 30% 7%

Overall

50 -60%

Stage I Stage II Stage III

.

final Effjcacy lmmunogenicity and Safety Analyses ol a Nine - Valent Human Papillomavirus Ifeccine in Women Aged 16 26 Years: A Randomised Double- Blind Trial lancet 2017:390:2143-2159 Purpose: A nine-valent HPV vattine (9vHPV ) was developed which covers add ilional strainsol HPY compared to the quadrivalent vaccme (qHPY ). Ihis study reported the efficacy ol the 9vHPV vatcine. Methods A random ted double - hind efficacy trai comparing thenine valent HPV vaccine (9vHW ) to the quadrivalent HPYvacune ( qHPY|in 14215 women the primary outcomes weie incidence ol high grade cervical, vulvar , and vaginal diseases related to HPV 31.33, 45.52. and 58 ar.d non - inferiority of anti - HPY 6. It.16.and 18 mean litres. Results: The incidence of high - grade cemcal vulrar, and vaginal disease was 0.5 cases per WOOD person yrfor the 9vHPV group compared to 19 cases per 10000 persoo yr loi the qHPV group. HPV 6, 11 K. and 18 titres were non - inferior in the 9vHPVgroup compared to the qHPV group. There were noclwiica ' fy meaningful diHcrencesin severe adverse effects between groups. Conclusions: The 9 > HPV vaccine is elfectrve at preventing infection , cytology! abnormalities, and “ gh grade lesions and may offer broader protection agaxist HPV and ceivical cancer compared to the qHPV vaccine.

-

.

in width

-

,

Obvious pniamelrial involvement , bul not up to pelvic wall Extends to pelvic wall, and /or involves lower 1/3 ol vagina , and / or causes hydronephrosisor non functioning kidney, and/or involves pelvic and/ or para aortic lymph nodes

IIB III

m

Cervical Camer Prognosis 5 yr Survival 99% Stage 0

.

Stromal invasion >5 mm deep and < 2 cm wide

IIA1 IIA 2

The Bethesda Classification System is based on cytological results of a Pap test that permits the Examination of cells but not tissue structure. LSIL. HSIL. or cervical carcinoma is a histological diagnosis, requiring a tissue sample via biopsy of suspicious lesions seen during colposcopy

-

-

.

MIA

Involves lower 1/3 vagina bul no extension into pelvic wall

NIG

Extension into pelvic side walland/or hydronephrosis or non - functioning kidney

me

Involvement of pelvic and/or para aortic lymph nodes , irrespective of tumour sire and extent

IIIC1

Pelvic lymph nodes metastasis only

IIIC 2 IV

Paraaortic lymph node metastasis Carcinoma has extended beyond true pelvis or has Involved ( biopsy proven ) the mucosa ol the bladdci or rectum ( bullous edema docs not permit a case lo he allotted lo stage IV )

IVA

Spread of the growth toadjacent oigans ( bladder or redum )

IV 6

Distant metastases

-

-

-

.

-

Treatment: Prevention and Management

Prevention: HPV Vaccine • two vaccines currently approved (Gardasil*, Cervarix’)

Table 28. Comparison of Two Vaccines against Human Papillomavirus ( HPV ) Gardasil • Cervarix

.

.

Viral Strains Covered

6.11. 16.18 31.33, 45.52 and 58

Route of Administration

IM

Schedule of Dosing

2 Dose: Second dose administered 6 12 mo after first dose 3 Oose: 0.2. 6 mo Local: redness, pain , swelling General: headache, lowgrade fever. Gl upset

Side Effects

16.18 IM

-

-

-

Approved Age

females ages 9 45. males ages 9 45

Contraindications

Pregnant women and women who are nursing (limited

0.1, 6 mo Local: redness, pain, swelling General: headache, low grade fever Gl upset

.

rm L J

-

females ages 9 45

data )

-

. .

+

•Garda H 9 cil \ u cover * type 31, 33.45 52 and 58; also used to prevent genital wart * * *

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GY50 Gynaecology

•should be administered before onset of sexual activity ( i.e. before exposure to virus ) for optimal benefit of vaccination

• may be given at the same time as hepatitis B or other vaccines using a different injection site • not for treatment of active infections • most women will not be infected with all four types of the virus at the same time, therefore vaccine is still indicated for sexually active females or those with a history of previous HPV infection or HPVrelated disease Abnormal Pap Tests in Pregnancy • incidence: 1 in 2200 • Pap test at initial prenatal visit if overdue for routine Pap test • if abnormal Pap or suspicious lesion , refer to colposcopy • if diagnostic conization required , should be deferred until T2 to minimize risk of pregnancy loss if invasive cancer ruled out, management of dysplasia deferred until completion of pregnancy ( may deliver vaginally ) if invasive cancer present, management depends on prognostic factors, degree of fetal maturity, and patient wishes general recommendations in Tl: consider pregnancy termination, management with either radical surgery ( hysterectomy vs. trachelectomv if desires future fertility ), or concurrent chemoradiation therapy recommendations in T 2 / T3: delay of therapy until viable fetus and (.'-section for delivery with concurrent radical surgery or subsequent concurrent chemoradiation therapy Table 29. Management of Abnormal Cervical Histology and Cervical Cancer Histology Result from Colposcopy

Management

Normal

If histology results normal and cytology > LSIL then repeat colposcopy In 6 mo Women «25 yr If cytology is ISIl , ASCUS. or normal , then annual Paps by primary care provider « 3 years , followed by return lo normal screening It cytology is HSIL. then consider pathology review, and /or reassessment every 6 12 mo in colposcopy Women * 25 yr If HPV •: routine Pap screening every 3 yr If HPV : follow up colposcopy with cytology and HPV test ( if 30 yr or older ) in 1 yr

.

LSIL

-

-

Women »25 yr

HSIL CINII / CIN III

.

Excisional procedures|e.g. cold knife LEEP) or laser preferred Those with positive margins should have follow up with colposcopy and directed biopsies and /or endocervical

-

curettage Women «25 yr Colposcopy every 6 mo for 2 yr or treatment may be acceptable based on patient preference Repeal colposcopy + treatment (e.g . LEEP. cold knife cone) i endocervical curettage

-

AIS

LEEP if future fertility desired (and lesion' 2 cm ) Simple hysterectomy il future fertility is not desired

Stage IA1 ( noLVSI )

. .

Stage IA 2 IB1 IB 2

Typically treated with radical hysterectomy and pelvic lymphadencdomy (sentinel nodes or pelvic lymph node dissection ) If high chance of adjuvant radiation then consider primary chemoradiation as more morbidity occurs from double modality treatment (surgery and radiation ) Equal cure rates may be obtained with primary radiation therapy: advantage of surgery: may accurately stage and grade and more targeted adjuvant therapy Advantage is that ovaries can be spared if premenopausal, better sexual functioning For fertility preservation (if tumour «2 cm ), may have radical trachelectomy ( removal of cervix and parametria ) and nodes instead of radical hysterectomy for early - stage disease Chemoradiation therapy il adverse high risk prognostic factors on radical surgical specimen , such as: positive pelvic lymph nodes, positive parametria , and / or positive margins or adverse cervical factors ( 2 or more): deep stromal invasion , sice > 4 cm. LVSI

-

-

..

Stages IB3 ( »4 cm ), II III IV

Primary chemoradiation therapy CT to assess extent of disease: evaluate pelvic and para aortic nodes for positive nodes on PEI: primary chemoradiation with extended field Rl Hysterectomy generally notsuggested following primary treatment with curative intent

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GY51 Gynaecology

Fallopian Tube •least common site for carcinoma of female reproductive system (0.3%) •usually serous epithelial carcinoma • new evidence shows that some serous ovarian cancers originate in the fallopian tube • more common in fifth and sixth decade

Clinical Features • classic triad present in minority of cases, but very specific watery discharge ( most specific): “ hydrops tubae prolluens" vaginal bleeding or discharge in 50 % of patients crampy lower abdominal / pelvic pain • most patients present with a pelvic mass (see Pelvic Mass, GY42 and Ovary, GY44 for guidelines regarding diagnosis/investigation) Treatment

• same as for malignant epithelial ovarian tumours, see Table 25, GY45 • salpingectomy ( removal of fallopian tubes to prevent ovarian cancer)

Vulva BENIGN VULVAR LESIONS

Non-Neoplastic Disorders of Vulvar Epithelium • biopsy is often necessary' to make diagnosis and /or rule out malignancy: 1. Lichen sclerosus subepithelial fat becomes diminished ; labia become thin, atrophic, with membrane-like

epithelium and labial fusion pruritus, dyspareunia, burning, bleeding, ulceration, excoriations ‘figure of 8' distribution most common in postmenopausal women but can occur at any age patients should be monitored for malignancy, due to increased risk ofSCC treatment: high potency topical steroid (dobetasol ), likely long term treatment necessary 2. Lichen simplex chronicus surface of labia majora is thickened and hyperkeratotic, leather -like in appearance pruritus and burning, often at night most common symptoms typically occurs in postmenopausal women treatment: medium - or high-potency steroid cream based on symptom severity + nighttime antihistamines 3. Lichen planus autoimmune disorder where T cells attack basal keratinocytes peak incidence at age 30 60 3 variants including erosive, papulosquamous, and hypertrophic can extend into vaginal canal and cause loss of structure (desquamative vaginitis ) can have oral lichen planus in oral cavity treatment: ultrapotent steroid cream BID until plaques resolve, vaginal suppositories, or immunosuppressive therapies (e.g. cyclosporine) are all accepted

-

-

-

Any suspicious lesion ot the vulva should be biopsied

Tumours

• papillary hidradenoma, nevus, fibroma, hemangioma

MALIGNANT VULVAR LESIONS

Epidemiology

• 5% of genital tract malignancies

• 90% SCC; remainder melanomas, basal cell carcinoma, Paget’s disease, Bartholin’s gland carcinoma Type 1 disease: HPV-related (50-70%) more likely in younger women 90% of vulvar intraepithelial neoplasia ( VIN ) contain HPV DNA (usually types 16, 18) Type 11 disease: not HPV-related, associated with current or previous vulvar dystrophy

n

usually postmenopausal women

LJ

Risk Factors

• HPV infection • VIN: precancerous change which presents as multicentric white or pigmented plaques on vulva ( may only be visible at colposcopy )

+

• progression to cancer rarely occurs with appropriate management treatment: local excision (i.e. superficial vulvectomy ± split thickness skin grafting to cover defects if required ) vs. ablative therapy (i.e. laser, cauterization) vs. local immunotherapy (imiquimod)

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GY52 Gynaecology

• history of cervical cancer • cigarette smoking • immunodeficiency • vulvar lichen sderosus Clinical Features

• most lesions occur on the labia majora, followed by the labia minora ( less commonly on the clitoris or perineum )

• localized pruritus, or white, red , or skin coloured papules, nodules, or plaques most common

• less common: ulcer, bleeding, discharge, pain , and dysuria • patterns of spread local groin lymph nodes (usually inguinal, then spreading to pelvic nodes)

hematogenous Investigations • ± vulvar biopsy

• always biopsy any suspicious lesion • do not remove entire lesion during biopsy (allows for site identification through sentinel LN injection if malignant ) Prognosis

• depends on stage: particularly nodal involvement (single most important predictor followed by tumour size) lesions > 4 cm associated with poorer prognosis • overall 5 yr survival rate: 79% Treatment

• 1'KiO Stage I ( tumour confined to vulva; no extension to adjacent perineal structures): radical local excision

metastases : modified radical vulvectomy

• I IGO Stage 11 ( tumour of any size with extension to adjacent perineal structures, no nodal '

)

• 1TGQ stage lll - IV ( extension to any of: proximal 2 /3 of urethra , proximal 2 /3 of the vagina, bladder

mucosa , rectal mucosa, or fixed to pelvic bone, or large/distant nodal metastases): sentinel lymph node biopsy followed by surgical resection of residual primary and adjuvant chemotherapy or radiation

Vagina BENIGN VAGINAL LESIONS

• inclusion cysts cysts form at site of abnormal healing of laceration (e.g. episiotomy) no treatment required • endometriosis dark lesions that tend to bleed at time of menses » treatment: excision • Gartner’s duct cysts remnants of Wolffian duct seen along side of cervix • treatment: conservative unless symptomatic • urethral diverticulum can lead to recurrent urethral infection, dyspareunia • treatment: surgical correction if symptomatic MALIGNANT VAGINAL LESIONS

Epidemiology

.• -

-

• primary carcinomas of the vagina represent 2 3% of malignant neoplasms of the female genital tract 80 90% are SCC

-

more than 50% diagnosed between 70 90 yr

Risk Factors

• associated with HPV infection (analogous to cervical cancer ) • increased incidence in patients with prior history of cervical and vulvar cancer

n LJ

Investigations • cytology

significant false negative rate for existing malignancy (i.e. if gross lesion present, biopsy) • colposcopy • Schiller test ( normal squamous epithelium takes up Lugol's iodine) • biopsy, partial vaginectomy (wide local excision for diagnosis) • rule out disease on cervix, vulva, or anus ( most vaginal cancers are metastatic from one of these sites) • staging

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Toronto Notes 2023

Clinical Features Table 30. Clinical Features of Malignant Vaginal Lesions Type Clinical Features Vaginal Intra - Epithclial Neoplasia (VAIN) Squamous Cell Caicinoma (SCO)

Ciades: analogous to cervical dysplasia Most common site is upper 113 ol posterior wall ol vagina Asymptomatic Painless vaginal discharge (often foul smelling) and bleeding Vaginal bleeding especially during/post coitus Urinary and/or rectal symptom 2° to compression

-

Adenocarcinoma

-

Most are metastatic,usually from cervix, endometrium, ovary,or colon Most primaries are dear-cell adenocarcinomas Iwo types: non-DES and OES syndrome

Treatment

• Stage I

radiation therapy: for tumours >2 cm diameter or tumour involvement of the middle or lower vagina surgical excision: radical hysterectomy, upper vaginectomy, and bilateral pelvic lymphadenectomy • Stage II-1V: primary radiation with or without chemotherapy

Gestational Trophoblastic Disease /Neoplasia • refers to a spectrum of proliferative abnormalities of the trophoblast

• GTD = abnormal, can be benign or lead to the malignant form, called GTN Epidemiology • 1/ 1000l pregnancies

• marked geographic variation (as high as 1/125 in Taiwan ) •80% benign , 15% locally invasive, 5% metastatic • cure rate > 95%

HYDATIDIFORM MOLE ( GTD) Complete Mole • most common type of hydatidiform mole • diffuse trophoblastic hyperplasia, hydropic swelling of chorionic villi, no fetal tissues or membranes

present

• 46 XX or 46XY, chromosomes completely of paternal origin (90%) • One sperm fertilizes egg with reduplication or two sperm fertilize empty egg • 15 -20% risk of progression to malignant sequelae

• risk factors

• geographic ( most common in those of South East Asian background ) others ( maternal age > 40 yr, P-carotene deficiency, vitamin A deficiency not proven )

prior molar pregnancy • clinical features often present during apparent pregnancy with abnormal symptoms /findings vaginal bleeding (97%) • hyperemesis gravidarum ( 26%) • excessive uterine size for LMP ( 51%) hyperthyroidism ( 7%) • theca -lutein cysts >6 cm ( 50%) P-hCG >1000001 U/ L preeclampsia (27%) no fetal heartbeat detected, due to absence of fetal parts

-

With development of HTN early in pregnancy (i.e. 6 mo Rclrcalment with lupron ' alone not recommended because ol effects on bone density

.

Endometriosis leiomyomata DUB Precocious puberty

S /E: hot flashes, sweats, headache, vaginitis, reduction in bone density, acne Gl upset C /I: pregnancy, undiagnosed vaginal bleeding, breastleeding

.

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Toronto Notes 2023

GY57 Gynaecology

Table 33. Common Medications Drug Name (Brand Name) Action

mcnotropin (Pergonal )

Human gonadotropin with FSH and IK effects; induce ovulation and stimulate ovarian follicle

Dosing Schedule

Indications

75 -150 IU ol FSH and IH IM once Infertility dally n 7-12 d then 10000 IDHCG 1 d alter last dose

.

development

Side Effects (S/ E), Contraindications (C /I), Drug Interactions (D/I) S/ E: bloating, irritation at injection site, abdominal/pelvic pain, headache N / V multiple pregnancy C/I: primary ovarian failure, intracranial lesion (e.g. pituitary tumour), uncontrolled thyroid/ adrenal dysfunction, ovarian cyst (not PCOS), pregnancy, undiagnosed uterine bleeding

.

.

. .

metronidazole (Flagyl : )

Bactericidal: forms toxic metabolites 2 g P0 x 1 dose or 500 mg P 0 which damage bacterial DNA BID x 7 d

nexplanon ( etonogestrcl implant)

Releases progestin which causes decidualization of endometrium and thickening of cervical mucus, may suppress ovulation

oxybulynin (Ditropan )

Anticholinergic: relaxes bladder smooth muscle, inhibits involuntary detrusor contraction

May increase doses by 5 mg weekly to a maxof 30 mg/ d

tolterodinc ( Octroi )

Anticholinergic

1- 2 mg P0 BIO

Overaclive bladder (urge incontinence)

S /E: anaphylaxis, psychosis, tachycardia, dry moulh / cyes headache, constipation, urinary retention, chest pain, abdominal pain C/I: glaucoma, gastric /urinary retention,use with caution if impaired hepatic /renal function

trancxamic acid

Anil- fibrinolytic: reversibly inhibits plasminogen activation

1-1.5 g 110 010 for first 4 d of cycle Max 4 g/ d Ophthalmic check if used for several wk

Menorrhagia

(Cyklokapron )

S / E: N / V, diarrhea, dizziness, rare cases ol thrombosis, abdominal pain MSK pain C/I: thromboembolic disease, acquired

ulipristal acetate (Fibristal | - withdrawn from market in 2020 urofollitropin

Selective progesterone receptor modulator ISPRM)

Bacterial vaginosis,trichomonas vaginitis

S /E: headache, dizziness N / V diarrhea, disulfiram like reaction (flushing, tachycardia, N/V) C/I: pregnancy (1st trimester ) 0/1: cisapride, warfarin, cimelrdine, lithium, alcohol, amiodaionc , milk thistle, caibamarcpinc

Contraceptive effects last up to 3 yr

Contraception Disorders of menstruation

Sec tables 7-10.6Y15 CYVand fable 12, 6Y18

5 or 10 rrig/ d P0

Ovciacllvc bladdei (urge incontinence)

S /E: dry mouth / eyes, constipation, palpitations, retention, dizziness, headache C/I: glaucoma. Gl ileus, severe colitis, obstructive uropathy use with caution if impaired hepatic / renal function

.

.

.

disturbances of colour vision, subarachnoid hemorrhage, age 20% of the total WBC differential consists of blasts, this is acute leukemia and is a medical emergency

-

.

Illustrations: Ayalah Hutchins and Merry Shiyu Wang 2012 and Danielle Sayeau 2017

PLATELETS •

small, purple, anuclear cell fragments

Bone Marrow Aspiration and Biopsy •sites: posterior iliac crest /spine, sternum (aspiration only) •analyses: most often done together • aspiration: takes a fluid marrow sample for cellular morphology (includes iron stain ), flow cytometry, cytogenetics, molecular studies , and microbiology (C&S, acid -fast bacilli smear and culture, and PCR ) note: differential diagnosis for a “dry tap”: MF, hairy cell leukemia, BM infiltration biopsy: takes a sample of intact BM to assess histology (architecture ) and immunohistochemistry only aspirates, not biopsies, can be obtained from the sternal site

Indications • unexplained CBC abnormalities •diagnosis and evaluation of infiltrating cancers: plasma cell disorders , leukemias, and solid tumours

•diagnosis and staging of lymphoma or solid tumours •evaluate iron metabolism and stores (gold standard, but rarely done) •evaluate suspected deposition and storage disease (e.g. amyloidosis, Gaucher’s disease) •evaluate fever of unknown origin, suspected mycobacterial, fungal , and parasitic infections, or

granulomatous disease •evaluate unexplained splenomegaly • confirm normal BM in potential allogeneic hematopoietic cell donor

Important Considerations •do not perform a BM biopsy if there is evidence of infection over the targeted skin site • risk of procedure: 1 / 100 chance of bleeding , very rare infection risk

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H6 Hematology

Common Presenting Problems Anemia Definition • a decrease in RBC mass that can be detected by Hb concentration, Hct, and RBC count adult males: Hb < 130 g / L or Hct 96% of cases of PV only send if low/normal EPO level • ferritin (iron deficiency can mask the diagnosis; if iron deficient with reticulocy tosis, suggestive of PV ) Treatment

• if primary: see Polycythemia Vera, H 43 • if secondary: treat underlying cause 02 for hypoxemia, CPAP for sleep apnea, surgery for EPO-secreting tumours, counselling and education (e.g. smoking cessation, work environment ), use the lowest dose possible if on androgen therapy often cardiologists will be hesitant to treat high Hct in cyanotic patients

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Thrombocytopenia Definition

cases of thrombocytopenia

• platelet count

I Immune

• ITP

• Viral (HIV )*

• Systemic ( SLE) • Alloimmune • HIT • Drug -induced*

Non

i -

bypass

illumine

• DIC • HP

• HUS • Preeclampsia • HELLP • APS

*ln hospitalized patients most common causes of thrombocytopenia are drugs and infection

Figure 3. Approach to thrombocytopenia

Adapted from: Cedi Essentials at Medicine

Thrombocytosis Definition

• platelet count > 450 x 10’/ L

• primary thrombocytosis ( uncommon ): due to MPNs (e.g. CML, PV, primary MP, and ET; rarely associated with MDS) • reactive/secondary thrombocytosis (common ): acute phase reactant (e.g. surgery, inflammation, infection, trauma, bleeding, iron deficiency, neoplasm, ischemic injury, and hyposplenia/asplenia ) Clinical Features

• history: trauma, surgery, splenectomy, infection, inflammation, bleeding, iron deficiency, prior diagnosis of chronic hematologic disorder, and constitutional symptoms ( malignancy ) • vasomotor symptoms: headache, visual disturbances, lightheadedness, atypical chest pain, acral dysesthesia, crythromelalgia, livedo reticularis, and aquagenic pruritus risk, bleeding risk ( rare ) clotting • • physical exam: splenomegaly is a common finding among patients with MPNs Investigations

• CBC and differential, peripheral blood film , serum ferritin • non -specific markers of infection or inflammation (e.g. CRP, HSR, ferritin ) • if reactive process has been ruled out , BM biopsy may be required to rule out MPN / MDS Treatment • primary: ASA ± cytoreductive agents (e.g. hydroxyurea, anagrelide, interferon -a) • secondary: treat underlying cause

Pancytopenia Definition

• a decrease in all hematopoietic cell lines below normal reference ranges Clinical Features

• anemia: fatigue (see Anemia , H6 ) • leukopenia: recurrent infections (see Neutropenia , H 9 )

• thrombocytopenia: mucocutaneous bleeding (see thrombocytopenia , H7 )

j

Investigations • CBC and differential, peripheral blood film, serum ferritin, reticulocyte count, PT, PTT, blood type and screen, complete metabolic panel, B12, folate • non -specific markers of infection or inflammation (e.g. CRP, HSR, ferritin ) • workup as per Figure 4, H 9 and presenting symptoms/ physical exam • if reactive process has been ruled out , BM biopsy may be required

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H9 Hematology

Toronto Notes 2023

(

)

Pancytopenia

T

[HypocellularBM )

(

i Cellular BM

)

I • Acquired aplastic anemia • Inherited aplastic anemia

• SomeMOSs

• MF

• Overwhelming infections

• Toxic depression ol BM

1" BM disease • MDS • Lymphoma

• Leukemia • Myeloma

• Anorexia nervosa

2° to systemic disease • SLE • Hypersplenism

• Vitamin B »

• Folate deficiency

• Alcoholism • TB

• Sarcoidosis

• PNH

• HIV • MF

Figure 4. Approach to pancytopenia

Neutrophilia Definition

• variable definition, but generally an ANC >7.7 x lO’/ L ( WHO definition ) Etiology

• primary neutrophilia CML, chronic neutrophilic leukemia other MPNsPV ET MF hereditary neutrophilia (autosomal dominant ) chronic idiopathic neutrophilia in otherwise healthy patients leukocyte adhesion deficiency • secondary neutrophilia stress/exercise/epinephrine: movement of neutrophils from marginated pool into circulating pool obesity • infection inflammation: e.g. rheumatoid arthritis (RA ), 1BD, chronic hepatitis, Ml, PE, and burns • malignancy: hematologic (i.e. marrow invasion by tumour ) and non-hematologic (especially large cell lung cancer) • medications: glucocorticoids, (3-agonists, lithium, G CSF

-

..

-

Clinical Features

• signs and symptoms of fever, inflammation , malignancy to determine appropriate further investigations

• including LAD and organomegaly • examine oral cavity, teeth , peri - rectal area , genitals, and skin for signs of infection Investigations

• CBC and differential: mature neutrophils or bands > 20% of total WBC suggests infection /

inflammation • blood film: left shifted WBt.'s, Dohle bodies ( intracytoplasmic structures composed of agglutinated ribosomes), toxic granulation, and cytoplasmic vacuoles in infection

• may require BM biopsy if MPN suspected Treatment

• directed at underlying cause

Neutropenia Definition

• mild: ANC 1.0-1.5 X lO’/ L

• moderate: ANC 0.5-1.0 x lO’/ L (risk of infection starts to increase) • severe: ANC 50 x 10’/ L Etiology

• infection • drugs • asplenia

• intoxication

• malignancy • hemorrhage • acute hemolysis Investigations/ Treatment

• marked left shift ( myelocytes, metamyelocytes, and bands in peripheral blood smear) • rule out CML and chronic neutrophilic leukemia • detect and treat underlying cause

a

Approach to Lymphadenopathy History

-

• constitutional / B symptoms ( seen in TB, lymphoma, other malignancies )

• growth pattern : acute vs. chronic • exposures: cats (cat scratch - Bartonella henselae ) , ticks ( Lyme disease - Borrelia burgdorferi ) , and high risk behaviours ( HIV )

-

• joint pain /swelling, rashes ( connective tissue disorder )

• pruritus (seen in Hodgkin lymphoma ) • medications (can cause serum sickness -> lymphadenopathy ) Clinical Features • determine if lymphadenopathy is localized or generalized • generalized: typically features of systemic diseases ( HIV, TB, EBV, SLE, medications, sarcoidosis, lymphoma ) • localized: typically reactive or neoplastic cervical ( bacterial/ mycobacterial infections, ENT malignancies, and metastatic cancer) • supraclavicular ( highest malignancy risk) right (mediastinal, bronchogenic, esophageal cancer ) left ( gastric, gallbladder, pancreas, renal, and testicular /ovarian cancer) axillary (cat scratch fever, breast cancer, and metastatic cancer) • epitrochlear ( infections, sarcoidosis, and lymphoma ) • check for splenomegaly, constitutional symptoms Investigations • (. BC and differential, blood film • if generalized, consider tuberculin test, HIV UNA, VDRL, MonospotVEBV serology, antinuclear antibodies ( ANA ), and imaging • if localized and no symptoms suggestive of malignancy, can observe 3 4 wk ( if no resolution > excisional biopsy to preserve lymph node architecture ) • in areas difficult to access ( retroperitoneal, mediastinal / hilar ), multiple core biopsies may be more practical / feasible • FNA should NOT be used for diagnostic purposes in lymphoproliferative disease (excisional biopsy is the gold standard ) FNA is helpful for recurrence of solid tumour malignancy

-

ConstitutionaUB-Symptoms • Unexplained temperature >38"C • Unexplained weight loss (>10% of body weight in 6 mo) • Night sweats

Drugs that can Cause Lymphadenopathy • Allopurinol • Atenolol • Captopril • Carbamazepine • Cephalosporins Gold • Hydralazine • Penicillin Phenytoln • Primidone Pyrimethamine • Ouinidlne • Sulfonamides • Sulindac

-

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.

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Table 7. Inflammatory vs. Neoplastic Lymph Nodes Feature

Inflammatory

LJ

Neoplastic

Consistency

flucluanl/sofl

Firm/hard

Mobility

Mobile

Matted/immobile

Tenderness

lender

Non -lender

Size

2.5% •

-

HbT: 90 100 %

Treatment • lifelong regular transfusions to suppress endogenous erythropoiesis • iron chelation (e.g. deferoxamine, deferasirox, and deferiprone) to prevent iron overload in organs and the formation of free radicals ( which promote tissue damage and fibrosis) • folic acid supplementation if not transfused • allogeneic BM transplantation ( potentially curative) or cord blood transplant • gene therapy ( to encode adult Hb A ) or CRISPR-Cas 9 gene editing (to allow for increased fetal Hb production ) under study • splenectomy ( now performed less frequently)

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H21 Hematology

Toronto Notes 2023

p - Thalassemia Intermedia Definition

• clinical diagnosis in patients whose clinical manifestations are too mild to be classified as P thalassemia major, but too severe to be classified as p thalassemia minor

-

-

Clinical Features

• wide variety of clinical phenotypes

• in most cases of p-thalassemia intermedia, both P- globin genes affected

• three main mechanisms account for the milder phenotype compared to p-thalassemia major: ( 1) subnormal (vs. absent ) p-chain synthesis, (2) increased number of y chains, and (3) coinheritance of a- thalassemia ( in some cases)

• complications more commonly seen in p - thalassemia intermedia than p - thalassemia major include extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis, pulmonary hypertension , and growth retardation Treatment

• most patients only require periodic transfusions, although regular transfusions may eventually be

necessary in adulthood (third to fourth decade of life) • folic acid supplementation if not transfused • iron chelation therapy is required since iron overload develops due to ineffective erythropoiesis and subsequent hepcidin downregulation

a- Thalassemia Definition

• defect(s) in a genes • similar geographic distribution as P -thalassemia, but higher frequency among Asians and Africans Clinical Features

• I defective a gene (aa / a -): clinically silent; normal Hb, normal MCV • 2 defective a genes (cis: aa / or trans: a /a ): normal Hb, decreased MCV • N.B. cis 2 gene deletion more common in Asia vs. trans 2 gene deletion more common in Africa this leads to increased risk of fetal hydrops in offspring of patients from Asia vs. Africa • 3 defective a genes (a / ): HbH ( P4 ) disease; presents in adults, decreased Hb, decreased MCV, and splenomegaly • 4 defective a genes ( / ): Hb Barts (y4) disease ( hydrops fetalis); usually incompatible with life

--

-

- -

-

-

- --

——

Investigations

• CBC and iron studies (for iron overload ) • peripheral blond film - screen for HbH inclusion bodies with supravital stain • Hb electrophoresis can be used to identify HbH disease, but may miss I - or 2 - gene deletions; definitive diagnosis with UNA genotyping Treatment

• referral for genetic/prenatal counselling • depends on degree of anemia 1 or 2 defective a genes: no treatment required • HbH disease: similar to p-thalassemia intermedia Hb Barts: no definitive treatment - majority of pregnancies terminated ( fetal / maternal mortality risk ), intrauterine transfusion, stem cell transplants

t blood viscosity

Sickle Cell Disease Definition • autosomal recessive sickling disorders are most commonly caused by a Glu -> Val substitution at position 6 of the p-globin chain (chromosome 11) resulting in HbS variant, rather than HbA ( normal adult Hb) increased incidence of HbS allele in patients with Sub Saharan African, Indian, Middle liastern , or Mediterranean heritage (thought to be protective against malaria ) • SCO occurs when an individual has two HbS genes ( homozygous, HbSS ) or one HbS gene * another mutant P globin gene (compound heterozygote ) most commonly HbS P thal and HbSC disease

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I

flow ^Blood slows

-

--

ipO,

1

t

Distorted RBC sickle cells

1*

Deoxy HbS

T H' HbS polymers

CO,

'

Impaction

Infarction

Figure 8. Pathophysiology of sickling

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Pathophysiology

• at low pO’, deoxyHbS polymerizes leading to rigid crystal-like rods that distort membranes -> ‘sickles’ • the pO:level at which sickling occurs is related to the percentage of HbS present • sickling is aggravated by acidemia, increased C02, increased 2,3- DPG, fever, and increased osmolality • fragile sickle cells then cause injury in two main ways 1. fragile sickle cells hemolyze ( nitric oxide depletion ) 2. occlusion of small vessels ( hypoxia, ischemia reperfusion injury )

-

& • Functional Asplenism: increased susceptibility to infection by

encapsulated organisms

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+

. . •

• S pneumoniae N meningitidis • H influemae

Salmonella (osteomyelitis)

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H22 Hematology

Toronto Notes 2023

Clinical Features

• sickle cell trait ( HbAS ): patient will be asymptomatic except during extreme hypoxia or infection increased risk of renal medullary carcinoma

.

SCD -SS ( HbSS) chronic hemolytic anemia « jaundice in the first year of life retarded growth and development ± skeletal changes splenomegaly in childhood; splenic atrophy in adulthood • SCD SS often presents with acute pain episode 1. aplastic crises toxins and infections (especially parvovirus B19) transiently suppress B\1 2. splenic sequestration crises usually in children; significant pooling of blood in spleen resulting in acute Hb drop and

-

shock uncommon in adults due to asplenia from repeated infarction 3. vaso occlusive crises ( infarction ) may affect various organs causing ischemia- reperfusion injury (especially in back, chest, abdomen, and extremities), fever, and leukocytosis

-

$

Ischemic or hemorrhagic stroke, vascnlopathy Hemorrhage, blindness Infarcts. DUO syndrome

Brain

Eye

liver Lung

Acute chest syndrome, longterm pulmonary hypertension

Gallbladder

Slones Hyperdynamic How murmurs Enlarged (child): atrophic [adult]

Heart Spleen

Kidney

Hematuria, loss of renal concentrating abiity. proteinuria

Intestines Placenta

Acute abdomen Stillbirths

can cause a stroke or a silent M 1

precipitated by infections, dehydration, rapid change in temperature, pregnancy, menses, and alcohol 4. acute chest syndrome acute illness characterized by fever and /or respiratory symptoms new pulmonary infiltrate on chest x- ray precipitated by pulmonary infection, fat embolism, and pulmonary infarction • SCD-SC ( HbSC ): most common compound heterozygote I in 833 live births in African Americans, common in West Africa milder anemia than HbSS similar complications as HbSS but typically milder and less frequent (exception is proliferative

-

-

Organs Affected by Vaso Ocdusive Crisis Organ Problem

Penis

Priapism

Digits

Dactylitis

Bone

Infarction, inlection, avascular necrosis (femoral and humeral head) leg ulcers (ankle)

Skin

sickle cell retinopathy, glomerulonephritis, and avascular necrosis) spleen not always atrophic in adults Investigations

• sickle cell prep (detects sickling of RBCs under the microscope in response to 0:lowering agent ):

determines the presence of a HbS allele, but does not distinguish HbAS from HbSS • Hb electrophoresis distinguishes HbAS, HbSS, HbSC, and other variants • all newborns in developed countries typically screened for SCD

Table 13 , Investigations for Sickle Cell Disease CBC

HbAS Normal

HbSS Increased reticulocytes, decreased Hb, and decreased Hct

Peripheral Blood

Normal; possibly a few target cells

Sickled cells

Hb Electrophoresis

HbA fraction of 0.6S|6S%) HbS lr action ol 0.35 (35%|

No HbA, only HbS and HbF ( proportions change with age); normal amount of HbA 2

Treatment • genetic counselling • HbAS: no treatment required • HbSC: treatment as per HbSS, but is dictated by symptom severity

. HbSS1. folic add to prevent folate deficiency

2. hydroxyurea to enhance production of Hbl; mechanism of action: stops repression of Hb- y chains and / or initiates differentiation of stem cells expressing this gene presence of HbF in the sickle cell RBCs decreases polymerization and precipitation of HbS short term harms ( within 6 mo): dose- related leukopenia , thrombocytopenia, anemia, and decreased reticulocyte count; decreased sperm production , mucositis, skin ulcers long term harms: birth defects in offspring of people receiving the drug, growth delays in children receiving the drug, and cancer in both children and adults who receive the drug 3. treatment of vaso-occlusive crisis supportive care: oxygen, hydration ( reduces viscosity), correct acidosis, analgesics /opiates indication for exchange transfusion: Hb 1 month comparing hydroiyurea with placebo, standard therapy or other interventions.

Results 8 RCTswere included . 889 total patients (bothadoltsand children with SCO). When compared lo placebo, hydroxyurea was associated with statistically significant improvements in pain alteratioo ( pain crisis frequency, duration, intensity, hospital admissions and opioid use), measures of fetal hemoglobin and neutrophil coonts and fewer occurrences of acute chestsymdroene and blood transfusions. Differences in quality ol life and adverse events (including serious or life-threatening events) were not statistically significant. Conclusion: Ev, fence suggests that hydroxyurea can effectively decrease the frequency nf pain episodes and other acute complications m patients with SCD. However, data on the long term henetts and risks ol hydroxyurea is still Insufficient.

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H23 Hematology

5. screen for complications regular blood work ( CBC, reticulocytes, iron indices, BUN, LFTs, and creatinine) urinalysis annually ( proteinuria and glomerulopathy)

transcranial doppler annually until 16 yr (stroke prevention ) retinal examinations annually from 8 yr (screen for retinopathy ) echocardiography once in late childhood /earlv adulthood ( screen for pulmonary hypertension ) 6. future therapies gene therapy voxelotor crizanlizumab

Autoimmune Hemolytic Anemia

Ab Allotype

Warm ( 75 90% cases)

Cold

IgG

IgM

Agglutination Temperature

37°C

4 - 37’C

Positive lor IgG t complement

Positive for complement

Idiopathic Secondary to lymphoproliferative disorder (e.g Cll, Hodgkin lymphoma) Secondary to autoimmune disease (e.g. Sit ) Pregnancy Drug-induced (e.g. penicillin, quinine, methyldopa)

Idiopathic Secondary to infection (e g. mycoplasma pneumonia F 6 V HCV syphilis) Secondary to lymphoprohlciatlvc disorder (e g. macroglobulinemia Cll)

Blood Film

Sphcrocytcs

Agglutination

Management

Treat underlying cause Folic acid

treat underlying cause Folic acid Warm patient/ avoid cold Rituximab regimen (Ist -line) Plasma exchange ( 2nd line for high IgM levels) low dose alkylating agents (chlorambucil, cyclophosphamide) or interferon maybe useful but less effective

( direct antiglobulin test )

.

Corticosteroids (Ist-line) Folic acid Rituximab |2nd- line to steroids) Immunosuppression Splenectomy

-

overload. Primary Outcome: Secondary stroke recurrence rale and quantitative liver iron content Results: Stroke recurrence rate was significantly lower in patients on transfusionsldeferasiror as compared to those initiated on hydroxyurea / phlebotomy (0 % vs. 10V P'0.05). Differences in Over ironcontent between the two treatmentaims were not statistically different (16.6 mgfg dry weight liver in transfusions/deferasirox vs.15.7 mg'g in hydroiyurea phtebotomy). Conclusion: Iransfuvo s and chelation remain the preferred management strategies lor pediatric patients with SCA stroke and iron overload.

.

Direct Coombs Test Etiology

.

.

Table 14 . Classification of AIHA

-

Stroke Willi Transfusions (hanging to Hydroxyurea (SWiTCH) Bood 2012;119:3925-32 Purpose: Tocompare standard treatment ( transfrrsionsfchelation) to alternative treatment (hydroiyureafphlebotomy) lor children with Mine tell anemia (SCA) stroke,and non overload. Methods:133 pediatric patients were randombed to (1) continuation of monUtly erythrocyte transfusions with oral delerasiroi (28.2 6.0 mgfkgJd) or (2) initiation on hydroxyurea (20 mgikgfd escalated to manmum tolerateddose (HTD) *26.2 •4.9 mg/ kg d) with discontinuation of transfusions at MID and monthly phlebotomy (5 -111 ntUkgi'mo|for iron

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Microangiopathic Hemolytic Anemia / Thrombotic Microangiopathy Definition

Schistocyte

• hemolytic anemia due to intravascular fragmentation of RBCs

Etiology • see 'lhrombotic thrombocytopenic Purpura and Hemolytic Uremic Syndrome, H 3I • see Disseminated Intravascular Coagulation, H 34 • eclampsia , HI:LLP syndrome, AI ' LP • malignant hypertension •

vasculitis

Vessel wall 6 o

6

• malfunctioning heart valves • metastatic carcinoma • drugs (calcineurin inhibitors, quinine, simvastatin) • infections (severe CMV or meningococcus) • catastrophic APS

o

8

Investigations • blood film: schistocytes • hemolytic workup (CBC, reticulocyte count, LDH , haptoglobin , indirect bilirubin ) • Coombs test: negative • urine: hemosiderinuria , hemoglobinuria

100 fL see -igure 2 , H l'

•

6

Table 15 . Comparison Between Megaloblastic and Non - Megaloblastic Macrocytic Anemia Megaloblastic

Non - Megaloblastic

Morphology

Laige. oval , nucleated IIBC precursor Hypetsegmenled neutrophils

large round RBC Normal neutrophils

Pathophysiology

Failure of DMA synthesis resulting in asynchronous maturation of R 8C nucleus and cytoplasm

Reflects membrane abnormality with abnormal cholesterol metabolism

Causes of Macrocytic Anemia

A8CDEF

Note: MDS is a non.megaloblastic macrocytic anemia Dial commonly presents with oval macrocytosls

Alcoholism (liver disease) B' j deficiency Compensatory reticulocytosis Drugs (cytotoxic, azidothymidine) / Dysplasia Endocrine (hypothyroidism) Folate deficiency /Fetus (pregnancy)

Vitamin B12 Deficiency Characteristics of Megaloblastic Macrocytic Anemia

• B12 (cobalamin ) • binds to intrinsic factor ( IF) secreted by gastric parietal cells • absorbed in terminal ileum • total body stores sufficient for 3 4 yr

• Pancytopenia

• Hypersegmented neutrophils • Megaloblastic BM

-

Etiology Table 16. Etiology of Vitamin B12 Deficiency Diet

Gastric

Intestinal Absorption

Genetic

Strict vegan More likely to present in

Mucosal atrophy Gastritis, autoimmune Pernicious anemia (see

Malabsorption

Iranscobalamin II deficiency IF receptor defect

below) Postgastrectomy

Stagnant bowel Blind loop, stricture Fish tapeworm Resection of ileum Drugs Neomycin , biguanides. proton pump inhibitors It 0 anesthesia , metlormin

paediatric population

Vegetarian in pregnancy Malnutrition

Crohn 's , celiac disease, pancreatic insufficiency H. pylori

.

.

Pathophysiology of Pernicious Anemia • auto- Abs produced against gastric parietal cells leading to achlorhydria and lack of IF secretion • IF is required to stabilize Bi ’ as it passes through the bowel

• decreased IF leads to decreased ileal absorption of B 12 • may be associated with other autoimmune disorders ( polyglandular endocrine insufficiency ) • most common in Northern European White populations, usually >30 yr ( median age of 60 yr ) Clinical Features • neurological ( severity of anemia and neurological sequelae depends on deficiency ) peripheral neuropathy ( variable reversibility )

usually symmetrical, afi ccting lower limbs more than upper limbs spinal cord ( irreversible damage ) subacute combined degeneration posterior columns: decreased vibration sense, proprioception , 2-point discrimination, and '

paresthesia

pyramidal tracts: spastic weakness, ataxia • cerebral (common, reversible with Bi > therapy) confusion , delirium, and dementia • cranial nerves ( rare) optic atrophy Investigations

• CBC, reticulocyte count anemia often severe ± neutropenia ± thrombocytopenia • MCV >110 fL • low reticulocyte count relative to the degree of anemia (< 2%) • serum B12 and RBC folate caution: lower serum Bi ’ leads to low RBC folate; absence of Bi ’ results in folate polyglutamate synthesis failure • alternatively, can measure elevated urine metabolites ( methylmalonatc, homocysteine) • blood film oval macrocytes, hypersegmented neutrophils

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H 26 Hematology

Toronto Notes 2023

• BM

• hypercellularity

nuclear-cytoplasmic asynchrony in RBC precursors ( less mature nuclei than expected from the development of the cytoplasm ) •bilirubin and LDH • elevated unconjugated bilirubin and LDH due to breakdown of cells in BM •Schilling test ( radiolabeled B 12 test, rarely done ) to distinguish pernicious anemia from other causes (e.g. anti IT antibody, anti parietal cell antibody )

-

-

Treatment

• treatment dose = vitamin B 12 1000 pg 1M weekly or 1000-1200 pg PO once daily if intestinal absorption intact; route and duration depends on cause • maintenance dose (once replete) = vitamin B 12 1000 pg 1M monthly or 1000 pg PO once daily • watch for hypokalemia and rebound thrombocytosis when treating severe megaloblastic anemia

Folate Deficiency • uncommon in developed countries due to extensive dietary supplementation (enriched in flour ) • folate stores are depleted in 3-6 mo • folate commonly found in green, leafy vegetables, and fortified cereals • maternal folate deficiency is associated with fetal neural tube defects Etiology

Table 17. Etiology of Folate Deficiency Diet / Deficiency Alcohol use disorder Substance misuse Elderly/infants Poor intake

Malabsorption

Drugs

Increased Demand

Celiac disease

Antifolate (methotrexate)

IBD Short bowel syndrome

Anticonvulsants (phenytoin) Alcohol Oral contraceptive

Pregnancy Hemolysis Prematurity Exfoliative dermatitis/psoriasis Hemodialysis

Clinical Features

• anemia, mild jaundice, glossitis, diarrhea , confusion , pallor

• consider social history, alcohol use disorder /substance misuse, very poor diet (e.g. elderly, depressed ) Investigations • similar to B12 deficiency (CBC, reticulocytes, blood film, RBC folate, and serum B12) • if decreased RBC folate, rule out B12 deficiency as cause Management

Never give folate alone to an individual with megaloblastic anemia because it will mask B2 deficiency and neurological degeneration will continue

• folic acid 1-5 mg PO once daily x 1- 4 mo; then 1 mg PO once daily maintenance if cause is not reversible

Hemostasis Stages of Hemostasis 1. Primary Hemostasis • cellular defense - involves the platelet and VWI; predominantly • goal is rapid cessation of bleeding; main effect is on mucocutaneous bleeding • vessel injury results in collagen /subendothelial matrix exposure and release of vasoconstrictors

• blood flow is impeded and platelets come into contact with damaged vessel wall ( figure 12a , H 27 ) « adhesion: platelets adhere to subendothelium via VWT • activation: platelets are activated resulting in integrin activation, shape change, and granule release • aggregation: activated GPlIbllla on platelets binds soluble ligands, which results in aggregation and the formation of a localized platelet plug

Phases of Hemostasis • Primary Hemostasis Vascular response and platelet plug formation via VWF • Secondary Hemostasis Fibrin clot formation • Fibrin Stabilization Fibrinolysis

2. Secondary Hemostasis • platelet plug is reinforced by production of a fibrin clot ( figure 12b, H 27 ) • extrinsic ( initiation ) pathway: initiation of secondary hemostasis

• intrinsic (amplification ) pathway: amplification once secondary hemostasis has started via positive feedback

• both the intrinsic and extrinsic pathways converge onto the common pathway, which results in thrombin generation and fibrin formation

Check out this educational module created by St. Michael's Hospital residents and hematology faculty: www. coagtesting.com

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3. Fibrin Stabilization • conversion from a soluble to an insoluble, cross linked clot

-

4. Fibrinolysis

• once healing is initiated , clot dissolution is mediated by the fibrinolytic system

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H 27 Hematology

Toronto Notes 2023

INACTIVE

EXTRINSIC PATHWAY

ACTIVE

INTRINSIC PATHWAY

HMWK Tissue Damage

”

Aspirin Clopidogrel Ticlopidine GPIIb/ llla inhibitors Dipyridamole

rO-

r.

Ls

Xlla

Tissue Factor

i

LUMEN OF BLOODVESSEL

+

- VII -

COMMON PATHWAY

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Fondaparinux

LMWH

12 mo from diagnosis • refractory: post splenectomy

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H29 Hematology

Toronto Notes 2023

Pathophysiology primary or secondary I I P • an acquired immune-mediated disorder ( pathophysiology not completely understood ) increased platelet destruction anti- platelet Abs bind to platelet surface -> increased splenic clearance • helper T cell and cytotoxic T cell activation «

-

-

impaired platelet production

Clinical Features

• variable presentation: asymptomatic, fatigue, minimal bruising, mucocutaneous bleed (e.g. purpura, ecchymoses, petechiae, continuous epistaxis, menorrhagia ), and intracranial hemorrhage • assess for symptoms/signs suggesting a secondary cause Investigations

• CBC: thrombocytopenia • PT and P I T: normal • peripheral blood film: decreased platelets, giant platelets ( rule out platelet clumping )

.

• H1V HCV

• H . pylori testing ( urea breath test, stool antigen, or endoscopy) vitamin Bn, ANA, C3, C4, APLA, quantitative immunoglobulins (to rule out underlying immunodeficiency') depending on clinical symptoms • blood group RhD typing • BM aspirate and biopsy: increased number of megakaryocytes BM aspirate and biopsy should be considered pre-splenectomy or if there is suspicion of diminished BM function (systemic symptoms, failed traditional 1TP and/or abnormal blood film ) Treatment

• rarely indicated if platelets >30 x lO’/ L unless active bleeding, trauma, or surgery

• emergency treatment (active bleeding (CNS, Gl, or GU ) or in need of emergency surgery ) general measures: stop drugs that reduce platelet function, control blood pressure, minimize trauma

-

corticosteroids: prednisone (0.5 2 mg/ kg /d ) or dexamethasone (40 mg PO once daily x 4 d ) if corticosteroids contraindicated: IVIg 1 g / kg x I dose, to be repeated if necessary ( raises platelet count faster than corticosteroids) « IVIg can be used with corticosteroids when a more rapid increase in platelet count is required antifibrinolytic: tranexamic acid ( I g PO T1D or 1 g 1V q8 h) if mucosal bleeding platelet transfusion: for refractory, major bleeding, or need for urgent surgery (expect that platelet recovery will be diminished ) • emergency splenectomy: may be considered, vaccinations prior if possible ( S’, pneumoniae , N. meningitidis, and H. in fluenzae type b) management of intracranial bleeding: IV steroids, IVIg, platelet transfusion • non -urgent treatment ( platelet count 100 x lO’/ L « partial response: platelet count 30 -100 x 10 / L ’ • no response: platelet count 100 X lO Vl Self -limited (no thrombotic risk) • May continue with heparin therapy • Onset 24 -72 h

.

*

.

LMWH is also associated with HIT but the risk is less than unfractionated heparin (2.6% in UFH vs. 0.2% in LMWH)

Table 23. The 4 T Pre - Test Clinical Scoring Model for HIT Category

2 Points

1 Point

O Points

Thrombocytopenia

Platelet count lall >50% AND platelelnadir > 20 x 10 /!

Platelet count fall 30 - 50% OR plateletnadir 10 -19 x 10 VL

Platelet count fall > 30%

Clear onset between 5-10 d ol

Consistent with fall in platelet count at 5 -10 d but unclear ( e.g. missing platelet

’

liming of Platelet Count Fall

heparin exposure OR platelet count fall at

Vitamin K Dependent Factors Vitamin K antagonists (e.g. warfarin) affect function of these factors: 1972 Canada vs.Soviets" X DC, VII II proteins C and S

. ..

PT should improve within 24 h of adequately dosed vitamin K repletion (onset is in 6 12 h): if not. search for other causes

-

American Society of Hematology Choosing Wisely Recommendation Do not administer plasma or prothrombin complex concentrates for non emergent reversal of vitamin K antagonists (e.g. outside of the setting of major bleeding, intracranial hemorrhage,

-

or anticipated emergent surgery)

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H3-I Hematology

Toronto Notes 2023

Disseminated intravascular Coagulation Definition • excessive, dysregulated release of piasmin and thrombin leading to intravascular coagulation and

DIC is a spectrum which may include thrombosis, bleeding, or both

fibrinolysis • depletion of platelets, coagulation factors, and fibrinogen • risk of life- threatening hemorrhage and / or thrombosis Factor Levels in Acquired Coagulopathies

Etiology • occurs as a complication of many other severe medical, surgical, or obstetrical conditions • widespread endothelial damage and extensive inflammatory- cytokine release

Factor

Liver Disease

Endothelial Injury

Reticuloendothelial Injury

Vascular Stasis

Other

APS Intravascular hemolysis e.g.incompatible blood,malaria Tissue injury e.g. obstetric complications, trauma. burns,crush injuries

Infections/sepsis Vasculitis

Liver disease Splenectomy

Hypotension Hypovolemia

Acule hypoxia '' acidosis (check lactate)

Metastatic adenocarcinoma Aortic aneurysm Giant hemangioma

DIC

V

*

N

n

«

a

a »

VH

Kt

N

*

Table 27. Etiology of DIC Activation of Procoagulant Activity

Vitamin KDef

PE Important Etiologies of DIC

OMITS Ob stetric complications Malignancy Infection Trauma Shock

Malignancy e.g. solid tumours, hematologic malignancies (especially APL) Snake venom, fat embolism,heat stroke

Clinical Features • presence ofboth hemorrhage and clotting Table 28. Clinical Features of DIC Signs of Microvascular Thrombosis

-

Signs of Hemorrhagic Diathesis

Neurological:multi focal infarcts, delirium, coma, seizures Skin:focal ischemia.superficial gangrene, purpura fulminans Renal: oliguria, azotemia, cortical necrosis Pulmonary: ARDS Gl: acute ulceration,liver dysfunction Adrenal failure:adrenal hemorrhage or infarction SBC:m croangiopathic hemolysis (schistocytes)

General:Bleeding from any site in the body (secondary lo decreased platelets and coagulation factors)

Neurologic intracranial bleeding Skin:petechiee. eahymosis. oozingfrom puncture sites Renal:hematuria Mucosal: gingival oozing,eprstaxis massive bleeding

Clinical Prediction of DIC International Society of Thrombosis and Hemostasis (IS TH) Calculator Presence of an underlying, predisposing condition is a requirement DIC diagnosis is defined as >5 points

.

'

Investigations • peripheral blood smear: schistocytes • primary hemostasis: CBC , decreased platelets • secondary hemostasis: prolonged INR ( FT ), F I T', 'IT, decreased fibrinogen and other factors • fibrinolysis: increased FDPs or D dimers and short euglobulin lysis time ( i.e. accelerated fibrinolysis) • extent of fibrin deposition: urine output and RBC fragmentation

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Treatment

individualize supportive therapy according to underlying condition: recognize early and treat underlying disorder - supportive measures: hemodynamic and /or ventilator support, aggressive hydration, and RBC transfusion if severe bleed • in bleeding phase ( recommendations from 1STH Guidance Statement 2013): treat the underlying condition transfuse platelets in patients with active bleeding if platelet count 1.5 times normal ) or decreased fibrinogen (

10


{

10

HU

-

Table 29. Differential Diagnosis for Abnormal Coagulation Testing

_

r ~t

Increased PT/ INR Only

Increased PTT Only

Both Increased

Warfarin Vitamin K deficiency Factor VII deficiency Liver disease factor VII inhibitors

Intrinsic factor deficiency:Factor VIII ( Hemophilia A), factor IX (Hemophilia S). Factor XI. FactorXIl Heparin. DOACs Antiphospholipid Ab Intrinsic factor inhibitors ( e_ g. Factor VIII)

Deficiency of common pathway factors: Prothrombin (Factor II), fibrinogen FactorV. Factor X Severe liver disease FactorV FactorX prothrombin, and fibrinogen inhibitors Excessive anticoagulation Severe vitamin K deficiency

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H35 Hematology

Toronto Notes 2023

Hypercoagulable Disorders Hypercoagulability Workup - Venous Thrombosis • workup for hypercoagulable state is controversial and should be considered ONLY if it will alter treatment decisions • includes inherited or acquired thrombophilia hypercoagulability workup may be considered in patients with: multiple recurrent thromboses warfarin -induced skin necrosis or neonatal purpura fulminans ( protein C or S deficiency)

thrombosis at an unusual venous site abnormal blood work, constitutional symptoms, or physical exam findings suggestive of cancer arterial thrombotic events due to a hypercoagulable state are typically associated with APS, HIT, IAK 2+ MPNs, and PNH, not hereditary thrombophilias

• workup ( if indicated ) • initial CBC, blood smear, coagulation studies, liver / renal function tests, urinalysis, and hemolysis markers ( if anemic ) malignancy history, age appropriate cancer screening serology" APLA (lupus anticoagulant will be affected by anticoagulation ) depending on CBC, consider JAK2 post-treatment (or >6 wk, as protein levels are depleted /consumed by dot ) antithrombin activity' ( not on heparin ) proteins C, S activity ( not on warfarin ) • note: most of these tests do not change management, and a negative test does not rule out a hypercoagulable state • decision to pursue hypercoagulability workup should be made in consultation with a hematologist SELECTED CAUSES OF HYPERCOAGULABILITY

Activated Protein C Resistance ( Factor V Leiden ) • most common cause of hereditary thrombophilia • 3-7% of European White population are heterozygotes point mutation in the Factor V gene ( R506Q) results in resistance to inactivation of Factor Va by activated protein C

-

Prothrombin Gene Mutation ( PT ) G 20210A • 1-3% of European White population are heterozygotes • G to A transposition at nucleotide position 20210 of the prothrombin gene promoter region results in increased levels of prothrombin, thus increased thrombin generation

Protein C and Protein S Deficiency • protein C inactivates Factors Va and Villa using protein S as a cofactor • protein C deficiency homozygous or compound heterozygous: neonatal purpura fulminans heterozygous type 1: decreased protein C levels type II: decreased protein C activity acquired: liver disease, sepsis, DIC, warfarin, and certain chemotherapeutic agents • 1/3 of patients with warfarin necrosis have underlying protein C deficiency • protein S deficiency type I: decreased free and total protein S levels type 11: decreased protein S activity type Ill: decreased free protein S levels acquired: liver disease, DIC, pregnancy, nephrotic syndrome, inflammatory conditions, and warfarin Antithrombin Deficiency • in absence of heparin: antithrombin slowly inactivates thrombin. In the presence of heparin: antithrombin rapidly inactivates thrombin • causes/etiology: autosomal dominant inheritance, urinary losses in nephrotic syndrome, or reduced synthesis in liver disease • diagnosis must be made outside window of acute thrombosis and anticoagulation treatment (acute thrombosis, heparin , systemic disease all decrease antithrombin levels ) • deficiency may result in resistance to UFH ( LM WH may be considered, with monitoring of anti Xa

levels) • heparin resistance: suspect if >35000 IU of UFH required during 24 h use

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Elevated Factor VIII Levels • an independent marker of increased incident and recurrent thrombotic risk, but levels can also be increased in numerous states as an acute phase reactant, therefore its clinical use is controversial

Differential Diagnosis of Elevated D Dimer Arterial thromboembolic disease (e.g. Ml cerebrovascular accident, acute limb ischemia. AFib. intracardiac thrombus) • Venous thromboembolic disease (e.g. DVT. PE) • Abnormal fibrinolysis (e.g. use of thrombolytic agents) • Surgery /trauma (e.g. tissue ischemia, necrosis) • Vaso ocdusive episode of SCD • Renal disease (nephrotic syndrome, acute/chronic renal failure) • Pregnancy-related (e.g. normal pregnancy, preedampsia. eclampsia) Cardiovascular related (e.g. cardiovascular disease. CHF) • Severe infection/sepsis/inflammation , systemic inflammatory response syndrome

.-

.

-

.

..

-

DIC

Malignancy Severe liver disease • Venous malformation

.

• Isolated prolonged INR is most commonly due to Factor VII deficiency in the extrinsic pathway since it has the shortest half life • Isolated elevated PTT is usu al ly due to factor deficiency or inhibitors in the intrinsic pathway

-

American Society of Hematology Choosing Wisely Recommendations 1 Do not test for thrombophilia in adult patients with venous thromboembolism occurring in the setting of major transient risk factors ji.e. surgery, trauma, or prolonged immobility) 2. Do not use inferior vena cava filters routinely in patients with acute venous thromboembolism

Common Causes of Hypercoagulability

CALM APES Protein C deficiency APS Factor V Leiden Malignancy Antithrombin deficiency Prothrombin G20210A Increased Factor VIII (Bght) Protein S deficiency

Causes of Both Venous and Arterial Thrombosis indude: APS MPN HIT Distal venous dot with patent foramen ovale PNH

.

Protein C protein S.and AT1II are decreased during acute thrombosis therefore to test for deficiency, they must be tested outside of this time period

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H36 Hematology

Toronto Notes 2023

Congenital Dysfibrinogenemia

• may predispose to thromboembolic disease, bleeding, or both Disorders of Fibrinolysis

• includes congenital plasminogen deficiency, tPA deficiency, but association with VTE risk is not dear Antiphospholipid Antibody Syndrome • definition : I clinical and £ I laboratory criteria • clinical: arterial or venous thrombosis, recurrent (>3) early pregnancy losses < 10 wk, one late fetal loss £ 10 wk ( morphologically normal ), or premature birth before 34 wk due to ( pre)eclampsia or placental insufficiency laboratory ( must be confirmed on two occasions, tested £ 12 wk apart ): anticardiolipin IgG and IgM, anti p2 glycoprotein !Ab, or lupus anticoagulant • mechanism: not well understood, Abs interact with platelet membrane phospholipids causing increased activation; can also interfere with thrombin regulation, fibrinolysis, and inhibit the protein C pathway • see Rheumatology. RH 13

-

Definition • thrombus formation and subsequent inflammatory response in a superficial or deep vein

• includes superficial thrombophlebitis, DVT, and PE • thrombi propagate in the direction of blood flow (commonly originating in calf veins) • DVT is more common in lower extremity than upper extremity ( upper extremity DVT are increasing due to more central venous access lines) • incidence 1% if age >60 yr • most important sequelae of DVT are PE ( 50% chance with proximal DVT) and chronic venous insufficiency • acutely, PE can result in cardiorespiratory failure and death ( rare in treated patients), most severe chronic sequela of PE is chronic thromboembolic pulmonary hypertension (CTEPH)

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Etiology ( Virchow’s Triad)

• endothelial damage • exposure of procoagulant proteins on dysfunctional endothelium promotes thrombosis • decreases inhibition of coagulation and local fibrinolysis ( • changes to vessel wall integrity may result in turbulent blood low • venous stasis immobilization (e.g. post-Ml, CHE, stroke, and postoperative) inhibits clearance and dilution of

coagulation factors • hypercoagulability • inherited (see Hypercoagulable Disorders, H 35 ) acquired age (risk increases with age) surgery (especially orthopaedic, thoracic, Gl, and GU ) trauma (especially fractures of spine, pelvis, femur, or tibia, and spinal cord injury) neoplasms ( especially pancreas, stomach, lung, lymphoma, bladder, testicular, colorectal, and gynaecologic - based on the Khorana score) blood dyscrasias (MPNs, especially PV, ET ), PNH, hyperviscosity (multiple myeloma, polycythemia , leukemia, and SCD ), hemolytic anemias prolonged immobilization (e.g. CH1;, stroke, Ml, and leg injury) hormone related ( combined OCP, hormone replacement therapy, and selective estrogen receptor modulators)

• pregnancy •

Workup should include: Complete history and physical Age appropriate screening: Mammogram Pap PSA colonoscopy Additional imaging/laboratory testing based on clinical suspicion Close follow-up

. .

.

-

Venous Thromboembolism

-

9

Malignancy is a Common Cause ol Acquired Hypercoagulability

APS

• heart failure ( risk of DVT greatest with right heart failure and peripheral edema )

New York Heart Association ( NYHA ) Class III and IV • idiopathic ( 10 20% are later found to have cancer )

-

Clinical Features of DVT

• absence of physical findings does not rule out disease • unilateral leg edema, erythema , warmth, and tenderness; purple -blue colour may indicate severe linib-threatening thrombus • palpable cord (i.e. thrombosed vein )

• phlegmasia alba dolens ( white appearance) and phlegmasia cerula dolens (acute pain and edema ) with massive thrombosis • Homan s sign ( pain or resistance with foot dorsiflexion ) is unreliable

Screening tor Occult Cancer in Unprovoked VIE (SOME ) ICJM 2015:373:697-704 Purpose: In assess the efficacy of a screen ing program for occult cancer that employs CT of the abdomen and pelvis in patients experiencing their hist unpranked episode ol VIE. Methods: Patients (i 854|were randomly assigned to limited occult-cancer screening or limited occultcancer screening plus Cl. Results: 3.2% ol patients in the limited screening group and 4.5% oi patients in the limited -screening pbs Cl gioup received a new diagnosis of occult cancer between the randomliation point and 1 year followup (P 0.28). Four occult cancers were missed by the tailed screening strategy, whip live occult cancers were missed by the limited screening plusCI strategy|PM.O). Conclusion: Routine screening with CT In patients who hada first unprovokedVIE dldnol provide a clinically significant benefit

-

-

-

-

.

Although lupus anticoagulant prolongs PTT, this is a misnomer, as its main clinical feature is thrombosis

Risk uf VIE in Hospitalized Patients Receiving Ineffective Antitbiombotic Therapy Risk Factor RR (95% Cl) P-value

Age >75 yr Cancer Previous VIE Obesity

-

1.79 (1.18 2.71) 1.58 (1.01 2.51) 1.67 (1.01 2.77) 0.94 (0.59 1.51)

0.M7 0.08 0.91

-

Hocmone therapy 0.51 (0.08 3.38) 0.70 1.08 (022 1.62) 0.82 Heart failure 0.89 (0.55 1.43) 0.72 NYHA III

-

-

1.48 (0.84 2.6) 0.27 Acute infectious 1.50 (1.00-2.26) 0.06 NYHA IV

disease

-

Acute rheumatic 1.45 (0.84 2.50) 0.27 disease

-

Source: JAMA 7004:1&4:963 HB

Virchow's Triad Endothelial damage Blood stasis Hypercoagulability

+

Differential Diagnosis of DVT • muscle strain or tear, lymphangitis or lymph obstruction, venous valvular insufficiency, ruptured

popliteal cysts, cellulitis, and arterial occlusive disease

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H37 Hematology

Toronto Notes 2023

Investigations for DVT

• D- dimer test only useful to rule out DVT if negative with low clinical suspicion of disease ( Modified Wells' Pre - test Probability 1) and no other acute medical issues; positive result may be non specific • doppler ultrasound is most useful diagnostic test for DVT

-

-

Wells’ Score for Predicting DVT

• Paralysis, paresis, or recent

sensitivity and specificity for proximal DVT 95%

• sensitivity for calf DV T -70%

»

• venography is the gold standard, but is expensive, invasive, and higher risk • CT pulmonary angiogram or V/ Q scan if PE suspected

•

Post-Thrombotic Syndrome • development of chronic venous stasis signs and symptoms secondary to a deep venous thrombosis • symptoms: pain, venous dilatation, edema, pigmentation, skin changes, and venous ulcers • clinical severity can be assessed using the Villalta score

• large impact on quality of life following a DVT • treatment: extremity elevation, exercise, compression stockings, and skin / ulcer care • for clinical features and treatment of PE, see Respirolocv, R 19

•

Purpose

.

Total Score Interpretation 3-8: High probability 1-2:Moderate probability, - 2-0: Low probability

• prevent further clot extension ( minimum 3 mo duration ) • prevent acute PE (occurs in up to 50% of untreated patients)

.

• reduce the risk of recurrent thrombosis (duration depends on presence of other risk factors ) • treatment of massive iliofemoral thrombosis with acute lower limb ischemia and/or venous gangrene ( phlegmasia cerulea dolens) • limit development of late complications (e.g. post-thrombotic syndrome, chronic venous insufficiency, and chronic thromboembolic pulmonary HTN )

-

• consider empiric treatment in patient with moderate / high suspicion of DVT and low risk of bleeding, if diagnostic imaging will be delayed (definitive imaging should be obtained at first opportunity ) DOACs apixaban or rivaroxaban alone ( with loading dose ) • dabigatran or edoxaban require 5 10 d of parenteral anticoagulation ( usually LM WH ) prior to initiation contraindications: during pregnancy, in breastfeeding women there remains limited evidence in severe renal deficiency and some clinicians do not use DOACs in this population

.

• •

Approach to Treatment of Venous Thromboembolism

Initial Treatment

• •

orthopaedic casting of lower extremity (1) Recently bedridden (>3 d) or major surgery within past 4 wk (1) Localized tenderness in deep vein system (1) Swelling of entire leg (1) Calf swelling >3 cm compared to the other leg (measured 10 cm below the tibial tuberosity) (1) Pitting edema greater in the symptomatic leg (1) Collateral non-varicose superficial veins (1) Active cancer or cancer treated within 6 mo (1) Alternative diagnosis more likely than DVT (e.g. Baker's cyst, cellulitis, muscle damage, superficial venous thrombosis) (- 2)

-

Modified Wells’ Score Same as above except with 1 additional point for a history of DVT or major surgery within past 12 wk. and the i:::e interpretation is DVT likely for >2 points and DVT unlikely for 2.0 for 2 consecutive days DOACs apixaban or rivaroxaban: INR not used, patients with CrCl >15 mL / min dabigatran ( factor lla inhibitor ) or edoxaban: LMWH or IV heparin for at least 5 d before initiating dabigatran, INK not used , patients with CrCl >30 mL/ min important drug interactions to consider for DOACs cancer patients; LMWH more effective than warfarin at preventing recurrence of venous thrombosis In cancer patients; DOACs are as effective as LMWH ( more bleeding observed for patients with Cii cancer taking rivaroxaban or edoxaban )

-

Duration of Treatment with Vitamin X Antagonists jVKA] in Symptomatic Venous Thromboembolism Cuch. ane DB Syst Rev 2014 X00 01367 Purpose: lo evaluate the efficacy and safety of va nous durations of theiapy w ith VKA In patients with symptomatic VIE. Study Selection : dels comparing various durations of therapy with VKA m patientssymptomatic VIE Results: II studies ( total 3716 pari c pan Is) were Included A significant leducbon in the (Ask ol recurrent VIE was observed during prolonged VKA treatment ( tl 0.20 95% Cl 0.11 toO.38 ) *dependent ol Use lime elapsed since the imdex thrombotic event. Patients receiving prolonged treatment were at increased risk of bleeding coinpicalwos( U 2.(0 95% Cl 1.51 to 4.49). Conclusion: Treatment with VKAstrongly reduces the risk of recurrent VIE for as long as they are used. Therapy should he discontinued when the risk of harm from major bleeding (which remains constant orei time) is of greater concern than the absolute risk of re ament VIE (which declines over time).

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Common Medications that Interact with Warfarin Acetaminophen (interference with vitamin K metabolism) Allopurlnol NSAIDs (Gl injury) Fluconazole Metronidazole Sulfamethoxazole Tamoxifen

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Toronto Notes >023

H38 Hematology

LMWH typically reserved as long term therapy for patients unable to tolerate oral anticoagulants (e.g. unable to absorb oral medications, high risk bleeding patients with intraluminal G1 malignancy) • duration of anticoagulant treatment provoked V I E with transient risk factor: 3 mo provoked V I E with ongoing risk factor: consider indefinite therapy with annual reassessment first unprovoked proximal DVT or PE: >3 mo, consider indefinite therapy with annual reassessment second unprovoked VTE: consider indefinite therapy cancer-associated DVT: consider indefinite therapy for as long patient has active malignancy ( in patients who have cancer in remission, anticoagulation is usually extended for 3-6 mo post last treatment ) inferior vena cava filters temporary filter indicated only if acute DVT (1 adcktional risk factor (e.g. active cancel previous VTE. sepsis, acute neurologic disease. ISO)

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H 39 Hematology

Toronto Notes 2023

Hematologic Malignancies and Related Disorders MATURATION OF CELLS

Acute Lymphocytic Leukemia ( ALL)

Chronic Lymphocytic Leukemia ( CLL) NaTve

Multiple Myeloma ( MM)

Lymphomas

Germination

») -

B lymphocytes Hematopoietic stem cell

Lymphoid progenitor

•

Plasma cell

Leukemia: malignant cells arise in 8M that may spread elsewhere (including blood, lymph nodes, and lymphoid tissue) Lymphoma: malignant cells arise in lymph nodes and lymphoid tissues that may spread elsewhere (including blood and 8M) BUT the location where the malignant cells are found does not solely define the type of hematologic malignancy classified based on the characteristics of the cell (histology, histochemistry, immunophenotyping, cytogenetics, molecular changes)

T-lymphocytes

MATURATION

Acute Myelogenous Leukemia ( AML)

Myeloproliferative Disorders

01

CELLS

>

Neutrophils Granulocytes

Chronic Myelogenous Leukemia (CML)

Eosinophils

"

Basophils Hematopoietic stem cell

Myeloid progenitor

if

Monocytes

w

K . - >’ , > Platelets

--

>

Red Cells

blood or BM at presentation

C lassification: divided into myeloid (AML) and lymphoid (ALL) depending on whether blasts are myeloblasts or lymphoblasts, respectively

Chronic Myelomonocytic Leukemia ( CMML)

> Essential Thrombocytosis

^^

Acute Leukemia Definition (WHO): presence of 20% blast cells or greater in the peripheral

Polycythemia Vera

Typical Age of Presentation of Leukemias ALL: Children and older adults CML: 40- 60 yr AML, CLL: >60 yr

Figure 15. Hematopoietic derivation of hematologic disorders

Auer rods are pathognomonic for AML

( Hematological Malignancies and Related Disorders )

(

Lymphoid Disorders

I

Lymphomas

Leukemia

• Hodgkin • Non-Hodgkin • B Cell • T Cell • Other cell origin

• ALL

• CLL

)

(

I

Plasma Cell Dyscrasias

• Multiple myeloma

Myeloid Disorders

)

t Leukemia

•AML

• MGUS

MPNs

•PV •ET

•CML •IMF

le g NK )

• Waldenstrom's

macroglobulinemia

Figure 16. Overview of hematologic malignancies and related disorders

Bask Initial Workup for all Hematologic Malignancies: 1 ALL WOMEN OF CHILDBEARING AGE must have a b-HCG before initiation of treatment of any cancer diagnosis 2. ALL PATIENTS MUST HAVE Hepatitis 8 surface antibody (HBsAb), Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb) collected irrespective of cancer diagnosis and must be treated to avoid reactivation 3 All aggressive lymphoma patients must be screened for HIV 4. All patients must be screened for TB risk factors

.

.

Myeloid Malignancies Acute Myeloid Leukemia Definition •

rapidly progressive malignancy characterized by failure of myeloid cells to differentiate beyond blast stage

Cure: survival that parallels agematched population Complete Remission: tumour load below threshold of detectable disease (normal peripheral blood film, normal BM with 20% ( normal is 20% BM or peripheral blood lymphoblasts, with samples collected for flow cytometry, q'togenetics, and molecular studies • Ph chromosome in ~25% of adult ALL cases • CBC: increased leukocytes > 100 x 109/ L (occurs in 50% of patients ); neutropenia, anemia , or thrombocytopenia • screen for TLS: increased uric acid , K ', POTJ -, low Ca1 , , high LDH • screen for DIC: FT, aPTT, fibrinogen • CXR: patients with ALL may have a mediastinal mass • CT C/ A / P and testicular ultrasound to screen for extranodal disease • mandatory lumbar puncture to assess for CNS involvement (ensure adequate platelet count and PT7 FIT and delay until blasts have cleared from peripheral blood ) at the time treatment is initiated • HIV, HBV, HCV serologies, CMV Ab testing Treatment

• eliminate abnormal clonal cells 1. induction chemotherapy: to induce complete remission,


2 mmol / L

-

SOFA score >2 10% mortality risk in patient with suspected infection Hospital mortality with septic shock >40%

qSOFA score 1. Respiratory rate >22/min 2. sBP pro - inflammatory cytokine release -> spread of immune response beyond local environment > unregulated , exaggerated systemic immune response > vasodilation and hypotension > distributive shock and reduced 0 : delivery to tissues -> anaerobic metabolism and lactic acid production -> metabolic acidosis -> multiple organ failure Clinical Features history: symptoms and signs specific to an infectious source (e.g. cough , headache, dysuria , purulent exudate, rash ) • general symptoms of infection: fever, chills, pain, dyspnea , cool extremities, fatigue, malaise, anxiety, confusion physical: abnormal vitals (e.g. fever, tachypnea, tachycardia, hypotension ), flushed skin, altered mental status, local signs of infection (e.g. pharyngitis, septic arthritis, neck stiffness, skin wounds/ulcers, or murmurs)

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis 3) in 2016 re defined sepsis using the Sequential Organ Failure Assessment (SOFA) score for diagnosis and Ouick SOFA (qSOFA) for screening of end organ failure. The terms severe sepsis and systemic response inflammatory response syndrome (SIRS) arc no longer part of the sepsis

-

-

-

-

definition

Investigations • CBC and differential, electrolytes, urea, creatinine, liver enzymes, ABG, lactate, 1NR, PTT, troponin, blood C &S x2, urinalysis, urine C&S, and cultures of any wounds or lines • CXK ( other imaging depends on suspicion of focus of infection ) • nasopharyngeal swab/stool /sputum cultures, throat swabs, genital swab, LP as indicated Treatment (see Respiroloav, R33)

• respiratory support: O’ ± intubation • cardiovascular support : IV fluids ± blood transfusion i vasopressors + ICU • IV antibiotics ( empirical, guided by suspected source) consider broad spectrum antibiotics (e.g. piperacillin / tazobactam or meropenem ) ± additional agents depending on patient risk factors, suspected etiology or focus of infection, and local microbial susceptibilities ( ± aminoglycoside for drug- resistant Gram-negatives or vancomycin for

MRSA ) breadth of empiric coverage should take into account i ) estimated adequacy of spectrum of activity and ii ) degree of instability or severity of infection narrow once organism and susceptibilities are known • source control: procedure to control focus of infection (catheter removal, abscess drainage) • hydrocortisone IV may be added in patients with septic shock unresponsive to fluid resuscitation and

vasopressors

Leprosy (Hansen’s Disease) Etiology

-

• Mycobacterium leprae: obligate intracellular bacteria , slow growing (doubling time 12.5 d ), survives in macrophages

• bacteria transmitted from nasal secretions, potentially via skin lesions • invades skin and peripheral nerves leading to chronic granulomatous disease Clinical Features

• lesions involve cooler body tissues (e.g. skin, superficial nerves, nose, eyes, larynx ) • spectrum of disease determined by host immune response to infection i. paucibacillary “tuberculoid ” leprosy (intact cell- mediated immune response) S hypoesthetic lesions, usually hypopigmented, well-defined, dry early nerve involvement, enlarged peripheral nerves, neuropathic pain may be self-limited, stable, or progress over time to multibacillary "lepromatous" form ii. multibacillary “lepromatous" leprosy (weak cell-mediated immune response)

>6 lesions, symmetrical distribution leonine facies ( nodular facial lesions, loss of eyebrows, thickened ear lobes) extensive cutaneous involvement, late and insidious nerve involvement causing sensory loss at the face and extremities iii. borderline leprosy lesions and progression lie between tuberculoid and lepromatous forms

Investigations

• skin biopsy down to fat or slit skin smears for Al- B staining, PCR '

LJ

• histologic appearance: intracellular bacilli in spherical masses ( lepra cells), granulomas involving cutaneous nerves Treatment

+

• regimens based on WHO recommendations

• paucibacillary: dapsone daily + rifampin monthly + clofazimine monthly AND low dose clofazimine once daily x 6 mo

• multibacillary: dapsone daily + rifampin monthly + clofazimine monthly x 12 mo AND low dose clofazimine once daily for 12 mo

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ID22 Infectious Disease

Toronto Notes 2023

• treatment of leprosy ( along with other precipitants of immune responsiveness such as viral illness, immunization, hormonal fluctuations of pregnancy and parturition ) can cause an immune reaction to killed or dying bacteria (e.g. erythema nodosum leprosum [ a type of antigen -antibody complex

-

deposition panniculitis ] and reversal reaction [ upgrading cell mediated immune response!): symptomatic management with NSAlDs if mild, prednisone with 12-24 wk taper if severe; thalidomide for erythema nodosum leprosum

Prognosis

• curable with WHO approved treatment regimens

• complications: muscle atrophy, contractures, blindness, trauma /superinfection of lesions, crippling / loss of digits and limbs, erythema nodosum leprosum, social stigmatization due to clofazimine hyperpigmentation • long post- treatment follow- up warranted to monitor for relapse and immune reactions

s

Lyme Disease Etiology/Epidemiology

• spirochete bacteria: Borrelia burgdorferi ( North America ), B. garinii, B. afzelii ( Europe and Asia ) • transmitted by Ixodes tick • reported in 49 of the 50 U.S. states, but most cases occur in the Northeast, the Midwest, and Northern California • as a result of climate change, Lyme disease has spread into higher latitudes. In Canada, reported in southern and southeastern Quebec, southern and eastern Ontario, southeastern Manitoba, New Brunswick, and Nova Scotia, as well as southern British Columbia • small rodents ( mice) serve as primary reservoir, while larger animals (white tailed deer ) serve as hosts for ticks • human contact usually May August in fields with low brush near wooded areas, but may start earlier in the spring or later in the fall as a result of warmer winters due to climate change • infection usually requires >36 h tick attachment • as a result of climate change, other tick-borne diseases are expected to increase in prevalence: Anaplasmosis, Babesiosis, Powassan virus, and B. miyamotoi disease

-

BAKE a Key Lyme Pie Bell's palsy Arthritis Kardiac block Lyme Erythema chronicum migrans

-

Clinical Features

• stage 1 (early localized stage: 7- 14 d post - bite)

malaise, fatigue, headache, myalgias erythema migrans: expanding, non pruritic bulls-eye (target ) lesions ( red with clear centre) at site of tick bite • stage 2 (early disseminated stage: weeks post infection ) CNS: aseptic meningitis, CN palsies ( CN VII palsy ), peripheral neuritis cardiac: heart block or myocarditis • stage 3 (late persistent stage: months to years post- infection ) may not have preceding history of early-stage infection MSK: chronic monoarticular or oligoarticular arthritis • acrodermatitis chronicum atrophicans (due to B afzelii ) • neurologic: encephalopathy, meningitis, neuropathy

-

.

Investigations • order Public-Health - Lab-approved Lyme disease testing and interpret results on basis of symptoms • a negative test for Lyme Disease does not preclude a tick-borne disease; further testing may be

indicated if symptoms are present Prevention

• early identification , investigation of symptoms, and reporting of tick -borne illnesses • use of protective clothing ( tuck pants into socks), insect repellent, inspection for ticks, and prompt removal of tick • doxycydine single dose prophylaxis within 72 h of removal of an engorged Ixodes scapularis tick in hyperendemic area (local rate of infection of ticks S20% ) for patients >8 yr who are not pregnant or

lactating Treatment

• stage 1: doxycycline/amoxicillin/cefuroxime • stage 2-3: ceftriaxone or doxycydine rn

LJ

Toxic Shock Syndrome Etiology superantigens produced by some strains of S . aureus or GAS cause widespread T-cell activation and proinflammatory cytokine release (1L- 1, IL-6, TNF) of disease is precipitous and leads to acute fever, shock, multiorgan failure course • • staphylococcal Toxic Shock Syndrome (TSS) involves the production of superantigen toxic shock syndrome toxin I ( TSST I ) • streptococcal TSS involves the production of superantigens SPEA, SPEB, SPEC

+

-

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1D23 Infectious Disease

Toronto Notes 2023

Risk Factors

• staphylococcal: tampon use, nasal packing, wound infections (e.g. postpartum vaginal or cesarean or surgical infections ) • streptococcal: minor trauma, surgical procedures, preceding viral illness (e.g. chickenpox), use of NSAlDs

Clinical Features and Investigations

• acute onset • staphylococcal TSS • T >38.9°C sBP 290 mmHg

• diffuse erythroderma with subsequent desquamation, especially on palms and soles

• involvement of 3 or more organ systems: Gl (vomiting, diarrhea ), muscular ( myalgia, increased CK ), mucous membranes ( hyperemia), renal, hepatic, hematologic ( thrombocytopenia ), CNS (disorientation ) isolation of S. aureus is not required for diagnosis ( S aureus is rarely recovered from blood in TSS)

.

• streptococcal T SS

•

sBP 2 of coagulopathy, liver involvement, ARDS, soft tissue necrosis ( necrotizing fasciitis, myositis, gangrene), renal impairment, erythematous macular rash that may desquamate

Treatment

• supportive care, fluid resuscitation , surgical debridement of infected tissue • streptococcal: IV penicillin and clindamycin and ± IVIG • staphylococcal: for methicillin-susceptible S. aureus: clindamycin + doxacillin (IV ); for MRSA: clindamycin + vancomycin x 10-14 d

Cat Scratch Disease Etiology

• Bartonella henselae: intracellular bacteria • cat - to- human transmission via cat scratch / bite Clinical Features • skin lesion appears 30 d post-inoculation • may be followed by fever, malaise, tender regional lymphadenopathy • in some patients, organism may disseminate causing 1 UO, hepatosplenomegaly, retinitis, cncephalopathy, infective endocarditis, uveitis • in patients with advanced HIV, can present with violacious nodular skin lesions t underlying bone involvement, known as “bacilliary angiomatosis” • usually self-limited Investigations

• serology, PGR , lymph node biopsy Treatment • the disease may be self-limited but treatment is recommended by the Infectious Disease Society' of America with a 5 d course of azithromycin for immunocompetent patients with mild to moderate

illness

• needle aspiration of painful suppurative lymph nodes may hasten the relief of symptoms • combination therapy consisting of doxycycline or azithromycin plus rifampin often used for disseminated disease ( neuroretinitis, hepatosplenic involvement )

Rocky Mountain Spotted Fever Etiology • Rickettsia rickettsii: obligate intracellular GN organism • reservoir hosts: rodents, dogs • vectors: Dermacentor ticks in North America; Rhipicephalus ticks in Mexico and Central America

• organisms cause inflammation of endothelial lining of small blood vessels, leading to small hemorrhages and thrombi

LJ

• can cause widespread vasculitis leading to headache, and CNS changes; can progress to death if treatment is delayed Clinical Features

+

• usually occurs in summer following tick bite • influenza - like prodrome: acute onset fever, headache, myalgia, nausea /vomiting, anorexia • macular rash appearing on d 2-4 of fever begins on wrists and ankles, then spreads centrally to arms/legs/ trunk /palms/ soles • occasionally “spotless” ( 10% of patients)

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Toronto Notes 2023

ID2 I Infectious Disease Investigations

• skin biopsy and serology ( indirect fluorescent antibody test ) Treatment • empiric doxycycline, usually 5-7 d (treat for 3 d after defervescence)

West Nile Virus Epidemiology

• virus has been detected throughout the United States and much of southern Canada (Ontario and

Manitoba) • case -fatality rates in severe cases are 10%

-

Transmission

• primarily from mosquitoes that have fed on infected birds (crows, blue jays) • transplacental, blood products (rare ), organ transplantation

• rising temperatures linked to increased mosquito survival and geographical range, increased biting rates, increased replication of virus within mosquitoes, shorter reproduction rates, and longer transmission seasons. Climate change also affects bird migration patterns and timing, causing changes in virus spread Clinical Features

• 80% are asymptomatic

• most symptomatic cases are mild (West Nile fever): acute onset of headache, back pain, myalgia, anorexia, maculopapular non -pruritic rash involving chest, back, arms • severe complications: encephalitis, meningoencephalitis, and acute flaccid paralysis (especially in those >60 yr ) Investigations

• IgM antibody in serum or CS1: is the best test (cross reactivity with yellow fever and lapanese encephalitis vaccines, and with dengue fever and St. Louis virus infection ); may not reflect current illness as IgM antibody can last for >6 mo

• viral isolation by PCR from CSF, tissue, blood, and fluids (all have low sensitivity due to transient viremia ) • CS1 : elevated lymphocytes and protein if CNS involvement

-

Treatment and Prevention

• treatment: supportive

• prevention : mosquito repellant ( DLL I , picaridin ), drain stagnant water, community mosquito control '

programs

Syphilis Etiology

-

• Treponema pallidum: thick motile spirochetes historically detectable by dark field microscopy • transmitted sexually, vertically, or parenterally (rare) Clinical Features

.

.

• see Dermatology D38 and Gynaecology CiY30 • multi stage disease 1 . primary syphilis ( 3 90 d post infection ) painless chancre at inoculation site (any mucosal surface) regional lymphadenopathv acute disease lasts 3 6 wk, 25% progress to secondary syphilis without treatment 2. secondary syphilis systemic infection ( 2 8 wk following chancre) maculopapular non-pruritic rash including palms and soles generalized lymphadenopathy, fever, malaise, headache, aseptic meningitis, ocular/otic

-

-

=

Argyll Robertson Pupil Accommodates but does not react to light

-

-

-

syphilis condvlomata lata: painless, wart like lesion on palate, vulva, or scrotum ( highly infectious ) 3. latent syphilis asymptomatic infection that follows untreated primary/secondary syphilis early latent (< 1 yr post infection ) or late latent/ unknown duration ( > l yr post infection ) increased transmission risk with early latent; longer treatment duration required for late latent 4. tertiary syphilis ( 1-30 yr post-infection ) gummatous syphilis: nodular granulomas of skin, bone, liver, testes, brain aneurysm and aortic insufficiency aortic • 5. congenital syphilis causes spontaneous abortions, stillbirths, congenital malformations, developmental delay, deafness most infected newborns arc asymptomatic clinical manifestations in early infancy include rhinitis (snuffles), lymphadenopathy, hepatosplenomegaly, pseudoparalysis (bone pain associated with osteitis), and rash (usually maculopapular and involving palms and soles )

-

-

-

Those with Untreated 1* or 2° Syphilis 1/3 Cure 1/3 L atent indefinitely 1/33° syphilis

Causes of False Positive VDRL and RPR Tests

Vi ( uses ( mononucleosis, hepatitis) Drugs and substance misuse Rheumatic fever Lupus and leprosy

n j

+

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ID23 Infectious Disease

Toronto Notes 2023

late onset manifestations ( >2 yr of age) include saddle nose, saber shins, Glutton joints, Hutchinson’s teeth, mulberry molars, rhagades, CN VIII deafness, interstitial keratitis, juvenile paresis

6. neurosyphilis

headache, dementia , difficulty in coordination , paralysis, sensory deficits, personality changes, Argyll Robertson pupils, tabes dorsalis can occur from secondary stage onward

-

Patients with 2° or 3° syphilis treated with penicillin may experience a JarischHerxheimer reaction , lysis ol organisms releases pyrogens thought to cause fever, chills, myalgia, and flu like symptoms that may last up to 24 h

-

Investigations

•syphilis tests are conducted by Public Health labs. Thus, order set for syphilis is simplified and does

not require specification of which test to complete. Below are details on what tests are conducted at the Public Health lab • initial screening tests: traditionally' non -treponemal tests ( RPR, VRDL), or treponemal tests in some jurisdictions ( EIA, CMIA, CL1A) confirmatory tests: treponemal tests ( TPPA , FTA ABS, MHA TP, T PI ) • LP for neurosyphilis if: seropositive and symptoms of neurosyphilis or treatment failure/other tertiary symptoms, or with HIV and late latent / unknown duration syphilis; consider in others • for congenital syphilis, LP is essential; long bone x-rays may also be helpful

.

-

-

Treatment

• for r, 2", early latent: benzathine penicillin 2.4 million units IM x I (i

• for 3", late latent: benzathine penicillin G 2.4 million units IM weekly x 3 • if truly allergic to penicillin: doxycydine 100 mg PO BID x 14 d is a second line therapy (x 28 d in late disease) • for pregnant patients allergic to penicillin, oral desensitization techniques are considered safe • neurosyphilis: aqueous penicillin G 16 24 million units /d IV x 14 d ± single dose ofhenzathine penicillin • for congenital syphilis, penicillin GIV x 10 d • see Family Medicine, FM46 for generalized ST1 workup

VDRL

Venereal Disease Research Laboratory Rapid Plasma Reagin

RPR EIA

Enzyme Immunoassay Chemiluminescent

CHA

ImmunoAssay ChemiLuminescent Microparticle ImmunoAssay FTA ABS Fluorescent Treponema Antibody Absorption MHA TP Microhemagglutination Assay T. pallidum TPPA T. pallidum Particle Agglutination Assay TPI T. pallidum immobilization

CMIA

-

-

-

test

-

Tuberculosis Etiology, Epidemiology, and Natural History • 1 /3 of the world’s population is infected with TB

• contracted by aerosolized inhalation of Mycobacterium tuberculosis, a slow growing aerobe (doubling time 18 h ) that can evade innate host defenses, survive, and replicate in macrophages • inhalation and deposition in the lung can lead to one of the following outcomes 1. immediate clearance of the pathogen 2. latent TB: asymptomatic infection contained by host immune defenses ( represents 90% of

infected people ) 3. primary TB: symptomatic, active disease ( represents 5% of infected people) 4. secondary TB: symptomatic reactivation of previously dormant TB ( represents 5- 10% of those with latent TB, most often within the first 1-2 yr of initial infection ) at a pulmonary or extrapulmonary site

Tuberculous Polyserositis Pleural * pericardial * peritoneal effusions ( usually from granuloma breakdown that spills TB into pleural cavity very rare)

-

Risk Factors

• social and environmental factors

travel or birth in a country with high TB prevalence (e.g. Asia, Latin America, Sub-Saharan Africa, Eastern Europe ) • the incidence of TB is 25 times higher in Canadian born Indigenous peoples ( highest in lnuit ) compared to Canadian born non lndigenous peoples • personai /occupational contact, crowded living conditions, low socioeconomic status (SES), people experiencing homelessness, 1VDU • host factors • immunocompromised (especially HIV ), including extremes of age • immunosuppressed (TNF a inhibitors, glucocorticoids) silicosis chronic kidney disease requiring dialysis diabetes

-

-

-

-

• malignancy and chemotherapy

substance use (e.g. drug use, alcohol use disorder, smoking )

Clinical Features

• primary infection usually asymptomatic, although progressive primary disease may occur, especially in children and immunosuppressed patients • secondary infection /reactivation usually produces constitutional symptoms (fatigue, anorexia , night sweats, weight loss) and site- dependent symptoms 1. pulmonary TB chronic productive cough f hemoptysis, fever, night sweats, weight loss, chest pain , anorexia CXR consolidation or cavitation , lymphadenopathy, predominantly upper lung findings but

variable non - resolving pneumonia despite standard antimicrobial therapy 2. miliary' TB widely disseminated spread especially to lungs, abdominal organs, marrow, CNS CXR: multiple small 1 -5 mm millet seed -like lesions throughout lung

+

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ID26 Infectious Disease

Toronto Notes 2023

3. extra pulmonary TB organ • lymphadenitis, pleurisy, pericarditis, hepatitis, peritonitis, meningitis, • can occur in any osteomyelitis (vertebral = Pott disease), adrenal (causing Addison disease), renal , ovarian

-

Investigations

•screening for latent TB may be done via TST or IFN-y release assay (1GKA) both can be used to diagnose prior TB exposure. IGRA has fewer false positives as it does not detect antigens In B(Xi vaccine or most types of non tuberculosis mycobacteria

-

neither should be used for active TB diagnosis or monitoring anti-TB treatment response • TST preferred when repeat testing planned to assess risk of new infection (e.g. serial testing in healthcare) IGRA when BCG vaccine after 1 y/o, vaccination more than once, or unable to return for preferred • reading •diagnostic tests/investigations for active pulmonary TB • sputum specimens (either spontaneous or induced ) should be collected for APB smear and culture; the three specimens can be collected on the same day, a minimum of 1 h apart BAL if other lung pathology (e.g. lung cancer) also suspected, or TB suspected despite negative sputum samples • CXK classic triad : apical posterior infiltrates, lung volume loss, cavitation atypical features: hilar/ mediastinal lymphadenopathy, non -cavitary infiltrates signs of complications: endobronchial spread, pleural effusion, pneumothorax G hon complex : a parenchymal granuloma, indicating a previous tuberculosis infection, and an involved hilar lymph node on the same side

-

Prevention •primary prevention airborne isolation for active pulmonary disease BCG vaccine ~80% effective against paediatric miliary and meningeal TB effectiveness in adults debated ( anywhere from 0 80%) recommended in high incidence communities in Canada for infants in whom there is no evidence of HI V infection of immunodeficiency; widely used in other countries •prevention of reactivation of latent infection rifampin ( R11 ) (10 mg/ kg (600 mg maximum )) daily for 4 mo (active disease must be ruled out) isoniazid ( INH ) (15 mg/ kg (900 mg maximum )) + pyridoxine ( B6) and rifapentine ( RPT ) (dose by

-

-

Positive TST Test If induration at 48- 72 h >5 min if immunocompromised, dose contact with active TB >10 mm all others; positive PPD: CXR; decision to treat depends on individual risk factors False( ) : poor technique, anergy immunosuppression, infection 65 y/o, pregnant , or risk of hepatotoxicity •exlrapulmonary TB: same regimen as pulmonary TB but increase to 12 mo in bone/ joint, CNS, and miliary/disseminated TB + corticosteroids for meningitis, pericarditis •for patients taking INH, pyridoxine should be added in cases of diabetes, renal failure, malnutrition, substance use disorders, seizure disorders, pregnancy/ breastfeeding, risk of neuropathy •empiric treatment of suspected MDR or extensively drug resistant ( XDR ) TB requires referral to a

-

specialist

• MDR = resistance to INH and rifampin ± others

XDR = resistance to INH t rifampin i fluoroquinolone + >1 of injectable, second-line agents very difficult to treat, global public health threat, 5 documented cases in Canada from 19972008 suspect MDR TB if previous treatment failed , exposure to known MDR index case, or

-

immigration from a high risk area • note: TB is a reportable disease to Public Health ( please see Public Health Agency of Canada website for more information )

ri i

j

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ID27 Infectious Disease

Toronto Notes 2023

HIV and AIDS

w

p 24 - capsid protein gp41 * fusion and entry gp120 - attachment to host Tcell

Epidemiology Canadian Situation ( Public Health Agency of Canada, 2016 ) • estimated 65040 Canadians living with HIV infection at the end of 2016, 20% unaware of HIV- positive

status • 2090 new infections were reported in 2013: MSM account for 53% of cases, PWID 19% Global Situation ( WHO and UNAIDS Core Epidemiology Slides, July 2018 ) • estimated 36.7 million people living with HIV/AIDS at the end of 2016 « estimated 1.8 million newly infected in 2016 • estimated 1 million AIDS- related deaths in 2016

Etiology

m

Homozygosity for A 32 mutation in CCR5 gone confers relative resistance to HIV

infection Heterozygosity for A 32 mutation in CCR5 gene associated with slower disease course

gpi 20

gp 4 l

• HIV is a retrovirus that causes progressive immune system dysfunction , predisposing patients to various opportunistic infections and malignancies • HIV virion includes an envelope ( gp 41 and gpl 20 glycoproteins), matrix ( pl 7), and capsid ( p 24), enclosing 2 single -stranded copies of RNA plus enzymes in its core • virion glycoproteins bind CD4 and CCR 5/CXCR4 on CD4 + T lymphocytes (T- helper cells) to fuse and enter the cells • RNA converted to dsDNA by viral reverse transcriptase; dsDNA is integrated into host genome by viralintegrase • virus DNA transcribed and translated using host cell machinery, post - translational modifications include proteolytic activity of virally encoded protease enzymes • newly produced virions bud out of host cell, incorporating host cell membrane; additional maturation steps are required before virion is considered infectious • exact mechanisms of CD 4 depletion incompletely characterized but likely include direct viral cytopathic effects, apoptosis, and Increased cell turnover

p17 matrix

-

Lipid bilaycr

- p24 capsid

Reverse

Modes of Transmission

transcriptase

Integrase

Table 20, Modes of Transmission in Adolescents and Adults by Site and Medium Sub - Location HIV Invasion Site Transmission Medium Transmission Probability

per Exposure Event

Female genital tract

Vagina , edocervix. endocervix

Semen

1 in 200 to 1 in 2000

Male genital tract

Inner foreskin , penile urethra

Cervicovaginal and rectal secretions and desquamations

1 in 700 to 1 in 3000

Intestinal tract

Rectum

Semen

1 in 20 to 1 in 300

Upper Cl tract

Semen

Placenta

Pi

1 in 2S00 Maternal bioodlgemtal secretions 1 in S to 1 in 10

Chorionic villi

(intrapartum ) Breastmilk

1 in S to 1 in 10

Maternal blood ( intrauterine)

1 in 10 to 1 in 20

Contaminated blood products 95 in 100 to 1 in 150 Sharp / needleslick injuries Adapted with permission horn Macmillan Publishers Ltd . , triad Ik F McEMhMJ , Setting Uie stage: host Invasion by HIV. Nat Rev Immunol

Blood stream

.

2008:8:447-457. NOTE: these estimates are lor 'all comers' i.e they estimate Uansinission risk lor anyone with HIV Inlcction and do not take into account treatment status of the HIV * person (In contrast to results ol PARTNER study )

.

—.

INA

p7 nucleocapstd

Protease

p24 capsid iPStuort Janlzen 2012 J

Figure 7. HIV viral particle

r LJ

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Toronto Notes 2023

ID28 Infectious Disease

Natural History Sciual Activity without Condoms a ltd Ink ol HIV Ttansmissioa in Scrodiffcrcnt Couples when t he HIV Positive Partner is using Suppressive Antiretroviral therapy JAMA 2016:316f 2):171-181 Purpose: to evaluate the rate ot withsi coupte HIV transmission (tieteroseiual and MSM ) during periods of se « wthoutcondoms and when the HIV* partner had HIV -1 IHA « 200 topes / ml. Methods Prospective, observational PAIINIR study , enrolled 1 IWHIY serodifferent couples ( in which the HIV* partner wastakng ART|who reported having condo mless so. Primary outcome was risk of with in couple HIVtransmtssion to HIV - partner. Results: Enrol led couples p'ovded 1238 elghie couple-years ol follow -up. Couples reported condomless sev for a median ol 2 yr and condon ess set with other partners was reported by 108 HIV - MSM and 21 heteroseicais. While 11 HIV - partners became HIV* (10 MSM; 1 ireteiose» ual|, no phylogeneticaiiy linked transmissions occurred over eligible coupleyears ol fo ow - up ( within - couple HIV transmission * 0, 95% Cl 0.30-0.71 pei 100 couple -years). Conclusions: A- ong serodrfferer t heteroseual end MSM couples in which HIV * partner was usi g ART a d who reported cordomless sev, during median 1.3 pf couple follow up. there weie no documented cases of wilhui coupSe transmission .

-

-

C04 cell count Anti HIVI antibodies Viral loads

-

Figure 8. Relationships between CD4 T-cell count, viral load, and anti- HIV1 antibodies Acute (Infection) Retroviral Syndrome • 10 -90% experience an acute non specific illness ( may include fever, pharyngitis, lvmphadenopathy,

-rash arthralgias, myalgias headache - , Cil symptoms, oral ulcers, weight loss) 2 6 wk post exposure lasting 10 15 d ,

,

.

• hematologic disturbances ( lymphopenia, thrombocytopenia ) • 10 -20% present with aseptic meningitis, CN palsies, or other neurological presentations; HIV RNA and /or p24 may be detected in CST • associated with a high level of plasma viremia and therefore high - risk of transmission

Asymptomatic (Latent ) Stage • during latent phase, HIV infects and replicates in CD 4 t T lymphocytes ( lymph nodes) • normal CD4 count in adults: 500 - 1100 cells / mm 3 • CD 4 count drops 60 -100 cells/ mm 3 per yr but is variable • by 10 yr post-infection, 50% have advanced HIV ( i.e. AIDS ), 30% demonstrate milder symptoms, and < 20 % are asymptomatic if untreated Definition of AIDS • HIV positive AND one or more of the clinical Illnesses that characterize AIDS, including: opportunistic infections (e.g. Pneumocystis jiroveci pneumonia ( P|P, previously PCP ), esophageal candidiasis, CM V, Mycobacterium avium complex ( MAC ), TB, toxoplasmosis), malignancy ( Kaposi 's sarcoma, invasive cervical cancer ), wasting syndrome OR CD4 5 mm or contact with case of active IB CD4 count < 50 cells/ mm 5

INH * pyntome daily x 9 mo

200 copies/ mL ) • ensure that viral load > 40 is not just a transient viremia or ‘blip’; confirm medication adherence, assess drug interactions, perform resistance testing

+

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ID30 Infectious Disease

Toronto Notes 2023

Table 23. Anti- Retroviral Drugs Class Nucleoside reverse transcriptase inhibitors ( hails)

Drugs

Mechanism

Adverse Effects

abacavir (ABC) emtricltabine|FTC) lamivudine (3TC) lenofovir disoproxil fumarate (IDF) tenofoviralafenamide ( TAF ) zidovudine ( AZT ) drdanosine (ddl) stavudme ( d41) Combination Tablets:

Incorporated into the growing viral DNA chain, thereby compettnrely inhibiting reverse transcriptase and terminating viral DNA growth

Lacbc acidosis (often secondary lo mitochondrial toxicity)

.

Non-nucleoside reverse delavitdine ( DLV) transcriptase inhibitors doravinne (DOR) (NNRTIs) efavirenz (£FZ) etravirine (ETR) nevirapine (NVP) rilphririne (RPV)

Non-competitively inhibit function of reverse transcriptase,thereby preventing viral RNA replication

Protease inhibitors (Pis)’

Prevent maturation ol infectious virions by inhibiting the cleavage of poly proteins

(INSTIs)

atazanavir (ATV) amprenavir ( APV )

cabotegravir dolutegravir (DIG) ehritegravir (EVG) raltegravir (RAL) enfuvirtide (T-20)

Fusion inhibitor (only used if resistance) CCR 5 antagonist maraviroc (MVC)

.

.

'

Integrase strand transfer inhibitors

Bash

Nausea ' vomiting/diarrhea Bone marrow suppression ( AZT ) Peripheral neuropathy (ddl d 4!) Orug induced hypersensitivity ( ABC) Pancreatitis ( ddl ' dAT ) Myopathy ( AZT)

AZTilTC (Combivir l AZT /3TC/ ABC (Trizivir *) ABC/3TC (Kivexa ‘ ) TDFi'TIC (Truvada ' ) TAF ’FTC ( Oescovy : )

darunavir (DRV) darunavi' cobicistat ( DRV / c) Iopinavir . ritonavir ( LPV / f ) nelfinavir |NFV) ritonavir (RTV ) tipranavir (TPV) indinavir bictegravir

Lipodystrophy

Rash.Stevens-Johnson syndrome CNS: dizziness, insomnia, somnolence, abnormal dreams (efavirenz) Hepatotoxicity (nevirapine - avoid in females with CD4 >250. men with CD4 »400) CYP3A4 interactions Lipodystrophy, metabolic syndrome Nausea 1 vomiting/ diarrhea Nephrolithiasis (indinavir) Rash (APV) Hyperbilirubinemia (atazanavir Indinavir) CTP3A4 interactions Hyperlipidemia

.

.

Inhibits integration ol HIV DNA mlo the human genome thus preventing HIV replication

Lactic Acidosis • Occurs secondary to mitochondrial toxicity • Symptoms include abdominal pain, fatigue, nauseavomiting, muscle weakness

Lipodystrophy Body fat redistribution (mainly with old ARVs) • Lipohypertrophy (e. g. dorsal fat pad. breast enlargement increased abdominal girth) thought to be caused primarily by protease inhibitors • Lipoatrophy (e. g. facial thinning, decreased adipose tissue in the extremities) is thought to be caused by thymidme analogue NRTIs such as d4T and AZT • Metabolic abnormalities: lipids (ixreased LDL increased TGs) glucose (insulin resistance T2DM) increased risk of CVD

.

.

.

Inhibit viral fusion with T-celts by Injection site reactions, rash, inhibiting gp41. p revelling cell infection infection, diarrhea, nausea, fatigue Inhibit viral entry by biockung host OCRS Fever, cough,dizziness co-receptor

'Standard of care ts to pharracologically boost most Pis with ritonavir to increase concentrations

Single Tablet ART Regimens reduces pill burden and increases adherence • generally better tolerated

•

Table 24. Single Tablet ART Regimens Name Biktanry

‘

Genvoya 5 Complera: Odefsey: Stribild ' Triumeq: Atripla ;

Contents

Common Side Effects

bictegravir 'emtricitabinehenofovii alafenamide

nlprnrinei'emlricitabineilenofovir alafenamide elxritegravi r ' cobicista(/emIri cilabine / ten ofovir

good side effect profile good side effect profile good side effect profile good side effect profile good side effect profile

dolategraviriabacavir lamivudine efamreni'tenofovir 'emtricitabine

good side effeetprofile use only in HLAB *5701 negative patients psychiatric events, vivid dreams

I

lenolonr emtricilabine/elvilegravirfcobicistal rilphrirmei'emtricitabineiTenofovir '

.

.

.

Recommended ARV Regimens for Treatment-Naive HIV-infected Adults initial regimens for treatment ( most include an integrase inhibitor and a pair of NRTTs ): 1. bktegravir /TAF/FTC 2. Dolutegravir/ABC/3TC ( in patients confirmed to be HLB‘5701 negative ) 3. dolutegravir + (TAF or TDF) /(FTC or 3TC) 4. raltegravir + TAF ( or TDF)/FTC 5. DTG/3TC • note: not all regimens are available in all regions •

Recommended ARV Regimens for Individuals of Childbearing Potential • there is an increased risk of neural tube defects in infants born to women on dolutegravir at time of conception • it is not known if other INSTIs also increase risk of neural tube defects • therefore, before beginning an INSTl -containing treatment regimen in individuals of childbearing potential, the following should be considered: completing a pregnancy test • a discussion on risks and benefits of dolutegravir, and lack of information on other INSTIs « for individuals attempting to conceive: RAL + TDF/FTC, TDF/3TC, or ABC /3 FC are preferred regimens; D IG regimens to be used as an alternative only • for individuals not attempting to conceive but are sexually active and not using contraception, consider effectiveness/tolerability, patient preferences in decision for individuals using effective contraception, treatment approach is similar to that of individuals in the general population with HIV

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ID31 Infectious Disease

TARGETSITES FOR ANTIRETROVIRAL DRUGS ( A ) Fusion inhibitor IBICCR 5 antagonist ICI Nucleoside reverse transcriptase inhibitors ( NRTIsl (Cl Nucleotide reverse transcriptase anhibitors (Cl Non-nucleoside reverse transcriptase inhibitors INNRTIs) 101 Integrase strand transfer inhibitors (INSTIs) IEI Proteaseinhibitors ( Pis )

PROCESS OF MULTIPLICATION 1 Binding 2. Fusion and uncoating 3 Reverse transcription 4. Integration .

5 Translation

2 FUSIONAND UNCOATING

6 Assembly and budding 7. Maturation

1 BINDING

3. REVERSE TRANSCRIPTION

Early identification of HIV is essential for patients to receive the maximal benefit from ART

.

Efficacy Safety, and Elfect on Sexual Behaviour of On Demand Pre Exposure Prophylaxis for HIV iiMen who have Sex with Men : An Observational Cohort Study Lancet HIV 2017:4:402- 410 Purpose: Assess the efficacy , safety , ard effect of on - demand pre exposure prophylaxis ( Pr (P|on sexual

-

-

-

behaviour . Methods : Men and transgender women who have sex with men. previously enrolled in the placebo controlled ANRSIPERGAU trial. On demandtenofovir dsopioail fumarate ( 300 mg ) and emlricitabine (200 mg) to be taken before and after sexual intercourse and participants assessed for incidence of HIV. PrtP adherence, safety, and sexual behaviour. Jesuits: if IV incidence was 0.19 '100 person - years (95 % Cl 0.01-1.081 vs. 6.60 ,1100 person -)*a>s (95% Cl 3.60-11.05) in the placebo group, relative risk reduction of 97%. Drug -related 61 events were reported in 14% of participants buiwete -limiting. Parte pants reporting condomless sex attheir last receptive anal intercourse increased from 77 to 86 % at 18 mo follow- up. Conclusions: On -demand oral PiEP is highly effective a1 preventing HIV infeebon among high-risk MSM. Ibis represents an alternative to daily PrEP.

.

sen

^ TRANSLATION

6.ASSEMBLY AND

BUDDING

Use of a Vaginal Ring Containing Dapivirine for HIV -1 Prevention inWomen

HEIM 2016:375:2121-2132

-

Purpose: Toevaluate whether longer acting methods of anti- retroviral therapy ( i.e. vaginal rings) may sim pi ify use of medications an d provide HIV-1 protection.

.

Methods: Phase 3 randomized, double- blind, placebo-cnntrolled trial of monthly vaginal ring containing dapivirine In women (aged 18 45) , n Malawi South Africa , Uganda , and Zimbabwe. Results: Among 2629 women enrolled, tne Incidence of HIV -1 infection was 3.3/100 person - years in dapivirine group and 4.&T00 person - years in placebo group. Post hoc analysis identified higher rales of HIV-1 protection in women >21 yr (56% , 95% Cl 31-71) but notamong those

]

.

• infection with E histolytica occurs when the cysts are transmitted via the oral-fecal route in areas of poor sanitation that have been contaminated by other infected humans, or via sexual activity • seen in migrants, travellers, institutionalized individuals, Indigenous peoples, MSM

marcreevst

1

Clinical Features 1. asymptomatic carriers 2. amoebic dysentery • abdominal pain, cramping, colitis, dysentery, low grade fever with bloody diarrhea secondary’ to local tissue destruction, and ulceration of large intestine 3. amoebic abscesses (liver abscesses, see General and Ihoracic Surgery, GS52) most common in liver ( hematologic spread ); presents with right upper quadrant pain, weight loss, fever, hepatomegaly • can also occur in lungs and brain

Lung abscess Liver abscess

Investigations • serology, fecal /serum antigen testing, stool microscopic exam ( for cysts and trophozoites), colon biopsy, single stool for multiplex enteric parasite PCR

%

03/

lonmotile

cyst

(infective)

i 4i

J

Motile

-

• E. histolytica indistinguishable microscopically from the non - pathogen E. dispar (distinguish by specific stool antigen detection or multiplex stool PCR assay )

Ingestion of

trophozoite

Inotmlectivel

Figure 10. Entamoeba life cycle

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ID36 Infectious Disease

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Treatment and Prevention

• metronidazole

• for invasive disease or cyst elimination: follow with iodoquinol or paromomycin • aspiration of hepatic abscess if risk of abscess rupture, poor response to medical therapy, or diagnostic

. good personal hygieneshedding iodoquinol purification uncertainty asymptomatic cyst

:

,

•

or paromomycin alone of water supply by boiling, filtration ( not chlorination )

Giardia lamblia Etiology

• infection with (i. lamblia occurs via the fecal-oral route with the ingestion of cysts from water /food contaminated by infected humans and other mammals (especially in the Rockies)

• risk factors: travel, camping, institutions, daycare centres, MSM Clinical Features • giardiasis ( “ beaver fever") symptoms vary from asymptomatic to self limited mild watery diarrhea to malabsorption syndrome (chronic giardiasis where the parasite coats the small intestine and thus prevents fat absorption ) nausea, malaise, abdominal cramps, bloating, flatulence, fatigue, weight loss, steatorrhea no hematochezia ( no invasion into intestinal wall ), no mucous in stool

-

Investigations

• multiple stool samples (daily x 3 d ) for microscopy; single stool for multiplex enteric parasite PCR; stool antigen used occasionally • occasionally small bowel aspirate or biopsy Treatment and Prevention

• metronidazole; nitazoxanide if symptomatic • good personal hygiene and sanitation, water purification ( iodine better than chlorination ), outbreak investigation

Trichomonas vaginalis Etiology

infection with T. vaginalis occurs via sexual contact Clinical Features • often asymptomatic (10-50%), especially males (occasionally urethritis, prostatitis) • Trichomonas vaginitis (see Gynaecology. GY 26) • vaginal discharge ( profiise, malodorous, yellow-green or grey, frothy), pruritus, dysuria, dvspareunia

Trichomonas causes 2S% of vaginitis

Investigations

• wet mount ( motile parasites), antigen detection, culture • urine PCR to detect in males Treatment

• metronidazole for patient and partner (s)

Cryptosporidium spp. Etiology

• infection with Cryptosporidium spp. via the fecal-oral route occurs with the ingestion of cysts from water contaminated by infected humans and other animals ( including cows) • risk factors: summer and fall, young children (daycare ), MSM, contact with farm animals, immunodeficiency Clinical Features

• range from self-limited watery diarrhea ( immunocompetent ) to chronic, severe, non -bloody

diarrhea with nausea/ vomiting, abdominal pain, and anorexia resulting in weight loss and death (i m munocompromised ) n

Investigations • modified acid-fast stain of stool specimen, microscopic identification of oocysts in stool or tissue, stool antigen detection by direct fluorescent antibody, single stool for multiplex enteric parasite PCR

L J

Treatment and Prevention

• supportive care

+

-

• in HI V + patients, ( reinitiate ART and try to increase their CD I count to >100; if fails, try nitazoxanide or macrolides • good personal hygiene, water filtration

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ID37 Infectious Disease

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Blood and Tissue Infections Mtfluquinr lor Prerenting Malaria during Travel to Endemic Arras Gxhrant Ot Spt ler 2O1);CD0OW91 Purpose losuinmarne efficacy and siletycrf mefloquine used as propter lasts loi malaria in

Plasmodium spp. (Malaria ) Etiology

• transmission of Plasmodium spp. ( P. falciparum , P. vivax, P. ovale, P. malariac , P. knowlesi ) primarily occurs during the blood meal of an infected female Anopheles mosquito

• sporozoites injected during the blood meal then infect human liver cells, where they multiply and are released as merozoites; merozoites infect RBCs and cause disease

• infection with malaria parasites can also occur via vertical transmission ( rare) or blood transfusion

-

• occurs in tropical /subtropical regions (sub Saharan Africa , Oceania , South Asia , Central America,

.

Southeast Asia South America )

Clinical Features

• flu -like prodrome ( may include fever, chills, fatigue, diaphoresis , cough , rash , arthralgias, myalgias, headache, Gl symptoms)

• paroxysms of high spiking fever and shaking chills (due to synchronous systemic lysis of RBCs) that can last several hours P. vivax and P. ovale: chills and fever x 48 h but can be variable

P. malariac: chills and fever x 72 h but can be variable P. falciparum: less predictable fever interval, can be highly variable • abdominal pain, diarrhea, myalgia, headache, and cough • hepatosplenomegalv and thrombocytopenia without leukocytosis • >90% of patients infected with P. falciparum are ill within 30 d • relapsing malarial attacks may occur after many months due to the reactivation (entering the erythrocytic cycle) of dormant liver hypnozoites of either P. ovale or P. vivax • complications: P. falciparum ( most common and most lethal): CNS involvement (cerebral malaria = seizures and coma), severe anemia, acute kidney injury, ARDS, primarily responsible for fatal disease P. knowlesi , and rarely P. vivax,can be fatal

trartlltts. Methods tandomned control Inals|l« elficacgr and saletrl and noo tandonsiied cohoit studies (lor sale If ) to compere prophflattie meflciqiune with placebo, no treatment , or alternathre antimalarlal

.

agent lesnlts : Participants weie mote likeif to discontinue mefloquine (ft) rs. asouaquoiiepioguaml p%| due toeditrsf effects ( including nausea, vomiting, abnormal dreams, insomnia, ancetf , and depressed mood during travel). Do difference in serious adverse effects or discontinuation due toedveise effects wasioond between mefloquine anddoifCfdlne or

mefloquine and cMoroquine. Conclusions: Absolute ns* ol malaria during short term travel appears low with mefloqune doiftfClme. and atovaguoneprognaml therapy. Choice ol agent depends on how individual travellers assess importance ol specific adverse effects, pill burden, and cost.

.

$

Malaria is the most common fatal infectious disease worldwide

Investigations

• CBC screen (assess for triad of: thrombocytopenia, elevated LDH, and anemia)

• microscopy: blood smearql 2-24 h (x3) to rule out infection thick smear (Giemsa stain ) for presence of organisms thin smear (Giemsa stain ) for species identification and quantification of parasites • rapid antigen detection tests

.

RCR

Treatment and Prevention

• all spp. of malaria can lead to severe infection ( P. falciparum most likely to cause severe disease and

death ) • markers of severity: clinical features + parasitemia in any patient with clinical evidence of severe disease: parenteral treatment (artemisinin combination therapy ) • P falciparum: most areas of the world show chloroquine resistance check local resistance patterns artemisinin combination therapy (e.g. artesunate i doxycydine or artemether lumefantrine) atovaquone / proguanil combination ( Malarone*) quinine i doxycydine or clindamycin • mefloquine and artemisinin resistance increasing in southeast Asia (check local resistance ) • P vivax, P ovale: chloroquine (and primaquine to eradicate liver forms) • P. vivax, chloroquine resistant: atovaquone/ proguanil + primaquine or quinine and doxycydine + primaquine • P. malariac, P. knowlesi: chloroquine • prevention with antimalarial prophylaxis (although quality may vary regionally ), covering exposed skin , insecticide treated bed nets, insect repellent • prevention of relapse for P. vivax: primaquine or the newly FDA licensed tafenoquine ( in patients £ 16 y/o who are receiving appropriate antimalarial therapy for acute R vivax infection )

. .

-

-

.

-

-

I Sporozoites enter blood via mosquito bile, inlect iver l Hepatic infiltration 3 Inlect red blood cells 4 Trophozoite divides asexually many times to produce schizont (contains merozoites ) 3 Red blood cell tyses and merozoites attack other red blood cells (chills and fever)

6. Male and female gametocytes (from

merozoitesl ingested by mosquito during

bite 7. Male and female gametocytes (from merozoites) fuse m mosquito gut; produce ookinete 8. Ookinete matures into an oocyst which contains individual sporozoites; migrates to mosquito salivary glands

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Figure 11. Life cycle of Plasmodium

spp.

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ID38 Infectious Disease

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Trypanosoma cruzi Etiology

• found in Mexico, South America, and Central America • transmission by reduviid insect vector ( “ Kissing Bug" ), which defecates on skin and trypomastigotes in the stool are rubbed into bite site or intact mucous membranes by host trypomastigotes can penetrate intact buccal mucosa when orally inoculated (e.g. via sugar cane sweetened unpasteurized juices) • also transmitted via placental transfer, organ transplantation, blood transfusion, and ingestion of food or drink contaminated by an infected triatomine congenital acquisition increasingly recognized as a risk factor for Chagas disease being detected in non endemic areas

-

-

Clinical Features • American trypanosomiasis ( Chagas disease) acute: usually asymptomatic, local swelling at site of inoculation (Chagoma ) with variable fever, lymphadenopathy, cardiomegalv, and hepatosplenomegaly if inoculation via conjunctiva: “ Romana’s sign:" usually unilateral acute myocarditis, pericardial effusion, meningoencephalitis in severe cases chronic indeterminate phase: asymptomatic but increasing levels of antibody in blood; most infected persons (60 70%) remain in this phase, and do not go on to manifest a determinate form of Chagas disease chronic determinate: leads to chronic dilated cardiomyopathy, esophagomegaly and megacolon 10-25 yr after acute infection in 30-40% of infected individuals

See Landmark Infectious D isessc Trials table lot more information on the 8MEFIT trial. It details therole of trypanocidal thera py in patients with established Chagas cardiomyopathy.

-

.

Investigations

• wet prep and Giemsa stain of thick and thin blood smear, serology, PCR

Classic Triad of Congenital Toxoplasmosis • Chorioretinitis • Hydrocephalus • Intracranial calcifications

Treatment and Prevention • acute: benznidazole or nifurtimox • indeterminate: increasing trend to treat as acute infection for children and adults under age 50 • chronic determinate: sy mptomatic therapy, surgery as necessary including heart transplant, esophagectomy, and colectomy; there is unlikely a clinical benefit to antiparasitic treatment at the

;v.

determinate stage of disease • insect control, bed nets

Cat ingests

mouse

Toxoplasma gondii

'

.

I:

paras te

Etiology • infection with 21 gondii occurs through exposure to cat feces (oocysts), ingestion of undercooked meat (tissue cysts), transplacental transmission, organ transplantation, gardening without gloves (cat oocyst exposure), whole blood transfusions, contaminated water sources

\

Sheds resistant oocysts in stool

J

Sporozoites

Mouse (intermediate host )

Clinical Features

• congenital result of acute primary infection of mother during pregnancy ( TORCH infection ) stillbirth ( rare), chorioretinitis, blindness, seizures, severe developmental delay, microcephaly • initially asymptomatic infant may develop reactivation of chorioretinitis as adolescent or adult blurred vision, scotoma, ocular pain , photophobia, epiphora, hearing loss, developmental delay • acquired • usually asymptomatic or mononucleosis like syndrome in immunocompetent patient infection remains latent for life unless reactivation due to immunosuppression • immunocompromised ( most commonly AIDS with CD4 < 200) • encephalitis with focal CNS lesions seen as single or multiple ring enhancing masses on CT ( headache and focal neurological signs) lymph node, liver, spleen enlargement, and pneumonitis • chorioretinitis

(required for completion of sexual cycle)

Livestock (ingestion of poorly cooked meat!

Direct ingestion (handling kitty

-

-

Investigations

-

• serology, CSF Wright Giemsa stain, antigen or DNA detection ( PCR ); pathology provides definitive diagnosis • immunocompromised patients: consider CT scan ( ring-enhancing lesion in cortex or deep nuclei ) and ophthalmologic examination Treatment and Prevention • no treatment if: immunocompetent, not pregnant, no severe organ damage • immunocompromised: pyrimethamine + sulfadiazine + folinic acid • pregnancy: spiramycin if fetal status unknown, pyrimethamine + sulfadiazine + folinic acid if confirmed or highly suspected fetal infection, avoid undercooked meat and refrain from emptying cat

litter boxes

. HIV: TMP/SMX

Figure 12. Life cycle of Toxoplasma gondii

1/3 of Ontario's population is infected with Toxoplasma gondii

n u

+

• proper hand hygiene, cook meat thoroughly to proper temperature

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ID39 Infectious Disease

Toronto Notes 2023

Helminths

=

E

Roundworms - Nematodes

©

l T

Table 26. Nematodes (Roundworms ) Transmission

Nematode

Epidemiology

Ascaris lumbricoides

to: :e ~:st Human feces, ingestion common in tropical and of contaminated food subtropical areas) or water containing

eggs

Ingestion of eggs

Trichuris trichiura ( whipworn)

Worldwide (most common in tropical areas)

Onchocerca volvulus

Sub-Saharan Africa. Latin America

Wuchererio boncrolti

Tropics

Loo loo

West and Central Deerfly bite African rainforest (e.g. Cameroon.Central African Republic)

Enterobius vermiculoris ( pinworm )

in soil Blackfly bite

Mosquito bite

Human host: fecal- oral self -inoculation and fomiteperson- to person transfer Adult worms live in cecum and deposit eggs in peri- anal skin

Worldwide

Clinical Presentation

Treatment

Often asymptomatic,abdominal discomfort Heavy infections may cause intestinal blockage, growth Impairment Cough, dyspnea,pulmonary infiltrates from larval migration through lungs (Loffler 's syndrome)

Mebendazole OR albendazole OR pyrantel pamoate OR ivermectin

Diarrhea|* mucous,blood), abdominal pain, rectal prolapse, stunted growth

Mebendazole OR albendazole

River blindness (onchocerciasis). dermatitis

Ivermectin * doiycydine

Diethylcarbamazine * doiycydine Oamage to lymphatics causes lymphadenopathy lymphedema, lymphatic filariasis (elephantiasis), hydrocele Tropical pulmonary eosinophilia

.

loiasis is mostly asymptomatic. Symptomscan include episodic angioedema (Calabar swellings) and subconjunctival migration resulting in eye pain and ifching

Surgical removal of adult worms, diethyrlcarbamazme albendazole

Asymptomatic earners or severe nocturnal peri-anal itching (pruritus ani) Occasional vaginitis, ectopic migration to appendix or other pelvic organs Abdominal pain, nauseaVomiting with high worm burden

Sticky tape test eggs adhere to tape applied to perianal skin (need S-7 tests to rule out) Eiammabon of perianal skin at night may reveal adult worms Usually no eosinophilia as no tissue invasion Mebendazole,albendazole; pyrantel in pregnancy Change underwear,bathe in morning, pajamas to bed wash hands,trim fingernails Treat all family members simultaneously Reinfection common

.

1. Embryonated eggs ingested bytunns

2 Larvae hatch in small intestine 3. Females migrate out anus at night

Figure 13. Life cycle of Enterobius

.

Strongytoides

stercorolis ( threadworm)

.

Subtropical, tropical Fecal contamination ol and temperate soil: transmission via (mclud ng southern US) unbroken skin, walking barefoot Autoinfection: penetration of larvae through Gl mucosa or perianal skin Adult worms live in mucosa of small intestine

One of few worms able to multiply in human host Mostly asymptomatic infection or can have pruritic dermatitis at site of larval penetration Transient pulmonary symptoms during pulmonary migration of larvae |eosinophilicpneumonrtis ^ Loffler 's syndrome) Abdominal pain, diarrhea,pruritus ani larva currens (itchy rash) Hyperinfection: occasional fatal cases caused bymassive autoinfection in immunocompromised host; immunoablative therapy, including high-dose corticosteroids, is the most common risk factor for disseminated infection

.

Ivermectin anchor albendazole

-

^

vvv V

.

'

V©

1 Larvae penetrate intact skin of host 2. Larvae migrate to lungs via bloodstream 3. Larvae crawl up trachea and down to Gl tract ( cough/swallow) 4. Adult worms in intestine 5. Eggs produced in bowel 6. Larvae 7. Bowel movement containing larvae

Figure 14. Life cycle of Strongyloides

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ID 10 Infectious Disease

Toronto Notes 2023

Flatworms - Cestodes/ Trematode Table 27. Cestodes/ Trematodes (Flatworms) Treatment

Epidemiology

Transmission

Worldwide , but more common in places with poor sanitation

Undercooked pork (larvae) , Taeniasis: mild Gl symptoms human leces (eggs} Cysticercosis: mass lesions in CNS. eyes, skin , seizures

Taenia saginota ( bed tapeworm)

Worldwide , but more common wherever contaminated raw beelis eaten

Undercooked beef (larvae)

Taeniasis: mild Gl symptoms

Praziquantel

Diphyllobothrium

Europe. North America , Asia

Raw fish

Vitamin Bit deficiency leading to macrocytic anemia and posterior column deficits Liver /lung cysts ( enlarge between 1 20 yr ; may cause mass effect or rupture) Risk ol anaphylaxis if cystic lluid released during surgical evacuation

Praziquantel

Clinical Presentation

CEST00 ES Taenia solium ( pork tapeworm }

latum

.

-

Rural areas sheep raising countries

Ichinocoecus granulosus

TREMATODES

.

Clonorchis

Japan, Taiwan China

sinensis

Southeast Asia

.

Schistosoma spp

.

Africa , Southeast Asia , focal In Western Hemisphere

Dog feces (eggs)

-

Corticosteroids albendazole * praziquantel for most cysticercosis Anti epileptics if seizures Praziquantel for adult tapeworm in gut ( taeniasis)

Albendazole t praziquantel alone Surgery » perioperative albendazole Percutaneous aspiration * perioperative albendazole

Raw fish

Exists In bile ducts , causes inflammation and sometimes cholanglocardnoina

Praziquantel

Fresh water exposure

Chronic sequelae secondary lo long term infection |c.g. chronic liver disease, squamous cell carcinoma |SCC ) ol the bladder )

Praziquantel

Schistosoma spp. Etiology

.

.

.

infection with Schistosoma spp. ( S niattsonl , S', hcniatobitim, S iaponicum ) occurs following penetration of unbroken skin by their larvae (cercariae ) which are found in infested fresh water • adult worms live in terminal venules of bladder/ bowel passing eggs into urine/ stool • schistosomes cannot multiply in or pass between humans • more common in individuals from sub - Saharan Africa , South America, Asia , Caribbean, Eastern Mediterranean / North Africa Clinical Features

• most asymptomatic; symptoms seen in travellers ( nonimmune ) • swimmer’s itch: pruritic skin rash at site of penetration (cercarial dermatitis) • acute schistosomiasis ( Katayama fever ): hypersensitivity to migrating parasites ( 4 - 8 wk after infection ) fever, hives, headache, weight loss, cough , abdominal pain , chronic diarrhea , high -grade eosinophilia • chronic schistosomiasis (can persist for years ): S. mattsoni , S japonicum • worms in mesenteric vein , eggs in portal tracts of liver and bowel heavy infections: intestinal polyps, portal and pulmonary HIN, splenomegaly ( 2° to portal HTN ), hepatomegaly

.

T . Eggs released into water

2. Snail ( intermediate host )

releases infective larvae 3. Infective cercariae 4 Penetrate skin 5 Migrate to portal blood stream; mature in liver 6. Migrate to Gl and GU

S. hcinatobiiiiii

-

worms in vesical plexus, eggs in distal ureter and bladder induce granulomas and fibrosis hematuria and obstructive uropathy; associated with squamous cell bladder cancer neurologic complications: spinal cord neuroschistosomiasis ( transverse myelitis), cerebral or cerebellar neuroschistosomiasis ( increased ICP, focal CNS signs, seizures) pulmonary complications: granulomatous pulmonary endarteritis, pulmonary H TN , cor pulmonale; especially in patients with hepatosplenic involvement

-

Investigations • serology ( high sensitivity and specificity), CBC (eosinophilia , anemia , thrombocytopenia ), loopmediated isothermal amplification, circulating serum antigen test • S. mansoni, S. japonicum: eggs in stool, liver U / S shows peri- portal fibrosis, rectal biopsy • S. hematobium: bladder biopsy, eggs in urine and occasionally stool, kidney and bladder U /S

r -»

c.J

Treatment and Prevention • praziquantel • add prednisone if acute schistosomiasis or neurologic complications develop • proper disposal of human waste, molluscicide ( pesticide against molluscs), avoidance of infested fresh water while travelling

Figure 15. Life cycle of Schistosoma

+

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ID 11 Infectious Disease

Ectoparasites • scabies, lice • see Dermatology, D33 Table 28. Important Exposures Insect 8ites Mosquito

Plasmodium spp. ( Malaria ) Dengue Chikungunya lymphatic filariasis (Elephantiasis) West Nile encephalitis Yellow Feyer Japanese encephalitis Zika

lick

Borrelia burgdorlerULyme Disease ) Rickettsia rickeltsii ( Rocky Mountain Spoiled Fever )

fty

Ityponosoma brucei spp. ( African sleeping sickness) Leishmonio spp . (leishmaniasis) Bartonella bocillitormis ( Bartonellosis) Yersinia ( Plague)

Flea

Tunga penetrans ( lungiasis)

Mammal Bites Oog/ Cal

Rabies. Pasleurella anaerobes Streptococcus , S. aureus 8orlonellohenselae. letanus

Human

Streptococcus S. aureus , oral anaerobes, Eikenella

.

.

.

.

Oral Exposures

.

-

Unpasteurired Milk

Brucella spp., non tuberculous Mycobacteria, Salmonella , C. coli Listeria

Undercooked Meat/Fish

Enteric bacteria helminths, protozoa (e.g. Toxoplasma) Hepatitis A/ E Norovirus cholera. Salmonella , Shigella , Giardia poliovirus, Cryptosporidium. Cydospora

Water

.

.

.

Environmental Exposures

.

.

Freshwater

Leptospira spp., schistosomes Acanthamoeba , Naegleria fowled

Soil

Hookworms. Toxocara spp. (visceral larva migrans) Leptospira interrogans ( leptospirosis)

.

Adapted with permission Irorn lancet 2003:361:1459 1469 *

Travel Medicine General Travel Precautions • vector-borne: long sleeves, long pants, hats, insecticides (containing permethrin) applied to clothes, belongings, and bed nets; and skin repellents (e.g. DHET, icaridin ) applied to exposed skin • food / water: avoid eating raw meats /seafood, uncooked vegetables, and milk /dairy products; drink only bottled beverages, chlorinated water, boiled water • recreation: caution when swimming in schistosomiasis -endemic regions (e.g. Lake Malawi ), fresh water rafting /kayaking, beaches that may contain human /animal waste products, near storm drains, after heavy rainfalls • prophylaxis: malaria (chloroquine, mefloquine, atovaquone t proguanil, doxycydine ), traveller's diarrhea ( bismuth salicylate, rifaximin ) •standard vaccines up to date ( hepatitis B, MMR , tetanus /diphtheria, varicella , pertussis, polio, influenza) • travel vaccines: hepatitis A / B , Japanese encephalitis, typhoid fever, yellow fever , rabies, ET'EC, cholera • sexually transmitted and blood borne infections: safe sex practices, avoidance of percutaneous injury through razors, tattoos, piercings

-

Infectious Diseases to Consider • vector- borne: malaria, dengue fever, chikungunya, yellow fever, spotted fever rickettsioses, West Nile virus, trypanosomiasis, Japanese encephalitis, tick-borne encephalitis , leishmaniasis, Zika virus, filariasis •sexually transmitted: HIV, HBV, acute HSV, syphilis, usual S'l'ls, e.g. gonorrhea and chlamydia • zoonotic: rabies, hantavirus, tularemia, Q fever, anthrax, brucellosis, Ebola •airborne: TB, measles, varicella • food / water: HAV, HEV, brucellosis, typhoid, paratyphoid, amoebiasis, dysentery, traveller’s diarrhea, cholera, Campylobacter spp. • soil / water: schistosomiasis, strongyloidiasis, leptospirosis, cutaneous larva migrans, histoplasmosis,

ri LJ

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paracoccidioidomycosis

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ID 12 Infectious Disease

Toronto Xotes 2023

Fever in the Returned Traveller Etiology

• commonly identified causes of fever in the returned traveller parasitic: malaria ( 20-30% ) viral: non specific mononucleosis-like syndrome (4 25%), dengue (5%), viral hepatitis (3%) bacterial: typhoid from Salmonella ( 2 7%), rickettsioses ( 3%) diverse group of causative pathogens: traveller’s diarrhea (10 20%), respiratory tract infection (10 15%), UT1/STI (2-3%) l'ever in a returned traveller from a malaria endemic area is considered malaria until proven otherwise • can be caused by routine infections that are common in non travellers (e.g. UR TT , UTT ) • less commonly, fever can be due to non infectious causes ( e.g. DVT/PE, drug fever, inflammatory disorder unmasked by travel acquired infection )

-

-

-

-

-

-

-

-

'

History

• pre-travel preparation

• travel itinerary: when, where, why, what, who, how ? dates of travel (determine incubation period ) season of travel: wet or dry destination: country, region ( urban or rural ), environment ( jungle, desert, etc ) purpose of trip • persons visiting friends and family are more likely to be exposed to local population and pathogens style of travel: lodgings, camping, adventure travelling

.

local population: sick contacts • transportation: use of animals • exposure history • street foods, untreated water: increased risk of traveller's diarrhea, enteric fever uncooked meat / unpasteurized dairy: increased risk of parasitic infection • body fluids (sexual contacts, tattoos, piercings, IVDU, other injections) increased risk of HBV, HCV, HIV, UC, C trachomatis, syphilis animal /insect bites: increased risk of malaria, dengue, rickettsioses, rabies • fever pattern • incubation period: use the earliest and latest possible dates of exposure to narrow the differential diagnosis and exclude serious infections • < 21 d: consider malaria, typhoid fever, dengue fever, chikungunya, Zika, rickettsioses, traveller's diarrhea, respiratory tract infections (e.g. 1L1, COV1D 19); exclude HBV, TB • >21 d: consider malaria, TB, typhoid fever; exclude dengue fever, chikungunya, traveller’s diarrhea , rickettsioses • body systems affected: Cil, respirator)', CNS, skin

.

-

Investigations

• all travellers with fever should undergo the following tests blood work: CBC and differential, liver enzymes, electrolytes, creatinine, thick and thin blood smears x3 ( for malaria), blood C&S urine: urinalysis, urine C&S if dysuria or other localizing signs • special tests based on symptoms, exposure history, and geography « stool: C&S, O& P

. «

CXR

viral serology ( hepatitis, HIV ) dengue serology for lgM, dengue PCR

Treatment

• empiric treatment if ongoing fever for 48-72 h and negative malaria smears and all cultures pending • travelled to India, Southeast Asia: azithromycin ± doxycycline • travelled elsewhere: ciprofloxacin ± doxycycline

n

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ID-13 Infectious Disease

Toronto Notes 2023

Table 29. Fever in the Returned Traveller Illness

Geography/ Timing

Malaria

Africa India Central and Sooth America Southeast Asia Usually rural,

Pathogen

. .

Plasmodium

.

night-biting mosquitoes Dengue

Incubation Period 7- 30 d to mo

falciparum Plasmodium vim P. maloriae P. orole P. knowlesi

oryr

Dengue viruses 1- 4

3 d to 2 wk

Tick Typhus

Mononucleosis

Zika Virus Disease

Treatment

Fever and flu-like illness (shaking chills, headache, muscle aches, and fatigue) Nauseai'vomitmg and diarrhea Anemia and jaunSce Plasmodium falciparum: (severe) kidney failure, seirures.menial confusion,

Blood smear (thick and Ihin) x 3 Rapid diagnostic test ( with smeai or PCR confirmation) Antigen detection PCR

Artesunate ( for severe disease) * Malarone 8. doxycyclme. or

clindamycin

Quinine sulfate •doiycydine

or clindamycin Chloroquine * primaquine

Sudden onset of fever, headache, retro- orbital Anti - dengue IgM positivity pain, myalgias, and arthralgias PCR

Symptom relief: Acetaminophen (avoid using NSAIDs and ASA because of antiplatelet properties)

Leukopenia

Thrombocytopenia hemorrhagic manifestations (rare in travellers)

Global but mostly Indian subcontinent

Salmonella

Mediterranean.

Sickettsia

Global

M. tuberculosis

3 to 60 d

1 to 2 v/ k

Caribbean. EBVorCMV Central and South America

30 to 50 d

Africa. Southeast Asia. South America: spreading

Unknown likely 3 to 12 d

Zika virus

Stool, urine, or blood culture positive for S. If phi or 5. Paratyphi

Fever, headache,myalgia, spotted rash Eschar at site of tick bite Thrombocytopenia Elevated liver enrymes

Serology Presence of classic tick eschar

DoxycyCline

CXR

Isoniasd (lNH) rifampin (RIF), pyratinamide (PZA). ethambutol ( EMB) •Vitamin B6

lymphadenopathy. splenomegaly

Atypical lymphocytes on blood smear and positive heterophilic antibody (monospol) test

Acetaminophen or NSAIDs. fluids

Headache,malaise,myalgia,arthralgia,mild fever, rash, conjunctivitis

RT - PCR Serology

Rest, fluids, analgesics/ antipyretics (avoid NSAIDs until Dengue ruled out), condom use avoid pregnancy

Fever,cough, hemoptysis

Variable

Sputum culture and acid - fast slain Nucleic Acid Amplification Test (NAAT )

Malaise, fatigue,pharyngitis,

.

Ouinolone antibiotic (e _g_ ciprofloxarin). ceftriaxone,or

Sustained fever 39 -40 C (103M04:F) Abdominal pain, headache,loss of appetite, cough, constipation S

enterica serotype Ifphi or serotype Paratyphi

South Africa. India

18

Diagnosis

prostration, coma,death,respiratory failure

SoutheastAsia. Caribbean Usually urban, day-biting mosquitoes

Typhoid ( enteriefever)

Clinical Manifestations

macrolide

.

.

Fever of Unknown Origin Table 30. Classification of Fever of Unknown Origin (FUO ) - Temp >38.3°C/101°F on several occasions

Causes of Nosocomial FUO B, C, D, E

-

Classical FUO

Nosocomial FUO

Neutropenic FUO

Duration >3 wk

Hospitalized patient Infection not present/incubating on admission

Neutrophil count 500 ml or is expected to fall to that level in 1- 2 d

HIV infections Duration >4 wk for outpatients >3 d for hospitatriedpatients

Diagnosis uncertain after 3 outpatient visits or 3 d in hospital or 1wk of intensive ambulatory investigation

Diagnosis unceitain after 3 d of investigation, including at least 2 d incubation of cultures

Diagnosis uncertain after 3 d of investigation, including at least 2 d incubation of cultures

Da gnosis uncertain after 3 d of investigation, including at least 2 d incubation of cultures

-

HIV associated FUO

.

Bacterial and fungal infections of respiratory tract and surgical sites Catheters (intravascular and urinary) Drugs

Emboli

Etiology of Classic FUO

-

• infectious causes ( 30%) • TB: extrapulmonary ( most common ), miliary, pulmonary (if pre-existing disease) • abscess: subphrenic, liver, splenic, pancreatic, perinephric, diverticular, pelvic, psoas osteomyelitis bacterial endocarditis ( culture negative ) other: viral (CMY, EBY, HIV'), bacterial ( brucellosis, bartonellosis), fungal ( histoplasmosis, cryptococcosis ), parasitic ( toxoplasmosis, leishmaniasis, amoebiasis, malaria ) • neoplastic causes ( 20%) most commonly lymphomas (especially non- Hodgkin ) and leukemias, multiple myeloma, myelodvsplastic syndrome solid tumours: renal cell carcinoma ( most common ), breast, liver ( hepatocellular carcinoma ), colon, pancreas, or liver metastases • collagen vascular diseases ( 30%) • SLH, RA, rheumatic fever, vasculitis ( temporal arteritis, polyarteritis nodosa ), juvenile RA, Still disease • miscellaneous ( 20%) drugs (e.g. anti - microbials, anti - arrhythmics), factitious fever • sarcoidosis, granulomatous hepatitis, IBD hereditary periodic fever syndromes (such as familial Mediterranean fever) • venous thromboembolic disease: RE , DVT • endocrine: thyroiditis, thyroid storm, adrenal insufficiency, pheochromocytoma • unknown in 30-50% despite detailed workup

-

-

-

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ID4 I Infectious Disease

Toronto Notes 2023

Approach to Classic FUO

• careful and repeated history: travel, environmental/occupational exposures, infectious contacts, medication history, immunizations, TB history, sexual history, past medical history, comprehensive review of systems ( including symptoms that resolved before interv iew) • thorough physical exam: fever pattern, rashes (skin, mucous membranes), murmurs, arthritis, lymphadenopathy, organomegaly • initial investigations as appropriate • blood work: CBC and differential, electrolytes, urea, Cr, calcium profile, liver enzymes, HSR, CRP, ferritin, muscle enzymes, RF, ANA, serum protein electrophoresis (SPEP), blood film • cultures: blood (x3 sets), urine, sputum, stool C&S and O& P, other fluids as appropriate • serology: HIV, Monospot , CMV IgM, syphilis • imaging: CXR, abdominal imaging • if there are diagnostic clues from any of the above steps, proceed with directed exam, biopsies or invasive testing as required, followed by directed treatment once a diagnosis is established if no diagnosis with the above, consider empiric therapy vs. watchful waiting without intervention: patients that remain undiagnosed despite extensive workup have good prognosis • immunocompromised hosts have increased susceptibility to infections from pathogens that are typically low virulence, commensal, or latent

Infections in the Immunocompromised Host Factors that Compromise the Immune System • general: age (very young or elderly), malnutrition • immune disease: HI Y, malignancies, asplenia (functional or anatomic ), hypogammaglobulinemia, neutropenia DM • iatrogenic: corticosteroids, chemotherapy, radiation treatment, anti-TNF' therapy, other immunosuppressive drugs (e.g. in transplant patients)

.

Table 31. Types of Immunodeficiency Type

Conditions

Vulnerable To

Cell-Mediated Immunity

HIV.Hodgkin,hairy cell leukemia, cytotoxic drugs.SCID, DiGeorge syndrome

Latent viruses Fungi Parasites Non- tuberculosis mycobacterium (NTM)

Humoral Immunity

CU,lymphosarcoma,multiple myeloma,nephrotic syndrome,protein losing enteropathy, burns, sidde cell anemia, asplenia, splenectomy, selective Ig deficiencies WiskoU Aldrich syndrome

Encapsulated organisms (1pneumoniae, H. inllueiuae M.meningitidis Salmonella enterico serotype lyphi, G8SI

-

-

Neutrophil Function

.

.

.

.

Chemotherapy, myelodysplasia, paroiysmal nocturnal Catalase -producing organisms \Slaphylocoaus hemoglobinuria, radiation, cytotoxic drug therapy.C3 or C5 Serratia Mocantia Aspergillus ) deficiencies,chronic granulomatous disease

.

.

Febrile Neutropenia Definition • fever (S38.3°C/101*ForS38.0°C / 100.4°1; for SI h) • neutropenia: ANC 4 in fatty acid oxidation defect) Treatment

• varies according to inborn error of metabolism but includes dietary restrictions, toxic metabolite sequestrants, enzyme replacement, etc. • in the presentation of acute decompensation potentially caused by an inborn error of metabolism, discontinue feeding to prevent further buildup of toxic metabolites Table 9. Presentation and Management of Select Metabolic Disorders Galactosemia

PKU

Inheritance and Incidence

GSD Type 1 ( Von Gierke Oisease)

MSUD

Tay- Sachs Disease

1in 10000: autosomal 1 in 60000: autosomal 1in 185000, recessive disease (mutations inPW

recessive disease

1 in 100000 : 1 in 320000: autosomal recessive autosomal recessive autosomal recessive disease (pathogenic disease 1in 20000 in disease 1in 3600 in variants in BCKDHA Ashkenazi Jewish Ashkenazi Jewish BCKDH8, and DBT genes),1in 25000 in Ashkenazi Jewish 1in 400 InMcnnoniles

.

gene)

.

.

.

Pathophysiology

Clinical Features

Deficiency ol phenylalanine hydroxylase prevents conversion of phenylalanine to tyrosine leading lo buildup of phenylalanine and its toxic metabolites Mothers who have PKU may have infants with multiple congenital abnormalities

Most commonly due to deficiency of galactose1-phosphate uridyltransferase leading to an inability to process lactose / galactose

Deduction or elimination of protein complex needed for amino acidsleucine, isoleucine, andvaline breakdown, leading to toxic build- up

Baby is normal at birth, then develops a musty odour eczema, hypertonia,

Signs of liver and renal failure, jaundice,failure lo

Feeding intolerance, failure lo thrive vomiting, lethargy, and maple syrup odour in urine and

.

tremors, and mental retardation Hypopigmentation due to low tyrosine levels (lair hair, blue irises)

thrive,and cataracts with ingestion of lactose/galactose Complications:

Increased risk of sepsis, especially l coli If the diagnosis is

.

not made at birth, liver and brain damage may become irreversible

.

cerumen May progress to irreversible mental retardation,

hyperactivity, severe failure to thrive, seizures, coma, cerebral edema, and death if inadequately treated

Mutations in C6K (cause of GSOta ) and SLC3JA4 (cause of

Mutations in HIXi gene, which encodes alpha subunit of GSDtb) genes prevent hexosaminidase A: effective conversion leads to intracellular of glucose- 6 accumulation of GM 2 phosphate to glucose, ganglloside lysosome Glucose - 6 phosphate dysfunction, and Is converted to neurodegeneration glycogen and fat which subsequently accumulate in cells, especially in the liver and kidneys

-

.

Various

fypicallyprescnts

between 3 - 6 mo ol age with

hepatomegaly, hypoglycemia,poor fasting tolerance, growth failure, and "doll -like' facies ( full cheeks with thin extremities) Complications: Lactic acidosis

.

presentations: infantile form (onset at 3 - 6 mo), juvenile form (onset at 2-6 yr), and adult or chronic form (onset at >10 yr)

Psychomolor regression, hypotonia increased startle response,

.

macular cherry red spot, seizures, and hearing impairment

hyperuricemia, hyperlipidemia. delayed puberty, renal disease, hypoglycemic seizures, hepatic adenomas, osteoporosis

Diagnosis and Management

PKU screening at birth Life-long dietary restriction of phenylalanine starting within the first 10 d ol life: especially important during pregnancy to maintain normal phenylalanine levels lo prevent maternal PKU effects on fetus large neutral amino acid (tyrosine) replacement BH 4 enzyme treatment, phenylalanine lyase treatment are other options

.

Screened for in many newborn screening programs but

MSUD is screened in most newborn screening programs,

generally present with liver failure and f . coli sepsis belore screening result

Serum amino acid evaluation ( leucine, isoleucine, alloisoleu cine, and

reported

valine) andurine organic acid analysis Protein -restricted high- carbohydrate diet to limit branched amino acid intake A trial of thiamine therapy in addition may be recommended for some infants

Elimination of galactose from the diet (e.g. dairy, breast milk ) Most infants arc led a soy - based diet

.

Hypoglycemia when interval between feeds are Increased (» 3- 4 h) ladle acidemia hypertriglyceridemia, and hepatomegaly Treatwith nutrition

Clinical suspicion 6 - Kexosaminidase enzyme activity ( scrum)

therapy Ismail

screening Treatment is supportive

.

.

frequent feedings, avoid fructose / sucrose / galadosc) continuous overnight feedings, raw cornstarch (for slow, sustained glucose release), vitamin supplementation, frequent blood glucose monitoring

.

Ashkenazi Jewish carriers often identified by preconception

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MG11 Medical Genetics

Landmark Medical Genetics Trials Trial Name

Reference

Clinical Trial Details

AmiClin Hulr 2016: 104 ( 2):334

Title: Glycomacropeptide for Nutritional Management of Phenylketonuria: A Randomircd Controlled Crossover Trial Purpose: To evaluateIhe eflicacy and safety of a low phenylalanine|Phe) diet in combination with either glycomacropeptide medical foods (GMP MFs) or Iradilional amino acid medical loods|AA MFs) in individuals with phenylketonuria (PKU ) Methods: Thirty early treated individuals aged 15 - 49 yr with PKU participated in a 2 stage, randomircd ciossovcr trial involving consumption ol a low Pile diet with AA - MFs or GMP MFs for periods of 3 wk each Results: Dietary management of PKU with GMP MFs compared lo AA Mfs resulted in highci intake among participants GMP Mfs were rated as more acceptable in terms ol taste and had less side effects Conclusions: GMP Mfs are sale lor dietary management of PKU GMP Mfs may improve dietary adherence for patients with

PHENYLKETONURIA

Glycomacropeptide for Nutritional Management of Phenylketonuria: A Random ! red Controlled, Crossover Trial

.

345

.

.

.

Mol Genet Melab 2018: 124 (1):27.38

.

.

.

PKU.

PRISM

.

Title: Pegvaliase lor Ihe Treatment of Phenylketonuria: Resullsof a longTerm Phase 3 Clinical trial Program (PRISM ) Purpose: Evaluate the eflicacy and safely of pegvaliase trcatmenl in adults with phenylketonuria (PKU) Methods: Pegvaliase - naive participants with blood Phe > 600 pmol/lwere randomircd to receive 20 mg /d or 40 mg /d of pegvaliase Results: Pegvaliase treatment was given to 261 participants Within 24 mo 68 4% of participants achieved blood Phe < 600 pmol/ L. Reductions in blood Phe were associated with neuropsychiatric outcomes, which were maintained with long - term treatment Ihe vast majority of adverse events (99%) were mild or moderate in seventy. Conclusions: Results from this trial suggest pegvaliase is safe and elftcacious in treating adults with PKU

.

.

.

.

.

.

CYSTIC FIBROSIS

Title: Study of Elcxacaftor / Teracaftor/lvacaftor in Children 6 through 11 Years ol Age with Cystic fibrosis and at least One F 508del Allele Purpose: Elexacaflor/teracaftor /ivacaltor as a combination therapy was effective in treating patients aged greater than 12 years with CF and an accompanying F508 del. This 24 - week study served to evaluate the efficacy of treatment in patients less than CSF > air (~ dark)

-

-

Magnetic Resonance Imaging • imaging technique that uses electromagnetic properties of tissue ( mainly water ) to produce images in virtually any plane. It does not use ionizing radiation • patient is placed in a magnetic field generated by electric current ; protons, typically from water molecules, align themselves along the direction of magnetization due to their intrinsic polarity. A pulsed radiofrequency beam is subsequently turned on and deflects all the protons off their aligned axes. When the radiofrequency beam is turned off, the protons return to their pre- excitation axis, giving off the energy they absorbed. This energy is measured with a detector and interpreted by software to generate MR images • MR image reflects signal intensity picked up by receiver. Signal intensity is dependent on: 1. hydrogen density: tissues with low hydrogen density (e.g. cortical bone, lung) generate little to no MR signal compared to tissues with high hydrogen density (e.g. water) 2. magnetic relaxation times (T1 and T2): reflect quantitative alterations in MR signal strength due to intrinsic properties of the tissue and its surrounding chemical and physical environment

-

Dilfusion Weightcd Imaging

-

Signal Intensity

Main Application

Signal intensity dependenton the Neuroradiology free molecular motion of water Decreased diffusion is Irypcrinlensc ( bright), whereas increased diffusion is hypointense (dark )

11 Wcightcd

Fluid is hypointense (dark ) and fat Body soft tissues is hyperintense ( bright)

T2-Weighted

Fluid is hyperintense ( bright) and fat is hypointense (dark)

Body soft tissues

Methods to Reduce the Risk of Contrast-Induced Nephropathy • Optimal: 0.9% NaCI at 1 mL/kg/h for 12 h pre-procedure and 12 h postcontrast administration • For same-day procedure: 0.9% Nad or NaHCOaat 3 ml/kg/h for 1-3 h preprocedure and for 6 h post-contrast

administration

Table 1. Differences Between Diffusion , T1- and T 2- Weighted MR Imaging Imaging Techniques

U

Remember that water is "white" on T 2 as "World War II"

Advantages

Sensitive for detection of acute ischemic stroke and differentiating an acute stroke from other neurologic pathologies Acule infarction and abscess collections appear hypeiinlenso due to restricted diffusion Often considered an anatomic scan since it provides a reference for functional imaging Often considered a pathologic scan since it will highlight edematous areas associated with certain pathologies

Positron Emission Tomography Scans • nuclear tracers arc employed (o produce images of functional processes in the body • current generation models integrate PET' and CT technologies into a single imaging device ( PET CT) that collects both anatomic and functional information during a single acquisition • positron producing radioisotopes, such as 18F, are chemically incorporated into a mctabolically active molecule (e.g. glucose). These are then injected into the patient, where they travel to and accumulate in the tissues of interest. As the radioactive substance decays, y rays are produced, and are detected by the PET scanner

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Contraindications to IV Contrast MADD Failure Multiple myeloma Adverse reaction previously Dr .' Dehydration Failure (renal, severe heart)

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Toronto Notes 2023

Mi l Medical Imaging

contraindications: pregnancy advantages: shows metabolism and physiology of tissues ( not only anatomic); in oncology, allows for diagnosis, staging, and restaging; has predictive and prognostic value; can evaluate cardiac viability • disadvantages: cost , ionizing radiation , availability

•

•

Contrast Agents Table 2 . Contrast Agents Imaging Modality

Types

X - Ray

Barium (c .g oral or rectal )

Radiopaque substance that helps lo delineate Intraluminal

lodinated agents (routes * oral. rectal IV)

anatomy: may demonstrate patency, lumen integrity, or large filling defects Delineates intraluminal anatomy: may demonstrate patency, lumen integrity, or large filling defects; under fluoroscopy, may also give information on function of an organ

CT

Advantages

.

.

Disadvantages

FDG PEI Imaging in Patients with Pathologically Verified Dementia JNucIMed 2000;4f (11):1920 8 Purpose : loconfirin two beliefs surrounding bilateral temporo parietal Irypometabolism an FDG PtI in Aliheimer 'sdrsease|AD|:|t) !I is the metabolic abnormality associated with DO and|2) that sensitivity, specificity, and diagnostic accuracy of this metabolic pattern allows for ADto be differentiated from other degenerative causes of dementia. Methods: FOG PET scans from 22 individuals with path olog it confirmation of AD d iagnosis were visually graded by aneipeiiecced nutlear medicine physician to identify dassK bilateral lemporo parietal hypometa holism . Results: Sensitivity, specificity, and diagnostic accuiacy ol bilateral temporo parietal hyporaetabolism for ID neie 93V 63%. and 82 %. respectively. Conclusions: Bilateral temporo - parietal hpometabolism is the classic metabolic abnormality associated with AD. FOG PET may identify this metabolic pattern and can be used clinically to differentiate dementia syndromes.

Contraindications

-

Previous adveise reaction to contrast : barium enema is contraindicated in tonic megacolon , acute colitis, and suspected perforation

Previous adverse reaction to contrast, renal failure. DM. pregnancy, multiple myeloma , severe heart failure, and dehydration

cGFR '60 may require preventative measures and followup

MR!

Gadolinium Chelates

Shortens 11 relaxation time , thereby increasing signal intensity in 11 weighted sequences: highlights highly vascular structures (e.g.

-

Risk ol nephrogenic systemic fibrosis in patients with end stage renal disease

-

Previous adverse reaction to contrast or end - stage renal disease (relative contraindication)

tumours) UfS

Microbubbles ( IV )

tiny gas bubbles crcalemany Interlaces and appear very echogenic . The microbubbles allow for echo enhancement of vascular structures or cavities ( l.e. echocardiography)

-

Contraindicated in individuals with right to left cardiac shunts or people with known hypersensitivity reactions

-

Chest Imaging Chest X- Ray Standard Views • PA : anterior chest against film plate to minimize magnification of the cardiac silhouette • lateral : better visualization of retrocardiac space and thoracic spine; more sensitive at detecting small

pleural effusions • improves localization of lesions when combined with PA view • AP : alternative to PA view for admitted or acutely ill patients who are unable to tolerate standing or transport; erect or supine; generally a lower quality film than PA because of magnified cardiac silhouette • lateral decubitus: can help to assess for pleural effusion and pneumothorax; however, POCUS can also

be utilized for both of these purposes • lordotic : angled beam allowing better visualization of apices normally obscured by the clavicles and

anterior ribs on PA and AP views

Posterior- anterior Position Lateral Position

Anterior - posterior Position Lateral Decubitus Position Lordotic Position

j

Figure 1. CXR views

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MIS Medical Imaging Approach to CXR

Basics

• ID: patient name, medical record number ( MRN ), sex, age • date of exam

• markers: right and / or left • technique: view (e.g. HA, AH, lateral ), supine or erect • indications for the study

• comparison: date of previous study for comparison ( if available) • quality of film: inspiration (10 posterior and 7 anterior ribs should be visible ), penetration (thoracic spine should be visible ), rotation (spinous processes should be equidistant from medial ends of clavicles), magnification ( AH films magnify the heart ), angulation (clavicles should be S shaped ) Analysis

• tubes and lines: check position and be alert for pneumothorax or pneumomediastinum • soft tissues: neck, axillae, pectoral muscles, breasts / nipples, chest wall nipple markers can help identify nipples ( may mimic lung nodules)

amount of soft tissue (check for any asymmetry), presence of masses, presence of air (subcutaneous emphysema ) • abdomen (see Abdominal Imaging, Mill ) free air under the diaphragm , air-fluid levels, distention in small and large bowel • herniation of abdominal contents (i.e. diaphragmatic hernia ) • hones: cervical spine, thoracic spine, scapulae, ribs, sternum , clavicles, proximal humerus lytic and sclerotic lesions, fractures • mediastinum: trachea, heart, great vessels cardiomegaly ( cardiothoracic ratio > 0.5 on HA ), tracheal shift , tortuous aorta, widened

mediastinum

• hila: pulmonary vessels, mainstem and segmental bronchi, lymph nodes • lungs: parenchyma, interstitium, pleura, diaphragm • abnormal iung opacity, pleural effusions or thickening right hemidiaphragm usually higher than left due to liver • right vs left hemidiaphragm can be discerned on lateral CXR due to heart resting directly on left

.

(§) Chest X - Ray Interpretation Basics ABCDEF AP. PA or other view Body position/rotation Confirm name Oate Exposure/ quality

Films for comparison Analysis ABCDEF Airways and hilar Adenopathy Bones and Breast shadows Cardiac silhouette and Costophrenic angle Diaphragm and Digestive tract Edges of pleura Fields (lung fields)

hemidiaphragm • please refer to Toronto Notes website for supplementary material on how to approach a C.'XR Anatomy

Localizing Lesions for Parenchymal Lung Disease

• silhouette sign: when two objects of the same radiodensity abut, they appear indistinguishable on imaging ( i.e. the silhouette expected at an anatomical border due to difference in density disappears) can be used to identify lung pathology (consolidation , atelectasis, mass ) and localize disease to specific lung segments this sign can be applied to imaging studies throughout the body • spine sign: on lateral films , vertebral bodies should appear progressively radiolucent (dark ) as one moves down the thoracic vertebral column; if they appear more radiopaque, it is an indication of pathology (e.g. consolidation in overlying lower lobe) • air bronchogram: branching pattern of air-filled bronchi made visible on a background of opacification ( i.e. solid or fluid - filled alveoli ) Table 3. Localization Using the Silhouette Sign Interface Lost

Location of Lung Pathology

SVC/right superior mediastinum

RUL

Right heart border

RML

Right hemidiaphragm

RLL

Aortic knob left superior mediastinum

LUL

Left heart border

Lingula

left hemidiaphragm

ILL

n LJ

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Toronto Notes 2023

legend

aI »2 aa apw

as ca cl co epa

di 9 VC

la Ibr Ipa v

mf mi

p3 p4

pa

costophrenic angle diaphragm gastric bubble

inferior vena cava left atrium left main stem bronchus left pulmonary artery left ventricle major fissure minor ftssuro posterior 3rd rib posterior 4th nb

sp

pulmonary artery right atrium right mainstem bronchus right pulmonary artery right ventricle scapula spinous process

St

sternum

sve

supenorvenacava trachea vertebral body

rbr rpa

rv sc

Lateral view

anterior 2nd rib aortic arch aorto' pulmonarv window anterior airspace carina clavicle coracoid process

main

ra

PA view

anterior 1st rib

tr vb

Figure 2. Location of fissures, mediastinal structures, and bony landmarks on CXR Note that anterior space is also commonly called retrosternal space

LUL

LLL t

1 ~ r

Front AP

^

Right-Lateral

Back AP

Left -Lateral

RUL Right Upper Lobe; RML: Right Middle Lobe; RLL: Right Lower Lobe; LUL: Left Upper Lobe; LLL: Left Lower Lobe

Figure 3. Location of lobes of the lung


0.5 cardiomegaly (myocardial dilatation or hypertrophy) pericardial effusion poor inspiratory effort /low lung volumes pectus excavatum ratio 18 yr undergoing an elective procedure requiring iodmated contrast were randomly assigned (1:1) to receive N 0.9% NaCl or no prophylaxis. The primary outcome was incidence of contrast -induced nephropathy deSned at an intitase in stium creatinine from baseline of >25% or 44 pmol.lwithin 2-6 d of contrast exposure, and cost-effectiveness of nD prophylaxis compared with IY hydration in the prevention ofcontrast- mduced nephropathy. Oeatinine was measured before 26 d and 2 -35 d after contrast- material exposure. Results: 660 consecutive patients were randomly assignedto receive no prophylaxis ( n-332) or IV hydration (n*328). No hydration and prophylaxis had srnidar rates ol nephropathy. No hydration was cost -savmg relative to hydration. No haemodialysis ot related deaths occnrred withm 35 days. 5.5% of patients had corspllcations associated with intravenous hydration Conclusion: No prophylaxis was found to be ron-inferior and cost-saving in prevent ng contrast induced nephropathy compared with IV hydration.

.

.

'

. .

.

Normal liver appears more dense than spleen on CT. If less dense, suspect fatty infiltration

Liver Mass DDx

SHs HCC Hydatid cyst Hemangioma Hepatic adenoma Hyperplasia (focal nodular )

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M115 Medical Imaging

.

Table 11 Imaging of Liver Masses

u/ s

CT

Hepatic Adenoma

Well -defined mass with hyperechoic areas due to hemorrhage

Well - defined hypervascular lesion with enlarged central vessel becoming slightly Isoattenuating in venous phase

Hemangioma

Homogeneous hyperechoic mass

Peripheral globular enhancement in arterial phase scans: ccnlral filling and persislcnl enhancement on delayed scans

Benign Mass

-

Well defined mass, central scar seen in 50% of cases

Focal Nodular Hyperplasia

-

Ill defined , irregular margin , hypoechoic

Abscess

contents Simplc / mulliloculatedcysl

Hydatid Cyst

Hypervascular mass in arterial phase and isoattenuation to liver in portal venous phase

Low attenuation lesion with an irregular enhancing wall low attenuation simple or mulliloculalcd cyst:

calcification Malignant Mass

HOC

Single/multiple masses, or diffuse infiltration

Mctastascs

Multiple masses of variable cchotcxturc

Hypervascular; enhances in arterial and washes out in venous phase with portal venous tumour thrombus

-

Usually low attenuation on contrast enhanced

scan

Pancreas • tumours • U/S: mass is more echogenic than normal pancreatic tissue • CT: preferred modality for diagnosis/staging • ductal dilation secondary to stone/ tumour MRCP: imaging of ductal system using MR I cholangiography; no therapeutic potential • ERCP: endoscopic injection of dye into the biliary tree and x-ray imaging to assess pancreatic and biliary ducts; therapeutic potential (stent placement, stone retrieval ) acute pancreatitis is a complication in 5% of diagnostic procedures and 10% of therapeutic

Re « ised ( stimotcs of Diagnostic TcstSensitivity and Specificity in Suspected Biliary Trad Disease rcli Intern Med 1998:15425732581 Purpose: In assess the sensitivity and specificity of tests used to diagnose choleithiasis and acute cholecystitis, including U /5, oral cholecystography , rad or jdeotide scanning with lech' et um, MRI .

*

or Cl.

Methods : Meta - analysts of studiesevalualing the use of different imaging moda > ties in the diagnosis n! biliary tract disease. Main outcomes were sensitivity and specificity of the different imaging modalities, usng the gold standard of surgery, autopsy, or 3 mo clinical follow up for cholelithiasis. Foi acute cholecystitis, pathologic findings, confirmation of an alteriutedisease or cbmcal resolution during hospdaluation for cholecysbtn were used as the

-

.

standard. Results: thirty studies were included. For evaluating choletthiasis, U /S had the best unadiusted sensitivity (0.97; 95% Cl 0.95- 0.99) and speeiWy (0.95, 0.88-1.00) and ad|usted (for indication bias) sensitivity (0.84 ; 0.76 0.92) and specificity I 0.99 ; 95% CI 0.97-1.00). lor evaluating acute cholecystitis, radionudeotide scanning has the best sensitivity (0.97: 0.96 -0-98) and specificity (0.90; 0.86- 0.95). Conclusion : U /S is the test of choce for degnosmg cholelithiasis and radionudeotide scanning is the superior test lor dug nos ng acute cholecystitis.

-

procedures Gallbladde

Biliary Tree • U /S; bile ducts usually visualized only if dilated, secondary to obstruction (e.g. choledocholithiasis, benign stricture, mass) • CT: dilated intrahepatic ductules seen as branching, tubular structures following pathway of portal

venous system • MRCP, ERCP, PTC: further evaluation of obstruction and possible intervention

“itis” Imaging Acute Cholecystitis • pathogenesis: inflammation of gallbladder resulting from sustained gallstone impaction in cystic duct , or in the case of acalculous cholecystitis, due to gallbladder ischemia or cholestasis (see General and Thoracic Surgery, GS56 ) • best imaging modality: U /S ( best sensitivity and specificity ); nuclear medicine ( H1 DA scan ) can help diagnose cases of acalculous or chronic cholecystitis • findings: most sensitive findings are presence of gallstones and positive sonographic Murphy’s sign ( tenderness from pressure of U /S probe over visualized gallbladder ). Secondary findings include thickened gallbladder wall (>3 mm ), dilated gallbladder, and pericholecystic fluid • management: admit, NPO, IV fluids, analgesia , cefazolin , and early laparoscopic cholecystectomy Acute Appendicitis • pathogenesis: luminal obstruction -> bacterial overgrowth

> inflammation / swelling > increased pressure > localized ischemia > gangrene / perforation > localized abscess or peritonitis ( see General and Thoracic Suruerv GS35 ) • best imaging modality: U /S or CT

.

.

Figure 20 ERCP; biliary tree ( A) common bile duct (B) cystic duct ( C) common hepatic duct (D) right hepatic duct (E) left hepatic duct

mm. Figure 21. Ultrasound: longitudinal view of an inflamed gallbladder Arrowheads show thickened walls and pericholecystic fluid

• findings: U /S: thick-walled appendix, appendicolith, dilated fluid - filled appendix, non - compressible; may also demonstrate signs of other causes of RLQ pain (e.g. ovarian abscess, 1 BD, ectopic pregnancy) CT: enlargement of appendix ( >6 mm in outer diameter ), enhancement of appendiceal wall, adjacent inflammatory stranding, appendicolith ; also facilitates percutaneous abscess drainage : admit , NPO, IV fluids, analgesia, cefazolin t metronidazole, and appendectomy management • Acute Diverticulitis pathogenesis: erosion of the intestinal wall ( most commonly rectosigmoid ) by increased intraluminal pressure or inspissated food particles -> inflammation and local necrosis -> micro- or macroscopic perforation (see General and Thoracic Suruerv, GS39)

-

r

+

•

• best imaging modality: CT, although U /S is sometimes used • contrast: oral and rectal contrast given before CT to opacify bowel

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LJ

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Figure 22 Ultrasound: inflamed appendix

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MI16 Medical Imaging

•findings:

cardinal signs: thickened wall, mesenteric infiltration , gas- filled diverticula , abscess

CT can be used for percutaneous abscess drainage before or in lieu of surgical intervention

• sometimes difficult to distinguish from perforated cancer (send abscess fluid for cytology and

follow up with colonoscopy) if chronic, may see fistula ( most common to bladder) or sinus tract ( linear or branching structures) • management: ranges from antibiotic treatment to surgical intervention: can use imaging to follow progression

Conput d Tomography and Ullrasonogtaphy to Detect Acute Appendicitis in Adults and A dolescenls Ann Intern Med 2004;M1:537 5d 6 Purpose: To review tile diagnostic accuracy of CT and lift in thediagnosrs otacute appendicitis Methods: Meta analyst of prospective studies evaluating the use of Cl or ll/S, followed try surgical or cinkal follow up io patients with suspected appendicitis. Patients >Uyt with a clinical suspicion ol appendicitis were eligible. Sensitivity and specificity using surgery or clinical lollow - upas the gold standard were the main outcomes studied. Results: Twenty two studies were included. CT [12 studies) had an overall sensitivity ol 0.94 (95% Cl 0.91 0.95) and a specificity ol 0,95 [0.93-0.96). 0)5 [14 states) had an overall sensitivity of 0.86 (0.83 0.88) and a specificity of 0.81 (0.78 -0.84). Conclusion: CT is more accurate lor diagnosing appendicitis in adults and adolescents, allhough verification biasand inappropilale blinding ol reference standards were noted in the included

'

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.

-

Acute Pancreatitis • pathogenesis: activation of proteolytic enzymes within pancreatic cells leading to local and systemic inflammatory response (see Gastroenterology, G48); a clinical/biochemical diagnosis •best imaging modality: imaging used to support diagnosis and evaluate for complications (diagnosis cannot be excluded by imaging alone) • U /S good for screening and follow up CT is useful in advanced stages and in assessing for complications (1st line imaging test ) •findings: n U /S: hypoechoic enlarged pancreas ( if ileus present , gas obscures pancreas) n CT: enlarged pancreas, edema, fat stranding with indistinct fat planes, mesenteric and Gerota’s fascia ( renal fascia) thickening, pseudocyst in lesser sac, abscess ( gas or thick-walled fluid collection ), pancreatic necrosis (low attenuation gas- containing non -enhancing pancreatic tissue), hemorrhage • management: supportive therapy n CT-guided needle aspiration and/or drainage of abscess when clinically indicated pseudocyst may be followed by CT and drained if symptomatic

-

Chronic Pancreatitis •pathogenesis: (see Gastroenterology G50) • best imaging modality: MRCP (can show calcification and duct obstruction ) •findings: U /S, CT scan , and MKI may show calcifications, ductal dilatation, enlargement of the pancreas, and fluid collections (c g pseudocysts) adjacent to the gland

.

..

Angiography of Gastrointestinal Tract • anatomy of the arterial branches of the G1 tract celiac artery: hepatic, splenic, gastroduodenal, left / right gastric superior mesenteric artery: jejunal, ileal, ileo-colic, right colic, middle colic inferior mesenteric artery: left colic, superior rectal • imaging modalities conventional angiogram: invasive ( usual approach via femoral puncture ), catheter used flush aortographv : catheter injection into abdominal aorta, followed by selective

arteriography of individual vessels CT angiogram: modality of choice, non - invasive using IV contrast ( no catheterization required )

Genitourinary System and Adrenal Urological Imaging Kidney, Ureter, and Bladder (KUB) X-ray

• a frontal supine radiograph of the abdomen • indication: useful in evaluation of radiopaque renal stones (exceptions: uric acid and indinavir stones), indwelling ureteric stents/catheters, and foreign bodies in abdomen • findings: addition of IV contrast excreted by the kidney (intravenous urogram ) allows better visualization of the urinary tract hut has been largely replaced by CT urography Abdominal CT

-

-

-

si - Ces

©

Ultrasound , Computed Tomography or Magnetic Resonantelmaging fur Acute Appendicitis in

Children Pediatr Radiol 2097;47:186 196 Purpose: Compare the accuracies of IKS Cl.and MRI for clinically suspected acute appendicitis in children. Methods: Search and meta -analysis. Ihe sensitivity, specificity , and the acta under the curve o( summary receiver operating characteristics were calculated

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.

and compared . Results:19 studies of UTS, 6 stud ies of CT and 4 studies of MRI . Ihe analysis showed that Ihe area under Ihe receiver operator charictenstcs curve ol MRI I 0.99S) was a title higher than that ol US [0.987) and Cl (0.982; P>0.0S). Conclusion: US CT.and MRI have high diagnostic accuracies ol clinically suspected acute appendicitis in chiMten overall with no significant difference

.

.

.

Angiography requires active blood loss 1-1.5 ml/min under optimal conditions for a bleeding site to be visualized in cases of lower Gl bleeding

Imaging Modafity Based on

Presentation • Acute testicular pain - Doppler. UTS • Amenorrhea - U/S, MRI (brain) Bloating - Plain film/CT (if abnormal) Flank pain = U/S, CT • Hematuria - U/S. Cystoscopy CT Infertility - HSG. MRI • Lower abdominal mass U/S. CT • Lower abdominal pain - U/S, CT • Renal colic = U/ S. KUB, CT • Testicular mass * U/S • Urethral stricture ~ Urethrogram

. . .

.

Renal Masses

n

• Bosniak classification for cystic renal masses • class l - ll : benign and can be disregarded • class Ill : should be followed • class 11I-1V: suspicious for malignancy, requiring additional workup

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Table 12. Bosniak Classification for Cystic Renal Masses Classes

Definition

Simple Renal Cysts

.

.

Class I

Fluid-attenuating well -defined lesion,no septation no cakificatioo no solid components, hailine - thm wall

Class II

Same as class I •* fine calcification or moderately thickened calcification in septae or walls:also includes hyperdense cysts|3 cm Complex Renal Cysts

Class III

.

Thick irregular wallsicalcifications ± septated enhancing walls, or septa with contrast

Renal CellCarcinoma

Class IV

Same as class III soft tissue enhancement with contrast (defined as >10 Hounsfield unit increase, characterizing vascularity) with de- enhancement in venous phase ± areas of necrosis

• plain CT KUB indications: general imaging of renal anatomy, renal colic symptoms, assessment of renal calculi (size and location ) and potential sequalae ( infection and obstruction ), and hydronephrosis prior to urological treatment •CT urography indications: investigation of cause of hematuria, detailed assessment of urinary tracts (excretory phase ), high sensitivity (95%) for uroepithelial malignancies of the upper urinary tracts, assessment of renal calculi phases: unenhanced, excretory • renal triphasic CT indications: standard imaging for renal masses, allows accurate assessment of renal arteries and veins, better characterization of suspicious renal masses - especially in differentiating renal cell carcinoma from more benign masses, and preoperative staging phases: unenhanced, arterial and venous (nephrographic), excretory Ultrasound •indications: initial study for evaluation of kidney size and nature of renal masses ( solid vs. cystic masses, simple vs. complicated cysts); modality of choice for screening patients with suspected hydronephrosis (no IV contrast injection, no radiation exposure, and can be used in patients with renal failure); TRUS useful to evaluate prostate gland and guide biopsies; Doppler VIS to assess renal

vasculature • findings: solid renal masses are echogenic ( bright on U/S), cystic renal masses have smooth welldefined walls with anechoic interior (dark on U/S), and complicated cysts have internal echoes within a thickened, irregular wall

Retrograde Pyelography •indications: visualize the urinary collecting system via a cystoscope, ureteral catheterization, and retrograde injection of contrast medium , visualized by radiography or fluoroscopy; ordered when the intrarenal collecting system and ureters cannot be opacified using intravenous techniques ( patient with impaired renal function, high grade obstruction, or allergy to IV contrast) • findings: only yields information about the collecting systems ( renal pelvis and associated structures), no information regarding the parenchyma of the kidney Voiding Cystourethrogram • bladder filled with contrast to the point where voiding is triggered • fluoroscopy (continuous, real-time x-ray) to visualize bladder during voiding •indications: males or young females with recurrent UTls, hydronephrosis, hydroureter, suspected lower urinary tract obstruction, suspected bladder trauma, or vesicoureteral reflux • findings: evaluation of bladder contractility and evidence of vesicoureteral reflux Retrograde Urethrogram

•a small Foley catheter placed into penile urethral opening, followed by instillation of contrast and radiographic imaging indications: used mainly to study strictures or trauma to the male urethra; first-line study if signs of urethral injury are present (i.e. trauma with blood at the urethral meatus, scrotal hematoma, or highriding prostate)

.

Figure 23. Triphasic CT of an angiomyolipoma: showing fat density with non -contrast scan, mildly enhancing with contrast

llttrzHHngrapky vs.Compiled Tcajgrspty far Sxspected lepkroftiiasb till 201t 37t1W0-THI) Fwytst: bnratgefe wtzia Se nfiat nfgxg oetsod for piiexS VTB ssspecsd ispknX- css sfioedd he CT or tt'SMetkods fc Ibcater preg*aic.oeparctis efesraess trial, rasdoaly assgtdd pctleiS « tttBwil saspetted xepkroteisa fc> aateyo IsSzl degaostic n2ss«ogrepfcy perioroed Sy ii es«gaq pkyseax (POCtfi). 115 perfumed Irj a 3d o pgst. oraMoosal Cl Cos parsecs:30 d mctesa of Ib -rsk dagnses wSl coeplaloo Sat cosld te reaid to s issed w tfeSjrt tagnsis fid tie S so aaiteSie radatxu epassre. tosdts Atotzl of 2755 paters irdaniert raodoozctiH.Ike ntxtete of fcgk-risk degsoses ttt coapkatiots a tke first 30 d dd so!vary accsfdcg to izagdg retrod Tie ceas 6 DO cnslafiR radatioo eqnsse was sgejocy losetiiaeU 5 groips.SdieneeiesS «eresnJa: across grasps letsri ED visas lospiaSzatioes.aid diagwstt acciracj M mi ifesigtStaiSj asoog

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MRI

• advantages: better contrast resolution and tissue discrimination , lack of exposure to ionizing radiation, safer contrast, ability to obtain imaging directly from multiple planes (coronal, sagittal, oblique) • indications: indicated over CT for depiction of renal masses in patients with previous nephron -sparing surgery, patients requiring serial follow - up (less radiation dosage), patients with reduced renal function, patients with solitary kidneys, clinical staging of prostate cancer (endorectal coil MRI )

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AL GRAWANY

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Renal Nuclear Scan

Table 13. Renal Scan Tests Type of Test

Uses

Radionuclide

Renogram

Assess renal function and collecting system: evaluation of renal failure, workup of urinary tract obstruction and renovascular HTN. investigation of renal transplant

IVSSmTc-pentetate (DTPA) or merfcatide (MAG 3).and imaged at 1-3 s intervals with a gamma camera over the first 60 s to assess perfusion

Assess renal anatomy:investigation of pyelonephritis and

^mfc- DMSA

Morphological

cortical scars

hhnlcglucoheptonate

ARTERIAL PHASE

Gynaecological Imaging Ultrasound • transabdominal and transvaginal are the primary' modalities, and are indicated for different scenarios • transabdominal requires a full bladder to push out air-containing loops of bowel indications: good initial investigation for suspected pelvic pathology

VENOUS PHASE

• TV US provides a panoramic pelvic view and enhanced detail of deeper /smaller structures by allowing use of higher frequency sound waves due to reduced distances • indications: improved assessment of ovaries, first trimester development, and ectopic pregnancy

Hysterosalpingogram • performed by x-ray images of the pelvis after cannulation of the cervix and subsequent injection of opacifying agent • indications: useful for assessing pathology of the uterine cavity and fallopian tubes, evaluating uterine abnormalities (e.g. bicomuate uterus), or evaluation of fertility (absence of flosv from tubes to peritoneal cavity indicates obstruction )

Figure 24. Triphasic CT of a renal cell carcinoma: showing arterial enhancing right renal lesion with venous washout (shunting )

CT /MRI • indications: evaluating pelvic structures, especially those adjacent to the adnexa and uterus • invaluable for staging gynaecological malignancies and detecting recurrence Sonohysterogram • transcervical saline introduction into uterine cavity to provide enhanced endometrial visualization

duringTVUS examination • indications: abnormal uterine bleeding, uterine cavity abnormalities that are suspected or noted on TVUS (e.g. leiomyomas, polyps, synechiae ), congenital abnormalities of the uterine cavity, infertility, recurrent pregnancy loss • contraindications: pregnancy, pelvic infection Table 14. Typical and Atypical Findings on a Sonohysterogram Finding

Typical

Atypical

Polyps

A well-defined,homogeneous, polypoid lesion isoectioic to tte endometrium with preservation of the endometnal-myometrial interface

Cystic components, multiple polyps,broad base, hypoechogemciiy or heterogeneity

leiomyoma

Well -defined, broad- based, hypoechoic solid masses witb shadowing. Overlying layer of endometrium is echogenic and distorts the endometrial -myometrial

Pedunculalion or multilobulated surface

.

Figure 25. Retrograde urethrogram demonstrating stricture in the membranous urethra

interface

Hyperplasia and Cancer

Adhesions

Diffuse echogenic endometrial thickening without focal abnormality, although focal lesions can occur. Endometrial cancer is typically a diffuse process,but early cases can be focal and appear as a polypoid mass

Mobile, thin, echogenic bands that cut across the endometrial cavity

Figure 26. Transabdominal U /S: pregnancy, 18 wk fetus Thick, broad- based bands that can completely obliterate the endometrial cavity, as in Asherman's syndrome

Pregnancy should always be ruled out by (J- hCG before CT of a female pelvis (or any organ system ) is performed

Figure 27. Hysterosalpingogram: left hydrosalpinx

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MI19 Medical Imaging

o

Adrenal Mass • imaging modality: most often identified on CT scan as ‘incidentaloma,’ can also use CT/ MR1 to distinguish benign from malignant masses Table 15. Adrenal Mass Findings on CT and MRI Factors

Adrenocortical Adenoma

Adrenocortical Carcinoma

Pheochromocytoma

Metastasis

Diameter (CT )

Usually *3 cm

Usually >4 cm

Usually >3 cm

Variable around 2 cnt'y>)

Slow (0.5-1cm/yr)

Variable

Other Findings

Usually low density due to intracellular fal

Hetrosis calcifications. and hemorrhage

Hemorrhage

Occasionally hemorrhage

MRI on T 2 Weighted Imaging

Isointense in relation to liver

Hyperintense in relation

Markedly hyperintense in relation to Inter

Hyperinlense in relation to liver

Growth

50% at 10 min

tokver

-

• • • • •

cm/yr)

.

Modality Based on Neuropathology Presentation • Cognitive decline ~ CT • Cord compression - MRI • Decreased level of consciousness - CT • Fish bone/other swallowed foreign body - CT • Low back pain, radiculopathy - MRI • Multiple sclerosis - MRI • Neck infection CT • Orbital infection - CT • Rule out bleed - CT • Rule out aneurysm - CTA MRA

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Seizure CT Sinusitis - CT Stroke CT, MRI Trauma “ CT Weakness, systemically unwell CT -

Neuroradiology Skull Films • rarely performed, generally not indicated for non-penetrating head trauma • indications: screening for destructive bony lesions (e.g. metastases ), metabolic disease, skull anomalies, postoperative changes and confirmation of hardware placement, skeletal surveys, multiple

Figure 28. Epidural hematoma

myeloma CT • CT is often the first line modality for most neuropathology, even in situations where MRI would lead to better characterization • CT is frequently the initial study performed because of its speed, availability, and lower cost acute craniofacial trauma: CT is best for visualizing “ bone and blood;" use MR1 when CT fails to detect an abnormality despite strong clinical suspicion acute stroke: MRI ideal, CT most frequently used acute headache with focal neurologic signs suspected hemorrhage (epidural, subdural, subarachnoid, intraparenchymal )

suspected hydrocephalus

• vascular structures and areas of blood-brain barrier impairment are bright (e.g. hyperdense or enhancing ) with contrast injection • Danger signs on head CT: space-occupying process, hemorrhage, edema, mass effect, midline shift, uncal and tonsillar herniation, loss of grev- white matter differentiation, hydrocephalus Myelography

-

Figure 29. Subdural hematoma

• introduction of water soluble, low-osmotic contrast media into subarachnoid space via lumbar puncture followed by x ray • largely replaced by MRI or CT myelogram • indications: excellent study for disc herniation , traumatic nerve root avulsion, patients with contraindication to MRI, extensive hardware from spinal surgery that may create MRI artifacts

-

MRI

-

• indications: finer neuroanatomic definition, better grey - white matter differentiation ( especially 11 weighted series), better evaluation of edema extent ( better tumour detection ), allows evaluation of structures obscured by bony artifacts on CT ( posterior fossa structures), multiplanar imaging helpful '

Figure 30. Subarachnoid hemorrhage

in preoperative assessment

Cerebral Angiography/CT Angiography /MR Angiography • indications: evaluation of vascular lesions such as atherosclerotic disease, aneurisms, vascular malformations, arterial dissections • conventional DSA remains the gold standard for the assessment of neck and intracranial vessels; however, it is an invasive procedure requiring arterial ( typically femoral ) access and catheter manipulation, which confers risk of vessel injury (e.g. dissection, occlusion, vasospasm, emboli ) • MRA methods ( phase contrast, time of flight, gadolinium -enhanced ) and CTA are much less invasive without risk to intracranial or neck vessels • MRA and CTA are often used first for the assessment of suspected T1A, subarachnoid hemorrhage, vasospasm, or aneurysms

Figure 31. Intraparenchymal hemorrhage

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MI 20 Medical Imaging

T

*

m 4

In

'

v mm

§

'

Figure 32. Hydrocephalus: ventricular dilatation (may see periventricular low attenuation due to transependyma ICSF flow)

Table 16. Two Types of Hydrocephalus Type

Cause

Communicaling / Eitraventricular

Impaired CSF reabsorption with unobstructed flow in ventricular

system: imaging shows all ventricles dilated

-

Obstruction within the ventricular system (e.g. mass obstructing the aqueduct or loramen ol Monro) ; imaging shows dilatation ol ventricles

Non Communicating

pronimaltothe obstruction

Nuclear Medicine

• SPECT imaging using m'l'c-exametazime ( HMPAO) and "mTc -bicisate ( ECU) assesses cerebral

"

blood flosv, as radionuclides diffuse rapidly across the blood -brain barrier and become trapped within neurons at a magnitude proportional to cerebral blood flow • ISEDG PET imaging assesses cerebral metabolic activity • indications: differentiation of residual tumour vs. radiation necrosis; localization of epileptic seizure foci, and evaluation of atypical dementia

Figure 33. Sagittal (A) and coronal (B) views of the vertebrobasilar circulation (note the incidental basilar tip aneurysm)

Approach to Head Computed Tomography • think anatomically, work from superficial to deep • scan: confirm the time and imaging of the correct patient, whether contrast was used , patient alignment , and presence of artiifact • skin /soft tissue: examine the soft tissue superficial to the skull for thickening suggestive of hematoma or edema; also evaluate the ear, orbital contents (globe, fat, muscles), parotid glands, muscles of mastication ( masseter, temporalis, pterygoids), visualize pharynx • bone and airspace ( use the bone window): check calvarium , visualize mandible, visualize C spine ( usually Cl and maybe part of C 2 ) for fractures, absent bone, lytic/sclerotic lesions; inspect sinuses and mastoid air cells for fractures or opacity that may suggest fluid, pus, blood , or tumour; status of the orbital floor in cases of facial trauma ( coronal series best ) • dura and subdural space: crescent shaped hyperdensity in the subdural space suggests subdural

-

-

hematoma; lentiform hyperdensity in the epidural space suggests epidural hematoma; check symmetry of dural thickness, where increased thickness may suggest the presence of blood • parenchyma: asymmetry of the parenchyma suggests midline shift ; poor contrast between grey and white matter suggests possible infarction, tumour, edema, infection, or contusion; a hyperdensity in the parenchyma suggests an enhancing lesions, intracerebral hemorrhage, or calcification; if central grey matter nuclei (e.g. globus pallidus, putamen, internal capsule) are not visible, suspect infarct, tumour, or infection • ventricles/sulci/cisterns: examine position of ventricles for evidence of midline compression /shift; hyperdensities in the ventricles suggest ventricular/subdural hemorrhage; enlarged ventricles suggest hydrocephalus; obliteration of sulci may suggest presence of edema causing effacement, possible blood filling in the sulci, or tumour; cistern hyperdensities may suggest blood, pus, or tumour

%

Approach to the CT Head Some - Scan Sore " Skin / Soft Tissue Brains - Bone/Airspace Demonstrate - Dura 'Subdural space Pushed - Parenchyma Ventricles Ventrides/SulciiCistems

-

TIAs are not associated with radiological findings

Figure 34. Insular ribbon sign (arrow): hypodensity of insular cortex representing early sign of infarction

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w

Selected Pathology

DOx for Ring Enhancing Cerebral Lesion

•see Neurosurgery, NS11 for intracranial mass lesions see Neurosurgery. NS35 for head trauma and Plastic Surgery. PL31 for craniofacial injuries •see Emergency Medicine, ER9 for spinal trauma •see Neurosurgery. NS28 and Orthopaedic Surgery. OR 25 for degenerative spinal abnormalities

-

MAGIC DR Metastasis Abscess Glioblastoma multKoimc Infarction (subacute.’chronic) Contusion /hematoma Demyelinating disease (e g. MS) Radiation necrosis

Cerebrovascular Disease (see Neurosurgery. NS21)

• pathogenesis of stroke: see Neurology. N 51 • best imaging modality: MRI •initial imaging modality: Cl

Table 17. Temporal Findings of Infarction with CT and MRI Time from Stroke

CT

MRI

Onset Hyperacute (0 -24 h)

Acute ( 24 h-1wit)

Usually normal nitnn 6 h Edema (loss of grey - white mailer differentiation “insular ribbon sign*,effacement of sulci,mass effect) Hyperattenuating artery “ hyperdense MCA sign" representing intravascular Ihrombus/emboh may be seen in ischenac stroke Hyperattenuating acute blood surrounded by edema may be seen in hemorrhagic stroke

-

Hypermteisityon DWI within minutes of arterial occlusion due to restriction of water movement indicative of cytotoxic edema Hypointensity on ADC within minutes Hypennteisily on T 2 /FLAIR approi malely 6 h alter onset due loedema (loss ol grey white matter differentiation

-

.

effacement of sulci,mass effect)

Increasing edema (seen as hypoattenuakon) may result Continued kyperintensity on DWI Hypointensity on ADC reaches nadir at 3 -5 d and begins to in significant positive mass effect increase Continued hyper intensity on T 2/FUUB

Subacute (1-3 wk)

Resolution of edema leads to increased attenuation of Continued kyperintensity on DWI due to *12 shine through * infarcted area that may regain near -normal density and Intensity on ADC continues lo rise,pseudo - normalizes at 10 15 d.and then surpasses that of surrounding normal tissue mask stroke “ fogging phenomenon” Continued kyperintensity on T2. FlAllt

Chronic (>3 wk)

Encephalomalaea (parenchymal volume toss) appears as hypoatlenuationwith negative masseHect

Figure 35. CT image of early infarct hyperdense artery

Hyperintensity on DWI/12/FLAIR progressively decreases ADC intensity remains elevated

• carotid artery disease best imaging modality: Duplex ( Doppler U /S) • other modalities: MRA or CTA if carotid angioplasty or endarterectomy is under consideration (conventional angiography reserved for inadequate MRA or CTA) Multiple Sclerosis ( see Neurology. N55) • best imaging modality: MRI has high sensitivity in diagnosing MS (>90% ) but low specificity (71-74% ) • characteristic lesion locations: juxtacortical ( grey-white junction ), periventricular, infratentorial, and spinal cord • cerebral lesions typical of MS:

Figure 36. DWI of patient with right frontotemporal infarct

involvement of the brainstem , cerebellum , and corpus callosum refers to perivenular regions of demyelination that are seen to radiate outwards into the deep periventricular region » plaques usually hyperintense on T 2, and hypointense on T1 perivascular and interstitial edema may be prominent; enhances with gadolinium contrast when actively inflamed • spinal cord lesions typical of MS: little or no cord swelling less likely to enhance with gadolinium contrast incomplete involvement of the cord in cross-section (dorsolateral common ) “ Dawson 's fingers ”

CNS Infections

• meningitis pathogenesis: inflammation of the pia or arachnoid mater, most often secondary to hematogenous spread from infection or via direct seeding of organisms through areas not protected by the blood-brain barrier (choroid plexus or circumventricular organs) • pathogens include: S. pneumoniae, H . influenzae, N . meningitidis, L . monocytogenes • best imaging modality: MRI (T2 weighted / FLAlR)

-

• findings:

meningeal enhancement ( following the gyri /sulci and /or basal cisterns), hydrocephalus (communicating), cerebral swelling, subdural effusion

• a normal MRI does not rule out leptomeningitis

• herpes simplex encephalitis (see Infectious Diseases, 1D18) pathogenesis: inflammation of the brain parenchyma secondary to infection with herpes simplex virus, asymmetrically affects the limbic regions of the brain ( i.e. temporal lobes, orbitofrontal region, insula, and cingulate gyrus) best imaging modality: MRI ( l l - and 12-weighted )

Figure 37. T2-weighted FLAIR (A) sagittal (B) axial images of multiple sclerosis with periventricular "Dawson’s Fingers”

r

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findings:

acute (within 4-5 d): asymmetric high intensity' lesions on T2 MR1 in temporal and inferior

frontal lobes strongly suggestive CT may show hypodensity in temporal lobe and insula; rarely basal ganglia involvement long- term may show parenchymal loss to affected areas • DDx: infarct, tumour, status epilepticus, limbic encephalitis • cerebritis cerebral abscess » pathogenesis: an infection of the brain parenchyma (cerebritis) which can progress to a collection of pus (abscess), most frequently due to hematogenous spread of infectious organisms, commonly located in the distribution of the MCA pathogens include: S. aureus (often in IV drug users, nosocomial ), Streptococcus , Gram negative bacteria, Bacteroides best imaging modality: MRI including DWI imaging series (abscess will be DW1 positive); CT still used as a viable alternative findings according to one of four stages of abscess formation: early cerebritis ( 1 3 d ): inflammatory infiltrate with necrotic centre, low intensity on TI, high intensity on T2 late cerebritis (4-9 d ): ring enhancement may be present early capsule (10-13 d): ring enhancement late capsule ( >14 d ): well demarcated ring-enhancing lesion , low intensity core, with mass effect; considerable edema around the lesion , seen as hyperintensity on T2

-

Musculoskeletal System

Figure 38. T2- weighted (FLAIR) coronal image of herpes simplex virus encephalitis affecting temporal lobes

Characterization of totiiofCiff Tears: Ultrasoiid . Magnetic Resonance Imaging Orthopaedics M17;4tem-e13fl Purpose De:erm c » « •»••« U4 or MRI is more accurate and precise m nabatxg the characteristics of full-thickness rotator ci5 tears in a surgical

_

is

Modalities

pogolation.

•see Imaging Modalities, M12 for advantages and disadvantages of the following:

Plain Film/X-Ray

• usually initial study used in evaluation of bone and joint disorders

• indications: fractures and dislocations, arthritis, assessment of malunion or nonunion, orthopaedic

hardw are, and bone lesions (initial ) • minimum of two orthogonal views ( usually AP and lateral ) to rule out a ffacture/assess bone lesion • image the joint proximal and distal to injury site to ensure there is no associated dislocation or second fracture site, particularly important with bony rings (e.g. radius/ ulna, tibia/fibula ) •soft tissue assessment limited, but can identify joint effusions (elbow, knee), soft tissue gas (necrotizing fasciitis) and radiodense foreign bodies CT

• evaluation of fine bony detail • indications: preoperative assessment of complex, comminuted, intra -articular, or detection of radiographicallv-occult fractures including scaphoid , skull, spine, pelvis, midfoot , and calcaneus •evaluation of soft tissue calcification/ossification and bone tumours

-

Methods: Re aiew of 1H patients who underwent repair of a full-thickness rotator cuff tear cner a 1 jt period. Of these patents.(1 had both preoperatie MB and U /5 for renew. I wee radiologists eta bated each UJS and MRI m a randomned. blinded fashion oo 2 occasions, tear sic retract on status, muscle atrophy, and fatty mStratao were analyzed and rapa red between tte 2 sodalities. Results: 114 measuremects were statistically smaher e both tear size (M.00T) and retraction status (P 0.001) compared with Mil. MRI showed greater mterobserver reliability m assessment of tear sac retraction status, and atrophy. Conclusion: Independent oisemrs are more Uefy to agree on measurements of fie characteristics a rotator cuff tears when using Mil compared with 111 is tear size increases, the 2 si age modakties show greaser differences in measuredeotof tear we and retractor status. U rS sap be best used to identrfg a tear, and Mil is superior for use in surgical planning for larger fears.

-

MRI

• indications: evaluation of internal derangement of joints ( e.g. ligaments, joint capsule, menisci, labrum cartilage), assessment of tendons and muscle injuries, characterization and staging of soft tissue and bony masses, infection of bone (osteomyelitis), occult fracture assessment

.

Ultrasound

•indications: tendon injury (e.g. rotator cuff, Achilles tendon ), detection and characterization of soft tissue masses ( i.e. cystic or solid ), detection of foreign bodies, U /S guided biopsy and injections, bone/ joint evaluation pre ossification (e.g. DDH in early months), dynamic imaging ( i.e. snapping hip, extensor carpi ulnaris subluxation ), small joint doppler assessment for arthritis • Doppler determines vascularity of structures

-

-

Nuclear Medicine (Primarily Bone Scan/Skeletal Scintigraphy)

-

• determines the location and extent of bony lesions using radiopharmaceuticals (99mTc methylene diphosphonate ) •increased binding when increased blood supply to bone and /or high bone turnover (active osteoblasts) •indications: bone lesion characterization, occult fractures (spine, scaphoid, small bones), bone pain of unknown origin, staging or restaging of cancer with bony metastases (or primary bone cancer), imaging of polyarthritis, imaging of arthroplasty complications like loosening or infection, osteomyelitis imaging when used to assess for osteomyelitis, usually done in combination with gallium or white blood cell scan • DDx of positive bone scan: bone metastases ( primary breast, prostate, lung, thyroid ), primary bone tumour, arthritis, fracture, infection, anemia, Paget’s disease • caution: bone tumours that do not elicit osteoblastic response are often occult on bone scan ( myeloma, highly vascular tumours such as RCC, or thyroid carcinoma )

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MI23 Medical Imaging

Approach to Bone X- Rays • identification : name, MRN, age of patient, type of study, region of investigation

• soft tissues: swelling, calcification /ossification • joints: alignment, joint space, presence of effusion , osteophytes, erosions, bone density, overall pattern , symmetry of affected joint • bone: periosteum, cortex , medulla , trabeculae, density, articular surfaces, bone destruction, bone production , appearance of the edges or borders of any lesions Figure 39. X-ray findings of first carpometacarpal joint: normal image (left ) and osteoarthritis (right) with joint space narrowing and subchondral sclerosis

Trauma Fracture/Dislocation

• description of fractures

• site of fracture ( bone, region of bone, intra-articular vs. extra-articular) • pattern of fracture line (simple vs. comminuted ) • displacement (distal fragment with reference to the proximal fragment ) • soft tissue involvement (calcification, gas, foreign bodies) • type of fracture ( stress vs. pathologic ) • for specific fracture descriptions and characteristics of fractures, see Orthopaedic Surgery. OR5

Arthritis • see Rheumatology for radiographic features of specific arthritides

Bone and Soft Tissue Tumours Bone Tumours

• benign bone lesions (e.g. hemangiomas, enostoscs, enchondromas ) are more common than malignant bone lesions • primary bone tumours are rare after 3rd decade; metastases to bone are relatively common after 3rd decade • MRI is helpful for detection , characterization, staging, soft tissue involvement and surgical planning • plain film is important for assessing pattern of destruction , mineralization , and aggressiveness • biopsy may be required if no primary is identified , or suspect primary bone tumour

Figure 40. X- ray findings of rheumatoid arthritis (A) compared with osteoarthritis (B)

• may present with pathological fractures or bone pain • most common metastatic bone tumours: breast, prostate, lung • for specific bone tumours, see Orthopaedic Surgery, OR 50 Soft tissue Tumours • soft tissue masses are most commonly benign • common benign soft tissue masses include lipomas, benign peripheral nerve sheath tumours, and

vascular malformations • soft tissue sarcomas are uncommon but require urgent workup and specialized treatment • U /S is helpful for differentiating lipoma from cyst from mass • MRI is helpful for diagnostic workup • if the mass is not clearly benign, biopsy or wide excision is required for diagnosis Patterns olcortical disturbance

Margination of lesions

Punched it

9

ixpinsile

indosteal Thin rim of sclerosis

77 -

f' f

i • |I r ’fllayered '

-

lytic * decreased density Sclerotic Increased density

-

hodmans friangle

411 •

•

#

-

Moth eaten

iaucerization

Periosteal new bone formation

.

Permeative

scalloping nvisible nargin

Thick rim of sclerosis

Patterns of medullary destruction

fa

stimulated

8

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Figure 41. Radiographic appearance of bone remodelling and destruction processes

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MI24 Medical Imaging

Toronto Notes 2023

Table 18. Distinguishing Benign from Malignant Bone Lesions on X-Ray Benign

Malignant

No periosteal reaction or benign appearing reaction (e.g. uniform smooth periosteal thickening as seen in a healing fracture)

Acute periosteal reaction Codman’s triangle "Onion skin" "Sunburst"

--

Sharp, well-demarcated borders, narrow zone of Iransilion (between lesion and normal bone,suggesting slow -growing lesion)

(suggesting fast-growing lesion)

Well-developed bone formation

Varied bone for mabon

Intraosseous and even calcification

Eitraosseous and irregular calcification

No soft tissue mass

Soft tissue mass present

No cortical destruction or uniform cortical destruction in some low grade and locally aggressive benign lesions

Aggressive cortical destruction or tumour infiltration without cortical destruction

Poorly defined borders,with a wide tone of transition, or infiltrative

Adapted from:Suckhoftt RW.Heckman J D. Rockwood and Green's Fractures in Adults.Volume1Philadelphia: lippincott Williams & Wilkins. 2001. . .

Infection Osteomyelitis

• modern workup includes MRI or x-ray x-ray can detect osseous destruction seen with subacute osteomyelitis ( >1 week ) or chronic change, and can detect lucencies surrounding infected orthopedic hardware • MRI is more sensitive, with loss of normal fatty T1 marrow signal diagnostic of esteomyelitis, and can also assess for extra osseous soft tissue involvement or spread • nuclear medicine ( mic, followed by 1 In - labeled white cell scan or gallium radioisotope scan ) may be used where available, or in the setting of hardware

"

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“

Septic Arthritis

•surgical emergency in large joints ( i.e. hip) •x-ray usually normal early •aspiration required if concern for septic arthritis •imaging modalities can detect joint fluid in some points, but imaging cannot rule out septic arthritis Necrotizing Fasciitis •surgical emergency •X-ray can detect gas, but absence does not rule out necrotizing fasciitis •in the perineum, referred to as Fournier's gangrene

•surgical referral required

Metabolic Bone Disease Osteoporosis

• reduction in amount of normal bone mass; fewer and thinner trabeculae; diffuse process affecting all bones typical sites of fragility fracture: spine, hip, pelvis. wrist, humerus, rib • DEXA: gold standard for measuring bone mineral density, typically' measured hip and lumbar spine • CAROC guidelines for use of DEXA: diagnosis, determining fracture risk /therapy, and monitoring diagnosis driven by 'l'-score: the number of standard deviations from the young adult mean, most clinically valuable osteopenia: -2.5< T-score 30 yr need mammogram first • further characterization of manimographic findings • guidance for interventional procedures

-

Breast MRI

Description • contrast - enhanced MRI of the breasts • sensitive for detecting invasive breast cancer (95 100% ) but specificity variable ( 37 97%) • for diagnosis, used only after mammography and U /S investigation • use as a screening modality is limited to high risk patients, in conjunction with mammography

-

-

-

Indications

• “ problem -solving" of indeterminate findings following complete mammographic and U /S workup • evaluation of occult primary in patients presenting with axillary metastases • evaluation of patients with suspected silicone implant rupture and problems associated with breast implants • evaluation of previously diagnosed breast cancer: positive margins, recurrence, response to chemotherapy

ME JM 2019:381:2091- 2102 Purpose: Eitremely dense breast 1issue is a risk factor for breasUancer with poor mammography detection. Data is needed on the use ol supplemental Ml to unprone early detection and reduce Interval breast cancers in such patients. Methods NJ teenier RCT where 40313 women with eitremely dense breast tissue and normal mammography were assigned toa group undergoing supplemental MRI oi to a group that received mammography streaming only. Ihe primary Pulcome was the between -group difference in the incidence mterval cancers during a 2 yr screening penpd. Results: he interval - canter rate was 2.5 per 1000 screenuigs m t e Mil v talion group and 5.0 per 1000 screenings in the mammography -only gioup (P < 0.001). Ihe MRI cancel - detection rate among the women who actually underwent MRI screening was 16 5 per WOO screenings. Ihe positive predictive value was 12.4% (95% Cl.14.2 to 21.2) for recall lor additional testing and 26.3% (95% Cl 21.2 lo 31.61 lor biopsy. Ihe false positive rate was 29.8 per 1000 screenings. Conclusion: Ihe use of supplemental MRI screening - women with eitremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone.

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MI30 Medical Imaging

Toronto Notes 2023

• high - risk screening

•

known BRCAI or BRCA 2 mutation , or other gene predisposing to breast cancer, or untested first degree relative of a carrier of such a gene mutation family history consistent with a hereditary breast cancer syndrome and /or estimated personal lifetime cancer risk > 25% high risk marker on prior biopsy (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ ) radiation therapy to chest ( before age 30)

-

-

Breast Interventional Procedures Description

• includes core needle biopsy, stereotactic biopsy, MRl -guided biopsy, abscess drainage, and cyst aspiration

Indications

• cystic mass: complex cyst, symptomatic, suspected abscess • solid mass: confirm diagnosis of a lesion suspicious for malignancy ( BI-RADS* Category 4 or 5) • suspicious calcifications: confirm diagnosis of a lesion suspicious for malignancy ( BI-RADS’ Category 4 or 5) - stereotactic biopsy • initial percutaneous biopsy procedure that was insufficient or discordant with imaging • presurgical wire localization of a lesion

Breast Findings Breast Masses

• definition: a space-occupying lesion seen in two different projections; if seen in only a single projection it should be called an “asymmetry” until its three-dimensionality is confirmed Table 20. Mammographic Features of Benign and Malignant Breast Masses Shape

Benign

Malignant

Oval,round, lobular

Inegular

•

.

Margin

Circumscribed, well-defined

Density

Radiolucent (oil cyst lipoma, fibrolipoma galactocele hamartoma)

Radiodense

Calcifications (amass)

Popcorn (hyalinizing fibroadenoma),lucent centred (oil cyst/fal necrosis),layering (milk of calcium),vascular,round, scattered

Pleomorphic (vary in size and shape), amorphous (indistinct),linelinear, coarse heterogeneous,regional,segmental,clustered

.

Indistinct,microlobulated spiculated

.

.

tapactof UF- F06 PET PETIT, asd PET Hit si Staging aid Naugcant asai Initial Staging Hoda lit; ia Breast Caacet Ckt tdMad 2021:46(4)J7T-232 Pnpost! mintte ;ipact of 1SF-FD5 PEI.PEI ' CT.ad PETillHoastagagad saaageaeat dr - g ratal staging of tireast caoce. Methods: Studies ntict reported 5 e proportion of breast oncer patients ntose cttiicel stage ormenegeseot nere altered tg PEI scansnere incorporated into a raadoas-efetis model Results:42J6 petiats froa 29 strides nere metoded ia tte poo led raadom-eSects codel.Pooled prcportions of elterelioss ia stage was 2S4 (954 CL 2ft Pi 30%) ad ro maaageneot mas S4 (953,CL M41D 2R). Conclusions lisa rffif -fGGPET. PELUorPEI KB leads to signi&cant ctsaages in s ging and ^ managemeit for tarty dagnosed drees!cancer paterts.PET staid Pe considered for raatae clrical nse for mtei staging of Breast caicer

Other Findings

• tubular density/dilated duct: branching tubular structures usually represent enlarged ducts (milk ducts); if they are clearly identified as such, these densities are of little concern • intramammary lymph node: typical lymph nodes are well-circumscribed, reniform and often have a fatty notch and centre; usually < 1 cm, and usually seen in the outer, often upper part of the breast; when these characteristics ( particularly fatty centre or notch ) are well seen, the lesion is almost always benign and insignificant • focal asymmetry: area of breast density with similar shape on two views, but completely lacking borders and conspicuity of a true mass; must be carefully evaluated with focal compression to exclude findings of a true mass or architectural distortion • if focal compression shows mass -like character - or if the area can be palpated - biopsy generally recommended

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MI31 Medical Imaging

Toronto Notes 2023

Landmark Radiology Trials Trial Name

Reference

Clinical Trial Details

NEJM 1998; 338:409 - 416

Purpose; to study the efficacy and safety of vena cava! filters in preventing the formation of PEs in patients with proximal DVI. Methods: RCT consisting of 400 patients with proximal OVI who were random iced to receive heparin in conjunction with either a

VASCULAR PROCEDURES

PREPIC

.

caval filter or no filter Results: 2 patients with the treatment group and 9 patients within the contiol group had experienced a PE within 12 d 37 patients within the treatment groupand 21 patients within the control group experienced recurrent DVT within 2 yr. Conclusion: 8 enefrts of vena caval filters were counterbalanced by their risks.Filters resulted in no significant difference in mortality or other outcomes and although they prevented PE within 12 d they increased the risk of recurrent DVT within 2 yr.

.

*

.

EVAR

NEJM 2010;362:1863-1871

Purpose: To understand Lie long term implications of endovascular repair of abdominal aortic aneurysms. Methods: RCT consisting of 1252 patients with abdominal aortic aneurysms were randomized to undergo an endovascular or open repair. The outcomes of interest included mortality, graft - related complications, and re-mtervenbons Results: The 30 d postoperative mortality was lower in the endovascular repair group (1.8% vs 4.3%).However , due to graft ruptures, the mortality rates equilibrated over time. The rates of graft -related complications and re-interventions were higher in the group thatunderwent endovascular repair Conclusion: Mortality at 30 d post - operation was significantly lower for endovascular repair compared to open repair. At the end of follow -up ( 5-10 yr). there was no significant difference in mortality and rates of complication were higher in the endovascular treatment group.

.

.

.

KCT 03702413

N Engl J Med 2022;386:1303 1313

Title: Endovascular Therapy for Acute Stroke with a Large Ischemic Region Purpose: Endovascular therapy is often avoided for patients with large cerebrovascular infarctions,however the benefits of endovascular therapy in combination with stroke medical care hasnot been studied. Methods: RCT consisting of 203 patients with occlusion of large cerebral vessels and an Alberta Stroke Program Early Computed Tomographic Score between 3 -5 Patients were randomized to receive endovascular therapy in conjunction with medical care or medical care alone. The primary outcome is a modified Rankin score between 0 and 3.90 - d post-tteatmenl Results: A larger proportion of patients treated with endovascular therapy in conjunction with medical care achieved a modified Rankin score between 0 and 3 (31%) compared to medical care alone (12.7%). Conclusion: In patients with large cerebrovascular occlusions,treatment with endovascular therapy in conjunction with medical care resulted in improved functional outcomes when compared to treatment with medical care alone.

.

.

VASCULAR PROCEDURES

EVAR

N Engl J Med 2022: 386:923

»2

Title: Thyroidectomy without Radioiodine in Patients with Low - Risk Thyroid Cancer Purpose: To assess the clinical benefit of postoperabve rad oiodine. after thyroidectomy in low- risk thyroid cancer. Methods: RCT consisting of 730 patients with low -risk differentiated thyroid cancer undergoing thyroidectomy. Patients were

randomized to either receive or not receive radioiodine.The outcomes of interest were the presence of abnormal radioiodine foci, abnormal neck ultrasound,or presence of increased thyroglobulin/lhyroglobulin antibodies. Results: There was no significant difference in postoperative abnormalities between pabents that received (4.1%) and did not receive postoperabve radio!nine ( 4.4%). Conclusion: The use of radioiodine is negligible in theprevenban of post - thyroidectomy abnormalities.

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MI32 Medical Imaging

Toronto Notes 2023

References .

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Boden WE O'Rourke RA leo KK et at. Optimal medical therapy with or without PCIfor stable coronary disease NEJM 2007:356:1503 1516. Brant WE, Helms CA.Fundamentals of diagnostic radiology. 5th ed. Philadelphia: Lippincott Williams and Wilkins 2018 . Canadian Association ol Radiologists (CAR) standard lor breast imaging. Ottawa: Canadian Association oIRadiologists 2016. Canadian Association of Radiologists (CAR) standard lor performance of breast ultrasound examination.Ottawa: Canadian Association of Radiologists, 2016. Canadian Association of Radiologists (CAR) standards for the performance of ultrasound-guided percutaneous breast interventional procedures. Ottawa: Canadian Association of Radiologists. 2003. Chen MYM, Pope XL Ott DJ. Basic radiology. 2nd ed. Hew York: Lange Medical BookslMcGr aw Hill,2011. Daffner RH. Clinical radiology: the essentials. 4th ed. Baltimore: WilliamsiWilkins 2013 . D'Orsi CJ, Sickles EA Mendel son EB et al. ACR BI- RADS 1 Allas Breast Imaging Reporting and Data System. Reston VA American College of Radiology; 2013 Erkoncn WE Smith WL. Radiology 101. Philadelphia: Lippincotl WilliamsiWilkins 2005. Fleckcnslcin P, Iranun-Jensen J Anatomy in diagnostic imaging 2nd ed Copenhagen: Blackwell Publishing 2001. Gay S Woodcock Jr RJ Radiology recall 2nd ed Baltimore: Lippincotl Williams ( Wilkins 20007. Goldstein S. Saline infusion sonohysteiogiam. Rose BD (editor ) Waltham: UpToOate. 2012. Goodman LR felson's principles of chest roentgenology: a programmed text 3rd ed Philadelphia: Saunders Elsevier 2007. Herring W. Learning Radiology: Rccogmcing the Basics 4th ed. Philadelphia: Elsevier|lmpiml) Elseviei • Health Sciences Division 2019. Joffe SA Scrvaes S Okon S et al Multi- detector row Cl urography in the evaluation oi hematuria Radiogiaphics 2003:23:1441 1455. Juhl JH Crummy A 8 Kuhlman JE ( editors). 7th ed Paul and Juhl'sessentials of radiologic imaging. Philadelphia: lippincolt Raven 2005. Kate DS Malh KR, Groskin SA. Radiology secrets. Philadelphia: Hanley and Belfus 1998. MacMahon H Haidich DP Goo JM etal. Guidelines for Management of Incidental Pulmonary Nodules Detected on Cl Images: From the Fleischner Society 2017.Radiology 2017:284:228- 243. Mettler FA Jr Huda W Yoshicumi IT,etal. Effective doses in radiology and diagnosbc nuclear medicine: a catalog. Radiology 2008:248:254-263. Novelline RA. Squire's fundamentals of radiology 6th ed.Cambridge:Harvard University Press. 2004. Ouellette H letreault P.Dinical radiology made ridiculously simple.Miami: MedMaster 2002. Owen RJ. Hiremath S. Myers A.el al. Canadian Association of Radiologists consensus guidelines for the prevention of contrast induced nephropathy: update 2012.Can Assoc Radiol J 2014:65:96-105. Som PM Curtin HD. Head and neck imaging,3rd ed. St. Louis: Mosby.1996. Smith 0 L HeldtJP, Richards GO etal. Radiation exposure during continuous and pulsed fluoroscopy. J Endourol 2013;27(3):384 - 388. Warner E Messer smith H Causer P et al.Cancer Care Ontario' s Program in Evidence - based Care. Magnetic resonance imaging screening of women al high - risk foi breast cancer: a clinical practice guideline 2007 Warner E Messer smith H Causer P et al. Magnetic resonance imaging screening of women al high - risk for breast cancer: a clinical practice guideline. Program in Evidence Based Care. Cancer Care Ontario, 2007. Wcissledcr R Rieumont MJ Wittenberg J. Primer of diagnostic imaging 2nd ed. Philadelphia: Mosby 1997 Young WE. Clinical practice Ihc incidentally discovered adrenal mass NEJM 2007:356:601- 610

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Nephrology David Buchan and Huaqi Li , chapter editors Karolina Gaebe and Alyssa Li, associate editors Wei Lang Dai and Camilla Giovino, EBM editors Dr. Damien Noone, Dr. Gemini l'anna , and Dr. Alireza Zahirieh, staff editors Acronyms

NP2

Basic Anatomy Review. Embryology of the Kidney Renal Structure and Function Renal Hemodynamics

....NP2

Assessment of Renal Function Measurement of Renal Function Urinalysis Urine Microscopy Urine Biochemistry

NP5

Electrolyte Disorders Sodium Homeostasis Hyponatremia Hypernatremia Diabetes Insipidus Potassium Homeostasis Hypokalemia Hyperkalemia Hyperphosphatemia

NP8

Hypophosphatemia Hypermagnesemia Hypomagnesemia

..

Acid-Base Disorders Metabolic Acidosis Metabolic Alkalosis Polyuria

.

NP17

Acute Kidney Injury

NP20

Parenchymal Kidney Diseases Glomerular Diseases Glomerular Syndromes Tubulointerstitial Disease Vascular Diseases of the Kidney Analgesic Nephropathies

NP22

Systemic Disease with Renal Manifestation.

NP33

Diabetes Scleroderma Multiple Myeloma Malignancy Chronic Kidney Disease: Management of Complications of CKD

NP36

Hypertension Hypertensive Nephrosclerosis Renovascular Hypertension Renal Parenchymal Hypertension

NP37

Cystic Diseases of the Kidney Adult Polycystic Kidney Disease Autosomal Recessive Polycystic Kidney Disease Medullary Sponge Kidney

NP38

End Stage Renal Disease.

NP39

Presentation of End Stage Renal Disease Renal Replacement Therapy Dialysis

NP41

Renal Transplantation

.NP42

Common Medications

NP43

Landmark Nephrology Trials

References

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+ XP 1 Nephrology

Toronto Notes 2023

Activate Windows Go to Settings to activate Windows.

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NP2 Nephrology

Toronto Notes 2023

Acronyms angiotensin converting enzyme inhibitor ACR albumin to creatinine ratio antidiuretic hormone ADH AC anion gap AIN acute interstitial nephritis AKI acute kidney injury ANA antinuclear antibody angiotensin receptor blocker ARB acetylsalicylic acid ASA ASOT anti -streptolysin-0 titer acute tubular necrosis ATN AV atrioventricular arteriovenous malformation AVM c - ANCA cytoplasmic antineutrophil cytoplasmic antibody C4S culture and sensitivity congestive heart failure CHF CKD chronic kidney disease Cr creatinine CrCI creatinine clearance CV cardiovascular CVVHD continuous veno venous hemodialysis OSW 5% dextrose in water OCT distal convoluted tubule DDAVP 1 desamino 8- d-arginine ACEI

-

-

Dl

-

vasopressin diabetes insipidus

Pronephros DIC

DKA DM ECF

eGFR ESR ESRD FENa FF FSGS GBM

GFR GN KAART

HBV HCTZ HCV HPF HSP HTN

HUS IVP IOC MDRD

disseminated intravascular coagulation diabetic ketoacidosis diabetes mellitus extracellular fluid estimated glomerular filtration rate erythrocyte sedimentation rate end-stage renal disease fractional excretion of sodium filtration fraction focal segmental glomerulosclerosis glomerular basement membrane glomerular filtration rate glomerulonephritis highly active antiretroviral therapy hepatitis B virus hydrochlorothiazide hepatitis C virus high power field Henoch Schonlein purpura hypertension hemolytic uremic syndrome intravenous pyelogram level of consciousness modification of diet in renal disease

-

NS normal saline p- ANCA perinuclear anti- neutrophil cytoplasmic antibody proximal convoluted tubule PCT Pneumocystis jiroveci PJP pneumonia polycystic kidney disease PKO parathyroid hormone PTH R& M routine and microscopy RAAS renin angiotensin-aldosterone system renal blood flow RBF RCC renal cell carcinoma RPF renal plasma flow rapidly progressive RPGN glomerulonephritis renal replacement therapy RRT renal tubular acidosis RTA SI ADH syndrome of inappropriate antidiuretic hormone systemic lupus erythematosus SLE SLED sustained low efficiency dialysis TBW total body water TIN tubulointerstitial nephritis thrombotic thrombocytopenic TIP purpura UAG urine anion gap urinary tract infection UTI

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U Mesonephros Degenerating pronephros

Basic Anatomy Review Embryology of the Kidney • originates from

urogenital ridge of the intermediate mesoderm • pronephros develops at the end of tvk 3, then degenerates along with adjacent pronephric duct, disappearing completely by end of wk 4 • mesonephros develops caudal to the pronephros in wk 4 , degenerates, and the remnants form the mesonephric ( Wolffian ) duct of the male reproductive system • metanephros develops caudal to the mesonephros in wk 5 from the metanephric blastema and the ureteric bud of the mesonephric duct, forming the definitive kidney excretory system: metanephric blastema -» nephrons ( Le. glomeruli, Bowmans capsule, PCT, loop of Henle, OCT) collecting system: ureteric bud > collecting ducts, calyces, renal pelvis, ureters • kidneys ascend from the pelvis into the retroperitoneum , gaining a blood supply from the abdominal aorta to form the renal arteries

=CF V Metanephros

Degenerating mesonephros

Renal Structure and Function The Nephron

basic structural and functional unit of the kidney, approximately 1 million per kidney • 2 main components: glomerulus and attached renal tubule • direction of blood flow: afferent arteriole -» glomerular capillaries -> efferent arteriole -> vasa recta ( the •

capillaries surrounding the tubules) -> renal venules

Metanephric

^

,

{Ureteric bud

\ j\ ephric duct

rn L

Figure 1. Kidney embryology The pronephros and mesonephros develop then degenerate in succession. Ultimately, the definitive kidney develops from the metanephric blastema and ureteric bud of the mesonephric duct

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Toronto Notes 2023

NP3 Nephrology

Table 1. Major Kidney Functions Function

Mechanism

Affected Elements

1. Waste Excretion

Glomerular filtration

Excretion of nitrogenous products of protein metabolism ( urea Cr )

lubular secretion

Excretion of organic acids ( urate ) and organic bases (Cr )

Tubular catabolism

lubular NaCI and water reabsorplion

Breakdown and excretion ol drugs (antibiotics , diuretics) and peptide hormones ( most pituitary hormones, insulin , glucagon ) Controls volume status and osmolar balance

Tubular K ’secretion Tubular H Secretion

Acid - base balance

2. Electrolyte Balance and Osmoregulation

Controls potassium concentration

HCOrsynthesis and reabsorplion

Acid - base balance

TubularCaT . Mij', POP transport

Alters Ca 1\ Mg!\ POrHomeostasis

Osmolytc synthesis

Increase osmolality ol medullary cytoplasm to match medullary concentration gradient

Erythropoietin production (cortex )

Red blood cell production Calcium homeostasis

*

3. Hormonal Synthesis

.

Vitamin 0 activation: 25|OH|Vitamin 0 converted to 1.2S(0H ):Vitamin D (proximal tubule)

Renin production ( juxtaglomerular apparatus) 4. Blood Pressure Regulation

5. Glucose Homeostasis

Alters vascular resistance and aldosterone secretion

Na * excretion

Alters ECF volume

Renin production

Alters vascular resistance

Gluconeogenesis (Irom lactate, pyruvate, and amino acids)

Glucose supply maintained in prolonged starvation

Clearance and degradation ol circulating insulin

Maintains glucose homeostasis

The Glomerulus • site where blood constituents are filtered through to the kidney tubules for excretion or reabsorption • filtration occurs across the glomerular filtration barrier (endothelium, GBM, podoevtes) into

Bowman’s space • there is a filtration barrier to albumin due to its size and negative charge, which is repelled by the negatively - charged GBM • consists of following cell types:

I . mesangial cells structural function: support glomerular capillaries; can alter GI R through contractile activity • secretory function: matrix components, pro - and anti -inflammatory cytokines, and chemokines secretions are responsible for minimizing the accumulation of macromolecules in the mesangial space and GBM 2. capillary endothelial cells part of the glomerular filtration barrier; help form the plasma filtration apparatus due to their fenestrated nature and glycocalyx; contribute to the production of the GBM interface with blood target for antibodies and contact site for neutrophils and lymphocytes 3. visceral cells ( podocytes) part of the glomerular filtration barrier; helps form the plasma filtration apparatus due to their interdigitated foot process forming slit diaphragms; contribute to the production of extracellular matrix proteins (collagen and laminin ) making up the GBM 4. parietal cells lines the interior of Bowmans capsule and contains a podocyte progenitor population 5. juxtaglomerular cells smooth muscle cells in lining of afferent arteriole; produce, store, and secrete renin

-

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Toronto Notes 2023

NPl Nephrology

Afferent arteriole

Renal Hemodynamic Parameters

-

RBF - 20 % olCO, U/mln RPF RBF'II Hct ) GFR 120 tnL /min in healtliy adult 199% ol this volume is reabsorbed) FF - GFR / RPF ( normally 20%)

-

--

-

Prostaglandins - dilation

NSAIOs constriction

Efferent arteriole

ACEI - dilation

Afferent arteriole

M.

Angiotensin II - constriction

Bowman's space

'

1

J

1

.

t

Proximal tubule

»

^

Juxtaglomerular cells A

•1» . , j

Efferent arteriole

-

Endothelium

2

Mesangial cell

8

%

Podocyte

( visceral epithelium)

S

Bowman's capsule

(parietal epithelium)

Figure 2. The glomerulus

The Renal Tubules • reabsorption and secretion occur between the renal tubules and vasa recta forming urine for excretion • each segment of the tubule selectively transports various solutes and water and is targeted by specific

diuretics

^

ang. II

NaVH'

exchange

Na ’/K

H’ Na '

o

—


decreased perfusion pressure > release of prostaglandin > afferent arteriolar dilation > increased Gl'- R ) tubuloglomerular feedback: changes in Na ' delivery to macula densa lead to changes in afferent arteriolar tone ( e.g . high Cil R > increased Na ' delivery > afferent constriction > decreased GFR ) filtration fraction • • percentage of RPF filtered across the glomeruli expressed as a ratio: IT' = GFR / RPF; normal = 0.2 or 20% • angiotensin If constricts renal efferent arterioles which increases IT, thereby maintaining Cil R • renin is released from juxtaglomerular apparatus in response to low Na ' delivery to the macula densa , which is an indicator of decreased RPF renin is an important enzyme in the RAAS pathway, that converts angiotensinogen to angiotensin 1

9 Glometular Filtration Rate

GFR XI

-

Kf|iP 6 (1)

ultrafillration coefficient

'

'

6P

hydrostatic pressure difference between glomerular capillaries

60

osmotic pressure difference between glomerular caplllatlcs and Bowman's space

6P - 411

net outward pressure

andBowman 'sspacc

'

'

'

Stimuli for Renin Release from Kidney: 1. Renal artery hypotension:1 in stretch of afferent arteriole 2. Sympathetic activation ( via juxtaglomerular cell Adrenergic receptors) 3. INa delivery to macula densa in OCT

Renin

Angiotensin II

Angiotensin I

Adrenal cortex

Stimulation of Na retention in the kidney

Aldosterone

Vasoconstriction

0-» o

1

t systemic blood

Via angiotensin II receptors

'Hypothalamus

t Fluid intake

Thirst

ADH release

Postorior pituitary g

volume and pressure

'

.

.

Angiotensin II Effects: 1. Vasoconstriction 2. T vascular smooth muscle growth 3. t Na * reabsorption 4. T aldosterone 5. T bicarbonate products

Angiotensinogen

Clincically relevant outcomes: 1. Net T total body water, sodium 2. t vascular tone

Considerable variation in GFR is observed based on age biological sex, ethnicity and BMI

————————— .

I

Aloxondro Ho 2022 aftor Francos Young 2005 Nicola Clough 2014

-

Figure 4 Renin-angiotensin aldosterone system

Assessment of Renal Function Measurement of Renal Function • most renal functions decline in parallel with a decrease in GFR • inulin clearance and iothalamate radiotracer are the gold standard for measuring GFR, but very rarely used clinically • clinically, GFR is estimated using serum creatinine concentration , [Cr], known as eGFR Cr filtered = Cr excreted (at steady state) Cr reasonably estimates GFR as it is freely filtered at the glomerulus with little tubular reabsorption

Crfiltered - Crexcreted [Cr]plasma x GFR [Cr]urine x urine flow rate ( mL/min ) GFR ~ Cr'urme x urine flow rate [Cr]plasma

-

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Toronto Notes 2023

XP6 Nephrology

however, Cr is a metabolite of creatine phosphate, and therefore increased muscle mass increases Cr production. Ihus, one needs to consider body mass, ethnicity, age, and biological sex when determining eGT'R there is also 10% to >50% tubular secretion of Cr, depending on renal function • newly discovered biomarkers such as Cystatin C, which are not affected by muscle mass, may provide more accurate eGFR values Ways to Estimate GFR Using Serum Creatinine Concentration 1. estimate GFR using CKD EP1 equation • the best current and most accurate equation

-

calculated using serum Cr, age, biological sex, and race overestimates Gl R, resulting in lower prevalence of CKD diagnoses when used instead of MDRD formula or Cockcroft Gault equation 2. measure CrCl 24 h urine collection calculation provides reasonable estimate of GFR Gl R /d = ( urine|Cr] x 24 h urine volume) /( plasma ( Cr ] ) must use same units for urine [ Cr ] and plasma [ Cr] 3. estimate GFR with new Cr and cystatin C based equations serum Cr and cystatin C values used with age and sex to estimate GFR (excludes the race variable ) • more accurate than CKD EPI with race omitted

-

-

-

-

-

At steady state [Cr]serum a 1/CrCI

-

CKD EPI Equation eGFR (ml/min/1.73 m*) 141 * minfSCr/n 1)a x max(SCr /K 1) 2 red cells per

4 WBCs per HPT • indicates inflammation or infection • if persistent sterile pyuria present (i.e. negative culture), consider: chronic urethritis, prostatitis, interstitial nephritis, calculi, allergic cystitis, interstitial cystitis, papillary necrosis, renal tuberculosis, viral infections, N. gonorrhoeae, C. trachomatis infection Eosinophils • detected using Wright’s or Hansel’s stain ( not affected by urine pH ) • consider AIN, atheroembolic disease n

Oval Fat Bodies • renal tubular cells filled with lipid droplets • seen in heavy proteinuria (e.g. nephrotic syndrome )

LJ

2. CASTS • cylindrical structures formed by intratubular precipitation of Tamm - Horsfall mucoprotein; cells may be trapped within the matrix of protein

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NP8 Nephrology

Toronto Notes 2023

Table 3. Interpretation of Casts Casts Hyaline Costs

Interpretation

Physiologic (concontialotl urine, lever, exercise)

RBC Costs

Glomerular bleeding (prolilerative GH, vasculitis)

WBC Casts

Inlection (pyelonephritis) Inflammation (interstitial nephritis)

Pigmented GranularCasts (heme granular casts, muddy brown)

AIN

Fatty Casts

Nephrotic syndrome (proteinuria >3.5 g/d)

Acute proliferative GN

3. CRYSTALS

• uric acid: consider acidic urine, hyperuricosuria, tumour lysis syndrome • calcium phosphate: alkaline urine • calcium oxalate: consider hyperoxaluria, ethylene glycol poisoning, nephrolithiasis • sulfur: sulfa-containing antibiotics

Urine Biochemistry • commonly measure: Na 1 , K\ C1-, osmolality, and pH • spot urine more useful to assess renal physiology, 24 h urine collection more reflective of mineral balance • no “ normal ” values; electrolyte excretion depends on intake and current physiological state • results must he interpreted in the context of a patient 's current state, for example: 1. ECF volume depletion: expect low urine ( Na* ) (kidneys should be retaining Na *) urine [ Na 1 ) >20 mmol / L suggests a renal problem or the action of a diuretic urine [ Na 1 j < 20 mmol / L suggests a prerenal problem 2. daily urinary potassium excretion rate should be decreased (3L • laboratory findings that may point to specific etiologies: hyperglycemia and /or glucosuria suggests osmotic diuresis secondary to uncontrolled diabetes mellitus hyponatremia may suggest free water intake secondary to polydipsia hypernatremia may suggest free water loss secondary to diabetes insipidus • check urine osmolality: Uimn < 100 mOsm / kg, consider causes of water diuresis ( Dl, psychogenic polydipsia ) Uoim 100 300 mOsm / kg, consider causes of mixed polyuria ( partial Dl , CKD) Uosm >300 mOsm / kg, consider causes of osmotic diuresis ( hyperglycemia, azotemia, excess solute intake) , P 12 for complete workup for diabetes • water deprivation test if suspected Dl, see Diabetes Insipidus,\ insipidus

-

Treatment

• specific to etiology

Acute Kidney Injury Definition

• abrupt decline in renal function leading to increased nitrogenous waste products normally excreted by the kidney • formerly known as acute renal failure Clinical Features • decreased G1;R • weight gain and edema • azotemia (increased BUN, Cr) • abnormal urine volume: formally 6 h but can manifest as anuria , oliguria, or

polyuria

The 2 most common causes of acute kidney injury in hospitalized patients are prercnal azotemia (decreased perfusion) and ATN; remember that prerenal failure can lead to ATN

Differentiating Prerenal from ATN

Prerenal

Table 10. Classification of Acute Kidney Injury CRITERIA

RIFLE

AKIN

KDIGO

Serum Creatinine

Increased 2- 3 times baseline

Increase of > 26.4 pmol / L or increase by > 50% within 48 h

Increase of s 26.4 pmol / l within 48 h or Increase by > 50% within 7 d

GfR

Decreased > 50%

N /A

H /A

Urine Output

12 h

6 h

«0.5 mL/kg /h for >6 h

Urine Microscopy

Normal

Unne|Na *|

< 20

Urine osmolality FENa Plasma|Ureaj/ |C«I lesponse

of Cr to fluid

ATH RBC. pigmented granular casts

>

500

Return to

baseline 1- 3 d

m £g/l 40

kgH 20 2% >1015

>

n

LJ

Persistent elevation

repletion

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Toronto Notes 2023

NP21 Nephrology

r (

Prerenal

AKI

)

[

)

T

Renal

]

T

T 1 Neurogenic

[ Hypovolemia ]

Disordered Autoregulation

•NSAIDs •ACEI/ARBs •Calcineurin inhibitors

T

Absolute

( cyclosporine, tacrolimus) •Hypercalcemia

•Hemorrhage

•Glloss •Skin loss

' Postrenal ( especially if solitary kidney ) ]

^

T Anatomic •Ureter •Bladder •Urethra

j

T Effective • Low cardiac output

• Cirrhosis

•Renal loss

T

i

Vascular

and orthostatic HR and BP changes, oliguria • Increased [urea] » Increased [Cr] • Urine [Ha *] 500 mOsrri Vg • Fractional excretion of Na * 2-3 % • Urine osmolality 250- 300 mOsm Vg

Figure 12 . Approach to AKI

Investigations • blood work: CBC, electrolytes, Cr, urea ( think prerenal if increase in urea is relatively greater than increase in Cr ), Ca 2 + , PO -P • urinalysis: albumin, hemoglobin, VVBCs, glucose, pH, urobilinogen , specific gravity • urine volume, C&S, R&M: sediment, casts, crystals • urinary indices: electrolytes, osmolality • urine chemistry: urine Na + and FENa • Foley catheterization (rule out bladder outlet obstruction ) • fluid challenge ( e.g. fluid bolus to rule out most prerenal causes ) • imaging: abdomen U /S (assess kidney size, hydronephrosis, postrenal obstruction ) • indications for renal biopsy • diagnosis is not certain • prerenal azotemia or ATN is unlikely • oliguria persists >2-4 d RPGN , signs of significant glomerular disease ( proteinuria, RBC casts) despite normal kidney size/echogenicity *

Treatment 1. preliminary measures

Taiag of lihfetioi cf Ren=l tepfeccaeit Therapy ii Acute Kidafj lajxry

EJM 2020353:240 -51 Firpose Sscdati: e s cst efetie fcn far | citistica of rega.'-repiaeiert tierapy n petets dt 111 win are cCxa#y B. Methods 1b t - ::- a tCTcrov - jtntica , patiati wti ill. Fcle fs were raatalf assgoed a receive c ecreteratid reg rea of reKhe?2cesKa; Serepy (n.tiead witoa 12:eftir igttij aterz »ere et) orcsi sd3rd stiitigj fn ltd recakeaacerert tteraj wes1sea raged s less rlcafc ns deve aced or ill »22 k(. be pr azrj octime was al-casse cortalty at 901 Results: 2427 of e» 3019 radonsed paterts were related j tie i»el piectioo-a -tiHtasalysa. Tte 90-day “ ortzlty was 433 cctbeacratratiil grajp aod 43JL n are steaded sratagy gi p|I8 LOO:95 !033 to 2.09. HI32L 4.-sag SO-dey sarrrors coaraaed referee oa recekealeceareat teray was 10.4L r tie acceleread jar aod S OL :tesaeadard yrmp ( 24 U t 95L 01243 2-43'). Jdietse eiera scared a 23.OL is tie accelerated goto and 163L w tie standard g rcp (M.001). Conclusion Aaxn) crocaly natertswith ac.te odrey iijiiy ao ecce ereted raial-repacereti ssargy was not assocated wta lower Eortatty risk ran standard staetegj atSOd. *

=-

,

=

=

-

.

.

« .

• prerenal correct prerenal factors: optimize volume status and cardiac performance using fluids that will stay in the plasma subcompartment ( NS, albumin, blood /plasma ), hold ACEI/ARB (gently rehydrate when needed, e.g. CHF ), and NSAIDs

• renal

address reversible renal causes: discontinue nephrotoxic drugs, treat infection, and optimize

electrolytes correct ECF volume, supportive care, consider corticosteroid or immunosuppressive therapy postrenal consider obstruction: structural (stones, strictures ) vs. functional ( neuropathy ) for obstruction to cause AKI, must have functional solitary kidney or obstruction affecting both kidneys treat with Foley catheter insertion , indwelling bladder catheter, nephrostomy, stenting 2. treat complications • fluid overload NaCl restriction high dose loop diuretics • electrolyte imbalances ( hyperkalemia, hyperphosphatemia, hypocalcemia , hypo/ hypermagnesemia, hyperuricemia ) • acid-base disturbances • adjust dosages of medications cleared by kidney ( e.g. amiodarone, digoxin, cyclosporine, tacrolimus, some antibiotics, and chemotherapeutic agents) • dialysis 3. definitive therapy depends on etiology

*

’

-

-

.

Avoid NSAIDs in patients with diarrhea, heart failure, or renal failure

Renal transplant is not a therapy for AKI

LJ

Drugs Implicated in Prerenal Azotemia • Diuretics

. .

NSAIDs ACEL ARBs

Prognosis • high morbidity and mortality in patients with sustained AKI and multi organ failure

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Parenchymal Kidney Diseases Glomerular Diseases HISTOLOGICAL TERMS OF GLOMERULAR CHANGES

Extent of Changes • histological terms describing the number of glomeruli affected in a given condition: diffuse: majority of glomeruli abnormal focal: some glomeruli abnormal • histological terms describing the extent to which individual glomeruli are affected in a given

condition global: entire glomerulus abnormal • segmental: only part of the glomerulus abnormal Types of Changes • proliferation : hyperplasia of one of the glomerular cell types ( mesangial, endothelial, parietal epithelial ), with or without inflammatory cell infiltration • crescent formation: parietal epithelial cell proliferation and mononuclear cell infiltration form crescent-shape in Bowman’s space ( hallmark of inflammatory glomerulonephritis) • membranous changes: capillary wall thickening due to immune deposits or alterations in basement

membrane CLINICAL FEATURES OF GLOMERULAR DISEASE

Important Points to Remember • glomerular diseases have diverse clinical features including hematuria , proteinuria , HTN , edema, and

decreased GFR • each glomerulopathy presents as one of four major glomerular syndromes (these are NOT

diagnoses)

1. asymptomatic urinary abnormalities proteinuria

-

- hematuria 2. nephritic syndrome

GN - acute rapidly progressive GN

-

3. nephrotic syndrome 4. ESRD • glomerulopathies can be caused by a primary disease or can occur secondary to a systemic disease • some glomerulopathies can present as more than one syndrome at different times The Nephritic-Nephrotic Spectrum • glomerular pathology can present with a clinical picture anywhere on a spectrum with pure nephritic (inflammation of glomeruli ) and pure nephrotic syndromes (abnormal glomerular permeability ) at

the extremes Nephrotic

Nephritic

Intermediate

Homaturia. i GFR

Proteinuria FSGS Membranous glomerulopathy Minimal change

Membranoproliterative GN

Diffuse proliferative GN Crescentic GN

Focal proliferative GN

• IgA nephropathy

• Idiopathic membranoproliferative GN • Hepatitis B, hepatitis C • SLE • Cryoglobulinemia Figure 13. Spectrum of glomerular pathology

Proteinuria • hallmark of nephrotic syndromes •composition of normal urine protein: albumin , lower molecular proteins (such as immunoglobulin light chain ), or proteins secreted by the tubular epithelial cells (e.g Tamm Horsfall mucoprotein ) • 24 h urine protein : gold standard to assess degree of proteinuria • upper limit of normal daily excretion of total protein is 150 mg / d daily excretion of albumin is 30 mg /d, albuminuria that persists for >3 mo • upper limit of normal is considered CK1) •spot / random urine ACR: used to screen for diabetic nephropathy and proteinuric renal disease

.

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NP23 Nephrology

Toronlo Notes 2023

• microalbuminuria: ACR >2.0 mg/mmol

• marker of vascular endothelial function • an important prognostic marker for CKD (see Diabetes Insipidus, NPI 2 ) • microalbuminuria is the earliest sign of diabetic nephropathy Pathologic Proteinuria

[ Protoinuria

)

Tubulointerstitial

• Normally low molecular weight

£

f

Physiologic

J

Pathologic

•Orthostatic

•Absence of proteinuria overnight •Usually resolves spontaneously

•Transient (exercise, fever, CHF)

I

*

Tubulointerstitial (impaired resorption) •0.5 g/d, casts, and /or hematuria) • CBC, glucose, electrolytes, 24 h urine protein and albumin, and Cr • urine and scrum Immunoelectrophoresis, abdominal/pelvic U/S • serology: ANA, RF, p- ANCA (MPO), c ANCA ( PR 3), C3, C 4, HBV, HCV, HIV, ASOT • consider urology consult and possible cystoscopy if not clearly a nephrologic source for hematuria or if >50 yr of age

-

LJ

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NP2I Nephrology

Glomerular Syndromes 1. ASYMPTOMATIC URINARY ABNORMALITIES

Clinical/ Lab Features • often have rapid decline in Gl R, anemia, elevated inflammatory markers, ECF volume replete, or

-

mildly overloaded • proteinuria (usually < 2 g/d ) and /or microscopic or macroscopic hematuria isolated proteinuria can be postural occasionally can signal beginning of more serious GN (e.g. I 'SGS, IgA nephropathy, amyloid, diabetic nephropathy )

-

hematuria with or without proteinuria IgA nephropathy ( Berger’s disease ): most common type of primary glomerular disease worldwide, frequently presents after viral upper respiratory tract infection (presents most frequently with gross hematuria ) more common in White and Asian papulations, and in the 2 nd and 3rd decades of life

may be associated with cirrhosis, HIV infection, celiac disease - mesangial deposition of IgA ( more dominant ) and C3 seen on immunofluorescence microscopy

-

potential treatment includes: RAAS blockers if proteinuria, steroids, and steroid sparing agents (azathioprine, cyclophosphamide, mycophenolate mofetil, and biologies such as rituximab) hereditary nephritis ( Alport Syndrome; Type IV collagen mutation ): X-linked nephritis often associated with sensorineural hearing loss; proteinuria < 2 g /d » thin basement membrane disease: usually autosomal dominant , without proteinuria; benign benign recurrent hematuria: hematuria associated with febrile illness, exercise, or immunization; a diagnosis of exclusion after other possibilities are ruled out 2. NEPHRITIC SYNDROME

[

£

j

Glomerulonephritis with Nephritic Features

1

£

1

Anti-GBM Mediated ( RPGN Type I) (15%)

Immune Complex Mediated (RPGN Type II)|24%)

Non-lmmune Mediated (RPGN Type III) 160%)

Double Antibody Positive Disease (RPGN Type IV)

Linear IF pattern due to IgG and C3 deposition along capillary loops

Granular pattern due to subendothelial or subepithelial deposits of IgG and C3

Pauci-immune: no immune staining

• Has features of Type I and Type III • Double antibody positive

[

*

)

]

C3 normal

With lung hemorrhage

Without lung

• IgA nephropathy • Henoch-Schonlein

I

V

anti - GBM »ve

.

T

• Goodpasture's disease

hemorrhage

purpura

• Anti-GBM disease

c

j

[

Decreased C3

i

• Membranoproliferative L- : . • SLE • Infective endocarditis • Post-infectious GN

ANCA tve

T

(

• Cryoglobulinemia

c -ANCA tve

1 • Granulomatosis with

polyangiitis

](

J I p-ANCAtve

]

• Churg-Strauss • Microscopic polyangiitis

Figure 15. Approach to nephritic syndrome

ACUTE NEPHRITIC SYNDROME

• a subset of nephritic syndrome in which the clinical course occurs over days • etiology can he divided into low and normal complement levels

• frequently immune - mediated , with lg and G3 deposits found in GBM ; but may be pauci - immune and caused by an ANCA vasculitis Clinical/ Lab Features proteinuria ( less than range for nephrotic syndrome, 0 X1. s e saderes:

ir

- -

aalps.proitCTni. jrj fitetioa saj tin rdej«ditl sredttia abitj for dselMttrre 3 "arajj of fcposseptrCs bet stti & Of rteireSed o Ctasgn u . > :q cal Ss3 (att - OU. SfrraC3) tiif taae iSiity Sofict reswssa totratsart 3rd aaj Oe aad oofj as

-

*

Stooteifoal cforaatiw. IirUunI lipatiMfaaiaantftrairre :33 teotntis. g.CKO'C:- Is cosO^atw att “asoswas-n agerts are eifecn aga«st orogtsso:& erd-stega rere: disease.losg-

-

Sra efS cacj las Oee a 4ero s‘raS4 oo y for

cjdopiosjtaride-Sased reg-eis.«tkt are associated a? cossderaMe adia-se effects,ia start- a -d red ara-tero trials,ojtsateoaiate notes Las derodstated a:leas:sis SareScacj CK:oared tnis pulse cycle gtsgtaarfeaal‘as a nore teraraSle toucij proile.If fafaa to respond 4y 6 EO cossder iHesf)lag“erapjL Flares foUonsg reassert are sot t co~ o a-d reg;re d gertteico-do. End -Stage leaal Disease: ajvs and trass? la tatoc a Sl£ taia teeg-tera xtrert a:d graft-sama ares corpara:le mti aose odseried -:o:-d aietc roa-SlE patrerts. T arsoartet o s SeDeSodofcSoice.

-

-

Systemic Lupus Erythematosus • see Rheumatology. RH 11 • lupus nephritis can present as any of the glomerular syndromes • nephrotic syndrome with an active sediment is most common presentation • GN caused by immune complex deposition in capillary loops and mesangium with resulting renal

-

>

-

-

-

injury • serum complement, ANA, anti- DNA levels are usually low during periods of active renal disease • children and males with SLE are more likely to develop nephritis

SLE Classification

1 Class I

M pre

Minimal

mesangial lupus nephritis

L

Lie : ,I I

Class II

i

i

Focal

gial

ive

:

i

Membranous

: ns vi

i

lupus nephritis

lupus nephritis

lupus nephritis

.

Treatment

Treatment

.

Treatment

Treatment

I

I Class I and II do not need treatment directed at renal lesions

i

Diffuse

Dm

Advanced sclerotic lupus nephritis

lupus nephritis

Treatment

Class IV

Lowest possible dose of steroids and observation

i

Steroids + cytotoxic drugs ( consider dialysis or renal transplant with severe disease )

1

Steroids ( controversial )

i

ESRD

planning

Prognosis Renal survival 85% at 10 years with early initiation of therapy Dialysis often ameliorates other symptoms of SLE

Figure 16. International Society of Nephrology /Renal Pathology Society classification of lupus nephritis 2003

IgA Vasculitis (Henoch-Schonlein Purpura ) • Systemic IgA vasculitis, tissue deposition of IgAl -dominant immune complexes affecting mostly

small vessels • seen more commonly in children

• purpura on buttocks and legs, abdominal pain , arthralgia, and fever • IgA and G3 staining of mesangium • usually benign , self limiting course, 10% progress to CKD

-

+

ANCA- Associated Vasculitis • c ANCA most commonly associated with the clinical picture of granulomatosis with polvangiitis • p ANGA most commonly associated with the clinical picture of microscopic polvangiitis • focal segmental necrotizing RPGN with no immune staining

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XP27 Nephrology

• may be indolent or fulminant in progression

• vasculitis and granulomas rarely seen on renal biopsy • treatment typically involves cyclophosphamide and prednisone Cryoglobulinemic Vasculitis

• cryoglobulins: monoclonal IgM and polyclonal lgG which precipitate at reduced temperatures, deposit in walls of small vessels

• presents as purpura , fever, Raynaud’s phenomenon, and arthralgias • at least 50% of patients have HCV • renal disease seen in 40% of patients ( isolated proteinuria / hematuria progressing to nephritic

syndrome ) • most patients have decreased serum complement (C 4 initially) • treat HVC, plasmapheresis • overall prognosis: 75% renal recovery Shunt Nephritis

• immune - complex mediated nephritis associated with chronically infected ventriculoatrial shunts inserted for treatment of hydrocephalus • commonly caused by S', cpidermidis

.

• presents as acute nephritic syndrome with decreased serum complement

• nephrotic range proteinuria in 25% of patients • treat by removing shunt and administering appropriate antibiotics; can consider a ventriculoperitoneal shunt

HIV-Associated Renal Disease 1. direct nephrotoxic effect of HIV infection, anti-retroviral drugs (e.g. tenofovir, indinavir ), and other drugs used to treat HIV-associated infections 2. HIV-associated nephropathy histology: focal and segmental glomerular collapse with mesangial sclerosis; “collapsing FSGS”

tubular cystic dilation and tubulo- reticular inclusions

• clinical features: predominant in African American men, heavy proteinuria, progressive renal insufficiency ( Apo - L- 1 risk genotypes ) • prognosis: kidney failure within 1 yr without treatment • therapy: short term , high dose steroids, ACEI, H A ART

-

Infective Endocarditis

• manifests as mild form of acute nephritic syndrome with decreased serum complement • S. aureus is most common infecting agent • treatment with appropriate antibiotics usually resolves GN Hepatitis B • can result in membranous nephropathy, membranoproliferative GN, and polyarteritis nodosa Hepatitis C

• can result in membranous nephropathy, membranoproliferative GN , and cryoglobulinemia Syphilis

• can result in membranous GN

Tubulointerstitial Disease

IgA nephropathy is the most common type of primary glomerular disease worldwide

TUBULOINTERSTITIAL NEPHRITIS

Definition

• cellular infiltrates affecting primarily the renal interstitium and tubular cells • functional tubule defects are disproportionately greater than the decrease in GFR • classified as acute or chronic Signs and Symptoms • manifestation of disease depends on site of tubule affected 1. proximal tubule (e.g. multiple myeloma, heavy metals) Fanconi syndrome: decreased reabsorption in proximal tubule causing glycosuria, aminoaciduria, phosphaturia , and hyperuricosuria proximal RTA (decreased bicarbonate absorption ): Type II RTA 2 distal tubule (e g. amyloidosis, obstruction ) distal RTA (decreased hydrogen secretion , usually hypokalemic ): Type 1 RTA

.

Features of Nephritic Syndrome PHAROH Proteinuria Hematuria Azotemia RBC casts Oliguria HTN

rt LJ

.

Na ' - wastingnephropathy ± hyperkalemia leading to Type IV RT A (where reduced renal bicarbonate production is

caused by hyperkalemia )

Presentation of Nephrotic Syndrome HELP Hypoalbuminemia Edema Lipid abnormalities

+

Proteinuria

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NP28 Nephrology 3. collecting duct (e.g. sickle cell anemia, analgesics, primary ciliary dyskinesia ) urinary concentrating defect leading to mild nephrogenic D1

polyuria 1. ACUTE TUBULOINTERSTITIAL NEPHRITIS

Definition

• rapid (d to wk ) decline in renal function • 10 -20% of all AK1 Etiology

• hypersensitivity

1. antibiotics: p lactams, sulfonamides, rifampin , quinolones, cephalosporins, fluoroquinolones 2. other: NSAIDs, allopurinol, furosemide, thiazides, triamterene, PPls, acyclovir, phenytoin, cimetidine • infections bacterial pyelonephritis, Streptococcus , brucellosis, Legionella , CM V, LBV, toxoplasmosis, leptospirosis, HIV, Mycoplasma

-

• immune

• SLIi, acute allograft rejection, Sjogren 's syndrome, sarcoidosis, mixed essential cryoglobulinemia ( renal ocular syndrome acute TIN plus uveitis) idiopathic •

-

-

Pathophysiology

• acute inflammatory cell infiltrates into renal interstitium Clinical Features

• AKI • if hypersensitivity reaction (common with antibiotics): may see fever, eosinophilia , skin rash , arthralgia, scrum sickness like syndrome ( particularly rifampin ) • if pyelonephritis: Hank pain and costovertebral angle tenderness • if drug reaction, AKI usually occurs 7 10 d alter exposure • other signs and symptoms based on underlying etiology • HTN and edema are uncommon

-

-

Findings

• urine

-

mild, non nephrotic range proteinuria and microscopic hematuria sterile pyuria, WBC casts eosinophils if AIN • blood work increased Cr and urea eosinophilia if drug reaction ( high negative predictive value, common in (1-lactam reactions) normal AG metabolic acidosis (RTA) hypophosphatemia, hypo- OR hyperkalemia, hyponatremia • gallium scan often shows intense signal due to inflammatory infiltrate • renal biopsy definitive - shows interstitial infiltrates and edema on biopsy Treatment

• treat underlying cause (e.g. stop offending medications, treat infection with antibiotics if present i.e. pyelonephritis) • corticosteroids ( maybe indicated in allergic or immune disease) Prognosis

• recovery within 2 wk if underlying insult can be eliminated • the longer the patient is in renal failure, the less likely they will have a full renal recovery 2. CHRONIC TUBULOINTERSTITIAL NEPHRITIS

Definition

• characterized by slowly progressive renal failure, moderate proteinuria, and signs of abnormal tubule function Etiology • persistence or progression of acute TIN may also involve concurrent glomerular manifestations • urinary tract obstruction: most important cause of chronic TIN ( tumours, stones, bladder outlet obstruction, vesicoureteral reflux ) • chronic pyelonephritis due to vesicoureteral reflux or UT1 with obstruction

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• nephrotoxins

exogenous analgesics: NSAIDs ( common ), acetaminophen cisplatin, lithium, cyclosporine, tacrolimus

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XP29 Nephrology

Toronto Notes 2023

heavy metals ( lead , cadmium , copper, lithium , mercury, arsenic) Chinese herbs (aristolochic acid ) endogenous hypercalcemia, hypokalemia, oxalate, uric acid • vascular disease: ischemic nephrosclerosis, atheroembolic disease • malignancies: multiple myeloma , lymphoma • granulomatous: TB, sarcoidosis, granulomatosis with polyangiitis • immune: SLE, Sjogren’s, cryoglobulinemia, anti GBM disease, amyloidosis, renal graft rejection, vasculitis • hereditary: cystic diseases of the kidney, sickle cell disease • others: radiation , Balkan (endemic) nephropathy

-

Pathophysiology • fibrosis of interstitium with atrophy of tubules , mononuclear cell inflammation

Signs and Symptoms • dependent on underlying etiology Findings • non AG metabolic acidosis • hyperkalemia ( out of proportion to degree of renal insufficiency ) • polyuria , nocturia • partial or complete l anconi ’s syndrome

-

'

• progressive renal failure with azotemia and uremia • urine: mild proteinuria , few RBCs and WBCs, no BBC casts • U / S: shrunken kidneys with irregular contours (differentiates acute from chronic etiology )

Treatment • stop offending agent or treat underlying disease l ' • supportive measures: correct metabolic disorders ( ( . a 2 ' , H() i ) and anemia 3. ACUTE TUBULAR NECROSIS

Definition • abrupt and sustained decline in (il -' R within minutes to days after ischemic / nephrotoxic insult • ( il R reduced ( this serves the purpose of avoiding life - threatening urinary loss of fluid and electrolytes from non - functioning tubules ) '

Etiology

( Acuto Tubular Necrosis") Toxins

Exogenous

£

• Antibiotics

- Aminoglycosides - Cephalosporins - Amphotericin B

• Antiviral (cidofovir) • Antineoplastics

- Cisplatin

- Methotrexate

• Contrast media • Heavy metals

• Ollier

- Huorinated anesthetic - Ethylene glycol

Ischemia

r Decreased Circulating Volume • Hemorrhage including post- surgical • Skin losses * Gllosses * Renal losses 1

Endogenous

• Endotoxins ( bacterial)

• Myoglobin

• Hemoglobin

• Tumour lysis syndrome • Multiple myeloma

Decreased Effective Circulating Volume

• Heart failure • Liver failure

tllKtivcncss of Pinentioo Strategies for Contrast - Induced Hepfiropatby : A Systematic Review and Meta - Analysis Arm Intern Med 20K:164f 6|:406 416 -

Purpose ro evaluate the comparative eftectiveness of interventions to reduce contrast -induced nephropathy n adults receiving contrast media . Methods Heta - a-natysisofRCIsHacety tysteme. sodium bicarbonate, statins, or ascorbic ltd that used IV or intra - arterial contrast media. Results: tow dose A acetyicjsteme IY saline «. l saline 1#» 0.15. 9S % C10.630.SS) M - acetylcysteine IV saline is IV saline (RR 0.69. 95% Cl 0.58 0.84). Stall ns M -acetytcysteiae IV sa me is. N acetytcysteine IV saline ( ItIt 0.52.95% Cl 0.29-0.93). Clinically Important. Out not statistcally significant , reductions were observed m sodium bicarbonate is. IV sal me stabns IV saline is. N saline, and ascorbic acid « IV saline. Conclusions: Greatest red action in contrast -induced nephropathy was seen with H -acetylcystwne pus IV saline andstatins plus N -acetylcysteme plus IV saline.

*

-

-

--

.

-

-

• Sepsis • Anaphylaxis

Vessel Occlusion

• Large or small renal artery involvement

Figure 17. Etiology of ATN

Clinical Features typically presents as an abrupt rise in urea and Cr after a hypotensive episode, sepsis, rhabdomyolysis, or administration of nephrotoxic drug • pre- renal AKI can eventually progress to ATN consists of three phases: oliguric: decreased urinary output from renal damage, azotemia, and uremia; lasts 10-14 d diuretic: urinary’ output >500 rnL /day (result of retained water, salt, and solutes during oliguric phase ) and tubular cell damage recovery: tubular function recovers

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NP30 Nephrology

Toronto Notes 2023

• physical exam may show signs of true or effective ECE volume depletion • most common cause of non-prerenal AK1 in hospitalized patients • urine: high l ENa (>2%), pigmented-granular casts

-

'

Risk Factors

-

• pre - existing CKD, pre existing cardiovascular disease, ECE volume depletion, multiple renal insults

Complications

• hyperkalemia: can occur rapidly and cause serious arrhythmias

increased P04 J , hypoalbuminemia

• metabolic acidosis, decreased Ca

“

Investigations

•blood work: CBC, electrolytes, Cr, urea, Cat + , PO4 J -, blood gasses • urine: R& M, electrolytes, osmolality, microscopic urinalysis searching for heme granular / muddy brown casts • ECU ( monitor for arrhythmias due to hyperkalemia ) •abdominal U /S • rule out other causes of prerenalfpostrenal azotemia and intrinsic AK1 (GN , AIN, vasculitis) • IV fluid challenge will not increase urine output or normalize serum creatinine in ATN, helps to differentiate ATN from pre- renal AK1 • if diagnosis is uncertain, biopsy Treatment

•largely supportive once underlying problem is corrected •consideration for early dialysis in scvere/ rapidly progressing cases to prevent uremic syndrome ( the

-

STARRT AK1 study addressing this is ongoing )

Prevention •correct fluid balance before surgical procedures •for patients with chronic renal disease requiring radiographic contrast: • isotonic saline

avoid giving diuretics, NSAIDS, ACE1, cyclosporine on morning of procedure if possible adjusted doses of nephrotoxic drugs in patients with renal insufficiency renal use • • use low dose non ionic, iso or low osmolal contrast agents

-

-

-

-

Vascular Diseases of the Kidney LARGE VESSEL DISEASE

Table 13. Summary of Vascular Diseases Large Vessel Disease Acute renal artery occlusion (infarct) Renal artery stenosis (ischemia ) Renal vein thrombosis

Medium Vessel Disease Kawasaki disease

Small Vessel Disease Hypertensive nephrosclerosis

Polyarteritis nodosa ANCAassociated vasculitis

Atherocmbolic renal disease thrombotic microangiopathy Scleroderma

Calcineurin inhibitor nephropathy HUS ANCA - associated vasculitis

1. RENAL INFARCTION ( ACUTE RENAL ARTERY OCCLUSION)

• important, potentially reversible cause of renal failure Etiology • abdominal trauma, surgery, embolism, vasculitis, extrarenal compression, hypercoagulable state, aortic dissection • kidney transplant recipients more vulnerable

Signs and Symptoms ( depend on presence of collateral circulation) • fever, N / V, Hank pain • leukocytosis, elevated AST, ALP • marked elevated LDH ( LDH > 4 x upper limit of normal with minimal elevations in AST/ALT strongly suggestive) • acute onset HT'N (activation of RAAS) or sudden worsening of long-standing HTN • renal dysfunction , e.g. elevated Cr ( if bilateral, or solitary functioning kidney)

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Investigations

• renal arteriography ( more reliable but risk of atheroembolic renal disease)

-

• contrast enhanced CT or MR angiography, duplex Doppler studies (operator dependent )

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Treatment

• prompt localization of occlusion and restoration of blood flow • anticoagulation , thrombolysis, percutaneous angioplasty or clot extraction , surgical thrombectomy • medical therapy in the long term to reduce risk (e.g. antihypertensives )

-

2. ISCHEMIC RENAL DISEASE (RENAL ARTERY STENOSIS) • chronic renal impairment secondary to hemodynamically significant renal artery stenosis or microvascular disease • significant cause of ESRD: 15% in patients > 50 yr ( higher prevalence if significant vascular disease) • usually associated with large vessel disease elsewhere • causes of renal artery stenosis atherosclerotic plaques (90%): proximal 1 / 3 renal artery, usually males > 55 yr, smokers fibromuscular dysplasia (1096): distal 2/3 renal artery or segmental branches, usually young females (typical onset 50 yrwithCKD|GFR 3 mo, with either GIR 90

1 it CKD

1

2

G2

lit CKO

1

1

G 3b

60 89 45 - 59 30 44

2 3 3

G4

15 29

3

2 3 3

G5

50 yr) seizures, accounting for 50 80% of cases

-

inherited cause

• epilepsy: disorder of the brain characterized by an enduring predisposition to generate epileptic seizures , and by the neurobiologic , cognitive, psychological , and social consequences of this condition diagnosis of epilepsy requires: 1 . at least two unprovoked seizures occurring more than 24 h apart 2. one unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) of two unprovoked seizures, occurring over the next 10 yr 3. diagnosis of an epilepsy syndrome etiologies: genetic; structural (e.g. prior stroke, tumour, meningo/encephalitis, perinatal insult,

vascular malformation, malformation of cortical development , neurodegenerative); or unknown Classification Seizure

I

'

Unknown Onset*

Generalized Onset

Focal Onset

I

A .v = re In p = rej A.' -. d ’ e =:;

.

’ Uni

i

Nonmotor

i

I

Hyperkinetic Myoclonic

Sensory

Autonomic Behaviour arrest Atonic Cognitive Clonic Epileptic spasms Emotional Automatisms

Uni- lateral

Focal tonic clonic

Tonic

Motor

-

l

Tonic clonic Clonic Tonic

i

Nonmotor ( absence)

1

Typical Atypical Myoclonic Myoclonic Eyelid Myclonic-tonic -clonic Myoclonia Myoclonic-atonic Atonic Epileptic spasms

1

MOW

-

Seizures and Dementia Neurodegenerative diseases can underlie seizures. Conversely, seizures can be a cause of dementia

Nonmotor Unclassified -

I

i

Tonic clonic Behaviour ariest Epileptic spasms

'Unknown Onset may be reclassified into focal or generalized onset with further information or future observed seizures I Unclassified comprises both seizures with patterns that do not fit other categories or lack information

Figure 16. International League Against Epilepsy ( ILAE ) 2017 seizure classification

Clinical Features • focal ( partial ) seizures

focal can secondarily generalize or remain focal focal without impaired awareness ( i.e. “simple partial seizures") 4 focal with impaired awareness (i.e. “complex partial seizures”) 4 secondarily generalized seizures focal aware ( formerly simple partial ) motor: dystonic posturing, clonic movements, forceful turning of eyes and /or head, focal muscle rigidity/jerking ± Jacksonian march (spreading to adjacent muscle groups ) sensory: unusual sensations affecting vision , hearing, smell , taste or touch » autonomic: epigastric discomfort , pallor, sweating , flushing, piloerection , pupillary dilatation • focal impaired awareness ( formerly complex partial ) patient may appear to be awake but with impairment of awareness classic complex seizure is characterized by automatisms such as chewing , swallowing, lipsmacking, scratching, fumbling, running , disrobing, and other stereotypic movements other forms: dysphasic, dysmnesic (deja vu ), cognitive (disorientation of time sense ), affective (fear, anger) , illusions, structured hallucinations ( music, scenes, taste, smells ), epigastric fullness

Temporal lobe seizures are suggested by an aura of fear, olfactory or gustatory hallucinations, and visceral or deja vu

sensations Frontoparietal cortex seizures are suggested by contralateral focal sensory or motor phenomena

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X 19 Neurology

Toronto Notes 2023

• generalized seizures absence ( petit mal ): usually seen in children, unresponsive for 5-10 s with arrest of activity, staring, blinking or eye- rolling, no post-ictal confusion; 3 Hz spike and slow wave activity on EEG • donic: whole body repetitive rhythmic jerking movements • tonic : whole body muscle rigidity in flexion or extension • tonic- clonic (grand mal ) • may have prodrome of unease or irritability hours to days before tonic ictal phase: muscle rigidity clonic ictal phase: repetitive violent jerking of face and limbs, tongue biting, cyanosis, frothing, incontinence • post-ictal phase: flaccid limbs, extensor plantar reflexes, headache, confusion, aching muscles, sore tongue, amnesia, elevated serum CK lasting hours, may have focal paralysis ( Todd’s paralysis) • myoclonic: sporadic contractions localized to muscle groups of one or more extremities • atonic: loss of muscle tone leading to drop attack Table 12. Classic Factors Differentiating Seizure, Syncope and Pseudoseizure Characteristic

Seizure

Syncope

Pseudoseizure*

-

AntiepBeptic Drug Monothf rspj for Epilepsy: A Hetwork Meta- An a lysis of Iwlividual Participant Data Cocltra D!Syst to 201?:C0011412 Purpose: To conparethe Its;to wt- drawal of & ea:nert. ioe!o remission. Ed Sue to first seizure of 10 enoep leptic drug treatneits for adults and childrec wifi partial onset seizures Methods Articles were iden: Sed ront Cochrane Epilepsj'sSoeoaltsed Register. CERTRAL. MEDLINE. SCOPUS, ard two clinical trial registers. Indn- dua patient data was identified for cetworic-meta analysis Results: Urhamarepine and least:g ne are suited e first - fine treatments for partial onset seizures with leretraceam asa suitable a te-atse. Evidence supports sodium valproate as first-hoe treatment for generalized tonic-clonic seizures ft lamotrigine and * leuetiracemm as suitable alteroatres. particularly for females of child-hearing age

*

-

( Psychogenic non epileptic

seizure) Timing

Day or night (especially front sleep)

Day

Day, other people present

Onset

Sudden , in any position

Early Symptoms or Signs

Possible specific aura

Gradual , upright position (not recumbent) Lightheadedness, pallor, diaphoresis, tunnel vision

Provoked by emotional disturbance or suggestion Variable

Duration

Brief orprolonged

Brief

Often prolonged

Incontinence

Common

Possible but rare

Post-ictal Motor Activity

Ho Confusion, aphasia, Todd's paresis, fatigue Synchronous, stereotypic. Occasional briel tonic stiffening, automatisms (common In complex can have 'convulsive syncope' partial), lateral tongue biting, eyes open or eyes rolled back

Injury

Common

Rare unless from fall

Rare

EEG

Usually abnormal tinierictal discharges

Normal

Normal

DDx of Convulsions

Syncope, psychogenic non-epileptic seizures, hyperventilation, panic disorder. TIA hypoglycemia, movement disorder, alcoholic blackouts, migraines (confusional , vertebrobasilar),

.

narcolepsy (cataplexy)

Rare Variable, often none Prolonged episodes, opisthotonos, eye closure. Irregular extremity movements, shaking head, pelvic thrust crying tongue biting at the tip

Note that seizures originating in the frontal lobes may look like psychogenic non-epileptic spells due to an abundance of repetitrve hyperkinetic movements: they often occur during sleep

,

-

‘Pseudosei zures do not rule out seizures (rot Lrcommon to have both)

• alcoholic withdrawal seizures may occur up to 2 d from the last exposure to alcohol (see Emergency Medicine EU 54 )

.

By law. the Ministry of Transportation in most provinces must be contacted for all patients who have had a seizure, patients will have their license suspended until seizure free for 6 mo. commercial drivers face a longer wait

Investigations

•CBC, electrolytes, Ca -+, Mg 2+ POt -5 , fasting blood glucose, Cr, liver enzymes, CK, prolactin • toxicology screen, EtOH level, AED level ( if applicable ) •CT/ MK1 ( if new seizure without identified cause or known seizure history with new neurologic signs/ symptoms) ( Note: Neuroimaging may be normal in up to 90% of cases following the first unprovoked seizure) • LP ( if fever or meningismus) • EECi ( Note: EEC is specific but not sensitive) Treatment •avoid precipitating factors • prognosis: risk of seizure recurrence increases with the number of unprovoked seizures at initial presentation , abnormal EEG , and presence of a neurological disorder • indications for AED: EEG with epileptiform activity, remote symptomatic cause (organic brain disease, prior head injury, or CNS infection ), abnormal neurologic examination or findings on neuroimaging, nocturnal seizure, recurrent unprovoked seizure • psychosocial issues: stigma of seizures, education of patient and family, status of driver’s license, pregnancy issues •safety issues: driving, operating heavy machinery, bathing, swimming alone • appropriate follow-up; refer for evaluation for possible surgical treatment if focal and refractory

EEG findings suggestive of predisposition to epilepsy: spike and wave discharges, polyspike and wave discharges, spike-wave complex discharges

EEG has a 17% sensitivity and 95% specificity after first unprovoked seizure, sensitivity increases to 51% if EEG is performed within 24 h If the first routine EEG is normal, a sleep-deprived sleep EEG should be considered to increase the likelihood of detecting an abnormality

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N20 Neurology

Toronto Notes 2023

Status Epilepticus • definition:

medical emergency involving unremitting seizure or successive seizures without return to baseline state of >5 min •complications: anoxia, cerebral ischemia and cerebral edema Ml, arrhythmias, cardiac arrest, rhabdomyolysis and renal failure, aspiration pneumonia / pneumonitis, death ( 20%) • initial measures: ABCs, vitals, monitors, capillary glucose ( SEAT ), ECG, nasal O ’, IV NS, IV glucose, IV thiamine, ABCs ( if respiratory distress/cyanotic ) • blood work: electrolytes, Ca Mg 2 ' , POt 3 , glucose, CBC, toxicology screen , EtOH level, AED levels • focused history : onset, past history of seizures, drug and alcohol ingestion , past medical history, associated symptoms, witnesses/collateral history • physical exam ( once seizures controlled ) : LOG , vitals, HEENT ( nuchal rigidity, head trauma, tongue biting, papilledema ), complete neurological exam , signs of neurocutaneous disorders, decreased breath sounds, cardiac murmurs or arrhythmias, urinary incontinence, MSK exam ( rule out injuries) • post-treatment stabilization: CT head, EEC, Eoley catheter to monitor urine output, urine toxicology screen, monitor for rhabdomyolysis, and IV fluids to maintain normal cerebral perfusion pressure

.

Medical Emergency:Status epilepticus can cause irreversible brain damage without treatment

The most common causes of status epilepticus in adults are failure to take AEDs, remote symptomatic causes, and stroke Despite being a common cause of seizures EtOH withdrawal is a rare cause of status epilepticus

.

Antiepileptic Drugs

•focal and most generalized seizures • valproate ( Depakene*), lamotrigine ( Lamict nl*), levetiracetam ( Keppra*), topiramate ( Topamax* ), phenobarbital ( Phenobarb' l, primidone, zonisamide, rufinamide ( Banzel* ), felbamate, benzodiazepines • primarily focal seizures ( ± 2° generalization ) carbamazepine ( Tegretol* ), phenytoin ( Dilantin*), gabapentin ( Neurontin* ), lacosamide ( Vimpat* ), oxcarbazepine ( Trileptal* ), eslicarbazepine acetate (Aptiom*), pregabalin ( Lyrica* ), tiagabine (GabitriP), vigabatrin (Sabril *) •absence seizure: ethosuximide ( Zarontin")

.

Convulsive seizures

Consider non-convulsive status epilepticus in a patient who has a persistent decreased level of awareness >20 min after a generalized seizure: order an EEG if unsure

Complex partial status epilepticus can resemble schizophrenia or psychotic depression

i

>5 min

Treat as status epilepticus

I

1. ABCs 2. Vital signs 3. Laboratory investigations 4. Glucose 50 mL IV 5. Lorazepam 0.1 mgkg IV at 2 mg/min

-

If fever or meningismus

I

Fosphenytoin 1000 1500 mg IV at 150 mg/ min

or

phenytoin 20 mg/ kg IV up to 30 rnglrg at a maximum rate of 50 mg/min

1

1. ICU 2. Continuous infusion of midazolaRVpropofoVpentobarfaital 3. Burst suppression ( on EEG )

Figure 17. Status epilepticus treatment algorithm

*

CT. lumbar puncture with Gram stain,

-

treat pre emptively with antibiotics

Teratogenicity of anticonvulsants includes neural tube defects, deft palate , urogenital malformations, and heart defects. Advise patient planning pregnancy to take1 4 mgd of folic add. Optimize AEDs with lowest possible dose associated with good seizure control, preferably monotherapy if possible. The risk of fetal malformations with AEDs is 2x the general population: highest risk associated with valproic acid and/or 2+ concurrent AEDs. Consider pre-conception AED levels if patient is well-controlled, monthly serum levels during pregnancy, and titrate AED to maintain pre conception serum levels. Refer to high risk OB for intrapartum fetal screening

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N 2 I Neurology

Toronto Notes 2023

Behavioural Neurology • see Psychiatry. PS23

Acute Confusional State/Delirium

.

Table 13 Selected Causes of Acute Confusion Vascular

Etiology

Key Clinical Features

Investigations

SAH

Thunderclap H /A increased ICP. menmgismus, loss of consciousness

Angiography il CT and LP negative

Focal neurological signs

CT. MRI

.

Stroke /TIA (ischemic or hemorrhagic)

Infectious

Fever H/A. nausea , photophobia meningismus

Encephalitis

Fever H /A t seizure Focal neurological signs Increased ICP

. .

CT. IP

• Feature 3: disorganized thinking • Feature 4: altered LOC

CUP MRI

CT with contrast ( often ring

Focal neurolog leal signs

enhancing lesion )

Diffuse axonal shear , epidural hematoma SDH

Trauma H « Increased ICP Focal neurological signs

Cl

Acute CHS vasculitis

Skin rash, active joints

ANA ANCA RF MRI Angiography

Paraneoplastic or autoimmune encephalitis (anti - NMDA - R )

Onset: psychiatric features , memory loss, seizures Delayed: movement disorder, and changes in BP, HR , and

Serum and CSF (test for presence of antibodies), seaich for primary

.

Autoimmune

.

.

Meningitis

Abscess

traumatic

CUP

Delidum Is a medical emergency carrying significant risk of morbidity and mortality. It is diagnosed when feature 1 AND 2 as well as feature 3 OR 4 are present: • Feature 1: acute onset and fluctuating course • Feature 2: inattention

It is often diagnosed using the Confusion Assessment Method

MRI

.

.

neoplasm

temperature Primary or secondary CHS neoplasm

Neoplastic

CT

Increased ICP Focal neurolog leal signs

MRI Search lor primary neoplasm il metastatic disease

Papilledema

Focal seizure with impaired

Seizure

SeeSeizure Disorders and

awareness, non -convulsive status Cpilepsy. N18 epileplicus, post ictal contusion Psychotic, mood , and anxiety Ho organicsigns or symptoms

Primary Psychiatric

FFG CT or MRI Workup for seizure triggers

Ho specific tests

disorder

Illicit drug use (e.g. cocaine)

Other

Chest pain , cough with black sputum , newonset seicure HIN increased ICP dyspnea

.

. .

Vital signs Serum chemisliy and electrolyte analysis Serum and urine toxicology

screen

Medications (e.g. anticholinergic side effects, benzodiazepines)

Flushing , dry skin and mucous Serum chemistry and electrolyte membranes, mydriasis with loss of analysis accommodation

Neuroleptic Malignant Syndrome

Antipsychotic medication use Muscle rigidity

Serum chemistry and electrolyte analysis

Hyperthermia Autonomic instability

Mild Neurocognitive Disorder (Mild Cognitive Impairment) Definition • cognitive changes with measurable deficits in one or more cognitive domains • preservation of independence or minimal impairment in ADLs and lADLs and not meeting criteria for major NCD • amnestic ( precursor to AD) vs. non -amnestic Epidemiology • mild NCD: 2 -10% at age 65 and 5 -25% by age 85

Risk Factors

.

• non - modifiable: age history of stroke or heart disease, and apolipoprotein E ( APOE) E4 genotype • modifiable: educational level and vascular risk factors (e.g. hypertension , diabetes mellitus, obesity ) Clinical Features • cognitive impairment with different subtypes • single domain vs. multiple domains (e.g. memory, visual spatial function, attention, executive function, language)

Prevalenccof Dcptessionin Patients with Mild Cognitive Impairment : A Syslemalic Review and Meta Analysis JAMA Psychiatry 2017;74:58 -67 Purpose: to estimate the prevalence of depression in Lidnnduatsinrith mild cognitive impairment. Methods: Review of articles with patients with mdd cognitive impairment as a primary study group, reported depression /depressive symptoms usvig a ta ' dated tool, and reported die prevalence of depression in patients with mild cognitive

-

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impairment.

tesnlts : Pooled prevalence of depression patients

cognitive Impairment was 3ft ( SS\ Cl •2nth/-3ftadd|. Pievalencein community - based populations (25%. 95% C119- 30 ) was significantly lower than clime- based populations (40% 95% Cl 32- 48). Conclusions: P evalenceof depression in patients with mild cognitive impairment is high.

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X22 Neurology amnestic ( memory impairment ) vs. nonamnestic ( memory function preserved ) • amnestic subtype is the most common and most associated with AD pathology important to ascertain that memory complaints represent change from baseline • neuropsychiatric symptoms: depression (50%), irritability, anxiety, aggression , and apathy

Investigations •establish a baseline for follow up •clinical interview with patient and caregivers is the cornerstone of mild NCD evaluation, including

-

detailed family history • neuropsychological testing

•

MMSE ( not sensitive to early cognitive change ) or MoCA ( more sensitive); should be done in conjunction with a history and neurological exam or with other neurocognitive tests if abnormal, follow up in one year to monitor cognitive and functional decline

SSi

Mild vs. Major |

-

role uncertain ; a non contrast brain CT is often ordered to evaluate for structural abnormalities (CVD, SDH , Nl’H , or mass lesion ); a MK 1 is helpful to establish baseline and to look for other

possible reversible causes of cognitive impairment

•-

•other testing to exclude treatable conditions (e.g. B deficiency, hypothyroidism , seizures, autoimmune encephalitis ) and underlying psychiatric conditions (e.g. depression )

I

r

NCD duo to • Frontotemporal NCO Alzheimer's disease • NCO with Lcwy bod N • Vascular NCO • Other causes o< NCO (traumatic brain injury substance mcdicatcn use, HIV infection,

.

prion disease, Parkinson s disease, Huntington s disease)

-

• neuroimaging

•

—— Toronto Notes 2023

ussagw V

Frontal lobo

Treatment

• non - pharmacologic management: exercise training for 6 mo is likely to improve cognition ; insufficient evidence to support or refute cognitive intervention , it may improve outcome on select cognitive measures • pharmacologic management: monitoring and management of hypertension and other vascular risk factors is recommended

-

• no evidence for cholinesterase inhibitors, anti inflammatory agents Prognosis •development of major NCD for age £ 65 is 14.9% after 2 yr • relative risk of major NCD is 3.3 after 2 5 yr

Temporal lobe

|

Executive 8chaviour function • Apathy

Language

Memory

• Semanbc dementia • Non-fluent

• Oisinhibbon

progressive

aphasia

Figure 18. Major NCD classification

-

Major Neurocognitive Disorder (formerly Dementia) • see

. PS24

Psychiatry

Definition

• acquired , generalized , and ( usually) progressive impairment of cognitive function associated with impairment in ADLs/ IADLs (e.g. shopping, food preparation, finances, medication management) • diagnosis of major NCD requires presence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual- motor, or social cognition ) based on : a ) concern of the individual or a knowledgeable informant AND b) substantial impairment in cognitive performance either documented by standardized neuropsychological testing or quantified clinical assessment

. see

Psychiatry, PS24 • in comparison , mild NCD does not affect ADLs mild NCD represents an intermediate stage between major NCD and normal aging

Epidemiology • major NCD: 1-2% at age 65 and

reaching as high as 30% by age 85 • major NCD due to AD is uncommon before age 60 • major NCD due to frontotemporal lobar degeneration has an earlier onset and represents a progressively smaller fraction of all NCDs with increasing age Etiology • see Table 14, N 23 • reversible causes: alcohol (intoxication or withdrawal, Wernicke’s encephalopathy), medication ( benzodiazepines, anticholinergics), heavy metal toxicity, hepatic or renal failure, Bi 2 deficiency, glucose, cortisol, thyroid dysfunction, NPH, depression ( pseudodementia), intracranial tumour, SDH,

and hypercalcemia • must rule out delirium History

• “geriatric giants” confusion /incontinence/falls memory and safety ( wandering, leaving doors unlocked , leaving stove on, losing objects, driving ) • behavioural ( mood, anxiety, psychosis, suicidal ideation, personality changes, aggression) polypharmacy and compliance (sedative hypnotics, antipsychotics, antidepressants, anticholinergics) • ADLs and IADLS • cardiovascular, endocrine, neoplastic, renal KOS, head trauma history

Sensitivity and Specificity

Tool

Sensitivity

Specificity

MMSE

81% 85%

82% 82%

76%

80%

Clinical Judgment

OSMN

Vitamin Biz Deficiency Symptoms • Macrocytic anemia, pallor. SOB, fatigue, chest pain, palpitations • Confusion or change in mental status (if advanced) • Decreased vibration sense • Distal numbness and paresthesia • Weakness with UMN findings • Diarrhea, anorexia

Major NCD Considerations for Management

ABCDs Aff ective disorders. ADLs Behavioural problems Caretaker, Cognitive medications and stimulation

Directives. Driving Sensory enhancement (glasses/hearing aids)

n LJ

Most common causes of rapidly progressive neurodegenerative dementia are CJD, frontotemporal lobar dementia, tauopathies diffuse Lewy body disease, and AD

.

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N23 Neurology

Toronto Notes 2023

• alcohol, smoking • collateral history

• family history'

Features of Early Major NCD vs. Normal Aging

Physical Exam

blood pressure hearing and vision neurological exam with attention to signs of parkinsonism , UMN findings • general physical exam with focus on CVD, patient-specific risk factors, and history • MMSE or MoCA , clock drawing , frontal lobe testing ( go/ no - go, word lists , similarities, proverb) • • •

Normal Aging

Forgetting Hie names of close

Forgetting the names

rule out reversible causes • CBC ( note MCV for evidence of alcohol use and Bt: deficiency ) , glucose , T SH , BID , RBC folate • electrolytes, Ll Ts, renal function , lipids, serum calcium CT head, MRI as indicated , SPECT (optional ) as clinically indicated : VDRL , HIV, ANA, anti -dsDNA, ANCA , ceruloplasmin, copper, cortisol , toxicology, heavy metals '

'

• issues to consider failure to cope, fitness to drive , caregiver capacity and wellbeing , power of attorney, legal will, advanced medical directives, patient and caregiver safety

of acquaintances

relations

Increased frequency of forgetting

Investigations •

Early Signs of Major NCD

Briefly forgetting part ofaneipenence

Repeating phrases' stories in the same conversation

Not putting away tings property

Unpredictable mood changes

Mood changes in response to

Decreased interest in activities and difficulty making choices

Changes in usual interests

appropriate causes

Table 14. Selected Causes of Major NCD ( Dementia ) Etiology

Key Clinical Features

Investigations

AUhemet's disease

Memory impairment Aphasia, aprama. agnosia

CT or Itfil. FOS PEI orSPECT

Dementia with Lewy bodies

CT or MRI. SPEC! Visual hallucinations Parkinsonism Fluctuating cognition REM sleep behaviour disorder Severe neuroleptic sensitivity CT or MRI.SPEC! Behavioural presentation: disrnhibrtion. perseveration. decreased social awareness mental rigidity, memory relatively spared Language presentation:progressiva non fluent aphasia , semantic dementia Genetic testing Chnrea Neurapsychiatnc symptoms

PRIMARY DEGENERATIVE

Frontofenporal dementia (e.g. Pick 's disease)

Huntington's disease VASCULAR Vascular cognitive impairment (previously Mufti - rafarct dementia )

,

-

Bradyphreuia wrtboet features of parkinsonism (slow thinking , slow rate of learning , slow gait) Dyseiecntive syndrome May be abrupt onset Stepwise deterioration d class but progressive deterioration is most *

CT or IttL SPECT

CHS vascu rtis

Systemic signs and symptoms of vasculitis

ANA: ANCA: RF Cl or MRI Angiography CT.MR1. IP

-

,

-

-

-

common ’

Cholinesterase Inhibitors for Dementia with lewy Bodies (OlBj. Parkinson's Disease Dementia ( POD ) and CognitiveImpairmeut ihParkinsoo's Disease (CIHDPD ) Cochrane DB Syst Per 2012;3:CD0065 M Purpose: Ic assess Bedhaq : ‘ r MMt «it cholmesterase inhibitors in Dll. POD. and CIND-PD Methods: Review of erodes hoc databases including NEDLINE. EMEASE. Psyr INFO and DMAHL Results: ThesihesrrI2 i5 l ddkdtd demonstrated therapeutic beseht of choinesterase inhibitors for globel assessment cognitive function, behavioural disturbance, cndadrwtmsof daify living. Chniinesterase iih&tms we ? associated with increased adierse events (OR 161) and drop out (OR 1.94). Adverse events were more corn on with rivastigmne but not * to doeepezl Fewer deads occurred in the treatment goto (OR 0.21) Conclusion: Cur.ea er deace swsorts use of cholinesterase m oitorsfor patents wits POO. baths role in 0 L 8 and CINO PO rssti!: . dea

-

-

INFECTIOUS

HIV

Fever. HA. nausea ( triad ofteo absent m cases of chronic meningitis) Meningismns Localizing neurological deficits Fever. FLA Increased ICP Localizing neurological def ats Seelnfect ccs Osrait: 1327

Crer.ttfe:dt -Jakob disease

Rapidly progressive, nyocloaits. akinetic mutism , parkinsonism , or cortical

SypteSs

symptoms Ataiia myoclonus, tabes dorsalis

Chronic meningitis

Chronic encephalitis

Chronic abscess

.

TRAUMATIC DrPose aioualshear.epidural hematoma , subdural hematoma

Trauma Hi Increased ICP. papilledema Localizing neurological signs

CTorMSI

O wth contrast. MRI KIV serology

EEC. Cl or MRI. IP

IP. CT. or MRI VDRL 0. MRI

RHEUMATOIOGIC

SLE

See Rheumatology, Shill

MRI

_

A A anti - dsONA

*

NEOPLASTIC

Primary or secondary brain lumour

.

( metastasis)

paraneoplastic encephalitis

OTHER Normal pressure hydrocephalus

rm

.

L J

Increased ICP Localizing neurological signs Systemic symptomsotcaccer

Cl with contrast MRI Paraneoplastic antibodies

Gail disturbances Urinary incontinence SeeNeurosL- tp; y . »S9

large volume IP

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CTotMRL

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N 24 Neurology

Toronto Notes 2023

Major or Mild Neurocognitive Dementia due to Alzheimer’s Disease • see Psychiatry, PS24

*

4 As and one D of AD

Definition • beyond criterion for NCD, the core features of AD include an insidious onset and gradual progression of cognitive and behavioural symptoms • typical presentation: amnestic mild phase: impairment in memory and learning sometimes accompanied with deficits in executive function • moderate-severe phase: visuoconstructional/ perceptual-motor ability and language may also be impaired • social cognition tends to be preserved until late in the course of the disease • atypical nonamnestic presentation (one of the following ): 1 language: aphasia, word-finding difficulty 2. visuospatial: object agnosia, prosopagnosia, simultanagnosia, alexia, limb apraxia 3. executive: reasoning, judgment, and problem-solving are affected

.

Pathophysiology • genetic factors minority (99% of right handed people have left

hemisphere language representation 70% of left handed people have left hemisphere language representation. 15% have right hemisphere representation, and 15% have bilateral representation

-

n LJ

comprehension • arcuate fasciculus association bundle connects Wernicke s and Brocas areas

+ Types of Paraphasias Semantic (e.g. “chair" for “table") Phonemic (e.g. “dable" for “table")

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N 28 Neurology

Toronto Notes 2023

Assessment of Language • assessment of context • handedness (writing, drawing, toothbrush, scissors ), education level, native language, learning

Aphasia localizes the lesion to the dominant cerebral hemisphere

difficulties • assessment of aphasia • spontaneous speech ( fluency, paraphasias, repetition , naming, writing, neologism , comprehension - auditory and reading )

s

APHASIA RUENCY

#

NON - FLUENT

I

1 aUENT

f

#

5 ©

COMPREHENSION

Poor

Poor

Good

Good

REPETITION

Poor

Poor

Good

Poor

Good

Poor

Good

NAMING

Poort r

1

Global

rPoof

Mixed TCA*

,r

POO'

Broca's

3

Poor t

rPoof

Motor TCA *

r

Wernickes

,

PooS

- -

Sensory TCA*

Good

-

Conduction

Po°r | Anomic

LESION LOCALIZATION

Posterior inferior frontal Sensory and motor Posterior inferior transcortical regions frontal lobe lobe and poster or superior temporal lobe

Frontal lobe watersf^ed Posteror superior Temporopsrets .-. 2* - r: L -rT .- . -rrbaseen MCA and ACA errporal obe

'.C^'i = PC*' Tr"t2' =i

fienaories

TCA-transcortiCal aphasa Transcortical aphasias are typically associated wth cerebral anoxa le.g. post-Ml,CO poisonrg nypotersior t

^ Figure 19. Aphasia classification

-

ocsosforleson

,

Apraxia Definition inability to perform skilled voluntary motor sequences that cannot be accounted for by weakness, ataxia, sensory loss, impaired comprehension, or inattention

•

Clinicopathological Correlations Table 15. Apraxia Description

Tests

Hemispheres

Ideomotor

Inability to perform skilled learned motor sequences

Blowing out a match, combing one's hair

Left

Ideational

Inability to sequence actions

Preparing and mailing an

Right and left

-

envelope

Constructional

Inability to draw or construct

Copying a figure

Right and left

Dressing*

Inability to dress

Dressing

Right

’Refers specifically to the inability to carry out the learned movements involved in construction, drawing, or dressing: not merely the inability to

construct, draw , or dress. Many skills aside from praxis are needed to carry out these tasks.

LJ

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N29 Neurology

Toronto Notes 2023

Agnosia Definition • inability to recognize the significance of sensory stimuli in the presence of intact sensation and naming

Clinicopathological Correlations Table 16 . Agnosias Description

Lesion

-

Apperceptive Visual Agnosia

Bilateral temporo occipital cortex Bilateral interior ternporo occipital junction

Associative Visual Agnosia

Inability to name an object presented visually 2° to disconnect between visual cortex and language areas Visual perception is intact as demonstrated by

Bilateial temporo - occipital cortex

.

-

Bilateral interior temporo occipital junction

visual matching

Coloui Agnosia

Inability to recognize lainlliar laces in the presence ol Intact visual perception and intact auditory recognition Inability lo perceive colour

Impaired Slcrcognosis

Inability lo identily objects by touch

Prosopagnosia

finger Agnosia

Inability to recognize , name, and point to

individual lingers

--

Bilateral temporo occipital areas or right Interior temporo occipital region

Parietal Lobe Lesions • Lesions of the dominant parietal lobe are characterized by Gerstmann's syndrome: acalculia , agraphia, finger agnosia, and left- right disorientation • Lesions of the non -dominant parietal lobe are characterized by neglect, anosognosia. and asomatognosia • Cortical sensory loss (graphesthesia. astcreognosis. impaired 2 point discrimination, and extinction) can be seen with left or right parietal lesions

Bilateral interior temporo - occipital lesions Anterior parietal lobe in the hemisphere opposite to iheallected hand

Dominant hemisphere parietal -occipital lesions

Mild Traumatic Brain Injury Definition

• mild TBI = concussion • trauma induced transient alteration in mental status that may involve loss of consciousness • hallmark symptoms: confusion and amnesia, which may occur within minutes • loss of consciousness ( if present ) less than 30 min , initial CCS between 13 -15, post - traumatic amnesia

-

Extent of retrograde amnesia correlates with severity of injury Rjgained from most distant to recent memories

65 yr Clinical Features • impairments following mild TBI somatic: headache, sleep disturbance, nausea , vomiting, and blurred vision cognitive dysfunction: attentional impairment , reduced processing speed , drowsiness, amnesia emotion and behaviour: impulsivity, irritability, depression • severe concussion: may precipitate seizure, bradycardia, hypotension, sluggish pupils • associated conditions: brain contusion, diffuse axonal injury, C-spine injury

Investigations • neurological exam to identify focal neurologic deficits • neurocognitive assessment * simple orientation questions are inadequate to detect cognitive changes initial assessment of severity is determined by GCS mild: 13-15, moderate: 9-12, severe: 3-8 * sideline evaluation: Standardized Assessment of Concussion , Westmead Post-Traumatic Amnesia Scale, Sport Concussion Assessment fool • neuroimaging x- ray skull: not indicated for routine evaluation of mild TBI CT head as indicated by Canadian CT Head Rules MR 1 not indicated in initial evaluation ; consider if continued or worsening symptoms despite normal CT

r

T

LJ

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X30 Neurology

Toronto Notes 2023

Treatment •observation for the first 24 h after mild TBI because of risk of intracranial complications • emergency department for assessment if any loss of consciousness or persistent symptoms •hospitalization with normal CT if GCS < 15, seizures, or bleeding diathesis; or abnormal CT scan •early rehabilitation to maximize outcomes OT, FT, SLP, vestibular therapy, driving, therapeutic recreation •pharmacological management of headaches, pain, depression • CBT, relaxation therapy •follow Return to Play guidelines ( www.thinkfirst.ca) Prognosis • most recover from mild TBI with minimal treatment, but some experience long- term consequences • patients with a previous concussion are at increased risk of subsequent concussions and cumulative brain injury • repeat TBI can lead to life threatening cerebral edema (controversially known as second impact syndrome) or permanent impairment •sequelae include:

post-concussion syndrome: dizziness, headache, neuropsychiatric symptoms, cognitive impairment (usually resolves within weeks to months) post- traumatic headaches: begin within 7 d of injury • post- traumatic epilepsy: approximately 2% risk post-mild TBI; prophylactic anticonvulsants are not effective post- traumatic vertigo

•

Neuro-Oncology Paraneoplastic Syndromes • see Endocrinology, K 56

Tumours of the Nervous System •

s

see Neurosurgery, NS 11

Movement Disorders Function of the Basal Ganglia •

the cerebral cortex initiates movement via excitatory ( glutamatergic) projections to the striatum, where they then activate two pathways: direct and indirect direct: cortex activates the thalamus, allowing movement indirect cortex inhibits the thalamus, preventing movement

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ndows.

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X32 Neurology

Toronto Notes 2023

Overview of Movement Disorders Table 17. Movement Disorder Definitions Akathisia

Subjective genera ned restlessness relieved by voluntary stereotypic movements |e.g. squirming)

Asterixis

Transient loss of muscle tone (negative myoclonus)

Athetosis

Slow writhing movements, especially distally

Ballism

Large- amplitude,involuntary, flinging movements tiiatare most commonly unilateral (hemiballism)

Bradykinesia

Slow, small amplitude movements

Chorea

Brief, unpredictable, irregular movements, flowing from one body part to another: can appear purposeful m milder forms

Oysdiadochokinesia

Inability to smoothly perform rapidly alternating movements

Dyskinesia

Any involuntary movement, but the term is often used to describe tire stereotypical movements that come with long term neurolepticuse (tardive dyskinesia) or levodopa use (ievodopa induced dyskinesia)

Dystonia

Co- contraction of agonist and antagonist muscles causing sustained twisting movements which can be tonic (dystonic postures) or phasic (dystonic movements)

Freezing

Episodes of halted motor action, especially during repetitive actions (e.g. walking)

-

In some cases, dystonias may occur only during voluntary movements and sometimes only during specific activities, such as writing, chewing, or speaking (task -specific dystonia)

Hemiballismus is most often due to a vascular lesion

Myoclonus

Brief muscle group contraction that is either focal, segmental, or generated

Myokymia

Spontaneous, fine, fascicular contraction of muscle

Stereotypies

Predictable, repetitive,involuntary movements that do not appear to have any purpose |commonly associated with intellectual disability or autism)

Tadiykinesia

Acceleration of movements e.g. accelerated walking Ifestrnation)

Tics

Stereotyped,nonrhythmic, and brief repetitive actions due to inner urge Can be phonic (vocal) or motor and can be suppressed

Tremor

Rhythmic and involuntary antagonistic muscle contractions

Myoclonus can be stimulus-sensitive (induced by sudden noise, movement, light, visual threat or pinprick)

In a young patient (jaw»lE>head

UE>head>lE>tongue

UE>voice>li

Characteristics

3 6 Hr pillrollmg

6-12 Hjfme tremor

‘5 HT coarse tremor

Worse with Associated Sx

Rest while concentrating “ TRAP "

Sustained posture (outstretched arms)

DDi

PD.Parkinsonism Wilson's disease, mercury poisoning, severe essential tremor

Affected Body Part

Finger to nose Cerebellar findings

± Autosomal dominant FHx

Treatment

.

Levodopacarbidopa ( Smemet : )

DBS

.

Physiologic,essential tremor Cerebellar disorders. Wilson's hyperthyroidism,hyperglycemia, disease. MS. anticonvulsants, heavy metal poisoning, CO alcohol,sedatives poisoning,drug toxicity, sedative / alcohol withdrawal

.

Alcohol

.

• Dampens essential tremor

Potentiates intention tremor during abstinence ( delirium tremens) • Does not improve resting tremor of PD

Treat underlying cause

Propranolol, primidone, topiraraate and other anticonvulsants, surgery ( thalamotomy.DBS)

.

2. Chorea •

Most of the time, essential tremor does not need treatment

HD, HD -like syndromes, neuroacanthocytosis, SLE, APLA syndrome, Wilson’s disease, CYD, tardive dyskinesia, senile chorea, Sydenham’s chorea, pregnancy chorea ( chorea gravidarum ), levodopa induced dyskinesia

Most common cause of chorea is drug therapy for PD (levodopa induced dyskinesias)

3. Dystonia • primary dystonia: familial, sporadic ( torticollis, blepharospasm , writer’s cramp ) • dystonia - plus syndromes: dopa responsive dystonia, myoclonus dystonia • secondary dystonia : stroke, CNS tumour, demyelination, drugs/ toxins ( L dopa, neuroleptics,

-

-

-

anticonvulsants, Mn, CO, cyanide, methanol ) • heredodegenerative dystonias: Parkinsonian disorders, Wilson’s disease, HD 4. Myoclonus • physiologic myoclonus: hiccups, nocturnal myoclonus • essential myoclonus: myoclonus-dystonia with minimal or no occurrence of dystonia • epileptic myoclonus

Palatal tremor can result from lesion to the Dentato-Rubro-Olrvary tract

• symptomatic myoclonus

+

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N33 Neurology

Toronto Notes 2023

• degenerative disorders: Wilson’s disease, HD, corticobasal degeneration • infectious disorders: C|D, viral encephalitis, AIDS- dementia complex • metabolic disorders: drug intoxication / withdrawal, hypoglycemia, hyponatremia , hyperglycemic hyperosmolar syndrome, hepatic encephalopathy, uremia, hypoxia • focal brain damage: head injury, stroke, mass

Parkinson’s Disease Etiology

sporadic: combination of oxidative stress to dopaminergic neurons, environmental toxins ( e.g. pesticides), accelerated aging, genetics • familial ( I0%): autosomal dominant a synudein or LRRK 2 mutations, autosomal recessive parkin, RINK I , or Dl l mutation ( juvenile onset ) • M P I P ( neurotoxin ) t

-

-

Epidemiology • prevalence of 0.3% in industrialized countries, but rises with increased age • second most common neurodegenerative disorder, after AD • mean age of onset is 60 yr Associated Factors

• risk: family history, male, head injury, rural living, exposure to certain neurotoxins

• protective: coffee drinking, smoking, estrogen replacement in post -menopausal women Pathophysiology

• loss of dopaminergic neurons in pars compacta of substantia nigra -> decreased dopamine in striatum » 1. disinhibition of the indirect pathway, and 2. decreased activation of the direct pathway -» increased inhibition of cortical motor areas • a-synudeinopathy: a-synudein accumulates in Lewy bodies and causes neurotoxicity in substantia

-

nigra Clinical Features

• diagnosis is based on clinical features:

1. Negative motor features bradykinesia: slow, small amplitude movements, fatigue from rapid alternating movements, difficulty initiating movement 2. Positive motor features resting tremor: typically 4 -6 Hz “ pill- rolling” tremor, especially in hands rigidity: lead - pipe rigidity with cogwheeling due to superimposed tremor 3. Asymmetric onset of tremor, rigidity, bradykinesia 4. Progressive course related findings: hypomimia ( reduced facial expression ), hypophonia, aprosody ( monotonous speech ), dysarthria, micrographia, shuffling gait with decreased arm swing freezing of gait: occurs with walking triggered by initiating stride or barriers/ reaching

destinations, lasting seconds postural instability: a late finding that presents as falls cognition: bradyphrenia (slow to think / respond ), dementia ( late finding ) behavioural: decreased spontaneous speech, depression, sleep disturbances, anxiety autonomic: constipation, urinary dysfunction ( nocturia , urgency, frequency ), sexual dysfunction, orthostatic hypotension , clinostatic hypertension sleep: REM sleep behaviour disorder, insomnia , hypersomnolence

Key Parkinsonian Features TRAP

Tremor (resting) Rigidity Akincsia / bradykinesia Postural instability

2015 MDS Clinical Diagnostic Criteria for PD • “Clinically Established PD" requires: • Cardinal Parkinsonism Manifestations: Bradykinesia with either resting tremor or rigidity • 2 or more supportive criteria (clear and dramatic beneficial response to dopaminergic therapy, levodopa induced dyskinesia, rest tremor of a limb, and/or olfactory loss/cardiac sympathetic denervation on MIB6 scintigraphy) • No absolute exclusion criteria and no red flags (see full diagnostic criteria Mov Disord 2015;30:1591 601)

-

-

-

Consider an Alternative Diagnosis if Atypical Parkinsonism Poor response to levodopa Abrupt onset of symptoms • Rapid progression Early falls • Early autonomic dysfunction Symmetric symptoms at onset Early age of onset («50 yr) • Early cognitive impairment • FHx of psychiatric disorders and/or dementia • Recent diagnosis of psychiatric

..

.

..

disease

• History of encephalitis

• Unusual toxin exposure • Extensive travel history

Treatment

• pharmacologic • mainstay of treatment: levodopa /carbidopa (Sinemet*) or levodopa / benserazide (Prolopa*) levodopa is a dopamine precursor. Both carbidopa and benserazide decrease levodopa peripheral metabolism , decreasing levodopa side effects and increasing its half life levodopa related fluctuation : delayed onset of response (affected by mealtime), end of dose deterioration ( “ wearing off "), random oscillations of on off symptoms major adverse effect of levodopa: dyskinesia treatment of early PD: levodopa, dopamine agonists, amantadine, MAOI : dopamine agonists, MAOI, anticholinergics (especially if prominent tremors ), catecholadjuncts • O- methyltransferase inhibitors • surgical thalamotomy pallidotomy • DBS (thalamic, pallidal, subthalamic) • psychiatric SSRls first line « TCAs ( beware fall risk, cognitive impairment, and worsening symptoms of PD)

-

-

-

-

- -

_

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-

N34 Neurology

Toronto Notes 2023

Other Parkinsonian Disorders • NCD with Lewy bodies: see Behavioural Neurology , N2I • progressive supranuclear palsy: tauopathy with limited vertical gaze (downgaze more specific that can be overcome by the oculocephalic reflex ), early falls, wide- based unsteady gait, axial rigidity, akinesia, dysarthia, and dysphagia • corticobasal syndrome: tauopathy with varied presentations but classically presenting with unilateral parkinsonism, dystonia / myoclonus, and apraxia ± “alien limbs” phenomenon; ± progressive non -fluent aphasia • multiple system atrophy: synucleinopathy presenting as either cerebellar predominant ( MSA -C, previously olivopontocerebellar atrophy) or parkinsonism predominant ( MSA P, previously nigrostriatal degeneration ); both are associated with early autonomic dysfunction ( urinary incontinence or orthostatic hypotension , previously Shy- Drager syndrome ) • vascular parkinsonism : multi- infarct presentation with gait instability and lower body parkinsonism; step wise decline over time; less likely associated with tremor

-

-

Dopamine Agonist therapy in Early Parkinson's Disease Cochrane OB Syst Her 2009;2:CDM 55(4 Study: Meta -analysis of trials oidopanne agon sts -

tart) N


1 yr since onset • persistent (chronic ) motor or vocal tic disorder: single or multiple motor or vocal tics ( but not both motor and vocal ) that have persisted for > 1 yr since onset • provisional tic disorder: single or multiple motor and/or vocal tics present for < I yr since first tic onset • other specified or unspecified tic disorder: symptoms characteristic of a tic disorder but do not meet full criteria • secondary tic disorders: encephalitis, C|D, Sydenham 's chorea , head trauma , drugs (stimulants, levodopa ), intellectual disability syndromes • ncurodegcncrativc diseases: neuroacanthocytosis, HD (see Huntington's Disease, N 34 ) Tic Types

• simple tics: short duration ( msec) • complex tics: longer (sec ), more purposeful and often include a combination of simple tics • motor tics jerking, shoulder shrugging, extension of the extremities • simple: blinking, head dystonic: bruxism ( grinding teeth ), abdominal tension , sustained mouth opening complex: copropraxia (obscene gestures ), echopraxia ( imitate gestures), throwing, touching

• vocal tics

simple: blowing, coughing, grunting, throat clearing complex: coprolalia ( shout obscenities ), echolalia ( repeat others' phrases), palilalia ( repeat own phrases)

Treatment

• mild tics: education , counselling, supportive care, Comprehensive Behavioural Intervention for T ics • debilitating tics: a - 2 adrenergic agonists ( guanfacine, donidine), antipsychotics (e.g. haloperidol , pimozide ), botulinum toxin, topiramate

Tourette’s Syndrome (Gilles de la Tourette Syndrome) DSM-V Definition

1. presence of both multiple motor and one or more vocal tics at some point during the illness, although not necessarily concurrently 2. tics may wax and wane in frequency but have persisted >1 yr since first tic onset (with no tic-free periods >3 mo) 3. onset is < 18 yr 4. not due to effect of a substance or another medical condition

Epidemiology • estimated prevalence among adolescents 3-8 in 1000 school -age children, M:F= 2-4:1 Signs and Symptoms • tics: wide variety that wax and wane in type and severity (see Tic Disorders - Tic Types) can be associated with the presence of premonitory feelings or sensations that are relieved by carrying out the tic can be voluntarily suppressed for some time can be worsened by anxiety, excitement, and exhaustion; improved by calm , focused activities • psychiatric: compulsive behaviour (associated with OCD and ADHD), hyperactive behaviour, “rages," sleep-wake disturbances, or learning disabilities

n LJ

+

Treatment • mild tics: (see Tic Disorders Treatment) • debilitating tics: DBS, (see Tic Disorders -Treatment)

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Toronto Notes 2023

NJ6 Neurology Prognosis

• typically begins between ages 4 -6

• peak severity occurs between ages 10-12, with a decline in severity during adolescence (50% are ticfree by age 18) • tic symptoms, however, can manifest similarly in all age groups and across the lifespan

Cerebellar Disorders Clinico-Anatomic Correlations

• vermis: trunk /gait ataxia • cerebellar lobe ( i.e. lateral ): rebound phenomenon, scanning dysarthria, dysdiadochokinesia, dvsmetria, nystagmus Symptoms and Signs of Cerebellar Dysfunction

-

• nystagmus: observe during EOM testing ( most common is gaze evoked nystagmus ) • dysarthria (ataxic): abnormal modulation of speech velocity and volume ( elicit scanning / telegraphic/ slurred speech on spontaneous speech) • hypermetric saccades • dvsmetria: under/overshooting the target during voluntary movement of limb or eye • dysdiadochokinesia: impairment of rapid alternating movements (e.g. pronation -supination task ) • rebound phenomenon: overcorrection after displacement of a limb • intention tremor typically orthogonal to intended movement, and increases as target is approached • hypotonia: decreased resistance to passive muscular extension (occurs shortly after injury to lateral cerebellum ) • pendular patellar reflex: knee reflex causes pendular motion of leg (occurs after injury to cerebellar hemispheres), pendular reflexes at triceps • truncal ataxia: on sitting, titubation ( rhythmic rocking of trunk and head ) • ataxic gait: broad based and lurching gait, difficulty with tandem gait ,

-

Wernicke- Korsakoff Syndrome • acute ( Wernicke’s encephalopathy) and chronic ( KorsakofFs psychosis) disorders caused by thiamine (vitamin Bl ) deficiency, see Psychiatry PS29 • etiology: alcohol use disorder, gastrointestinal disorders especially malabsorption, surgeries (e.g. gastric bypass), acquired immune deficiency syndrome, hemodialysis, malignancies • note that alcohol can also cause a cerebellar ataxia separate from thiamine deficiency; this ataxia can be due to cerebellar atrophy or alcohol polyneuropathy

.

Cerebellar Ataxias Congenital Ataxias

• early onset non - progressive ataxias associated with various syndromes as well as developmental abnormalities (e.g. Arnold-Chiari malformation, Dandy-Walker cysts) Hereditary Ataxias • autosomal recessive: Friedrich’s ataxia, ataxia with oculomotor apraxia, ataxia telangiectasia, ataxia with vitamin E deficiency Friedrich’s ataxia: prevalence 2 in 100000; typical onset between 8-15 yr signs: gait and limb ataxia, weakness, areflexia, extensor plantar reflex, impaired

proprioception and vibration, dysarthria death in 10-20 yr from cardiomyopathy or kyphoscoliotic pulmonary restriction • autosomal dominant: most commonly spinocerebellar ataxias (SCAs); 30+ types, most commonly due to CAG repeats • signs: ataxia and dysarthria, chorea, polyneuropathy, pyramidal and /or extrapyramidal features, dementia Acquired Ataxias

• neurodegeneration: multiple system atrophy, SCAs • systemic: alcohol, celiac sprue, hypothyroidism, Wilsons, thiamine deficiency, vitamin E deficiency • toxins: CO, heavy metals, lithium, anticonvulsants, solvents • vascular infarct, bleed, basilar migraine • autoimmune: MS, Miller-Fischer ( GBS) • primary and secondary neoplasm

n L J

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AL GRAWANY

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Toronto Notes 2023

X37 Neurology

Vertigo

s

• see Otolaryngology. 0112

Motor Neuron Disease

Face/throat iCramobulbul

: 5

Arm

I

iCervicall

:

Trunk (Thoracic )

Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease) Definition • progressive neurodegenerative disease that causes UMN and LMN symptoms and is ultimately fatal iLumbosacrall

Etiology •

idiopathic ( most common ), genetic (5- 10% familial, most commonly C9orf 72 mutation, other mutations include: SOD1, TARDBP)

Pathology • disorder of anterior horn cells of the spinal cord, cranial nerve nuclei, and corticospinal tract

Epidemiology • Sin 100000; incidence increases with age

_

L

Figure 22. Regions affected by ALS Adapted from: https://www.mda.orgdisease’ amyotrophic lateral.sclerosis/ srgn$ antS

-

- -

syrrptoms and labels: ALS and Other Motor Neuron Diseases ( 2017) lecture by Dr . Aaron Irenberg

Clinical Features • limb motor symptoms: segmental and asymmetrical UMN and LMN symptoms • bulbar findings: dysarthria ( flaccid or spastic or mixed ), dysphagia, tongue atrophy and fasciculations,

facial weakness and atrophy • pseudobulbar affect, FI D ( up to 10%) • sparing of sensation , ocular muscles, bowels, bladder, sphincters

Investigations • EMG: active and chronic denervation and reinnervation, fasciculations • NCS: to rule out peripheral neuropathy (e.g. multifocal motor neuropathy with conduction block ) • Cl'/MRl: to rule out spinal cord disease/compression Treatment

• riluzole ( modestly slows disease progression ) • symptomatic relief spasticity /cramping: baclofen , tizanidine ( Zanaflex * ), regular exercise, and physical therapy • sialorrhea : TCA (e.g. amitriptyline ), sublingual atropine drops, parotid and /or submandibular Botox* ( rare) • pseudobulbar affect: dextromethorphan and quinidine, TCA, SSR1 • edaravone is FDA and Health Canada approved; reduces functional decline by 33% in early stage ALS • non -pharmacologic: high caloric diet, ventilatory support (especially BiPAP ), early nutritional support (e.g. percutaneous endoscopic gastrostomy tube), rehabilitation ( PI', OT, SLP ), and psychosocial support

Prognosis

• median survival is 3 yr; death is typically due to respiratory failure

Other Motor Neuron Diseases • degenerative • progressive muscular atrophy ( progressive bulbar palsy ): only LMN symptoms with asymmetric weakness, later onset than ALS, 5-10% of patients in ALS centres (considered the isolated LMN version of ALS) • primary lateral sclerosis ( progressive pseudobulbar palsy ): UMN symptoms, later onset, not fatal , variable disability, 5 10% of patients in ALS centres (considered the isolated UMN version of ALS) • genetic spinal muscular atrophy: paediatric or adult-onset disease with symmetric LMN symptoms (genetic disorder) spino -bulbar muscular atrophy ( Kennedy disease): speech and swallowing difficulty and limb weakness ( X-linked genetic)

-

• infectious • post - polio syndrome • West Nile infection : residual asymmetric muscle weakness, atrophy

Safety and Efficacy of Edaravone in Bell Defiled Patients with Amyotrophic Lateral Sderosis: A fendomised . Double - Blind. Placebo-Controlled

Trial lancet Heurol 2017 ;16:505 -12 Purpose In assess the safety and eScacy of edararone in patients with early stage AIS Methods : 13 ? early -stage ALS set rests ceefrg stnogeni incloston criteria wera raodoofy ass g-ed to re cenre 60 mg IV edararone or IV sabre :acrid for 6 cydes (4 weeks / cycle with 2 weeks on. 2 weeks off ) for a ‘.ota! treatment duration of 24 weeks Pnaa-y Outcome: OifferencE in tie lersed ALS frrbonal Rat.ig Scale (ALSftS -RI score tom base me to 24 weeks Besnlts: TheALSFRS- R score caasgewas -5.01|Se 0.64|and - 7 . S010.66 ) in the eda »arone grousard placebo, respectively . The betweec -grocp ieasl sguares mean difference was 2.49 (S6 0.76. 9 SV 0 039 - 3.98: P‘0.0013), lias favourrgelareiane. Airese even's were similar a bo3 g-wps Condnsion: In early-sfage ALS pateris idertiied c ppst- ooc analysis of a previous pbase 3 study edaravone significantly reduced fee decree tf ,

MSRS-t scores

m

The only interventions shown to extend survival in ALS are riluzole and use of BiPAP. Edavarone in early ALS can decrease functional decline

Red Flags Inconsistent with ALS Sensory Sx. predominant pain, bowel Of bladder incontinence ocular muscle weakness

Denervation on EMG Fibrillations, positive sharp waves, complex repetitive discharges

Reinnervation on EMG Increased amplitude and duration of motor units

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Peripheral Neuropathies Diagnostic Approach to Peripheral Neuropathies 1. differentiate: motor vs. sensory vs. autonomic vs. mixed 2. pattern of deficit: symmetry, focal vs. diffuse; upper vs. lower limb; cranial nerve involvement 3. temporal pattern: acute vs. chronic; relapsing/ remitting vs. constant vs. progressive 4. history: PMHx, detailed I Hx, exposures (e.g. insects, toxins, sexual, travel ), systemic symptoms 5. detailed peripheral neuro exam: LMX findings, differentiate between root and peripheral nerves, cranial nerves, respiratory status

Diabetic Neuropathies • Peripheral neuropathy: pain or loss of sensation in a stocking-glove distribution ( hands and feet affected before arms and legs) • Autonomic anhidrosis, orthostatic hypotension, impotence, gastroparesis. bowel, and bladder dysfunction Mononeuropathy multiplex: nerve infarct or compression • Cranial neuropathy:CN III (pupil sparing) > IV > VI • Lumbosacral plexopathy fee. diabetic amyotrophy)

.

DDx of Demyelinating Neuropathy GBS. OOP. paraproteinemia, diphtheria,

.

radiculopathy

polyradiculopathy

ICE)

syndrome )

Icauda equina

plexopathy ( brachial )

mononeuropathy ( peroneal )

mononeuropathy multiplex

polyneuropathy

amiodarone Charcot -Marie- Tooth (including hereditary neuropathy with liability to pressure palsy), storage diseases, pressure palsy predisposition, paraneoplastic

Figure 23. Pattern of distribution for peripheral neuropathies

Classification • radiculopathy: dermatomal sensory deficit and myotomal weakness in distribution of single nerve root (e.g. C7) • often due to disc herniation or root compression causing radicular pain » little tactile anesthesia, as dermatomes overlap • polvradiculopathy: multiple dermatome sensory deficits and myotomal weakness • due to multiple nerve root lesions (e.g. cauda equina syndrome due to lumbosacral roots lesion ) • plexopathy: deficit matching distribution of a nerve plexus • due to lesion distal to nerve roots but proximal to origin of individual peripheral nerves

brachial plexopathy upper (C5 C7 ): LMX Sx of shoulder and upper arm muscles ( Hrb 's palsy) lower (C8 TI ): LMX Sx and sensory Sx of forearm and hand ( Klumpke’s palsy ) DDx: trauma, idiopathic neuritis, tumour infiltration , radiation, thoracic outlet syndrome (e.g. cervical rib) lumbosacral plexopathy ( rare, especially unilateral ) DDx: idiopathic neuritis, infarction (e.g. DM ), compression • mononeuropathy: single nerve deficit • carpal tunnel syndrome ( most common): compression of median nerve at wrist symptoms: wrist pain, paresthesia first 3 and Vi digits, ± radiation to elbow, worse at night signs: Tinel’s sign, Phalen’s test, thenar muscle wasting, sensor)' deficit EMG/ NCS: slowing at wrist ( both motor and sensory) etiology: entrapment, pregnancy, DM, gammopathy, rheumatoid arthritis, thyroid disease Bell’s palsy (most common cranial neuropathy): see Otolaryngology, OT23 • entrapment / compression: ulnar (compression at elbow'), median ( at pronator teres), radial (at spiral groove of humerus ), obturator (from childbirth ), peroneal (due to crossing legs or surgical positioning ), posterior tibial (tarsal canal ) • mononeuropathy multiplex: subacute involvement of multiple individual peripheral nerves in asymmetric, non-length -dependent manner; often painful • must rule out vasculitis or collagen vascular disease; consider MMN ( multifocal motor neuropathy) or MADSAM ( multifocal acquired demyelinating sensory and motor neuropathy), multiple compressive neuropathies • polyneuropathy: chronic progressive involvement of multiple peripheral nerves in symmetrical, distal predominant pattern • length -dependent, i.e. longest fibres affected first (stocking glove distribution ) sensorimotor, with progression of dysesthesia earlier and weakness later etiology: DM ( most common ), renal disease, substances, toxins, genetic, SLE, HIV, leprosy, alcohol, Bi:deficiency

-

-

Tinet’s Sign Tap lightly over the median nerve at the wrist the patients symptoms of carpal tunnel will be elicited in a positive test

Phalen’s Test Hold both wrists in forced flexion (with the dorsal surfaces of the hands pressed against each other ) for 30-60 s: test is positive if symptoms of carpal tunnel are elicited

Axonal neuropathies have decreased amplitude on NCS: demyelinating neuropathies have decreased conduction velocity on NCS

Ototoxic drugs (e.g. aminoglycosides) should not be given to diabetics Sensory neuropathy of the feet prevents them from adequately compensating for loss of vestibular function

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chronic inflammatory demyelinating polyneuropathy (C1DP) chronic relapsing sensorimotor polyneuropathy or polyradiculopathy with increased protein in CSF and demyelination (shown on EMG / NCS) • course is fluctuating, in contrast with the acute onset of GBS • treatment: first -line is prednisone; alternatives are plasmapheresis, 1 V 1G, and azathioprine

•

Table 19. Differential Diagnosis of Symmetric Polyneuropathy Vascular*

Etiology

Mechanism

Course

Modalities

Investigations

PAN

Ischemic

Chronic

S/M

SiI-Hi

: l In M]

RH 2 I

SIE

Ischemic

Chronic

See Rheumaloloqy.

Si' M

RH 11

Infectious

.

RA

Ischemic

Chronic

SIM

Soc Rheumatology RH8

HIV

Aional

Chronic

S /A

leprosy

Inliltralive

Acute

S/A

HIV serology leprosy serology Nerve biopsy

tyme

Atonal

Chronic

M

lyme serology

Immune *

GBS

Demyelination

Acute

M

Hereditary

CI 0 P HMSN

Demyelination Chronic Atonal /demyelinalron Chronic

Neoplastic

Paraneoplastic

Atonal /dcmyelinalron Chronic

S/ M S /M S/ M

IP | t ptolein. no t cells) IMG IP It protein) EMC

Myeloma

Aional /demyelination Chronic

S/ M

lymphoma

Atonal

Monoclonal gammopathy

Aional / Demyelination Chronic

Toxin

Metabolic

Chronic

M

S/ M

SPEP Bone marrow biopsy

Sub acute Sub acute

-

S/ M

GGT, MCV

Atonal

S/M

Urine heavy metals

Medications

Atonal

Sub - acute

S/ M

DM

Ischemic /axonal

Chronic

S/A

Drug levels Easting glucose. HbAIc, 2 h 0GTT

Hypothyroidism

Atonal

Chronic

S/ M

ISH T3 T4

Renal failure

Atonal

Chronic

S /A

Electrolytes. Cr. BUM

Sub - acute Sub acute

S/ M

Vitamin Bu

M

Urine porphyrins

Si' M

SPEP Nerve biopsy

Budeficiency

Atonal Atonal

Amyloid

Atonal

Sub - acute to chronic

poTyneuropathy eitnhitingclassic hereditary neuropathy phenotype. Screen lor CMI1A duplication/ deletion hnd Ci32 mutations.

antibodies SPEP Skeletal bone survey SPEP 8one marrow biopsy

Atonal

Porphyria

Genetic Testing Indicated for urPtogenic

Paraneoplastic

EtOH

Nutritional

.

electrophoresis

Genetic testing

Heavy metals (e.g. lead )

Other

Evaluation of Distal Symmetric Polyneuropathy: Hole cl laboratory and Genetic Testing Meuro'ogy 2005.12:185192 Screening laMests: flood glucose, serum Dr mil) metabolites, serum protemimmunohication

. .

A = autonomic: CIDP = chronic irillumrnutory demyelinating polyneuropathy: GGT = gamma - glutamyl transferase; HMSN = hereditary motor sensory neuropathy: M motor ; OGTT oral glucose tolerance test: PAN polyarteritis nodosa: RA rheumatoid arthritis:S sensory; SLE systemic lupus erythematosus: SPEP = serum protein electrophoresis * Neuropathies of vascular etiology usually present as mononeuropathy multiplex * Neuropathies of Immune etiology usually piesent as polyradiculopathy

=

-

-

=

=

=

Guillain- Barre Syndrome Definition

• acute (evolving over 4 wk or less ) rapidly evolving demyelinating inflammatory polyradiculoneuropathy that often starts in the distal lower limbs and ascends Etiology • autoimmune attack and damage to peripheral nerve myelin • usually preceded by viral/ bacterial infections Signs and Symptoms • sensory: distal and symmetric paresthesias, loss of proprioception and vibration sense, neuropathic pain • motor: weakness starting distally in legs and progressing proximally, areflexia • autonomic: blood pressure dysregulation, arrhythmias, bladder dysfunction

In GBS. IVIG and plasmapheresis lead to mote rapid improvement, less intensive care and less ventilation, but do not change mortality or relapse rate

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GBS is a neurological emergency due to risk of imminent respiratory failure

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Investigations • CSF: albuminocytologic dissociation ( high protein, normal WBC ) • EMG/ NCS: conduction block, differential or focal ( motor > sensory ) slowing, decreased 1 - wave, sural sparing

The most commonly identified antecedent infection in GBS is Campylobacter jejuni

Treatment • 1VIG or plasmapheresis, pain management, monitor vitals and vital capacity

-

-

Miller Fischer Variant of GBS Triad • Ophthalmoplegia • Ataxia Areflexia

Prognosis • peak of symptoms at 2-3 wk, plateau or resolution at 4 -6 wk • 5% mortality ( higher if require 1CU ), up to 15°u have permanent deficits

.

Neuromuscular Junction Diseases Clinical Approach to Disorders of the Neuromuscular Junction Table 20. Common Disorders of the Neuromuscular Junction Myasthenia Gravis

-

Lambert Eaton

Botulism

Ocular; Buliar Paresis

(early)

o

Neuromuscular Junction Disease

limb Weakness

• Diseases of the NMJ typically feature

Fatigability

• Fatigability can be tested by holding the arms out or by holding the ga2e in the upward position (especially in MG ) • Muscle weakness due to fatigability will improve with rest and /or ice

prominent fatigability

Post - Eiercise Enhancement Reflexes

N

«

«

Anticholinergic Si

++

Sensory Si

Associated Conditions

Thymoma

Small cell carcinoma

GISSS

Repetitive EMG Stimulation

Decremental response

Incremental response

t (rapid stimulation) ( slow stimulation )

Myasthenia Gravis

Ca:' channel

Etiology and Pathophysiology • autoimmune disorder of the NM ) , commonly associated with anti AChR or MuSK antibodies • 15% of patients with \1G have associated thymic neoplasia, 85% have thymic hyperplasia

-

Epidemiology • bimodal age of onset, 20s ( mostly women ) and 60s ( mostly men ) Clinical Features • fatigable, symmetric, or asymmetric weakness without reflex changes, sensory changes, or coordination abnormalities • ocular (diplopia/ ptosis ), bulbar ( dysarthria /dysphagial , and /or proximal limb weakness • symptoms may be exacerbated by infection , pregnancy, menses, and various drugs • respiratory muscle weakness may lead to respiratory failure

Investigations • repetitive stimulation: decrement in amplitude >10% • single fibre electromyography: shows increased jitter (80 100% sensitivity ) • spirometry: forced vital capacity may be used to monitor adequacy of respiratory effort over time • AChR antibody assay (50 -90% sensitivity ); anti-MuSK antibody may be used if seronegative for antiAChR antibody • CT / MR1 chest: screen for thymoma / thymic hyperplasia • edrophonium ( Tensilon*) test: assess for improvement over 2 min following edrophonium injection ( no longer performed )

NO CONTRACTION

-

® Minyan Wang 2012V

Figure 24. Myasthenia gravis

G

Tensilon! is a drug that inhibits acetylcholinesterase. It improves muscle function immediately in MG, but not in a cholinergic crisis. This test is infrequently used as this drug is no longer available . but if performed , a crash cart should be nearby as respiratory difficulty and/or bradycardia may occur

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Treatment

• acetylcholinesterase inhibitors (e.g. pyridostigmine): first line treatment • corticosteroids (e.g. prednisone ): mainstay of treatment if acetylcholinesterase inhibitors not effective • short-term immunomodulation (e.g. 1V1G and plasmapheresis): for crisis • long- term immunosuppression (e.g. azathioprine, cyclophosphamide, mycophenolate ): can be used as steroid-sparing therapy • Newer medications that are more disease specific: Eculizumab ( complement inhibitor ), Efgartigimod ( neonatal l'c receptor blocker) • thymectomy: option in non - thymomatous AChR-antibody- positive generalized MG (85% remission rate)

Prognosis

• 30% eventual spontaneous remission • with treatment, life expectancy is equal to that of a person without MG, but quality of life may vary

Lambert- Eaton Myasthenic Syndrome Etiology and Pathophysiology

• autoimmune disorder due to antibodies against presynaptic voltage-gated calcium channels, causing decreased ACh release at the NMJ • 50-66% are associated with small cell carcinoma of the lung

Randomized Trial of Thymectomy in Myasthenia Gravis MEJH 2016;375:511-22 Purpose: Toconaa ethe efficacyollkymectoniypMs prednisone vs. prednisone done in the treatment of M . Methods: 126 patients with generalized oonthynomatoos M6 Icliitical class H IV disease 60 yr • Shingrix* is a recombinant vaccine, recommended for patients >50 yr ( more efficacious than Zostavax*)

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Treatment

• medical: TCA ( e.g. amitriptyline), anticonvulsants (e.g. pregabalin, gabapentin ), analgesia (e.g.

-

opiates, lidocaine patch ), intrathecal methylprednisolone, topical capsaicin early treatment of acute herpes zoster with antivirals ( longer-acting famciclovir and valacydovir more effective) treatment of herpes zoster with corticosteroids does not decrease PHN surgical: spinal tractotomy, dorsal root entry zone lesion, DBS of thalamus

Painful Diabetic Neuropathy •see hndocrinologv. h 16 Approach •determine if pain is neuropathic or vascular • more likely neuropathic if pain is present at rest and improves with walking, pain is sharp/ tingling, more in feet » calves

-

Treatment

•level A: pregabalin •level B: venlafaxine, duloxetine, amitriptyline, gabapentin , valproate, rarely opioids, capsaicin

Complex Regional Pain Syndromes Definition • regional pain disproportionate to an inciting event (e.g. fracture, stroke), typically lasting 4-6 rvk

Diagnosis

• clinical diagnosis consistent with the Budapest Criteria: 1. continuing regional pain disproportionate to an inciting event 2. patient must have symptoms in 3 of the 4 categories, and must have signs in 2 of the 4 categories (a sign must be observed at the time of diagnosis): sensory: hyperesthesia and/or allodynia vasomotor: temperature and /or skin colour asymmetry sudomotor/edema: edema, sweating changes, and /or sweating asymmetry motor/trophic:decreased range of motion, motor dysfunc tion (weakness, tremor, dystonia ) and /or trophic changes ( hair, skin, nail ) 3. absence of any other diagnosis that would better explain the signs or symptoms • bone scintigraphy < 5 mo of symptom onset may support diagnosis ( negative test does not rule it out ) • MRI may help rule out other causes of regional pain if indicated

Classification • CRPS type 1 (reflex sympathetic dystrophy): minor injuries of limb or lesions in remote body areas precede onset of symptoms • CRPS type II (causalgia ): injury of peripheral nerves precedes the onset of symptoms Prevention

• early mobilization after injury/infarction Treatment

• goal of treatment is to facilitate function • conservative treatment education, support groups, PT, OT, smoking cessation • medical: topical capsaicin; I CA; NSAID; tender point injections with corticosteroid/lidocaine; gabapentin / pregabalin / lamotrigine; calcitonin or bisphosphonates; oral corticosteroids • surgical: paravertebral sympathetic ganglion blockade • refer to pain management clinic

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Headache •see Emergency Medicine. ER 23 and lamiiy Medicine. EM 36 Clinical Approach • history

pain characteristics: onset, frequency, duration, intensity, location, radiation , other specific features (e.g. worse in AM, worse with bending /coughing / Valsalva ) associated symptoms: visual changes, change in mental status, N / V, fever, meningismus, photophobia, phonophobia, temporomandibular popping/clicking, jaw claudication, neurological symptoms • precipitating/ alleviating factors ( triggering factors, analgesics), medications (especially nitrates, calcium channel blockers, NSAlDs, anticoagulants ), PMHx, l 'Hx • red Hags ( possible indications for CT scan /further investigation ) “SNOOP4”: Systemic symptoms or 2" risk factors ( fever, weight change, immunocompromised ); Any focal neurological symptoms on history or exam;; Onset sudden ( 'thunderclap' ); Older age ( new- onset headache > 50 yr); Pattern change; Positional; Progressive; Precipitated by Valsalva; Pregnancy CSVT/llH / Preeclampsia • physical exam • vitals ( including BP and temperature ), Jolt accentuation / Kernig’s/ Krudzinski 's, MSK examination of

-

-

head and neck

• HEEN l : fundi ( papilledema, retinal hemorrhages), red eye, temporal artery tenderness, sinus '

palpation, I M| full neurological exam ( including LOG, orientation, pupils (symmetry), and focal neurological deficits ) red Hags: papilledema, altered IOC, fever, meningismus, focal neurological deficits, signs of head trauma

Classification • primary tension , migraine , cluster , autonomic cephalgias , short - lasting unilateral neuralgiform headache with conjunctival injection and tearing ( SUNCT ) •.secondary • cervical OA , TM| syndrome, SAH , ICH , stroke, venous sinus thrombosis , meningitis/ encephalitis , trauma , increased ICP ( space - occupying lesion, malignant HTN , or IIH ) , temporal arteritis , sinusitis, acute - angle closure glaucoma , pre - eclampsia , post LP, drugs / toxins ( e .g . nitroglycerin use and analgesia withdrawal ); all can be associated with serious morbidity or mortality

-

Prevalence Age of Onset Sex Bias Family Histoiy location

Migraine

Cluster «

15 - 40

10 20 % 10 30

f >M

f -M

--

None Bilateral frontal Nuchal occipital

-

10 min 2 h Oaily attacks lor weeks lo months; mote common early AM or lale PM Constant , aching, stabbing Severe ( wakes Irom sleep )

Hours days

Onset/Course

Gradual, worse in

Gradual, worse in PM ; can also be acute Pulsating, throbbing

Ouality Severity Triggers / Provoking

Band - like , constant Mild - moderate (doesnotwakeyouup from sleep)

Palliating Associated Symptoms

Moderate-severe

Hunger

Noise / lighl Calfe in e/alcohol Hunger Stress

Sleep deprivation

Sleep deprivation

Rest No vomiting No photophobia

N /V

Depression

Anxiety Noise

Rest Photo/ phonophobia /osmophobia t Aura

Management

Non pharmacological: Eliminating known triggers Healthy lifestyle: sleep, diet ( protein for breakfast), exercise, hydration, be aware of technology use, vitamin/ minerals Psychological counseling Physical modalities (e.g. heat, massage) Pharmacological Vitamins /minerals - Magnesium citrate. Riboflavin (Vitamin B 2), Coenzyme 010, Melatonin ifinsomnia or difficulty falling asleep Simple analgesics: Tylenol, NSAlDs

20 40 M »f Retro orbital Supraorbital

Minutes days

PM

n

Unilateral > bilateral (in adults especially ) Frontotemporal

Duration

Episodic or chronic

Headache DDx

ER VISIT Ey e (acute angle closure glaucoma, sinusitis) Recurrent /Chronic ( migraine, tension, cluster, temporomandibular joint disease, cervical 0A) Vascular ( SAH ICH temporal arteritis) Infectious ( meningitis, encephalitis) Systemic (anemia, anoxia CO preeclampsia) ICP ( mass /abscess HTN encephalopathy IIH) Trauma (concussion SOH epidural headache)

. .

. .

. .. .

Trialof Gakaneiumabin Prevention ol Episodic Cluster Headache HE JM 2019:381: 132 41 Purpose Toinvestigate the efticacy and safety ol galcanetumab a t preventive treatment lor cluster

headache. Methods 106 patients who had m n . oneattacX every other dry mm. four total attacks, and mac eight attacks' d . pi us a history of cluster headache

.

Table 22. Headaches - Selected Primary Types Tension Type 30 40%

If CT is negative but clinically there is suspicion of SAH or meningitis, perform an LP

Acute Rxi'Abortive:

NSAlDs Triplans

Ergotamine Valproate Anti emetics CGRP Antagonists

-

Prophylaxis / Prevenlive:

TCA CCB Anticonvulsants (3 - Blockers

temporal

-

light fclOrt

Walking around Red watery eye Eyelid , forehead swelling Nasal congestion or rhinorrhea Unilateral Horner's Acute Rx 02 Sumatriptan ( nasal or injection ) Prophylaxis Verapamil

Lithium Methysergide Prednisolone Valproate CGRP antibody

cdildlti - i) 6 * re « S. r «e lfd3M 11 galcanerumabor placebo, administered SC al baseline and 1 month. Results: Alter 3 weeks, the mean reduction m the weekly frequency ol duster headache attacks was 8.2 attacks in the galcanetumab group is. S.2 m the placebo group (difference. 3.5/wk:95% Cl. 0.2-6.7: P 0.04 ) , and the proportion ol patients who had a reduction of >60% in headache frequency was 71% and 53% respecting ( P 0.046|. Incidence of adverse events were similar in both groups. Conclusion : Galcanetumab reducedthe weekly frequency of attacks ol episodic cluster headache. -

'

-

-

.

Antiepileptics in Migraine Prophylaxis: An Updated Cochrane Review C ephalag a 2015:35:51-62 Purpose: lo review the evidence for anticonvulsants in migraine propItylacbts. Study: Systematic meta - analysis ol 32 published and 3 unpublished prospective, controlled trials of regular use of anticonvulsants to prevent migranes and/or improve quality of life related to migraines. Results: Sodium valproate and toprramate were associated with a reduction of 4 d and1 d of headache per month, respecbveiy and patents taking either drug were more than 2 times as likely to experience greater than 50% reducton in headache frequency, vs. placebo. Neither drag was associated with undue

.

rates of adverse events, though higher doses of topiramate were associated with increased adverse

events. There is insufficient evidence of efficacy with other antiepileptic drags, including ga oapentin. for

rn

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'

migraine prophylaxis. Conclusions: Daily sodium valproate 400 mgand topiramate 50 mgare well tolerated and effective in prnpbyf actic treatment nf migraine headache in adults.

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Table 23. Prophylactic Management of Migraine Headaches Class

Drug

Evidence

Contraindications

Side Effects

p - blockcrs

Propranolol

A

A

Asthma. DM (mask hypoglycemia)

Fatigue

Timolol

CHF

lightheadedness

Metoprolol

B

Amitriptyline

A

Nortriptyline

C

Heart disease, glaucoma Avoid in elderly

Sedation Dry mouth Weight gain lighlheadcdness

TCA

CCDs AED

Depression

Flunariiine

A

Depression, obesity

Weight gain, depression, PD (rare)

Verapamil

B

Heart disease

Weight gam (4.5 - 9 kg ), constipation

Valproate

A

Liver,, pancreatic disease

Weight gain, elevated liver enzymes/ hyperammonemia, tremor, alopecia, teratogenic:neural tube defect

Topiramate

A

Renal disease

Paresthesia, acute angle - closure glaucoma, weight loss, cognitive: memory loss, difficulty concentrating, renal stone (rare)

Table 24 . Headaches - Selected Serious but Rare Secondary Types Meningeal Irritation

Increased ICP

Temporal Arteritis »60 yr

Agcol Onset

Any age

Any age

location

Generalized

Any location

Temporal

Onset/Course

Gradual; worse nocturnal and AM

Variable

Severity

Meningitis: houis-days SAH: thunderclap onset Severe

Severe

Variable, can be severe

Provoking

Head movement

lying down Valsalva Head low Exertion

Jawdaudication

Associated Symptoms

Heck stiffness Photophobia Focal deficits (e g. CN palsies)

N/ V Focal neurological symptoms Decreased LOC

Polymyalgia rheumatica Visual loss

Physical Signs

Kernig’ssign Brudzlnskl'sslgn Meningismus CT/ MRI with gadolinium. IP. antibiotics for bacterial meningitis

Focal neurological symptoms Papilledema

Temporal aitery changes: firm , nodular . Incompressible, tender

Management

Meningitis. SAH

Etiology

CT/MRI and treatment to reduce pressure Prednisone See Neurosurgery. IIS 6 and NS8 See Rheumatology, RH22

.

Tumour CSVT , IIH, malignant HTN

Vasculitis (GCA )

Migraine Headaches Definition (Common Migraine)

• > 5 attacks fulfilling each of the following criteria • 4 72 h in duration • 2 of the following: unilateral , pulsating, moderate severe ( interferes with daily activity ), aggravated by routine physical activity • 1 of the following: N / V, photophobia / phonophobia /osmophobia • not better accounted for by another diagnosis

-

-

Epidemiology

• 18nu females, 6% males; frequency decreases with age (especially at menopause ) • in pre pubertal children , more commonly seen in males; post pubertal, more commonly seen in females

-

-

Migraine auras can mimic other causes of transient neurological deficits (e.g. TIAs and seizures)

‘‘Menstrual Migraine" Subtype

Migraine headache that is associated with the onset of menstruation - usually 2 d before to 3 d after the onset of menstrual bleeding

Etiology and Pathophysiology • theories of migraine etiology

depolarizing wave of "cortical spreading depression" across the cerebral cortex that may cause an aura (e.g. visual symptoms due to wave through occipital cortex ) and activate trigeminal nerve afferent fibres • possible association with vasoconstriction /dilation • significant genetic contribution • triggers: stress, sleep excess/ deprivation , drugs (estrogen, nitroglycerin ), hormonal changes, caffeine withdrawal, chocolate, tyramines (e.g. red wine ), nitrites (e.g. processed meats)

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Signs and Symptoms • stages of uncomplicated migraine 1. prodrome ( hours to days before headache onset ) 2. aura 3. headache 4. postdrome • aura self-resolving symptom of focal cerebral dysfunction lasting 10 d / mo, or use of NSAlDs for >15 d/ mo) can lead to medication -overuse headaches

If patient presents to ED with severe migraine and NA/ consider treating with IV fluids and anti emetics

(chlorpromazine . prochlorperazine)

s

Sleep Disorders Overview of Sleep Recommendations • newborn: 18 h sleep (50% REM ), adolescents: 10 h, adults: 7 9 h but most get insufficient amounts • many older patients have reduced sleep as a consequence of underlying sleep disorders

-

Sleep Architecture • PSG measures: EEG, eye movements (electro -oculogram - EOG ), EMG, respiratory effort, oxygenation, ECG

Table 25. Sleep Stage Characteristics EEG

EOG

Muscle Tone

Alpha waves: high

Rapid,blinking

High

Slow, roving eye movements

High, but gradually dropping

K complexes ( high voltage negative and positive discharges) with sleep spindles (12-14 Hz) are central and midline

Still

High

Stage N3 (previously 3 and 4) SJow Wave Delta Sleep ( 20%)

Delta waves:low frequency (75 pV)

Still

Rapid Eye Movement Sleep (~2S%)

Sawtooth waves, mixed frequency,low voltage

Rapid eye movements

Waking State

The oral contraceptive pill is contraindicated with complicated migraine due to risk of stroke • Can still use non -estrogen based forms of birth control (e.g. copper IUD, Depo- provera shot

frequency (8 -12 Hz), moderate amplitude Beta waves: frequency >13 Hz low amplitude

Other Characteristics

Elements of Sleep History Initiation of sleep Events prior to bed Lights latency (estimated ) Restless legs Hallucinations Maintaining sleep Number of nighttime awakenings Sleep walking/talking Snoring / gasping Drearm/nightmares Consequences of sleep Restorative Morning headache Falling asleep In inappropriate setting

.

Stage N1(~5%)

*50% Alpha waves ( see above), mixed with slow wave activity (theta 4-7 Hz)

.

-

Stage M2 ( 50%)

-

.

Marker for very light quality sleep or sleep disruption

Drug Effects on Wakefulness and Sleep • Antihistamines increase sleepiness • Stimulants increase arousal • Caffeine (an adenosine antagonist) increas wakefulness • Benzodiazepines reduce amount of slow wave sleep and cause sleepiness

Low

Very low

Homeostatic sleep Reduced BP. HR. cardiac output, RR Growth hormone release

• Antidepressants (TCAMAOISSRI) reduce amount of REM sleep and prolong REM latency • Alcohol may hasten sleep onset but is associated with increased nightime arousals and poor sleep efficency

Irregular respiration HR variation Classical dreaming state

Avoid sleep medications (especially in elderly patients) due to increased risk of falls, pseudodepression , and memory loss

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N'I9 Neurology

Coma • see Neurosurgery, NS40

Insomnia Definition

• difficulty initiating or maintaining sleep, or waking up earlier than desired (leading to sleep that is chronically non restorative/poor quality ) despite adequate opportunity and circumstances for sleep

-

Types

• sleep state misperception, psychophysiologic insomnia (learned sleep- preventing associations i.e. clock watching), idiopathic ( lifelong difficulty) secondary causes psychiatric disorders (80% of psychiatric patients): i.e. depression and anxiety (see Psychiatry, PS12 and PS15 ) neurologic disorders: i.e. neurodegenerative disease, epilepsy, neuromuscular disorders sleep disorders: i.e. RLS ( sleep initiation difficulties ), sleep apnea (sleep maintenance difficulties) medical conditions: i.e. pregnancy, cardiorespiratory ( COPD/heart failure ), gastroesophageal reflux disease, pain (arthritis, fibromyalgia, cancer) drugs/toxins: i.e. caffeine, alcohol, stimulants, antidepressants, steroids, sedative withdrawal fatal familial insomnia: i.e. rare genetic prion protein mutation causing autonomic dysfunction

Treatment

sleep log, sleep hygiene, stimulus control, sleep restriction, relaxation response, CBT, melatonin

Sleep Apnea

.

• see Respirology R 29 Definition

• disorder of breathing in sleep associated with sleep disruption and consequent excessive somnolence (or drowsiness)

Epidemiology

• > 6% of the Canadian population • correlated with obesity • significant morbidity: HTN, stroke, heart failure, sleepiness, mortality ( accidents) Types • obstructive sleep apnea; etiology: collapse of airway due to low muscle tone in deep and REM sleep • central sleep apnea: no effort to breath >10 s; etiology: heart failure, opiates, brainstem pathology, myotonic dystrophy • mixed apnea: combination of both central and obstructive sleep apnea

Diagnosis

-

• PS(i or ambulatory sleep monitoring device apnea hypopnea index ( AHI ) or respiratory disturbance index ( RDI ) 5

Treatment

• weight loss, positional therapy, dental devices, CPAP (common ), surgery ( rare), ensure driving safety

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X50 Neurology

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Restless Legs Syndrome and Periodic Limb Movement in Sleep •RLS: urge to move legs accompanied by uncomfortable sensations that begin or worsen with rest, is partially or totally relieved with movement, and is worse in evening /night; these features cannot be

accounted for by another medical / behavioural condition • PLMS: involuntary, jerking movements of the legs during sleep, diagnosed with PSG •epidemiology: 10% North Americans, 90% of RLS have PLMS , 50% of patients with PLMS have RLS •associated conditions: peripheral nervous system ( radiculopathy, neuropathy ), pregnancy, iron deficiency, alcohol use, PD, uremia/renal failure Treatment •underlying contributors ( iron and B 12 supplementation ), dopaminergic agonists ( first line), clonazepam ( causes tachyphylaxis), gabapentin, opioids ( only exceptional circumstances )

•NOT recommended: levodopa /carbidopa (Sinemet*) which causes augmentation

Narcolepsy Definition • excessive daytime sleepiness (all narcolepsy ), cataplexy (loss of muscle tone with emotional stimuli, pathognomonic), sleep paralysis (unable to move upon wakening), hypnagogic and hvpnopompic

hallucinations ( vivid hallucinations while falling asleep or waking up, respectively ) Epidemiology • prevalence 1 in 2000, onset in adolescence/early' adulthood; life-long disorder

Etiology • presumed autoimmune attack on orexin/hypocretin system, post head injur)', MS, hypothalamic tumours; rarely familial

Diagnosis • based on clinical history and multiple sleep latency test findings of short sleep latency < 8 min and REM within 15 min of sleep onset on 2 /4 naps

Treatment • sleep hygiene and scheduled brief naps, restricted driving • alerting agents: modafinil ( non -amphetamine stimulant ), stimulant ( i.e. methylphenidate )

• anticataplectic: TCAs, SSRls, sodium oxybate

Parasomnias Definition • unusual behaviours in sleep with clinical features appropriate to stage of sleep

Etiology • in elderly, REM sleep behaviour disorder may be associated with PD; in children , slow wave sleep arousals (sleep walking ) may be associated with sleep-disordered breathing Diagnosis • dinical history in children, polysomnography in adults to exclude nocturnal seizures

Treatment • behavioural management ( safety, adequate sleep), clonazepam for REM sleep behaviour, tonsillectomy

if appropriate in children

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N 51 Neurology

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Central Nervous System Infections .

• see Infectious Diseases 1D17

Spinal Cord Syndromes • sec Neurosurgery. NS34

Hypertension Encephalopathy Acute severe HTN (typically d8P >130 or sBP >200) can cause hypertensive encephalopathy. Abnormal fundoscopic exam (papilledema , hemorrhages, exudates, cotton wool spots), focal neurologic symptoms N /V, visual disturbances, seizures, and change in IOC

.

Stroke Terminology • stroke: focal cerebral, spinal, or retinal infarction in a defined vascular distribution infarction is permanent tissue injury (confirmed by neuroimaging ) • 11A: transient ( < 24 h ), episode of neurological dysfunction caused by focal brain , spinal cord or retinal ischemia without acute infarction on CT or MR! may present with amaurosis fugax ( transient monocular painless vision loss)

Consider transfer of acute stroke patient to a designated stroke centre for neuroprotective or thrombolytic therapy, and endovascular therapy ( EVT) if the patient is seen in first few hours

'

Pathophysiology

-

Early seizure activity occurs In 5 25% of patients after ICH

• two major types: ischemic (~ 80% ) and hemorrhagic (~20%) 1. ischemic

arterial thrombosis: thrombus formation in artery ( local / / n situ ) large vessel: stenosis or occlusion of the internal carotid artery, vertebral artery, basilar artery, or middle/anterior / posterior cerebral arteries - mechanism: insufficient blood flow beyond lesion ( hemodynamic stroke) - underlying processes: atherosclerosis (most common cause ) , dissection , and

vasculitis small vessel / lacunar

- mechanism: chronic HTN and DM cause vessel wall thickening and decreased

luminal diameter affects mainly small penetrating arteries ( primarily basal ganglia , internal capsule, and thalamus) • cardioembolic: blockage of cerebral arterial blood flow due to thrombus originating from a cardiac source atrial fibrillation ( most common ), rheumatic valve disease, prosthetic heart valves, recent Ml, fibrous and infectious endocarditis systemic hypoperfusion ( global cerebral ischemia ) • inadequate blood flow to brain , usually secondary to cardiac pump failure ( e.g. cardiac arrest , arrhythmia, or Ml ) primarily affects watershed areas ( between the major cerebral arterial territories)

-

2. hemorrhagic

intracerebral hemorrhage hypertensive ( most common ): due to chronic arteriosclerosis which predisposes vessels to focal necrosis and pseudoaneurysm formation eventually leading to intraparenchymal hemorrhage; most common sites are putamen, caudate nucleus, thalamus, cerebellum , and

pons other: trauma , amyloid angiopathy ( associated with lobar hemorrhage), vascular malformations, aneurysms, vasculitis, drug use (cocaine or amphetamines ) • SAH , see Ncurosuruerv. NS 22 Stroke Syndromes According to Vascular Territory • ACA: contralateral leg paresis, sensory loss, cognitive deficits (e.g. apathy, confusion , and poor judgment ) • MCA: proximal occlusion involves contralateral weakness and sensory loss of face and arm cortical sensory loss may have contralateral homonymous hemianopia or quadrantanopia if dominant ( usually left ) hemisphere: aphasia • if non - dominant ( usually right ) hemisphere: neglect eye deviation towards the side of the lesion (away from the weak side )

Cerebral venous sinus thrombosis should be considered in the differential diagnosis of stroke and headache. It is an uncommon cause of either, but is associated with high morbidity and mortality. Patients often present with headache alone, but can have seizures,

focal neurological deficits, or cranial nerve palsies This is diagnosed with MRV or CTV. Treatment is typically

.

anticoagulation with heparin initially, then warfarin eventually

-

20 40% of patients with ischemic stroke may develop hemorrhagic transformation within 1 wk after the initial infarction Can be exacerbated by reperfusion injury (distal migration of clot as it dissolves) naturally or by use of thrombolytic therapy, endovascular therapy or anticoagulation

$

Blood work should only delay treatment if patient is on anticoagulants, low platelet count suspected, abnormal electrolytes suspected, or any bleeding abnormality suspected

Suspect an alternate diagnosis if fever, decreased LOC, fluctuating symptoms, gradual onset, no focal neurological symptoms, and /or positive symptoms

Infarcted area of brain tissue can often appear normal on CT during the first several hours after stroke onset, especially if in posterior circulation

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N52 Neurology

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• PCA contralateral hemianopia or quadrantanopia midbrain findings: CN 111 and IV palsy/ pupillary changes, hemiparesis thalamic findings: sensory loss, amnesia, decreased LOC if bilateral: cortical blindness or prosopagnosia hemiballismus • basilar artery « proximal ( usually thrombosis ): impaired EOM, vertical nystagmus, reactive miosis, hemi- or quadriplegia, dysarthria, ataxia, locked in syndrome, coma distal ( usually embolic, i.e top of the basilar syndrome ): somnolence, memory and behaviour «

See Landmark Nmrobgr trials for note information on tire ARISTOTLE triaL It detailsthe efficacy of a pirtaban an oraldrectfactorXa inhibitor, in reducing the risk of stroke, as compared to warfarin.

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abnormalities, oculomotor deficit • PICA ( lateral medullary or Wallenberg syndrome ): ipsilateral ataxia, ipsilateral Horners, ipsilateral facial sensory loss, contralateral limb impairment of pain and temperature sensation, nystagmus, vertigo, N / V, dysphagia, dysarthria, hiccups

• medial medullary infarct ( anterior spinal artery, which can be associated with anterior cord infarct ): contralateral hemiparesis ( facial sparing), contralateral impaired proprioception and vibration sensation, ipsilateral tongue weakness • lacunar infarcts (deep hemispheric white matter; involving deep penetrating arteries of MCA, circle of Willis, basilar and vertebral arteries): contralateral face, arm , leg hemiparesis • Common lacunar syndromes: sensorimotor stroke: weakness and numbness of the face/ arm / leg without other cortical signs ( i.e. aphasia, apraxia, visual loss) pure motor hemiparesis ( posterior limb of internal capsule or ventral pons): contralateral arm , leg, and face pure sensory loss ( ventral thalamic): hemisensory loss • ataxic hemiparesis ( ventral pons or internal capsule): ipsilateral ataxia and leg paresis dysarthria- clumsy hand syndrome (ventral pons or genu of internal capsule): dysarthria, facial weakness, dysphagia, mild hand weakness, and clumsiness Cortical Vascular Territories: Left Hemisphere

O G G

Branches of ACA

Area of anterior cerebral artery IACA )

Area of middle cerebral artery (MCA ) Area of posterior cerebral artery (PCA )

The National Institute of Health Stroke Scale (NIHSS) is a standardized clinical examination that determines the severity of an acute stroke: it can also be used to monitor response to treatment over time The scale uses 11 items that evaluate: LOC • Visual system • Motor system • Sensory system • Language abilities Scoring (x/42): 0-no stroke 1- 4-mild stroke 5 - 15- moderate stroke 16 20-modcrate to severe stroke 21-42-severe stroke

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'

Aspect Score: 10- Point Quantitative Score to Assess Ischemic Changes on CT Scan • 10/10 is normal and 220 mmHg or dBP >120 mrnHg, or in the setting of acute Ml, renal failure, aortic dissection ( IV labetalol first line if needed ) if patient receives tPA , target BP 180/ 105 mmHg • acutely elevated BP is necessary to maintain brain perfusion to the ischemic penumbra • most patients with an acute cerebral infarct are initially hypertensive but their BP will improve within 1 2d

-

-

-

-

Stroke Rehabilitation

• individualized based on severity and nature of impairment; may require inpatient program and

continuation through home care or outpatient services • multidisciplinary approach includes dysphagia assessment and dietary modifications, communication rehabilitation , cognitive and psychological assessments including screen for depression, therapeutic exercise programs, assessment of ambulation and evaluation of need for assistive devices, splints or

braces, vocational rehabilitation

Primary and Secondary Prevention of Ischemic Stroke Anti- Platelet Therapy

• primary prevention no firm evidence of a protective role for antiplatelet agents in low - risk patients without a prior stroke/TIA • secondary prevention initial choice: ASA, but other antiplatelet agents reasonable alternatives (clopidogrel or ASA/ dipyridamole) longer-term use of combined ASA and clopidogrel not recommended for secondary prevention unless there is an alternate indication (e.g. coronary drug-eluting stent requiring dual antiplatelet therapy), due to increased risk of bleeding and mortality Carotid Stenosis • primary prevention (asymptomatic) carotid endarterectomy is controversial: if stenosis >60%, risk of stroke is 2% per yr; carotid endarterectomy reduces the risk of stroke by 1% per yr ( but 5% risk of complications) • secondary prevention ( previous stroke/ TIA in carotid territory) carotid endarterectomy clearly benefits those with symptomatic severe stenosis ( 70 99% ), as well

-

.

Surgery VS9 • according to the CREST trial, endarterectomy and carotid stenting have similar benefits in a composite endpoint of reduction of stroke, Ml , and death; however, in the periprocedural period , stenting results in a higher rate of stroke, while endarterectomy results in a higher rate of Ml Atrial Fibrillation • primary and secondary prevention with anticoagulation classical risk stratification used CH Al)S2 score (0 6), but Stroke 2014 guidelines recommend that virtually all patients with atrial fibrillation without contraindication be anticoagulated 0 ( low risk, 1.9% annual stroke risk ): antiplatclet I ( intermediate risk 2.8% annual stroke risk ): anticoagulant or antiplatelet patient specific

-

-

.

-

-

-

ABCD;Score To predict/identify individuals at highrisk of stroke following TIA Age:1point for age >60 yr Blood pressure (at presentation): 1point for HTN (>140/90 mmHg at initial evaluation) Clinical features:2 points for unilateral weakness 1point for speech disturbance without weakness Duration of symptoms:1point for 10 - 59 min 2 points for >60 min DM:1point Stroke risk:0 3: low risk 4 5: moderate risk 6 7: high risk

.

.

. .- - - -

-

See laadnurk Nevtology lulls for IBOIC Mounition on the MMMMB urn. It complies the efficacy ol p eruUMOcn liiiuluniMl angioplasty and stenting (PUS) 1« aggiessire ordeal management in Intracraaial arterialstenosis.

-

decision * > 2 ( high risk , 4 18.2% annual stroke risk ): anticoagulant • anticoagulation therapy * warfarin (titrate to INR 2 3) * direct oral anticoagulants ( DOAC): dabigatran ( 110 or 150 mg PO BID), apixaban ( 2.5 or 5 mg PO BID ), rivaroxaban (15 or 20 mg PO once daily ), or edoxaban (30 or 60 mg once daily ) may be alternatives to warfarin and generally have a lower risk of ICH - Praxbind* reversal agent for dabigatran if necessary - Andexanet’ reversal agent for apixaban and rivaroxaban if necessary

-

CHADS2 St roke risk stratification for patients with atrial fibrillation CHF (1point) HIN sBP >160 mmHgftreated HTN (1 point) Age >75 yr (1 point) DM (1 point) Prior Stroke or TIA|2 points)

do not use DOAC in patients with mechanical heart valves or AT with valvular heart disease

Hypertension

• primary prevention targets: BP < 140/90 mmHg (sBP MAP, cerebral herniation down into foramen '

^

ICP inmHcj too

'

-

-

magnum

-

r ***-

80 60 40 20

0 Volume

*

When a mass expands

Eventually, further small Increment! m volume pioduco largor andlargor

within the skull, compensatory

mechanisms initially maintain a normal ICP

increments in ICP

Figure 5. ICP volume curve

.

Adapted from: Lindsay KW. Bone I Fuller G .

Neurology and Neurosurgery illustrated . With permission from Elsevier

2004 .

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NS6 Neurosurgery

Toronto Notes 2023

Cerebral Blood Flow • • • •

CBF - CPP / CVR CPP = MAP - ICP

brain receives about 15% of cardiac output ( ~750 mL / min ) CBF is the vital parameter for brain function, it depends on CPP and C V’ R CPP is the difference between MAP and ICP ( normal CPP > 50 mrnHg ) cerebral autoregulation: mechanism that maintains constant CBI despite changes in CPP, unless: • high ICP such that CPP < 40 mmHg • MAP > 150 mmHg or MAP < 50 mmHg ( these setpoints can be higher in hypertensives, thus important to avoid hypotension ) increased C02 = increased CBP via vasodilation O2 < 50 mmHg = increased CBF via vasodilation • brain injury: e.g. SAH , severe trauma

MAP Targets in Trauma TBI: MAP >80 mmHg SCI: MAP between 85- 90 mmHg in first 7 d post injury

Autoiegulation: CBF maintained despite change in CPP

ICP Measurement

i

• normal ICP 10 - 15 mmHg for adult , 3- 7 mmHg for child , 1.5 - 6 mmHg for infant; varies with patient

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t

position • ICP > 25 mmHg > end organ damage possible, treatment should be initiated • ICP > 40 mmHg > life - threatening emergency, urgent pressure reduction required ICP measurements should be considered in the context of underlying pathology when evaluating severity

1-

Acute Monitoring • indications include: severe FBI ( CCS < 8T ) t abnormal CT; or severe 'FBI and normal CT if two or more of: age > 40, BP < 90 mmHg, or abnormal motor posturing • methods: intraventricular catheter ( EVD) is the “gold standard ”; most accurate method and allows therapeutic drainage of CSF • parenchymal ICP monitor • non - invasive methods ( e .g . transcranial Doppler, CT/ MR 1 , fundoscopy, etc . ) fail to measure ICP accurately enough to be used as routine measurement techniques

Figure 6. Cerebral autoregulation curve

-

Chronic Monitoring • Licox monitor (intraventricular, intraparenchymal, subdural ), subarachnoid bolt ( Richmond screw), and epidural monitor

Elevated ICP

V

H 50 in 111 Hu < 60 iron Hu High BP Low BP or High ICP Cerebral perfusion pressure (MAP-ICP)

o

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pled liotri: Lindsay KW Bone I Fuller 6. Neurology and Neurosurgery illustrated. 2004. With permission from Elsevier

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LP can be used (or ICP monitoring, although it is not the most accurate. LP can precipitate tonsillar and uncal herniation with elevated ICP This procedure is absolutely contraindicated in the setting of suspected acutely raised ICP or obstructive hydrocephalus, and relatively contraindicated with known/ suspected intracranial mass

Etiology

• pathologic structure • intracranial mass ( tumour, cyst ) » cerebral edema vasogenic: BBB compromised (meningitis, hypertensive encephalopathy, tumour, late ischemia) cytotoxic: BBB intact (cell death in : early ischemia , brain injury, encephalitis, status

epilepticus) interstitial: transudation of CSF into periventricular white matter in hydrocephalus osmotic: osmotic gradient increases intracellular free H :0 (acute hyponatremia, hepatic encephalopathy ) other space occupying lesions: depressed skull fracture, foreign body, pus /empyema increased intracranial blood volume • space occupying blood: epidural and subdural hematomas, intraparenchymal and subarachnoid hemorrhages • venous obstruction ( venous sinus thrombosis , superior vena cava syndrome, cor pulmonale, venous sinus compression ) • impaired autoregulation ( hypotension, HTN , brain injury, status epilepticus ) • vasodilation ( increased p( X ):/decreascd pO’/decreased extracellular pH ) • increased intracranial CSF volume ( see Hydrocephalus , Tabic 7, NS9 ) non -obstructive: increased production ( rare, choroid plexus papilloma , secretory vestibular schwannoma ), decreased absorption (e.g. post-traumatic, post-SAH / lVH, post- meningitis) obstructive: blockage in CSF pathway • idiopathic intracranial HTN ( pseudotumour cerebri; see Idiopathic Intracranial Hypertension , VS,S')
ipsilalera ! EOM paralysis , plosis (CH III compression) Decreased LOC (midbrain compression ) Risk of PCA compression Contralateral hemiplegia t extensor lupgoing) plantar response 1 ipsilateral hemiplegia ("Kernohan's notch" - a false localizing sign resulting from pressure from the edge of the tentorium on the contralateral cerebral peduncle)

4. Upward

Cerebellar vermis herniates through tentorial incisura

Posterior lossa mass, brainstem or cerebellar infarction, exacerbated by ventriculostomy or ventriculoperitoneal (VP) shunt

Cerebellar infarct (superior cerebellar artery (SCA) compression) Hydrocephalus (cerebral aqueduct ol Sylvius compression )

5 . Tonsillar

Cerebellar tonsils tierniatc through loramen magnum

Infratentorial lesion following central lenlotial herniation following IP in presence ol intracranial mass lesion

Neck stillness and head lilt ( tonsillar impaction) Decreased LOC ( midbrain compression) flaccid paralysis Respiratory irregularities, respiratory arrest (compression ol medullary respiratory centres) Blood pressure instability (compression ol medullary cardiovascular centres)

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Treatment of Elevated ICP • treatment principle: treat primary etiology ( i.e. remove mass lesions, ensure adequate ventilation e.g.

in acute respiratory distress syndrome (ARDS)) • if elevated K . P persists following treatment of primary cause, consider therapy when ICP >20 mmHg • targets: ICP < 20 mmHg, CPP 60 70 mmHg, sBP > 100 ( ages 50 69) or >110 (age < 50 or >70) mmHg ( individualize targets based on patient 's clinical picture and progression ) '

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Table 6 . Management of Elevated ICP Intervention

Rationale

Elevate head of bed at 30" Maintain neck in neutral position

Increases 1. Jugular venous patency 2. Intracranial venous outflow with minimal effect on MAP

Fever Management

Acetaminophen or mechanical cooling

Decrease basal metabolic and oxygen demands in order to minimise brain injury

Prevent Hypotension

PRN: Fluid, vasopressors , dopamine, norepinephrine

Maintains CBP

Consideration

Treatment of Elevated ICP

ICP HEAD Intubate Calm (sedate)fComa Place drain/lfcralysis Hyperventilate Elevate head Adequate BP Diuretic (mannitol)

Conservative Measures Position

Normocarbia

Ventilate to pCOi 35- 40 mmHg

Prevents vasodilation

Adequate 02

Target pOa »60 mmHg

Prevents hypoxic brain injury

Osmolar Diuresis

Mannitol 20% IV solution 1-1.5 g/kg, then 0.25 g/kg Increases serum tonicity * osmolically drives fluid out of q6 h to serum osmolarily of 315-320 mOsm/kg brain Ads in 15- 30 min, maintain sBP >100 mmHg Hyperionic saline 3% comparable lo mannitol

Corticosteroids

Dexamethasone

-

Decrease vasogenic edema over subsequent days around brain tumour, abscess, blood No proven value In head Injury or siroke

Aggressive Measures

Sedation

Usually propolol Others: barbiturates / codeine, or fenlanyl /MgS04 Light - barbiturateslcodeine Heavy - fentanyl /MgS04

Reduces sympathetic tone Reduces HIN induced by muscle contraction

Paralysis

Vecuronium

Reduces sympathetic tone Reduces HTN induced by musdecontraction

Barbiturate- Induced Coma (refractory ICP )

Phenobarbital 10 mg/kg over 30 min. then 1mg/ kg qlh continuous inlusion

Reduce CBF and metabolism Decreases mortality , but no elfect on neurologic outcome No role lor the use ol hypothermia in head injury

Hyperventilate

Target pCOz 30 - 35 mmHg Avoid within 24 h following trauma Insert EVD (it acute) or shunt Drain 3- 5 mLCSF

Decreases CBF and thus ICP. but use lor Uriel periods only

Decompressive craniectomy

Allows brain to swell while reducing risk of herniation

Drain CSF Decompression

Irialof Decompressive Craniectomy for Traumatic Intracranial Hypertension NEJM 2016:375:1119-1130 Purpose loconpaie the effect ol decompressive craniectomy on Omul outcomes to that pi medcaf management in patients with traumabt brain myury ( 181) and refractory intracranial hypertension |HIH|. Methods Patients with TBI and refractory intracranial HIN >25 mmHg were randomiied to undergo decompressive craniectomy or receive ongo:g medical care. Primary outcome was Extended Glasgow Outcome Scale at 6 mo. lesntts: Patients treated with decompressive craniectomy had lower mortality rales|26.9% vs. 48.9 %) hst tighei rates ol disability 18.53, vs. 2.1% lower sewredisabiiity, 21.9% vs 14.4% upper severe dsabitty 154% vs 8.0% nodeidle disability). Conclusion: Compared lo medical care, decompressive craniectomy in patients with 181 and refractory intracranial HIN results m lower mortality but higher rates of vegetative slate and severe disability.

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Reduces intracranial volume

Idiopathic Intracranial Hypertension (Pseudotumour Cerebri) Definition • raised ICP with papilledema, but without: mass, hydrocephalus, infection , or hypertensive encephalopathy ( diagnosis of exclusion ) • diagnosed by modified Dandy’s criteria Etiology

• unknown ( majority ), but associated with: vascular: dural venous sinus thrombosis habitus/ diet: obesity, hypervitaminosis A endocrine: reproductive age, menstrual irregularities, Addison's/ Cushing's disease • hematologic: iron deficiency anemia , polycythemia vera drugs: steroid withdrawal, tetracycline, amiodarone, lithium, nalidixic acid, oral contraceptive, growth hormone, retinoids • risk factors overlap with those of venous sinus thrombosis; similar to those for gallstones ( “ fat, female, fertile, forties")

Epidemiology

--

Modified Dandy 's Criteria 1 Symptoms ol raised ICP 2 No localizing signs except CN VI palsy 3 Patient awake and alert 4. Normal neuroimaging without evidence of thrombosis 5. LP opening pressure >25 cm ECO, normal CSF 6. No better explanation for raised ICP

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• incidence: general population I 2 in 100000 per yr; women of childhearing age with obesity 19 21 in 100000 per yr

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Clinical Features

•symptoms: H /A in >90 %, nausea, transient visual obscurations, pulsatile tinnitus, diplopia can occur with CN VI palsy, neck/ back pain • signs: CN VI palsy can occur (otherwise no neurologic deficits), visual acuity and field deficits, papilledema, optic atrophy • morbidity: risk of blindness and severe visual impairment (6-24% risk ) are the major morbidity of idiopathic intracranial hypertension (11 H ), but are not reliably correlated to duration, symptoms, or clinical course • clinical course: usually self limited , recurrence in 10%, chronic in some

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Investigations • MRI brain ( with and without contrast ): slit- like ventricles and distended perioptic subarachnoid space, but otherwise normal rule out: venous sinus thrombosis, mass, infection, hydrocephalus • LP findings opening pressure >25 cmH ’O normal CSP analysis • ophthalmologic: fields, acuity, papilledema

Effect of Acetazolamide on Visual Function in Patients with Idiopathic Intracranial Hypertension and Mild Visual toss ( IIHTT )

-

JAMA 2014:311(16|:1641 1651 Purpose : to determine whether acetarolamide and a low - sodi un weight reduction diet is beneficial in impronrg ms- on compared to diet alone m patients with IIH and mild visual loss. Methods patients were landomited to Mirer a tow -sodium wreigM reduction diet plus the maiireally tolerated dosage of acetaiolamideor place So for

Smo. Desilts: Acelaiolamide was superior to placebo with regards toperimetric mean deviation improvement (P ^ O.05). papilledema grade improvement tP« 0.001). insios-related quality of life (H.003), and weight reduction (M1.001). Conclusion: Acetazolamide w tit low -sodium weight reduction diet resulted In Improvement in visual field function in patients with IIH and mildvisual loss.

Treatment

restriction • lifestyle change: encourage weight loss, fluid/salt • pharmacotherapy: acetazolamide (decreases ( ’SI production ), thiazide diuretic, or furosemidet

discontinue offending medications • surgery: if above fail, serial LPs ( temporizing ), optic nerve sheath fenestration ( if progressive impairment of visual acuity), shunt placement ( ventriculo-peritoneal, lumbo - peritoneal ) • long term: 2 yr follow- up, repeat imaging to rule out occult tumour, ophthalmology follow- up

Hydrocephalus • for hydrocephalus in children , see Paediatric Neurosurgery. NS 42 Definition

• accumulation of excess CS1; in the brain , functionally divided into obstructive and communicating • flow of CSF: produced by choroid plexus, lateral ventricles > foramen of Monro > 3rd ventricle > cerebral aqueduct of Sylvius > 4 th ventricle > foramen of Luschka ( lateral ) and Magendie ( medial ) > subarachnoid space where CSF is reabsorbed by arachnoid villi /granulations into dural venous sinuses

Classification

Table 7. Classification of Hydrocephalus Disorder

Obstructive ( Non Communlcatlng ) Hydrocephalus

-

Definition

Etiology

Findings on CT / MRI

CSF circulation blocked

Acquired

within ventricular system proximal to the arachnoid

Aqucductal stenosis: adhesions alter inlection , hemorrhage: gliosis, tumour|e g

granulations

medulloblastoma ) Intraventricular lesions: tumours , e g . 3rd

Ventricular enlargement proximal to block (enlarged temporal horns, ballooning frontal and /or occipital horns, enlarged 3rd 14th ventricles) Periventricular hypodensity/

..

.

ventricle colloid cyst, hematoma Mass causing tentorial herniation causing aqueduct /4th ventricle compression Others: neurosarcoidosis, abscess/ granulomas. arachnoid cysts

Congenital Primary aqueductal stenosis Dandy Walker malformation Arnold Chian malformation, myelomeningocele, enccphalocele ( see /’ot tfra / nc Hmosurgeiy #542 )

.

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Non - Obstructive ( Communicating )

Hydrocephalus

MosIcommonlyCSF absorption blocked at extraventricular site * arachnoid granulations, rarely CSF absorption is overwhelmed by increased production

Normal Pressure Hydrocephalus ( NPH )

Persistent ventricular dilation In the con text ol normal CSF picssure

Hydrocephalusfx

Ventricular enlargement resulting Irom atrophy ol surrounding brain tissue

Voeuo

.

~

-

.

All ventricles dilated

Normal aging Degenerative dementias: Alzheimer 's, frontotemporal Crculzleldt Jakob disease|sce Neuioloqy. N 2 ?|

Enlarged ventricles and sulci Cerebral atrophy

1. Lateral ventricles

- .

2. Choroid plexus 3. Third ventricle

-

-

.

*

lucency ( transependymal migration of CSF forced info extracellular space) Sulcal effacemenl, reduced visibility of Sylvian and interhemispherlc fissures

Post infectious ( #1 cause) * meningitis, abscess cysticercosis Post - hemorrhagic (* 2 cause) » SAH IVH. traumatic Leptomeningeal carcinomatosis metastatic meningitis Choroid plexus papilloma Idiopathic » NPH Idiopathic (50 % ) Others: SAH meningitis, trauma , radiation induced

.

CSF production - CSF reabsorption •500 mL/d in normal adults Normal CSF volume 150 mL (50% spinal 50% intracranial » 25 mL intraventricular, 50 ml subarachnoid)

-

4. Cerebral aqueduct ( of Sylviusl

5. Fourth ventricle

Enlarged ventricles without increased prominence of cerebral sulci

6. Foramina of Luschka and Magendie 7. Arachnoid granulations 8. Subarachnoid space 9. Confluence of sinuses Itorcula )

-2

rt

5

LJ

Figure 8. The flow of CSF

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NS10 Neurosurgery

Toronto Notes 2021

Etiology

• impaired CSF dynamics • obstruction of CSF How • decreased CSF absorption increased CSF production ( rarely in choroid plexus papilloma 0.4- 1% of intracranial tumours) • congenital and acquired causes Epidemiology

-

-

• estimated prevalence 1 1.5%; incidence of congenital hydrocephalus 1 -2 in 1000 live births Clinical Features , S7 ) • acute hydrocephalus: signs and symptoms of acutely elevated ICP (see Table 4\ • chronic /gradual onset hydrocephalus: (wk to mo; i.e. NPH ) presents with a classic triad ( Hakim’s triad ) • Ataxia ( magnetic gait ) i apraxia ( pressure of ventricle on lower extremity motor fibres > gait

Classic (Hakim's) Triad of NPH Progression “W *t wacky, wobbly " : Incontinence, dementia, ataxia

.

disturbance) • Incontinence ( pressure on cortical bowel / bladder centre )

• Dementia (subcortical ) Important Features to Note on CT and MRI ( ± contrast enhancement ) • Lesions (iedema, necrosis, hemorrhage) • MLS and herniations • Effacement of ventricles and sulci (often ipsilateral). basal cisterns • Single or multiple (multiple implies metastasis)

Investigations • imaging • CT/ MR 1 findings ( see Table 7, NS9 ) • ultrasound ( through anterior fontanelle in infants): ventriculomegaly size and location of lesions ( e. g. lVH ) mantle radionuclide cisternography can test CSF flow and absorption rate ( unreliable) • ICP monitoring (e.g. LP, EVD) may be used to investigate NPH and test response to shunting ( lumbar tap test )

.

Treatment

• EVD (acute hydrocephalus, intraventricular hemorrhage ) • intermittent LPs for transient communicating hydrocephalus (SAH , 1VH in premature infants )

Complications of Specific Hydrocephalus Treatments 1. VP Shunt: intra abdominal cysts, adhesions, ascites 2. VA Shunt: greater infection risk,

• eliminating obstruction ( i.e. excision of mass, posterior fossa decompression for Chiari malformation ) • endoscopic endoscopic third ventriculostomy (ETV ) ± choroid plexus cauterization (for obstructive hydrocephalus ) • endoscopic placement of aqueductal stent • shunt • VP: most common shunt ventriculopleural

septicemia, emboli 3. Ventriculopleural Shunt: pleural effusion, hydrothorax, respiratory distress 4. LP Shunt radiculopathy. CSF leaks, adhesions, arachnoiditis 5. ETV: 56% success rate, hypothalamic injury, iatrogenic basilar aneurysm

ventriculoatrial ( VA )

lumboperitoneal: for communicating hydrocephalus and pseudotumour cerebri Shunt Complications

Table 8. Shunt Complications Complication

Etiology

Obstruction ( most common ) Proximal Catheter Valve

Obstruction by choroid plexus Acute hydrocephalus signs and symptoms of increased "Shunt series" (plain x rays of entire shunt that only Buildup of proteinaceous accretions , blood , cells ICP rule out disconnection, break , tip migration )

Distal Catheter Infection (3 6%)

-

S. aureus P. owes Gram negative bacilli

fever, N / V. anorexia , irritability Meningitis Peritonitis Signs and symptoms of shunt obstruction Shunt nephritis ( VA shunt )

Slit ventricle syndrome, collapse of ventricles Chronic or recurring H /A often iclieved when lying leading lo occlusion ol shunt ports by ependymal down

CBC Blood culture Tap shunt for CAS ( LP usually NOT recommended )

C1/ MRI Slil like ventricles on imaging

-

lining

Seizures

-

Radionuclide "shunlogram "

Infection Disconnection or damage

5. epidermidis

Investigations

C!

(inflammatory or tumour )

-

Overshunting (10% over 6.5 yr )

Clinical Features

SDH Collapsing brain tears bridging veins (especially common in NPH patients)

Asymptomatic H /A, vomiting , somnolence

CT

Secondary craniosynostosis (children ): apposition and overlapping ol the cranial sutures in an infant following decompression ol hydrocephalus

Abnoimalhead shape

Clinical

CT EEC

Ventricular shunts only

(5.5% risk in 1st yr, 1.1% after 3rd yr)

Inguinal hemia (13 15% incidence when shunt inserted in childhood)

-

Increased intraperitoneal pressure /fluid results in hernia becomingapparcnt

Inguinal swelling, discomfort

+

U /S

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NS11 Neurosurgery

Spontaneous Intracranial Hypotension Definition

• low CSI; pressure t postural headache secondary to CSI:leak • symptoms not attributable to another disorder, no recent history of dural puncture Etiology • CSI; leakage from the thecal sac within or along the spinal canal Epidemiology

-

• incidence: ~2-5 in 100000 per yr, but likely underdiagnosed; M:l'=1:2 can occur at any age, but most frequently in 4th or 5th decade

Clinical Features

-

• symptoms: orthostatic H / A in 75 80%, tinnitus or auditory disturbance ( “ underwater feeling") in 50%, dizziness in 50%, nausea, vomiting, photophobia, meningismus • signs: CN 111, CN IV, CN VI palsy in < 10% • morbidity: misdiagnosis and underdiagnosis are common, leading to delays in treatment and inappropriate treatment for mimickers of intracranial hypotension • clinical course: usually self-limited, recurrence in 10%, chronic in some Investigations

• MKI brain with contrast: sagging of the brain (e.g. low cerebellar tonsils), pachymeningeal

enhancement, subdural hematoma or hygroma , pituitary hyperemia spine with contrast: extrathecal fluid collections/extrathecal contrast accumulation and /or MKI • meningeal diverticula • CT myelogram with contrast: preferred method to diagnose and localize CSF leak digital subtraction myelogram ( DSM ): combines fluoroscopy and ability to subtract background images to visualize small CSF leaks by contrast extravasation • LP: opening pressure round , well circumscribed, often ring enhancing , H- I edema , often multiple • contrast - enhanced MRI more sensitive, especially for posterior fossa • consider biopsy in unusual cases or if no primary’ tumour identified

Kidney ( RCC )'

n

61

6\ 3%

Melanoma •RCC Mcnul cell mclnorod

Treatment • medical

phenvtoin (or levetiracetam ) for seizure prophylaxis if patient presents with seizure dexamethasone to reduce edema given with H 2 blocker role of chemotherapy limited because of poor penetration across BBB targeted therapies are currently being investigated ( e.g. HGI’R ( epidermal growth factor receptor) inhibitors in patients with HCil ' R - mutant lung cancer and brain metastases)

-

• radiation

-

• SRS ( highly focused fraction of radiation targeted to tumour ): for discrete, deep seated /

inoperable tumours • mu Itiple lesions: use WBRT (upwards of 10 lesions ); consider SRS if < 4 - 10 lesions postoperative adjuvant radiotherapy consideration: SRS to surgical cavity following resection emerging evidence supports avoidance of WBRT and use of focal radiation to spare cognitive functions ( refer to Brown et al., 2016) • surgical » single /solitary lesions or dominant lesion with significant mass effect or symptoms: surgical resection and radiation in carefully selected patients

1. Heterogenous contrast enhancement 2. Ill defined borders (inliltrativel 3 Peiitumoural edema 4. Central necrosis j Compression of ventricles, midline shill y

-

+

Figure 11. High- grade glioma on CT

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XS15 Neurosurgery

Toronto Notes 2023

Prognosis • median survival without treatment once symptomatic is ~ 1 mo, with optimal treatment 6 9 nio; may be prolonged survival in some patient subgroups (e.g. HBR 2 / neu breast cancer, EGl 'R mutant lung

--

-

cancer ) the disease-specific Graded Prognostic Assessment ( DS-GPA) is a useful prognostic index • depending on primary tumour type, prognosis may depend on a combination of patient age, Karnofsky score, extent of extracranial metastatic disease, number of intracranial lesions, and

molecular disease subtype

Adult Diffuse Gliomas

-

• most common primary intra axial brain tumour, common in 4 th - 6th decades

-

Table 11. WHO 2021 Diffuse Gliomas Classification Type

WHO Grade’

Typical CT/ MRI Findings

Altered Molecular Profiles

Oligodendroglioma

2.3

Low grade: areas ol calcification on CT , t enhancement

Defining : IDH mulant

-

. .

Prognosis

-

Low grade: 10 yr

Ollier : TEH! promoler CIO fUBPI, N0TCH1

High grade: 5 yr

Low grade: mass effect, no Defining: IDH mutant and enhancement 1pf19 q codeleted

Low grade: 3 yr

High grade: enhancement

2, 3, 4

Astrocytoma

-

High grade: 1.5 2 yr High grade: complex enhancement

Glioblastoma

4

Necrosis ( ring enhancement)

Other : ATRX , TP53, C 0 KN 2 A /B Defining: IDH - wildtype

.

-

15 mo

.

Olher: TERT promoler chromosomes 7/10 EGER 'grade

-

Surgical Resection vs . Watchful Wailing in low Grade Gliomas fcin Oncol 2017: 28:19421948 Purpose: This study eie ~ ined the effect of up -frort surgery vs.watchful waiting for treatment of lowgrade gliomas on long term survival. Methods : Ihe study was designed as a population based parallel cohort study that compared outcomes from a hospital lav oaring watchful wailing ( n *6$ patients) and one favouring early resection ( n 8? patients), follow up was between 7 and 18 yr post dagnosis. The two groups were eq. ve ert in terms of baseline parameters. Results : Overall, surv.nral wassigmfkantly better with early surgical resection. Patients from the centre favouring watchful waiting had a nedan sur vival of 5.8 yr (95% Cl 4.5 7.21 whereas patients fiom the centre favounng early resection had a median survival of 14.4 yr (95% Cl 10.4-18.5). The enhanced survival benefit remained after adjusting for molecular markers. Conclusions : Early surgical resection of low grade gliomas Is associated with significantly Improved overall survival compared to watchful waiting.

based on natural history

Clinical Features • sites: cerebral hemispheres » cerebellum, brainstem, spinal cord • symptoms: recent onset of new/worsening H / A, N / V, seizure, ± focal deficits or symptoms of increased IGF

Investigations • CT/ MRI with contrast: variable appearance depending on grade hypodense on CT, hypointense on T1 MRI, hyperintense on T2 MR 1 • low-grade: most do not enhance and have calcification on CT • high grade: most enhance with CT contrast dye /gadolinium , possibly with central necrosis (especially if IDH wildtype)

-

• histology during surgical resection or biopsy Treatment • low-grade diffuse gliomas

-

close follow up, radiation , chemotherapy, and surgery are all valid options

• dedilferentiation to more malignant grade; typically occurs faster when diagnosed after age 45

Comparison ota Strategy favouring Early Surgical Resection vs a Strategy favouring Watchful Wailing in Lov*- 6 rade Gliomas JAMA 2012:308( 18):188t 18S8 Purpose: to examine’watchful waiting’vs. eaify surgical resection of low-grade gliomas. Study : A population -based paralel cohort study was undertaken between two hospitals Ihateach favoured different management approaches lor low grade gliomas ( biopsy and watchful wailing vs.early surgical resection ). Results: 66 patients were included from the watchful waiting hospital and 87 patients from Ihe early reseebon centre. Median follow - up was 7.0 and 7.1 p at each centre, the two groups were equivalent m feints ol baseline parameters. Overall, survival was significantly bettev wdh eaily surgical resection Iwatchlul waiting: median survival of 5.9 yr 95% Cl, 4.S -7.3 vs. early resection: median survival was no! reached due to prolonged lenglh of life, P'0.01). Conclusions: Early surgical resection of low -grade q onas is associated with better overall suruvtlas compared to watchful waiting.

.

surgery: maximal safe resection , not curative, trend towards better outcomes, provides tissue sample for histologic/ molecular characterization

XRT alone or postoperative prolongs survival ( retrospective evidence) chemotherapy: initial therapy in all patients with high - risk low-grade glioma • high -grade ditTuse gliomas • goal is to prolong “ quality" survival surgery gross total resection: maximal safe resection + fractionated radiation with 2 cm margin + concomitant and adjuvant temozolomide

-

except: nearing end - of -life; or extensive brainstem , bilateral, or dominant lobe GBM

involvement awake craniotomy for tumours in “eloquent ” regions (e.g. speech and language regions or near motor strip) stereotactic biopsy if resection not possible, followed by fractionated radiation with 2 cm margin

- expectant: based on functional impairment Karnofsky score < 70; patient’s/family’s

wishes chemotherapy: temozolomide ( agent of choice ); better response to temozolomide predicted by MGMT gene methylation multicentric gliomas • WBRT ± chemotherapy

•

•

Bevaciiumab Plus Radiolherapy - Temozolomide for Newly Diagnosed Glioblastoma NEJM 2014; 370:709 722 Purpose: fo evaluate the effect of combined bevaciiumab andXRI - tenoiolomidem the treatment of newly diagnosed glioblastoma. Methods: Patients with supratentorial GBM were randomly assigned to receive IV bevaciiumab (ir 458| or placebo plus XII and oral temoiolom Ide ( n 463) for 30 wh total in cycles, followed by bevacitumab or

-

-

placebo monotherapy. Outcomes were progression

-

free survival and overall survival. Results: the median progression -free survival was longer mlhe bevacizumebgroup compared with placebo (10.6 mo vs. 6.2 mo HR 0.64, 05% G 0.55 0.74|. although overall survival did not differ significantly between groups ( HR 0.88. 95% Cl 0.764.02). Baseline health - related quality - of life and performance status were maintained longei a the bevaciiumab group although there was a higfce frequency of adverse events. Conclusions: Ire addition of hevaciiumab to XRTtemorolomide improves progression tree sunmral but Ml overall survival ut patients with glioblastoma.

.

-

ri c.J

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NS16 Neurosurgery

Primary Central Nervous System Lymphoma

-

• highly aggressive, non - Hodgkin lymphoma confined to the CNS; 95% are large B-lymphocyte • brain t spinal cord, leptomeningeal, CSF, and ocular manifestations possible • intracranial lesions predominantly supratentorial

.

-

Clinical Features

• occurs in both immunocompetent and immunocompromised populations ( multifocal lesions in 2D

-

-

40% of immunocompetent patients, and in 30 80% of immunocompromised patients) • epidemiology: 0.47 in 100000 per yr; M:F=1.35:1; age of onset 50-70 (30-40 in immunocompromised individuals) •symptoms: focal neurological deficit , cognitive/ behavioural symptoms ± increased ICP or seizures or

CN palsies blurred vision + floaters if ocular involvement « high association with Epstein- Barr virus in patients with HIV

-

--

.

Investigations •CT: hyper or iso attenuated lesions; significant enhancement with contrast • MRI with contrast (imaging of choice): intensely enhancing lesions, often localized to periventricular space • immunocompetent -> homogenous enhancement ± minimal edema • immunocompromised > heterogenous or ring enhancement, necrosis, edema ± hemorrhage • restriction on diffusion imaging due to hypercellularity helpful to distinguish from other brain

-

Interim Results from the CATRON trial [EORTC study 2605 3 2 2054) of Treatment with C oncurrent and Adjuvant tlmoiolomlde for Ip 19 q Nonco- deleted Anaplastic Glioma: a phase 3 randomised , open label intergroup study lancet 2017:390(10103):1645 S3 Purpose fo assess the use ol radiotherapy vnth concurrent and adjuvant tenwolomide in adults with non co-deleled anaplastic gliomas. Methods: Patientswith newly diagnosed non co deleted anaplastic glioma were randomized to receive radiotherapy alone or with adjovant temozotamide: or torecerve radiotherapy with concurrent temozoiomde IS iug/m 2 per day with or without adjuvant temomlumide. Ihe primary endpoint was overall survival. Results: Overall survival at 5 years was 55 9% (35% Cl 4 ) 2 63 81 with and 44 1% (363 51 6) without adjuvant temozolonide. Grade 3-4 adverse events wereseen in 8 12% of 549 patients assigned temozolomide. and were mainly haematological and reversible. Conclusions: Adjuvant temozoiomide chemotherapy wosassooaled with i significant survival bentit in patients with newlydiagnosed non co-deleted anaplastic glioma.

-

tumours

-

-

-

-

-

-

-

• confirmation by stereotactic biopsy and histopathology • corticosteroids may prevent histopathological diagnosis > avoid until biopsy complete when clinically possible Treatment

methotrexate ( HDMTX ) + cytarabine + thiotepa + rituximab) preferred

-

• chemotherapy: first line treatment; induction therapy using M ATKix regimen ( high dose

•

1

•surgery: generally reserved for stereotactic biopsy; resection discouraged • radiation: WBRT used in consolidation therapy and for palliation; consider as second-line induction

-

/

therapy in HDMTX lneligiblc patients significant risk of neurotoxicity when combined with HDMTX

Prognosis • age and performance status are key prognostic factors

• median survival: 26 mo across all age groups; < 7 mo for patients 270 yrold

Meningioma • most common primary intracranial tumour, arising from arachnoid cap cells • sometimes calcified, often causes hyperostosis of adjacent bone (detectable on imaging) • classically see Psammoma bodies (“meningocytic whorls") on histology • location: 70% occur along the parasagittal convexity, falx cerebri, and sphenoid bone; other locations: tubcrculum sellae, foramen magnum, olfactory groove, and CPA Clinical Features • middle aged , slight female predominance ( M;P=1:1.8), many express the progesterone receptor (increase in size with pregnancy )

vl

'

A -2

3 1 . Homogenous contrast enhancement 2. Dural attachment Distinct margins

Figure 12. Meningioma on CT

WHO Classification of Meningioma (by histology) Grade 1: low-risk of recurrence Grade 2: intermediate risk of recurrence Grade 3: high-risk of recurrence

• many are asymptomatic and can he an incidental finding; when symptoms occur focal neurologic

deficits specific to location, ± seizures, symptoms of increased ICP molecular changes: between 40-80% of meningiomas contain mutations in chromosome 22 (involved • in suppressing tumour growth ); some have extra copies of PUG1:R and EGER; some are associated with mutations in the h' 1'2 gene Investigations

•CT with contrast: homogeneous, densely enhancing, along dural border (“dural tail"), well circumscribed, usually solitary (10% multiple, likely with loss of NE2 gene / 22q 12 deletion ) MRI with contrast: characterization of mass and provides a belter assessment of the patency of dura ) i

venous sinuses • angiography most are supplied by external carotid feeders ( meningeal vessels)

can assess venous sinus involvement, "tumour blush ' commonly seen ( prolonged contrast image )

Treatment

• conservative management: asymptomatic and /or non -progressive on CT/MK1 serial monitoring for interval growth changes •surgery: often curative if complete resection and Indicated when symptomatic and /or documented growth on serial C1/ MR1

Recommendationslor Management oi Meningiomas l ancet Oncol 2016; T 7(9):e383 391 European Association of Nemo- Oncology assessed available literature, rated scientific evidence, and graded recommendation levels. Key recommendations: 1. Firststandard therapy sgross total surgical resection (including imrotred dura ). 2. Alternative treatments include radiosurgery lot small tumours and fractionated Xtl in large/ previously treated tumours. 3. New treatment concepts combining surgery and radiosurgeiy/lractionated XRI to treat complete tumour volume are being developed. 4. Although pharmacological treatments are still experimental, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents ate candidates for future pharmacological approaches lo treat refractory meningioma ot all WHO grades.

-

-

t J

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•endovascular: embolization for highly vascularized, likely bloody, tumours to facilitate surgery • radiation: SRS may be an option for lesions < 3 cm partially occluding the superior sagittal sinus; SRS or XRT for non-resectable, recurrent atypical / malignant meningiomas

Prognosis

-

-

• 5 yr survival is >85% for Cirade 1, 60 90% for Grade II, and 35 65% for Grade 111

• depends on extent of resection • Simpson’s classification: degree of surgical resection completeness with symptomatic recurrence

Progressive unilateral or asymmetrical sensorineural hearing loss vestibular schwannoma until proven otherwise

-

Table 12. Simpson Grade of Meningioma Resection Grade

Criteria

I II

Macroscopically complete removal ol tumour, with excision of its dural attachment and of any abnormal bone Macroscopically complete removal ol tumour, with coagulation ol its dural attachment

III

Macroscopically complete removal ol tumour without resection or coagulation ol dural attachment or extradural extensions

IV

Partial removal ol tumour

V

Simple decompression with or without biopsy

Vestibular Schwannoma ( Acoustic Neuroma)

-

• slow growing (60% show no growth over 1 yr; average rate for growing tumours 1-2 mrn / yr), benign

-

posterior fossa tumour (8 10% of tumours) • arises from vestibular nerve of CN Vlll in internal auditory canal, expanding into bony canal and CPA • if bilateral, diagnostic of NF2 • epidemiology: 1.5 in 100000; all age groups affected , peaks at 4th -6th decades Clinical Features •early clinical triad: ( tumour < 2 cm ) unilateral progressive hearing loss 98% , tinnitus, and disequilibrium (compression ofCN Vlll ) • later clinical features tumour usually >2 cm: otalgia, facial numbness + weakness, changes to taste (due to CN V and VII compression, respectively) tumour usually >4 cm: ataxia, H /A, N/ V, diplopia, cerebellar signs (due to brainstem compression; ± obstructive hydrocephalus ) Investigations

• MKI with gadolinium or T 2 fast imaging employing steady - state acquisition (FIESTA ) sequence (>98% sensitive/specific ); CT with contrast 2 nd choice • audiogram, brainstem auditory evoked potentials, caloric tests

Figure 13 . Vestibular schwannoma (tumour in CPA)

Treatment

• expectant: serial imaging (CT/ MRI q 6 mo) and audiometry if tumour is small, hearing is still preserved, high perioperative risk, or elderly patient • radiation: SRS • surgery: if lesion >3 cm , brainstem compression , edema , hydrocephalus • curable if complete resection; (almost always possible) • operative complications: CS1 leak, meningitis, required shunt; CN V, VU , VIII dysfunction ( proportional to tumour size; only significant CN VIII disability if bilateral ) • implications for testing of family members of NT2 mutation carrier

Pituitary Adenoma • primarily from anterior pituitary, 3rd - 4 th decades, M = l-, associated with multiple endocrine neoplasia

-

type 1 ( MEN 1) syndrome • incidence in autopsy studies approximately 20 % •classification microadenoma < I cm; macroadenoma >1 cm endocrine active (functional/secretory) vs. inactive ( non functional ) most common functional: prolactinomas, adrenocorticotropic, GH producing • differential diagnosis: parasellar tumours (e.g. craniopharyngioma, tuberculum sellae meningioma ), carotid aneurysm

-

-

-

Go Look For The Adenoma Please GH, LH, FSH TSH. ACTH, Prolactin A compressive adenoma in the pituitary will impair hormone production in this order ( i.e. GH secreting cells are most sensitive to compression)

.

-

r >

LJ

Clinical Features • mass effects •H /A

+

• bitemporal hemianopia ( compression of optic chiasm ); hydrocephalus (3rd ventricle compression ) • invasive adenomas: CN III, IV, VI , V 2, VI palsy (cavernous sinus compression ); proptosis and chemosis (cavernous sinus occlusion )

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NSI8 Neurosurgery

• endocrine effects ( see Endocrinology, E 22 )

hyperprolactinemia ( prolactinoma): infertility, amenorrhea, galactorrhea , decreased libido AC i H production: Cushing's disease, hyperpigmentation GH production: acromegaly /gigantism panhypopituitarism: due to compression of pituitary (hypothyroidism , hypoadrenalism , hypogonadism ) DI - rare, except in apoplexy • pituitary apoplexy ( sudden expansion of mass due to hemorrhage or necrosis) • abrupt onset H /A, visual disturbances, ophthalmoplegia, reduced mental status, panhypopituitarism and Dl CSF rhinorrhea and seizures ( rare) signs and symptoms of SAH ( rare) Investigations

• formal visual fields , CN testing • endocrine tests ( prolactin level, TSH , 8 AM cortisol, fasting glucose, l 'SH / LH , insulin like growth factor 1 ( IGF I )), electrolytes, urine electrolytes, and osmolarity • imaging ( MK 1 with and without contrast )

-

-

Treatment

• medical for apoplexy: rapid corticosteroid administration ± surgical decompression for prolactinoma: dopamine agonists (e.g. bromocriptine ) for Cushing’s: serotonin antagonist (cyproheptadine ), inhibition of cortisol production (ketoconazole) for acromegaly: somatostatin analogue (octreotide ) ± bromocriptine endocrine replacement therapy • surgical endoscopic endonasal trans sphenoidal, and less commonly trans cranial approaches ( i.e. for

-

.

1 Antodor cerebral artory 2. Internal carotid artery (communicating part) 3. Pituitary gland 4. Oculomotor nerve 5. Trochlear nerve 6. Internal carotid artery (cavernous segment) 7. Ophthalmic nerve 8. Abducens nerve 9. Cavernous sinus 10. Maxillary nerve

Figure 14. Cavernous sinus

-

significant suprasellar extension ) • postoperative concerns: Dl , adrenal insufficiency ( Al ), CSF leak Dl and Al: AM cortisol, serum sodium and osmolality, urine output and specific gravity ( treatment - Al: glucocorticoids; Dl: desmopressin / DDAVP") • CSF rhinorrhea: test for p- transferrin Genetic Associations

• sellar masses have known associations with several classic oncogene mutations, including: MEN 1: loss-of-function mutations are common GNSA 1: activating mutations found in 40% of somatotroph adenomas AIP: mutations associated with familial pituitary' adenomas

-

Cerebral Abscess Definition

• pus in brain substance, surrounded by tissue reaction (capsule formation ) Etiology

• modes of spread: 10-60% of patients have no identifiable cause

• pathogens • Streptococcus ( most common ), often anaerobic or microaerophilic Staphylococcus ( penetrating injury) Gram - negatives, anaerobes ( Bacteroides, l:usobacterium ) in neonates: Proteus and Citrobacter (exclusively) immunocompromised: Toxoplasma, Nocardia, Candida albicans, Listeria monocytogenes, Mycobacterium , and Aspergillus Sources of Pus/Infection

• four routes of microbial access to CNS 1. hematogenous spread: arterial and retrograde venous adults: chest is most common source ( lung abscess, bronchiectasis, empyema ) • children: congenital cyanotic heart disease with K lo L shunt

• immunosuppression ( AIDS toxoplasmosis ) 2.direct implantation ( dural disruption )

--

[]

trauma

• iatrogenic (e.g. following LP, postoperative)

congenital defect (e.g. dermal sinus) 3.contiguous spread (adjacent infection ): from air sinus, naso/oropharynx, surgical site (e.g. otitis media, mastoiditis, sinusitis, osteomyelitis, dental abscess ) 4.spread from peripheral nervous system ( PNS) (e.g. viruses: rabies, herpes zoster)

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NS19 Neurosurgery

•common examples epidural abscess: in cranial and spinal epidural space, associated with osteomyelitis treatment: immediate drainage and antibiotics, surgical emergency if cord compression subdural empyema: bacterial /fungal infection, due to contiguous spread from bone or air sinus, progresses rapidly treatment: surgical drainage and antibiotics, 20% mortality meningitis, encephalitis (see Infectious Diseases. ID17) cerebral abscess

Li

Risk Factors • lung abnormalities ( infection, AVTs; especially Osler-Weber- Rendu syndrome / hereditary

hemorrhagic telangiectasia )

• congenital coronary heart disease: R - to- L shunt bypasses pulmonary filtration of microorganisms • bacterial endocarditis

• penetrating head trauma • immunosuppression (e.g. AIDS ) • dental abscess, poor dentition

1. Surrounding edema 2. Central low density (pus) 3. Ring enhancement

Clinical Features

• focal neurological signs and symptoms • H /A, decreased LOG • mass effect, increased 1CP and sequelae ( cranial enlargement in children ) • hemiparesis and seizures in 50% of cases • ± signs and symptoms of systemic infection ( low grade fever, leukocytosis)

Figure 15. Cerebral abscess on CT

-

Complications

• with abscess rupture: ventriculitis, meningitis, venous sinus thrombosis • CS1: obstruction • transtentorial herniation

Recommendations for Duration ol Antibiotic Therapy lor Brain Abscesses Int 1 Infect Bis 2010;14 Supp!4:S79 - 92 Systematic literature search 111:9 UEOIINE database for studies dur 1191988 2008 to nrethoilologicaly evaluate antibiotic therapy duration pertaining to brain abscess. Key recommendations: t . Prudent per od of 4 - 6 wk of antibiotic theiapy (or surgically heated abscesses. 2.6-8 wk of IV treatme nt for abscesses treated medically only. 3. 6 8 wk of IVtreatment lor multiple abscesses nrtien laiger ones are healed surgically.

.

Investigations

scan often first test in emergency department .•CT MR1

• imaging of choice • restriction on diffusion imaging ( also seen in lymphoma ) apparent diffusion coefficient (ADC) used to differentiate abscess ( black ) from tumour ( white)

may be normal, blood cultures rarely helpful and LR contraindicated if large mass • CSF: non -specific ( high 1CP, high WBC , high protein , normal carbohydrate ), rarely helpful, usually negative culture • WBC/ ESR

Treatment

• aspiration ± excision and send for Gram stain , acid - fast bacillus ( APB), C&S, fungal culture • excision preferable if location suitable • antibiotics empirically: vancomycin + ceftriaxone + metronidazole or chloramphenicol or rifampin (6-8 wk therapy ) revise antibiotics when C &S known • anticonvulsants (1-2 yr) • follow- up is done clinically and with MRI Prognosis • 10% mortality with appropriate therapy, permanent deficits in 50% of cases

-

-

Table 13. Stages of Cerebral Inflammation /Infection CT Features

Stage

-

Early cerebritis (1 3 d ) Low attenuation abnormality

Mass effect

-

Late cerebritis ( 4 9 d )

Early capsule formation (10-13 d)

Ring contrast enhancement , particularly in lale capsule

Late capsule

formation

formation (> 14 d)

MRI Features

Microstructural changes

Low 11 signal High 12 signal Patchy contrast enhancement Increased lesion demarcation

Neotrophil accumulation Tissue necrosis and edema

Seller demarcation ol lesion Ring contrast enhancement ll inner media

Sued MlWith (

,

Microglia andaslrocyte activation Macrophage and lymphocyte infiltration Microglia and astrocyte activation

-

formation ol thin , well vasculamed wall Microglia and astrocyte activation

' " , Wa

'

r “i

" '

hiCk CaPSU e mU iple ayerS Microglia and astrocyte activation

LJ

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NS20 Neurosurgery

Blood Table 14 . Comparison of Epidemiology and Etiology of Intracranial Bleeds Types of Hematoma / Hemorrhage

Etiology

Epidural Hematoma

Skull fracture causing middle

Epidemiology Clinical Features

meningeal bleed

.

M » f (4:1J associated with trauma

lucid Interval before loss of consciousness

.

Age »50 subarachnoid associated with bridging vessels trauma

Acute SDH

Ruptured

..

Ruptured

Prognosis

Treatment

CT Density and MRI Appearance of Blood Hyperdense

Craniotomy

Good with prompt management ; respiratory arrest can occur from uncal herniation; 89 % recovery at 6 mo

lenticular mass with sharp margins, usually limited by suture lines

No lucid interval,

crescentic mass,

hemiparesis,

crossing suture

pupillary

lines

Hyperdense

-

40 60 % mortality in patients requiring surgery

Craniotomy if bleed >1 cm thick

Hypodense Often asymptomatic, crescentic mass, crossing suture minor H /A , confusion , signs lines

MRIT1

MRI 12

Acute (< 72 h|

Hyperdense

Grey

Slack

Subacute k ft3*|

Isodense

White

White

Chronic

Hypo-dense

Black

Black

Cl

time

tfrrt)

-

M8M1- fcorpe Wuihfiglun Dllilge " MRI 12 Orto* cookie - Bl uV WluU Bl ick .

changes

Age > 50 ElOH users subarachnoid bridging vessels anticoagulated

Chronic SDH

CT Features

recurs

8.6% mortality at 6 mo with drain. 18.1% without

Honsurgical: NP0. IV normal saline |NS ), ECG , Foley , BP 120 150, vasospasm prophylaxis ( nlinodipine ): open

Traumatic; 0.6% mortality with isolated SAH in the setting of mild traumatic brain injury|GCS >13)

vs endovascular surgery to repair if

More severe IBI is

Burr hole to drain; craniotomy if

.

.

of increased ICR light

.

-

headedness

Trauma

SAH

.

spontaneous (aneurysms idiopathic, AVM )

.

Age 55- 60.20 % Sudden onset thunderclap cases under age 45 H /A , signs of increased ICP

Hyperdense blood in cisterns/fissures (sensitivily decreases over time)

-

.

typically associated with additional forms of brain injury.

rebleed; external ventricular drainage or internal CSf diversion may be needed if secondary hydrocephalus

.

HTN vascular

ICH

abnormality ,

.

tumours

infections,

.

-

Age >55 male, drug use (cocaine EtOH , amphetamine )

TIA likc symptoms, signs of increased ICP

.

Aneurysmal: 50% mortality at 1 month without treatment . 20 40% with moderate to severe disability with treatment

-

.

Hyperdense Medical : decrease BP Poor: 44% mortality due to cerebral herniation inlra parenchymal control ICP Surgical: craniotomy collection

coagulopathy

Epidural (Extradural) Hematoma Etiology • temporal parietal skull fracture; 85% are clue to ruptured middle meningeal artery; remainder of cases are due to bleeding from middle meningeal vein, dural sinus, or bone/diploic veins

-

Epidemiology • young adult, M:F= 4:1; rare before age 2 or after age 60 • 1-4% of traumatic head in juries

Clinical Features • classic sequence ( seen in < 3096): post traumatic reduced LOC, a lucid interval of several hours, then obtundation , hemiparesis, ipsilateral pupillary dilation, and coma • signs and symptoms depend on severity but can include H / A , N / V, amnesia, altered LOCI, aphasia, seizures, HTN , and respiratory distress • deterioration can take hours to days

-

Investigations • CT without contrast: “ lenticular-shaped ,” usually limited by suture lines but not limited by dural attachments ( not visible on initial CT in 8% of cases) Treatment

• admission , close neurological observation with serial CT indicated if all of the following are present small volume clot ( < 3() mL ), clot thickness < 15 mm , minimal midline shift ( MLS < 5 mm ), (iCS >8, no focal deficit • otherwise, urgent craniotomy to evacuate clot , follow - up CT

I Compression olvonlricloslMLSI

2. Blood

Figure 16. Extradural hematoma on CT

rn LJ

Poor Prognostic Indicators for Epidural Hematoma • Older age • Low CCS on admission • Pupillary abnormalities (especially nonreactive) • longer delay in obtaining surgery (if needed) • Postoperative elevated ICP

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• patients with initial epidural hematoma > 10 mL on CT within 2 h or epidural hematoma enlargement in temporoparietal region are more likely to develop epidural hematoma enlargement and require close CT follow - up at 5 6 h post impact • mannitol preoperative if elevated ICP or signs of brain herniation • reverse anticoagulation if on warfarin

-

Prognosis

• good with prompt management , as the brain is often not damaged • worse prognosis if bilateral Babinski or decerebration preoperatively • death is usually due to respiratory arrest from uncal herniation ( injury to the midbrain )

Compression of ventricles MLS

Blood

Subdural Hematoma Table 15 . Comparison of Epidemiology and Etiology of Acute and Chronic SDH Acute SDH

Chronic SDH

Time Course

1-2 d after bleeding onset

>15

Etiology

Rupture of vessels that bridge the subarachnoid space (c g. cortical artery,large vein, venous sinus) or cerebral

May start out as acute SDH Often due to minor injuiies or no history of injury Blood within the subdural space evokesan inflammatory response: Fibroblast invasion of clot and formation of neomembranes within days * growth of neocapillaries » fibrinolysis and liquefaction of blood clot |forming a hygroma) Course is determined by the balance of rcbleeding from noomcmbtancs and resorption of fluid

.

laceration

d after bleeding onset

Old blood

-

.

Risk Factors

Trauma, acceleration-deceleration injury, anticoagulants EtOH cerebral atrophy, infant head trauma, shaken baby syndrome

Advanced age, alcoholics, patients with CSF shunts, anticoagulants, coagulopathies, shaken baby syndrome

Clinical Features

Altered LOC, pupillary irregularity, hemiparesis Up to 50% of patients can present with coma from the time

May presentwith minor H /A confusion, language difficulties TIA -like symptoms, symptoms of raised ICP t seiiures progressive dementia, gait problem, light - headcdness Presents with global rather than focal deficits, such as disturbance of consciousness: “the great imitator * of dementia, tumours

.

of injury

..

.

Investigations

CT: hyperdense. concave, crescentic mass, crossing suture lines

CT: hypodense (liquefied clot), crescentic mass

Treatment

Indications lor craniotomy: if clinically symptomatic, hematoma >1cm thick MIS >5 mm CCS decreased by > 2 from time of injury to hospital admission, or ICP persistently >20 mmHg (optimal if surgery 1cm: craniotomy if recurs more than twice Good overall as brain usually undamaged, but may require repeat drainage

Figure 17. Subdural hematoma on CT

.

Use of Drains vs No Drains After Burr-Hole Evacuation For Treatment of Chronic Subdural Hematoma CochraoeDB Syst Rev 2016:|S):(DOI1402 Purpose: Tocompate eiternal subdural drams to no drains after burr - hole evacuation for treatment of chronic SDH Methods: Systematic renew with comprehensive search strategy databases eitracbog 9 RCTs|n*9G8 ) Results : SgrTirant reduction m the risk of recunence with subdural drains (RR 0 45.95% Cl 0.32 C-61) no strong evidenceod increase in com ptcations (RR 0.78 95% Cl 0.77-1.72) mortality (SR 0.78.95% Cl 0.45-1.33).poovfunctional outcome (SR 0.68 95% Cl 0.44 -1.05).

.

.

.

.

Conclusions

Cerebrovascular Disease Cerebrovascular disease may be divided into two general categories:

Ischemic Cerebral Infarction (80% of disease) • includes embolism , thrombosis of intracerebral arteries, vasculitis, hypercoagulability, etc. ( see Neurology Stroke , N 5 I )

.

1. Some evidence that postoperative drainageis effective in reducing the symptomatic recurrence of chronic subdural hematoma. 2.Ihe effect of drainage on the occurrence ol surgical complications, mortality,and xor functional outcomes is uncertain due to low quality evidence. 3.No strong evidence ol increase hi complications when drains aroused.

Intracranial Hemorrhage ( 20% of disease ) • includes SAH, spontaneous 1CH, 1VH • may occur due to ruptured intracranial aneurysms

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t. Anterior communicating artery. 30% 2. Middle cerebral artery. 20% 3. Internal carotid/posterior communicating artery. 30% 4 . Basilar bp. 2 % 5. Superior cerebellar artery, 3 % 6. Vertebrobasilar junction. 2% 7 Posterior inferior cerebellar artery. 3% 3

Types of Aneurysms 4

5

6

Saccular

§

Imi

Fusiform

Dissecting

Hemiuanicctomy in Older Patients with Extensive Middle - Cerebral - Artery Stroke N EJM 2014:370:1091 1100 Purpose lodeletm ne il early decompressive hetnicraniectomy reduces mortality among patients >60 yr. Methods: 112 patients > 60 yr (medan age 70 yr) wdh malignant MU infarction randomly assigned 10 conservative ICU treatment is. bemicraniectomy. Endpoint was survival without severe disability (modified Rankin scale score 0-4). Results: Ine proportion of patients who survived without seiere drsahil ily was 3 S \ m the bemicraniectomy group and 18% in the control group (OR 2.91. 95*o a 1.06-7.49). Modified Rankin scale scores in hemicramectomy vs. control group in terms of percentagesod patients: 0 2 (0% vs. 0%|, 3 or moderate dlsabakty (7% is. 3%). 4 or moderate severe disabil ty {32% is. 15% ), 5 or severe disahi lity (28 % us.13 %), ard 6 or death|33% n. 70 %). Infections were more frequent in the hemicramectomy group and herniation morefieguent in the control group.

.

Conclusions : Hemitraniectomy "(leased survival withoutseiere disability among patients >60 yr with a malignant MCA infarction.

7

^

© Jerry Won 2014, after Kristina Neuman 2011

.

Figure 18 Aneurysms of the Circle of Willis: figure outlines most common aneurysms In the vessels

Subarachnoid Hemorrhage Definition

• bleeding into subarachnoid space (intracranial vessel between arachnoid and pia) Etiology • trauma ( most common ) • spontaneous

• ruptured aneurysms ( 75 -80% )

• idiopathic ( 14-22%)

• AVMs (4-5%) • coagulopathies ( iatrogenic or primary ), vasculitides, tumours, cerebral artery dissections ( < 5%) Epidemiology • ~ 10-28 in lOOOOO population peryr • peak age 55 60, 20% of cases occur under age 45

-

Risk Factors • H1N • pregnancy/ parturition in patients with pre existing AVMs , eclampsia • oral contraceptive pill • substance use disorder (cigarette smoking, cocaine, EtOH ) • conditions associated with high incidence of aneurysms ( see Intracranial Aneurysms , XS2 -I )

-

Clinical Features of Spontaneous SAH • sudden onset ( seconds ) of severe “ thunderclap” H / A usually following exertion and described as the “worst headache of my life" ( up to 97% sensitive, 12 25% specific)

• N/V,photophobia

-

• meningismus ( neck pain /stiffness, positive Kernig's and Brudzinski ’s sign ) • decreased LOG (due to either raised 1GP, ischemia, or seizure ) • focal deficits: cranial nerve palsies ( GN 111, IV ), hemiparesis • ocular hemorrhage in 20 - 40% (due to sudden raised IGF compressing central retinal vein ) • reactive HTN

Hunt and Hess Grade (Clinical Grading Scale for SAH) Grade

Description

1

Mo 5« or mild H/ A and/ or mild meningismus

2

Grade 1 100000/mm 3 without significant drop from first to last tube ( in contrast to

-

traumatic tap)

elevated protein due to blood breakdown products • four vessel cerebral angiography ( “gold standard" for aneurysms ) • demonstrates source of SA H in 80 85% of cases • angiogram negative SAH: repeat angiogram in 7 14 d, if negative > “ perimesencephalic SAH " • MRA and CT angiography/angiogram (CTA): sensitivity up to 95% for aneurysms, CTA> MRA for smaller aneurysms and delineating adjacent bony anatomy

-

-

Blood in basal cisterns

World Federation of Neurological Surgeons ( WFNS) Grading of SAH

CCS Score

WfNS Grade

ll 1

-

Aphasia , Hcmiparesis or Hemiplegia

.

IS

2 3

tt-14 13-14

4

M2 36

S

pr

-

or -

*kilacl aneurysm

Blood in Blood in suprasellar cistern interhemisplieric fissure Nontraumatic Subarachnoid Hemorrhage in the Setting of NegathreCranial Computed

Tomography Results: External Validation of a Clinical and Imaging Prediction Rule A n imerg Med 2013:61|1|:110 Purpose: lo validate twodfosion rules for the dagnosisol SAH : (1|A cIvricM prediction rule stales that patients with acute severe H / A but without the dinical variables age > 40 yr, neck pain, loss of consciousness, oionsef ofH'Awith exertion are at low - risk for SAH; ( 2) An rmagirg prediction lule hoses diagnosis on non contrast cranial Cl loi patients vrl'nn 6 hof Hf onset. Methods: Matched case -contiol studyol SS patients at 21 emergency departments between 2000 and 2011, and diagnoses were verified by LP. Results: The clinical pied ci on rule fotdiagnosis of SAH was 97.1% sen si tire. 22.7% specific, and tad a negative likelr wod ratio of 0.13 Using the nagmg prediction rule resulted in a false negalne rate of 20%. Conclusions: Performing tte clinical and imag g rules together hasthe potential for maximizing sensitivity of prediction and reducing rates of IP. but using imaging alone can resell in missed cases.

-

*

Blood in

Blood on surface of tentorium

Sylvian fissures

Figure 19. Diagnosis of SAH

-

Positive

( NCCT }

03

—

(

'r

Stop

(Positive )

)

1

.

—-

6

r

] (

Stop

CT or MRA

T

C 1LPpositive

to

x>

] (

—

Slop

,

JI

positive

Diagnostic DSA

( )

i

f

No

rtf

(

ll

Diagnostic PSA

)

Gold Standard

OR (Clipping)

( Coiling)

Gold Standard Figure 20. Approach to SAH

Adapted from: de Oliveira Manoel et al. ( 2014) Subarachnoid haemorrhage Irom a neuroimaging perspective. Critical Care

Treatment

• admit to K!U or NICU oxygen / ventilation PRN

•

NPO, bed rest, elevate head of bed 30“, minimal external stimulation, neurological vitals ql h aim to maintain sBP = 120 -150 mmHg ( balance of vasospasm prophylaxis, risk of rebleed , risk of hypotension since CBF autoregulation impaired by SAH )

• cardiac rhythm monitor, Foley PRN, strict monitoring of ins and outs

• medications

IV NS with 20 mmol KC1/ L at 125- 150 cc/ h nimodipine 60 mg PO/ NG q 4 h x 21 d for delayed cerebral ischemia neuroprotection; may discontinue earlier if patient is clinically well seizure prophylaxis: levetiracetam ( Keppra* ) 500 mg PO/ IV q 12 h x 1 wk

• mild sedation PRN

•

.

-

—

s

( MRI/MRA ) ( LP ! .1

-

The Vasograde: A Simple Grading Scale for Prediction of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage Stroke 2015;46|7):1826TJ 31 Purpose: Patients are classically at risk of delayed ceietual ischemia (OCI) aftei aneurysmal SAH. Ihis study validated a grading scale - the VASOGRADE for prediction of DCI. Methods: Oata from three Phase II RCTs and a s ogle hospital series were used to assess the lelationshp between the VASOGRADE and DCI . Results: in a cohort of 746 patients, the VASOGRADE significantly predicted Ml (P < 0.001). lire YASOGRADE - Yellow had a tendency lor increased risk for DCI ( OR 1.31: 95% Cl 0.77-2.23) when compared With VASOGRADE - Green: those with VASOGRAOE - Red had a 3 fold higher tisk of DCI (OR 3.19; 95% Cl 2.07 4.50|. VASOGRADE had an adequate diswmuut c foi prediction of OCI {area under the receiver operating characteristics cune 0.63) and good calibration. Conclusions: Ire VASOGRADE results validated previously published risk charts in a large and d verse sample of SAH patients, which allows DCI risk stiatdication on piesentalon after SAH. It co Jd help to select patients at fugh nsk of OCI and standardize treatment protocols and research studies

--

-

-

-

r x LJ

.

neuroprotection the only validated neuroprotective agent is nimodipine studies on the use of IV magnesium and endothelin -A receptor antagonist ( clazosentan ) showed reduction in DCI and vasospasm , respectively, without any effect on functional outcome a trial on the use of statins did not show any neuroprotective benefit

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Complications

• vasospasm: vasoconstriction and permanent pathological vascular changes in response to vessel irritation by blood can lead to delayed cerebral ischemia and death onset: 4 -14 d post-SAH, peak at 6-8 d; most commonly due to SAH, rarely due to ICH / IVH • clinical features ( new onset ischemic deficit): confusion , decreased LOC, focal deficit (speech or motor, e.g. pronator drift ) risk factors: large amount of blood on CT ( high fisher grade), smoking, increased age, HT' N “symptomatic" vasospasm in 20 -30% of SAH patients “angiographic” vasospasm in 30-70% of arteriograms performed 7 d following SAH diagnosed clinically, and /or with transcranial Doppler ( increased velocity of blood flow )

VASOGRADE

WFNS

VASOGRAOi

Green

M

Yellow

13

Red

45

Modified Fisher scale 12 34 Any

-

-

risk of cerebral infarct and death treatment

hyperdynamic (“triple H” ) therapy using fluids and pressors, usually after ruptured aneurysm has been clipped/coiled direct vasodilation via angioplasty or intra arterial verapamil for refractory cases • delayed cerebral ischemia: neurological deterioration persisting > 1 h in the absence of any obvious contributing physiological, radiological, or laboratory abnormalities peaks 4-10 d post-ictus can progress to cerebral infarction and is associated with significant morbidity and mortality • mechanism behind DG is unclear, hut includes vasospasm, vascular dysautoregulation , neurotoxic effects from the blood breakdown products, inflammation, micro thrombi, and cortical spreading depolarizations » it is an essential target for SAH management ( 15-20%): due to blood obstructing arachnoid granulations hydrocephalus • can be acute or chronic, requires extraventricular drain or shunt, respectively • neurogenic pulmonary edema • hyponatremia: due to cerebral salt wasting ( increased renal sodium loss and EG; volume loss ), not

-

-

S1ADH • Dl

• cardiac: arrhythmia ( >50% have ECG changes), Ml, CHF Prognosis

• 10 -15% mortality before reaching hospital, overall 50% mortality ( majority within first 2-3 wk) • 30% of survivors have moderate to severe disability' • a major cause of mortality is rebleeding, for untreated aneurysms: • risk of reblecd: 4% on 1st day, 15 20% within 2 wk , 50% by 6 mo • if no rebleed by 6 mo, risk decreases to same incidence as unruptured aneurysm (2%) • only prevention is early clipping or coiling of “cold" aneurysm rebleed risk for “perimesencephalic SAH ” is approximately same as for general population

-

Intracranial Aneurysms Epidemiology • prevalence 1-4% (20-30% have multiple ) • 1;> M; 35 65 yr ( mean age of presentation is 50 yr)

-

Types

• saccular (berry) most common type located at branch points of major cerebral arteries (circle of Willis) 85 95% in carotid (anterior ) system , 5 15% in vertebrobasilar ( posterior ) circulation

-

• fusiform

-

atherosclerotic more common in vertebrobasilar system, rarely rupture

• infectious ( mycotic)

secondary to any infection of vessel wall, 20% multiple 60% Streptococcus and Staphylococcus

• 3-15% of patients with bacterial endocarditis

The Durability of Endovascular Coiling vs. Neurosurgical Clipping of Ruptured Cerebral

-

A ncurysms: 18 Yr Follow Up of The U K Cohort of the International Subarachnoid Aneurysm Trial (ISM) lancet 2015:385(9969):691 697 Methods: RCT comparing endovascular coiling treatment with craniotomyand dipping for luptured intracranial aneurysms in 2143 patients who were considered eligible for either modality or therapy between 1994 -2002.1644 patients were Mowed lor deaths and outcomes for 10-18.5 yr. Results: At 10 yr 83% of endovascular coiling group and 79% of neurosurgical clipping group were alive. 82% of patients treated with endovascular coiling and 78% of patients treated with neurosurgical dipping were independent. Fatients m the endovascular group were more likely to be alive and independent at 10 yr vs. neu rosurgery group (081.34, 95% Cl 1.07 1.67). Rebleeding risks from target aneurysm for endovascular group and neurosurgery groupwere 0.0216 (95% Cl 0.0121 0.0383) and 0.0064|95% CI 0.0024 0.0173), respectively . Conclusions: IThe probability of death or dependency was significantly greater in the neurosurgical group (vs. endovascular group) at 10 yr follow up. 2. Rebleeding was more likely in endovascular group ( vs. neurosurgical group), but risk wassaall at 10 yr follow up. 3. Probability of disability free survival was significantly greater in the endovascular group ( vs. neurosurgical group) at 10 yt follow - up.

-

.

-

.

-

-

-

-

Most Common Locations of Saccular Aneurysms • Anterior communicating artery (ACom): 30% • Posterior communicating artery (PCom): 25% MCA: 20% • Basilar tip: 7%

-

Risk Factors for Saccular Aneurysms Smok ing

HTN Adult Polycystic kidney disease Ehlers- Danlos syndrome Family history: >2 first-degree relatives

Risk Factors

• autosomal dominant polycystic kidney disease (15%) • fibromuscular dysplasia ( 7-21%)

.

j

AVMs

• connective tissue diseases ( Ehlers-Danlos syndrome, Marfan syndrome) • family history • bacterial endocarditis • Osier - Weber - Kendu syndrome ( hereditary hemorrhagic telangiectasia ) • atherosclerosis, HT N, and smoking • trauma

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Table 16. Five Year Cumulative Rupture Risk in Unruptured Aneurysms Based on Size and Location

- .

*7 mm 7-12 mm

0%

0%

2.5%

0%

2.6%

14.5%

13-24 mm

3%

14.5%

18.4%

Long Term Serial Screening for Intracranial Aneurysms in Individuals wilti a Family History d Aneurysmal Subarachnoid Hemorrhage: A Cohort Study lance!Neurol 2014:13:385 392 Purpose : Toei amine the y eld of long - term serial

6.4%

40%

50%

screening lor Intracranial aneurysms loi Individuals

Cavernous Carotid

v

24 mm

ACAorACom /MCA/ICA

Vertebrobasilar/ PC AtPCom

.-

ACA = anterior cerebral artery: ACom = anterior communicating artery: ICA - internal carotid artery: MCA - middle cerebral artery: RCA - posterior cerebral artery: PCom = posterior commuiicating artery. Table adopted Irorn the ISUIA Trial: lancet 2003:362:W3 !10

-

Clinical Features • rupture (90%), most often SAH , but 30% ICH, 20% IVH, 3% subdural bleed • sentinel hemorrhage ( “ thunderclap H /A") > requires urgent clipping /coiling to prevent catastrophic bleed • mass effect ( giant aneurysms) • ICA or ACom aneurysm may compress: the pituitary stalk or hypothalamus causing hypopituitarism the optic nerve or chiasm producing a visual field defect basilar artery aneurysm may compress midbrain , pons (limb weakness), or CN III PCom aneurysm may produce CN III palsy intracavernous aneurysms (CN 111, IV, VI, V 2, VI ) • distal embolization (e.g. amaurosis fugax ) • seizures • H / A ( without hemorrhage) • incidental CT or angiography finding (asymptomatic)

with a positive famdy history ol aneurysmal subarachnoid hemorrhage (aSAH ) (hroor more first degree relatives who have had aSAH or unruptured Intracranial aneurysms) Study: Screening results Iron April 11993 to April 1 2013wece reviewed in a cohortstudy. MSAor CIA was done from ages 16 -18 to ages 65 )0. Alter a negative screen, individuals were advised to contact IheOnme hsSyrfoi follow - up. Results: Aneurysms were identified in 11% of indivvduals al (list screening|n 458 ), 8% at second screening ( n 261) 5% atlhird screening ( n 128| and &% atfourth screening ( n*63|.Smoking ( OR 2.). 95% Cl 1.2- 5 j), history of previous aneurysms (3.9. 1.2 12.)). and fami al history ol aneurysms (3.5 1.68.1) were significant risk factorsfor aneurysm at first screening. History ol previous aneurysms vrastte only significant risk factor for aneurysms at follow -up screening ( HR 4.5 95% Cl 1.1 18.)). Conclusions: Ihe benefit ol long term screening in individuals with a family history of aSAH is substantial up to and after 10 yr of follow - up and twn initial

.

*

-

.

-

.

.

-

.

-

-

negative screens.

Investigations • CTA, MRA, cerebral angiogram

Treatment • ruptured aneurysms overall trend towards better outcome with early surgery or coiling (48-96 h after SAH ) treatment options: surgical placement of dip across aneurysm neck, trapping (clipping of proximal and distal vessels), coiling using (iuglielmi detachable coils, ( low diversion stents , wrapping ( last resort ) choice of surgery vs. coiling: consider location , size, shape, and tortuosity of the aneurysm , patient comorbidities, age, and neurological condition ; in general: endovascular coiling > clipping for ruptured intracranial aneurysms suitable for both treatments -> greater survival benefit at 1 yr with sustained effect for up to 7 yr post-treatment coiling: posterior > anterior circulation , deep/ eloquent location , basilar artery bifurcation / apex, older age, presence of comorbidities, presence of vasospasm clipping: difficult endovascular access, broad aneurysmal base, branching arteries at the aneurysm base, tortuosity /atherosclerosis of afferent vessels, dissection, hematoma , acute brainstem compression • unruptured aneurysms average 1.4% annual risk of rupture; predictors include: age, HTN , history of SAH, aneurysm size and location , and geographical region ( Finnish people 3.6 times increased risk ; Japanese people = 2.8 times increased risk ) no clear evidence on when to operate; need to weigh life expectancy • risk of niorbidity / mortality of SAH ( 20 -50 %) vs. risk of coiling ( 2% ) generally treat unruptureu aneurysms > 10 mm • treatment guided by balance of risks of SAH per ISUIA and PHASES and of intervention per centre experience and outcomes follow smaller aneurysms with serial angiography

The Unruptureil Intracranial Aneurysm Treatment

Score

Ffc.rc ogy 2015 :85 (101:881 839 Purpose: To develop an unruptured intracranial aneurysm ( UIA) treatment score|UIA!$|model lira! includes and quantifies key lectors involved in clinical deci si on - making m the management of UlAs and lo assess agreement for this model airo'g specialists in UIA management and research. Methods : An international mullidisup inary ( neurosurgery , neuroradiology neurology , clinical eptdeminlogyl group of 69 specaiists was convened to develop and validate the UIAIS model using a Delphi consensus method . Results: Hie UIAIS accounts lor 29 key factors m UIA

.

management. Conclusions: T'is novel UIA decs on guidance study captures an encellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty.

=

-

See landmark Neurosurgery Trials ta £> le for more information on the natural history ol unrupluied intracranial aneurysms and the risk associated with the repair.

Intracerebral Hemorrhage Definition • hemorrhage svithin brain parenchyma, accounts for ~ 10% of strokes • can dissect into ventricular system ( IVH ) or through cortical surface ( SAH )

Etiology • HT N ( usually causes bleeds at putamen , thalamus, pons, and cerebellum ) • hemorrhagic transformation ( reperfusion post - stroke, surgery, strenuous exercise, etc ) • vascular anomalies aneurysm, AVMs, and other vascular malformations (see Vascular Malformations, NS27 )

.

location of ICH • Basal ganglia/internal capsule (50%) • Thalamus (15%) • Cerebral white matter (15%) • Cerebellum/ brainstem - usually pons (15%) • Other (5%)

+

venous sinus thrombosis arteriopathies (cerebral amyloid angiopathy, lipohvalinosis, vasculitis )

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NS26 Neurosurgery

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• tumours ( 1%): often malignant (e.g. GBM, lymphoma, metastases ) • drugs (amphetamines, cocaine, alcohol, anticoagulants, etc.) • coagulopathy ( iatrogenic, leukemia, thrombotic thrombocytopenic purpura, aplastic anemia ) • CNS infections (fungal, granulomas, herpes simplex encephalitis) • post-trauma ( immediate or delayed, frontal and temporal lobes most commonly injured via coupcontrecoup mechanism )

• eclampsia • postoperative ( post carotid endarterectomy cerebral reperfusion, craniotomy ) • idiopathic

-

ICH Score Components • GCS score (3-4 2 pts; 5-12-1 pt, 13-15-0 pt) ICH volume (>30 cm~1 pt, 45 yr, known HTN, and putamen / thalamic/ posterior fossa ICH (yield 0%) • surgical

Wire 4c

-

-

*

craniotomy with evacuation of clot, treatment of source of ICH (i.e. AVM, tumour, cavernoma ), ventriculostomy to treat hydrocephalus

2 3

-

location

hfrdow*

0

Oogocct

I

OtepVzoonsOrainagt

0

Httpceswt

Presetf ZVU varies w? ukdntod by nddntg trio 3 individual Sperite Horti Safe scare horn the above table. -9- a 2 cn hnctx e rcr etoquetit locaticci without bawtage = Grade I

-

-

• indications symptoms of raised ICP or mass effect rapid deterioration (especially if signs of brainstem compression ) favourable location (e.g. cerebellar, non -dominant hemisphere) young patient (10 poor prognosis: massive hemorrhage (especially dominant lobe ), low GCS/coma , lost brainstem function medical reasons ( e.g. advanced age, severe coagulopathy, difficult location (e.g. basal ganglia, thalamus))

n

u

Prognosis • 30 d mortality rate 44%, mostly due to cerebral herniation • rebleed rate 2-6%, higher if HTN poorly controlled

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XS27 Neurosurgery

Toronto Notes 2023

Vascular Malformations Types • AVMs

• cavernous malformations ( cavernomas, cavernous hemangiomas / angiomas ) • venous angioma • capillary telangiectasias • AY1 (carotid -cavernous fistula, dural AYF, vein of Galen aneurysm ) • “angiographically occult vascular malformations” (any type, 10% of malformations)

Arteriovenous Malformations, Cavernous Malformations, and Dural Arteriovenous Fistulas Table 17. Comparison of Pathoetiology, Clinical Features , and Treatment of Arteriovenous Malformations, Cavernous Malformations, and Dural Fistulas Arteriovenous Malformations Definition

Cavernous Malformations

Dural Fistulas

Tangle of abnormal vessels /arteriovenous Benign vascular hamartoma shunts, with no intervening capillary beds consisting ol irregular sinusoidal or brain parenchyma; usually congenital vascular channels located within the brain without intervening neural tissue or associated large arteries/ veins

.

Several genes now described:CCM1 CCM2. CCM3

Epidemiology

--

.

.

.

Prevalence 0.14% M:F"2:1 average age Prevalence ol 0.10 2%, both sporadic and hereditary forms at diagnosis 33 yr 15 -20 % ol patients with hereditary described hemorrhagic telangiectasia (Osier -Weber Rendu syndrome) will have cerebral AVUs

Clinical Features Hemorrhage ( 40- 60%);small AVMs are more likely to bleed due to direct high pressure AV connections Seizures (50%); more common with larger AVMs Mass effect Focal neurologicalsigns secondary to ischemia ( high (low "steal phenomena ") localized H / A, increased ICP Bruit (especially with dural AVMs) May be asymptomatic (“silent")

Seizures (60%),progressive neurological deficit (50%), hemorrhage (20%), H/A Often an incidental finding Hemorrhage risk less than AVM. usually min or bleeds

Frstu 'as connecting dural arteries to dural veins or the dural sinus frequently occur at the transverse and cavernous sinuses,but can be found at every cranial dural sinus Hypothesised to be related to venous sinus thrombosis formation, and subsequent microvascular shunt lor.mat on within the dura between arteries and veins Unknown true incidence Constitute 10-15% of all intracranial vascular abnormalities

Asymptomatic,pulsatile tinnitus if involving sigmoid or transverse sinuses, bruits.H/A Carotid cavernous involvement classically produces proptosis, chemosis and bruits Symptoms of SAH, S 0H. or ICH

.

T 2-weighted image MRI|nonenhancing) Gradient echo sequencing (best for diagnosis)

MRI ( flow void), MRA Angiography (7% will also have one or more associated aneurysms)

Treatment

Surgical excision: Decreases risk of future hemorrhage and seizure Only appropriate for symptomatic lesions that are surgically Surgical excision is treatment of choice accessible (supratentorial lesions even in Spetzler - Martin gradesI - II with general good health are less likely to bleed than SRS is preferred tor small (50 or 50, previous Hx of cancer, pain unrelieved by bed rest constitutional

• see Orthopaedic Surgery

Extradural Lesions

symptoms

Post circulation Ant circulation

AXIAL SECTION OF

THORACIC SPINE

[ asciculus .Fasciculus .lateral corticospinal

Dorsal funiculus-

Posterior spinal artery

Dorsal horn ( sensory!

.

.

Increased ESR IV drug use immunosuppressed. fever Compression Fracture Age >50, trauma, prolonged steroid use

cuneatus

tract ( efferent )

Lateral hon ( autonomic! j 'jL * onlv present T1 LZS2 SS \

-

.

nf

Ventral horn

( motor )

Posterior spinal aa.

gracilis

Infection

Anterior

spinal artery

,O

Anterior

corticospinal

ateral -lfuniculus J

-Spinothalamic ( tract

afforcntl

Ventral funiculus

tract ( efferent)

Anterior

segmental medullary a .

Arachnoid mater

/ .Dura mater

interior spinal a.

Post & ant. reticular aa.

Branch to vertebral body & dura mater

-

Dorsal branch of intercostal a

Thoracic aorta

Spinal a.

r1 LJ

Intercostal a.

+

.

© Natalie Cormier 2D1S after Takami lijima

Figure 22. Vascular supply of spinal cord

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XS29 Neurosurgery

Toronto Notes 2023

Root Compression •radiculopathy is a pain and /or sensorimotor deficit syndrome that involves compression of a nerve root. Nerve compression generally occurs as a result of disc herniation, degenerative disc diseases (spondylosis), instability, and masses (rare) • patients generally present with referred pain, sensory changes ( numbness and /or tingling ) or weakness. Whereas patients might sometimes describe sensory changes in a dermatomal distribution, the referred pain will not be in a dermatomal distribution. The areas of pain and altered sensorium

may be incongruent

Sensory Fibres • Fasciculus gracilis/cuneatus: proprioception, fine touch, vibration • Spinothalamic tract: pain and

temperature Motor Fibres • Corticospinal tract: skilled movements

•muscle innervation has less overlap than sensory innervation and hence is a better predictor of level of

pathology Differential Diagnosis

•herniated disc • neoplasm ( neurofibroma, schwannoma ) •synovial cyst, abscess •hypertrophic bone /spur

Cervical Disc Syndrome Etiology

• nucleus pulposus herniates through annulus fibrosus and impinges upon nerve root, most commonly Clinical Features • pain in arm follows nerve root distribution, worse with neck extension, ipsilateral rotation, and lateral flexion (all compress the ipsilateral neural foramen ) • LMN signs and symptoms (diminished reflexes, non -spastic motor weakness) • central cervical disc protrusion may cause myelopathy as well as nerve root deficits

Disc herniations impinge the nerve root at the level below the interspace fie. C56 disc affects the C6 nerve root)

-

Investigations

• if red flags: cervical spine ( C-spine) x-ray, Cl', MR1 (imaging of choice) • only consider HMG /nerve conduction studies if diagnosis uncertain and presenting more as peripheral nerve issue Treatment

• nonsurgical • no bed rest unless severe radicular symptoms • activity modification, patient education ( reduce sitting, lifting) physiotherapy, exercise programs focus on strengthening core muscles • analgesics; NSAlDs are more efficacious • avoid cervical manipulation like traction • surgical indications anterior cervical discectomy is the usual approach ( posterior foraminotomy with discectomy is the other option ) • intractable pain despite adequate conservative treatment for >3 mo progressive neurological deficit Prognosis

• 95% improve spontaneously in 4-8 wk Table 18. Lateral Cervical Disc Syndromes

-

-

-

-

C4 5

C5 6

C6 7

C7 T1

Root Involved

C5

C6

C8

Incidence

2%

m.

C7

69%

10%

Sensory

Shoulder

Thumb

Middle finger

Ring finger.Sth finger

Motor

Deltoid,biceps,

Biceps, wrist extensors

Triceps

Digital flexors,intrinsics

Biceps,brachioradialis

triceps

Finger jerk (Hoffmann's

supraspinatus

Reflex

No change

rn

.

i J

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NS30 Neurosurgery

Toronto Notes 2023

Degenerative Cervical Myelopathy Definition • progressive degenerative process of cervical spine leading to canal stenosis; congenital spinal stenosis; degeneration of intervertebral discs; hypertrophy of dura or ligaments; subluxation; altered mobility; telescoping of the spine due to loss of height of vertebral bodies; alteration of normal lordotic curvature • resultant syndromes: mechanical neck pain, radiculopathy ( root compression), myelopathy (spinal cord compression)

Cervical spondylotic myelopathy is the most common cause of spinal cord impairment

'

Epidemiology

• typically begins at age 40-50, M>F, most commonly at the C5-C6 > C6-C7 levels Pathogenesis

• any of: disc degeneration / herniation, osteophyte formation, ossification , and hypertrophy of ligaments • pathophysiology includes static compression, dynamic compression, and vascular compromise

Clinical Grading Scores to Assess CSM • Modified Japanese Orthopaedic Association (mJOA) • Nunck Grade • Neck Disability Index

Clinical Features

• insidious onset of mechanical neck pain exacerbated by excess vertebral motion ( particularly rotation and lateral bending with a vertical compressive force Spurling's test ) • the earliest symptoms are gait disturbance and lower extremity weakness or stiffness • occipital H /A is common • radiculopathy may involve 1 or more roots, and symptoms include neck, shoulder, and arm pain;

paresthesias; and numbness • cervical spondylotic myelopathy may present with: weakness ( upper > lower extremity), lower extremity weakness (corticospinal tracts ) is most worrisome complaint decreased dexterity, loss of fine motor control sensor)' changes UMN findings such as hyperreflexia, clonus, and Babinski reflex funicular pain, characterized by burning and stinging ± Lhermitte’s sign ( lightning-like sensation down the back with neck flexion ) Investigations • x- ray of cervical spine ± flexion / extension (alignment, fractures ) • MR1 most useful for determination of compression of the neural element • CT is only used for better determination of bony anatomy (i.e. OPLL) • HMG/nerve conduction studies reserved for peripheral nerve investigation

A Clinical Practice Gnidetine for dtMaaagcntn: of Prints nritk DagncratinCtmul Mjelopatbj (OCM): iKoaandrionsta Patients with Mild. Moderate, aadSeme Disease and NonaayelcpatAic Patients witkEvidence of CordCoapressioo ( anterior approach generally preferred

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XS31 Neurosurgery

Toronto Notes 2023

• with preserved cervical lordosis -> posterior approach generally preferred surgical indications: myelopathy with motor impairment, progressive neurologic impairment, intractable pain • complete remission almost never occurs; surgical decompression stops progression of disease in almost all cases; 80'V, of patients experience neurological improvement •

Table 19.2017 Summary AO Spine- CSRS Guideline for the Management of Degenerative Cervical Myelopathy Guideline/Recommendation

Patient Population

Level of Recommendation

Severe DCM (raJOA 0-H) Moderate 0CM|mJ0A 1244)

Strong

Surgical intervention is recommended

Strong

Surgical intervention is recommended

Mild DCM {mJ0A 1S.1T)

Weak

Surgical intervention or structured rehabilitationis recommended: consider surgery if with neurologic deterioration or failure to improve

Non-myelopathic patients with cord compression and without radiculopathy

Weak

Prophylactic surgery is not recommended

Non-myElopathic patients with cord compression and with rad.allopathy

Weak

Either surgical intervention or nonoperative treatment (dose follow-up or structured rehabilitation)

Lumbar Disc Syndrome Definition

• compression of nerve roots caused by herniation of the nucleus pulposus through the annulus fibrosus of an intervertebral disc in the lumbar spine Etiology • posterolaterally herniated disc compressed nerve root exiting BELOW the level of the disc or the traversing nerve root • far lateral disc herniation compressed nerve root AT the level of the disc or the exiting nerve root • central herniation may cause cauda equina compression or lumbar stenosis ( neurogenic claudication ) Clinical Features • initially back pain, then leg pain > back pain • limited back movement (especially forward flexion ) due to pain • motor weakness, dermatomal sensory changes, decreased reflexes • exacerbation with Valsalva; relief with flexing the knee or thigh

• nerve root tension signs • straight leg raise ( SLR ) ( Lasegue’s test ) or crossed SLR ( pain should occur at less than 60° ) suggests L5, SI root involvement • femoral stretch test suggests L 2 , L3, or L4 root involvement

Figure 24. T2- weighted MRI of lumbar disc herniation

Investigations

• MRI is modality of choice • x- ray spine (only to rule out other lesions), CT ( bony anatomy) myelogram and post-myelogram CT (only if MRI is contraindicated )

-

-

See landmark Heu osa gery Inals table for mote i brmat ^ "e SPOBI trial fir outcomes of surgery *. rorooeraive care foe lumbar diseberniabun.

-

Treatment • •

nonsurgical (same as cervical disc disease) surgical indications: same as cervical disc and cauda equina syndrome

Prognosis • 95% improve spontaneously within 4-8 wTk • those who do not improve writh conservative treatment achieve symptom relief quicker with surgery than continuation of conservative management; however, the long-term outcome after surgery is comparable to conservative therapy • do not follow patients with serial MRIs; clinical status is more important at guiding management

-

=

-

Table 20. Lateral Lumbar Disc Syndromes 13-4

Magnetic Besoiaice Imaging in Follow -Up Asses saeni of Sciatica IBM 2013:3S85$9-M)0? Backgroud: Fo cn .:MB) is a coistroveisia ! etkod for nK Sr rg sciatica c patients wifi known liBSar-dsckertateo. Metlods: Paridpants (n 283|weierecruited froa a s ul2:eoas. parallel, raodomraed study coaparmg surgery aid conservative care loi sciatica (ae Sciatica trial). MBI and clinical assessment weie usderulei prMreatmett and 1 yi post tieatment to nsualiae disc herniation and ’ r i :~ evaluate outome. Besitts 1 p. 4sc tar ation was visible in 35% wis a fanuraieoutcome (complete, or nearly carpea sy jtom resolntjos) acid m 33% wifi ai uifavou cS ie aut:ire ( NI.70 ). A favourable outcome was -eocried v: 85% of patients with disc hen etoa erd 13% wiiewt isc heiniatioo (H)J0|. Conclusions: Aretoniccl abnormalities visible on itbeSrd 1011 p erne treatment forsciabca due to taber-dsc temaSoo cou d not distinguish patients witt resobtoa of their symptoms from patients still eipe ercog symptoms.

L4- 5

L5 -S1

Root Involved

L4

L5

S1

Incidence


37 wk GA ) P: number of preterm deliveries ( 20 +0 to 36 + 6 wk GA ) A: number of abortions and ectopic pregnancies (ending < 20 wk GA ) - induced ( therapeutic) and spontaneous ( miscarriage) L; number of living children

Physical Signs • uterine and abdominal enlargement • breast engorgement, areola darkening , and prominent vascular patterns • Goodell’s sign : softening of the cervix (4 6 wk GA ) • Chadwick’s sign: bluish discolouration of the cervix and vagina due to pelvic vasculature engorgement (6 wk GA ) • Hegar’s sign: softening of the cervical isthmus (6-8 wk GA )

-

Investigations • (5- hCG: peptide hormone composed of (5 subunits produced by placental trophoblastic cells maintains the corpus luteum during pregnancy positive in serum 9 d postconception, positive in urine 28 d after 1st day of LMP plasma levels double q48h in a normally developing pregnancy from the time it becomes detectable until it peaks at ~100000 ( approximately at 8-10 wk GA) then falls but continues to be measurable until delivery levels less than expected can suggest ectopic pregnancy, miscarriage, inaccurate dates, but found in some normal pregnancies • levels greater than expected can suggest multiple gestation, molar pregnancy, trisomy 21, inaccurate dates, some normal pregnancies, or kidney disease (slower clearance) • U /S:

Establishing the desirability of pregnancy in a patient with suspected or confirmed pregnancy informs the construction of an appropriate management plan

-

p hCG Rule of 10s 101U at time of missed menses 100000 IU at 10 wkGA (peak) 10000 IU at term

Trimesters T1: 1 14 wkGA T2:14-28 wk GA T3: 28-42 wk GA Normal pregnancy term: 37 42 wk GA

-

-

• transvaginal

• 5 wk GA: gestational sac visible • 6 wkGA: fetal pole visible • 6-8 wk GA: fetal heart activity visible ( I HR visible after 6 wk GA on TVUS)

• transabdominal • 6-8 wk GA: intrauterine pregnancy visible

Maternal Physiologic Adaptations to Pregnancy Table 1. Physiologic Changes During Pregnancy Changes Increased pigmentation of perineum and areola, chloasma (pigmentabon changes under eyes and on bridge of nose), linea nigra (midline abdominal pigmentation) Proliferation of skin tags

Skin

Spider angiomas Palmar eryUrema due to increased estrogen Striae gravidarum due toconnective tissue changes Hyper dynamic circulation Increased cardiac output, heart rate, and blood volume Decreased blood pressure: decreased PVR due to progesterone's effect on vascular smooth muscle and decreased venous return from enlarging uteruscompressing IVC and pelvic veins Increased venous pressure leads lo risk ot varicose veins, hemorrhoids, and leg edema

Cardiovascular

Hemodilution causes physiologic anemia and apparent decrease in hemoglobin andhematocrit Increased leukocyte count but impaired function leads lo improvement msome auto mmuoe diseases Decreased total protein largely due lo dilution and decreased serum albumin 6eslational thrombocytopenia: mild (platelets >70000 'pl) and asymptomatic, notmahees vrthm 2-12 wk following delivery Hypercoagulable state: increased risk of DVI and PE but also decreased bleeding at delivery PVR - pulmonary vascular resistance: IVC interior vena cava: FEV1 - forced expiratory volume in 1 second:CO cardiac output: GFR - glomerular

Hematologic

-

-

-

filtration rate: BUN blood urea nitrogen:GERD gastroesophageal reflux disease

+

-

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OBI Obstetrics

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Table 1. Physiologic Changes During Pregnancy Changes

Respiratory

Increased incidence of nasal congestion Increased & consumption to meet increased metabolic requirements Elevated diaphragm (i.e. appears more "barret chested'l Increased minute ventilation leads to decreased C02 resulting n ml respiratory alkalosis that helps C 02 diffuse across the placenta from fetal to maternal circulation Decreased total lung capacity (TIC), functional residual capacity (TRC) and residual volume|RV) No change in vital capacity (VC) and f EVr

.

Gastrointestinal

Increased incidence of gallstones due to progesterone causing increased gallbladder stasis Constipation due lo progesterone causing decreased Gl motility and hemorrhoids as a result of constipation and increased intra- abdominal pressure

Genitourinary

Increased urinary frequency due to increased total urinary output Increased incidence of U1Iand pyelonephritis due to urinary stasis (see Unoaiy freerInfection 0531) Glycosuria can be physiologic especially in 13 due b renal plasma Bow increase eiceedmg that ol GFR preventing reabsorplion of glucose as per the non-pregnant state: consider testing lor GDM if noted in first 2 trimesters Uretericand renal pelvis dilatation (R >L) due to progesterone induced smooth muscle relaiation and uterine enlargement Increased CO and thus increased GFR leads to decreased creatinine (normal irr pregnancy 35 - 44 mmoll). uric acid, and BUN

Neurologic

Increased incidence of carpal tunnel syndrome, sciatica, and Bell's palsy

Endocrine

Thyroid: moderate enlargement (not clinically detectable) andincreased basal metabolic rate Increased total thyroxine and thyroxine binding globulin (TBG) Normal free thyroxine indei and TSH levels Physiologic suppression of TSH in IIis common due to cross -reactivity of HCG to TSH receptors Adrenal: increased maternal cortisol throughout pregnancy (total and free) Calcium: decreased totalmaternal Ca 2*due bdecreased albumin free ionized C a (i.e. active) proportion remains the same due todecreased parathyroid hormone (PTH), resulting in increased bone resorption and gut absorption, and increased bone turnover (but no loss of bone density due to estrogen inhibition) [ see DiabetesMellitus. 0528)

.

PVR - pulmonary vascular resistance:IVC - inferior vena cava:FEV1- breed expiratory volume in1second:CO - cardiac output GFR - glomerular filtration rate; BUN

- blood urea nitrogen; GERD - gastroesophageal reflux disease

Antepartum Care • can be provided by an obstetrician, family physician, midwife, or multidisciplinary team ( based on patient preference and risk factors)

Preconception Counselling • 3-8 wk GA is a critical period of organogenesis, so early preparation is vital • PMHx: optimize medical conditions and review medications prior to pregnancy ( see Medical Complications of Pregnancy, OB28 and Medications, OBIS ) • supplementation folic acid: see Counselling of the Pregnant Patient , OBI 2 and Medical Complications of Pregnancy, OB28 • prenatal vitamins ( PN V ), consider iron supplementation in T 2 and T3 (earlier in cases of iron deficiency anemia ) • lifestyle/ social risk factors should be reviewed: smoking, alcohol ( abstinence should be encouraged leading up to and during pregnancy ), substance use (can lead to intellectual deficits and behavioural challenges in childhood ), domestic violence, occupational risks, poor social support, balanced nutrition, and physical fitness (see family Medicine ) • medications: discuss teratogenicity of medications so they may be adjusted , replaced , or stopped if

necessary • infection screening: rubella , HBsAg. VDRL. Pap smear, gonorrhea /chlamydia. HIV, I B testing based on travel and working in healthcare, history of varicella or vaccination , and parvovirus immunity if exposed to small children • genetic testing as appropriate for high risk groups ( see Prenatal Screening Table 2, OB7 ); consider genetics referral in known carriers, recurrent pregnancy loss/stillbirth, family members with developmental delay, birth anomalies, genetic diseases, and consanguinity

-

.

Family physicians and midwives can consider OB consultation for conditions including: • Insulin-dependent GDM • TOLAC • Multiple gestation • Malpresentation • Active antepartum hemorrhage PTL/PPROM • Failure to progress^descend • Induction/augmentation if high- risk • Tears: 3 rd or 4 th degree • Retained placenta • IUGR • Postpartum hemorrhage

.

Note: Guideline vary by Uistitubon and by ptowniid midwifery colege

*

*

Advise all patients capable of becoming pregnant to supplement their diet with 0.4 mgfd of folic acid (CTFPHC Grade II- 2- A Evidence)

Initial Prenatal Visit ri

uJ

• usually within 8- 12 wk of the 1st day of LMP or earlier if 35 ylo, bleeding, very nauseous, or other risk factors present

History

+

• GA by dates from the 1st day of LMP

• Naegele’s rule: 1st day of LMP + 1 yr + 7 d - 3 mo

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0B5 Obstetrics

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e.g. LMP = 1 Apr 2021, HDD = 8 Jan 2022 ( modify if cycle not 28 d by adding number of d >28 or subtracting number of d 5"o of pre pregnancy weight

-

-

Subsequent Prenatal Visits Timing • for uncomplicated pregnancies, SOGC recommends q4 -6 wk GA until 30 wk GA, q2-3 wk from 30 wk GA, and ql-2 wk from 36 wk GA until delivery Assess at Every Visit • estimated GA • history: PM, vaginal bleeding, leaking, cramping, questions, and/or concerns • physical exam: BP, weight gain , SFH, Leopold’s maneuvers (T3) to determine the lie, and presentation

of fetus • investigations: urinalysis for proteinuria in high risk women ( hypertensive patients ); FHR starting at 10 12 wk GA using Doppler U /S

-

-

Leopold’s Maneuvers

Symphysis Fuidal Height (SFH) Uterine fundus at pubic symphysis Fundus halfway from pubic 16 wk GA symphysis to umbilicus 20 wk GA Fundus at umbilicus 20 36 wk GASFH should be within 2 cm of GA

12 wkGA

-

SFH < Oates • Date miscalculation • IU6R • Fetal demise

• Oligohydramnios

-

• performed after 30 32 wk GA • first maneuver: to determine which fetal part is lying furthest away from the pelvic inlet • second maneuver to determine the location of the fetal back • third maneuver to determine which fetal part is lying above the pelvic inlet • fourth maneuver to locate the fetal brow

• Early engagement • Transverse 6e SFH > Dates • Date miscalculation • Multiple gestation • Polyhydramnios Large for GA (familial. DM )

. fibroids •

A First B. Second C . Third D. Fourtr

Figure 2. Leopold's maneuvers (T 3)

.

Reprinted with permission hom Essentials ol Clinical Examination Handbook. 6th ed. Lincoln. McSheltrey.Tran Wong

n LJ

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0B7 Obsicirics

Toronto Notes 2023

Prenatal Screening and Diagnostic Tests Screening Tests

• testing should only occur following counselling and with informed consent from the patient Table 2. High- Risk Population Screening Tests Disease (Inheritance)

Population(s) at Risk

Thalassemia ( Alt )

Individuals from these regions: Mediterranean CBC ( Mean Corpuscular Volume (MCV ) and South East Asia Western Pacifrc, Africa Middle Mean Corpuscular Hemoglobin (MCH)), Hb electrophoresis, or HPLC East Caribbean South America

Screening Test(s)

. .

.

.

.

.

CBC ( MCV and MCH) Hb electrophoresis, or Individuals Irom these regions: Africa, Caribbean Mediterranean Middle East India, HPLC

Sickle Cell ( AR)

.

.

South America Cystic Fibrosis (CF) ( AR)

.

Family history ol CF in patient or partner or medical condition linked to CF like male infertility

CFIit gene DNA analysis

.

.

lay Sachs Oiseasc ( AR )

Ashkenati Jewish* French Canadians Cajun

Eniymc assay HEXA or ONA analysis HEXA gene

FragileXSyndrome ( X linked)

Family history - confirmed or suspected

ONA analysis: FMR -1 gene

-

AR autosomal tecessive;HEXA « hexosaminidase A; HPLC 5 high peifotmance liquid chromatography 'If both partners are Ashkenazi Jewish, test for Canavan disease and Familial Dysaulonomia (FD); if family history of a specific condition, look for carrier status: e.g Gaucher disease , CF, Bloom syndrome Niemann-Pick disease, etc In all cases, if both partners are positive, refer lor genetic counselling.

.

.

.

Table 3. Gestation- Dependent Screening Investigations Gestational Age (wk)

Investigations

Preimplantation

Preimplantation genetic testing (or aneuploidy Preimplantation genetic testing lor monogenic ( single gene) disorders, Preimplantation genetic testing for structural rearrangements

812

Details

.

.

All require IVF

-

Routine T2 U/S at 18 22 wk GA Helps to Determine:

• Number of fetuses • GA (if no prior U/S)

Dating U/S possible Pap smear, chlamydia /gonorrhea testing, urine CBS (detect asymptomatic bactenuria) HIV VDRl , HBsAg. Rubella IgG. Parvovirus IgM il symptomatic pi IgG if hiqlwisk [ small child at home or daycare worker / primary teacher ) Varicella IgG II no history of disease / immuniiation, CBC blood groupand screen

.

.

.

• •

.

10

NIPT

Measures cell- free fetal DNA in maternal circulation

10 -12

CVS

Diagnostic test NOT screening

11-14

eFTSor IPS Part 1

1114

NT U/ S

Measures 1. NT on U/S 2. p - hCG 3. PAPP- A 4. Placental growth factor (eFIS only) 5. MSAFP (eFIS only)

15 16 to term

Amniocentesis

Diagnostic lest NOT screening

15 - 20

IPS Part 2

Measures 1. MSAFP 2 p - hCG 3. Uiicoii|ugnted estrogen (cslriol or pE 3| 4 Inhibit) A

>

-

Location of placenta Fetal anomalies

.

.

DDx of Increased MSAFP

.

.

15 20

MSS

18 -20 to term

FM [ quickening )

18 -20

U/S for fetal sire, anatomy assessment, and placental location

24 -28

Gestational Diabetes Screen 0GCT SO g

28

Repeal CBC t ferritin RhIG lor all Rh - negative women

35 37

GBS screen

Measures 1. MSAFP 2. p - hCG 3. Unconjugated estrogen (estriol or pE3| 4. InhibinA

Incorrect GA >1 fetus (e.g. twins) Fetal loss ONID • Abdominal wall defects (e.g.

• • •

.

omphalocele)

See Diabetes Melhtus. OBIS

.

See [ oily Onset Croup 8 Streptococcus 0830

Discuss contraception,menses, breastfeeding, depression, mentalhealth, and support Physical e«din: breast exam, pelvic exam including Pap smear lonly if due as pet provincial screening), wounds assessment (perineum or CO scar) MSS is alsoreteucd to as IIIpie Screen; a Inhlbiri A Is also tested, a Is referred to as Quadruple Screen 6 wk postpartum

Can consider ordering AFP to screen tor ON IDs in women with 8MI >40

+

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Toronto Notes 2023

0B8 Obstetrics ULTRASOUND SCREENING • 8-12 wk GA: dating U /S ( most accurate form of pregnancy dating ) measurement of crown- rump length ( margin of error: ± 5 d ) • HDD should be based on T1 U/S if available 11-14 wk GA: U /S for NT measures the amount of fluid behind the neck of the fetus early screen for trisomy 21 ( may also detect cardiac anomalies and other aneuploidies like Turner syndrome ) • NT measurement is necessary for the FI'S and IPS Part 1 • 18-20 wk GA: growth and anatomy U /S ( margin of error: ± 10 d ) • earlier or subsequent U /S performed when medically indicated

.

NON- INVASIVE PRENATAL TESTING ( NIPT )

• analyze maternal blood for circulating cell - free fetal DNA (ccffDNA ) at 9 wk GA onwards. Requires dating U /S for accuracy Advantages

• increased accuracy ( high detection rate ( UR ), low false positive rate ( l- PR )) • trisomy 21 ( UR 99%, 1' PR 0.1%), highly sensitive trisomy 18 ( UR 96%, l- PR 0.1%) trisomy 13 ( UR 91%, l'PR 0.1% ) Turner syndrome ( UR 90%, l ' PR 0.2%) • other disorders ( UiGcorge syndrome, Gri Uu Ghat syndrome, Prader - Willi syndrome, Angelman syndrome, XY disorders) • earlier timing with results available in 1 2 wk where parents can potentially have a CVS at 10 12 wk GA for diagnosis over an amniocentesis after 15 wk GA '

-

-

-

-

-

Disadvantages

does not screen for ON 'I' U not covered by most provincial health insurance systems need to confirm with invasive testing ( it is a screening test , not a diagnostic test ) obtaining a result depends on sufficient fetal fraction ( affected by the GA, maternal obesity, and presence of a chromosome aneuploidy in either the placenta or the mother ) does not test for all aneuploidies • • gives no result in 1 5% of cases ( insufficient fetal fraction , more common with elevated BMl ) • • • •

-

Table 4 . Comparison of FTS , MSS, and IPS MSS

cFTS

IPS

-

1114 wk GA: U /S nucItal Iranslucency 1M 4 wkOA : eHS blood 15 20 wk GA : MSS blood Including inhlbin A

1 b 20 wk GA

11 link GA

-

.

Risk estimate for Risk estimate lor ON ID , trisomy 21 trisomy 18 Sensitivity 85 30% 1.0 N 1 D: increased MSAFP Iscnsitivity 80 90 % ) 2% FPR Patients with positive screen should be offered 2. trisomy 21: decreased MSAFP Increased U /S and / or amniocentesis or NIPI (covered in 8 hCG , decreased pF 3 (sensitivity 65%) 3. trisomy 18: decreased MSAFP decreased some provinces , sell - pay in others) Note: Uselul when patient wants results 8 hCG. decreased p!3. decreased inhibin A (sensitivity 80 %) within II Only ollcred alone il patient missed the time more accurate estimate ol trisomy 21 risk window lor IPSoreFIS than MSS sensitivity 85%|whcn combined with age) 8% baseline FPR for trisomy 21. lower for NIO and trisomy 18 5% FPR Patients with positive screen should be offered Patients with positive screen should be offered CVS amniocentesis, or NIPI (covered in some U /S amniocentesis, or NIPt (covered in some provinces, sell- pay in others) provinces, self - pay in others) Disk estimate lor 1. trisomy 21 ( Down syndrome): increased Nl Increased p hCG decreased PAPP A 2. trisomy 18: increased Nl decreased PAPP A

.

- .

.

-

. .

-

.

-

.

.

. .

.

.

Note:In twins. eFTS MSS and IPS aie not applicable: screen with NT NIPT for chromosomal abnoinialities and MSAFP for ONTDs

Diagnostic Tests • diagnostic tests available: amniocentesis

CVS Indications

• age >35 yr ( increased risk of chromosomal anomalies) • risk factors in current pregnancy • abnormal U /S • abnormal prenatal screen ( IPS, el ' TS, MSS, or NIPT ) • past history /familv history of: chromosomal anomaly or genetic disease either parent a known carrier of a genetic disorder or balanced translocation

• •

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+

consanguinity >3 spontaneous abortions

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0B9 Obstetrics

Toronto Notes 2023

AMNIOCENTESIS

• U /S- guided transabdominal extraction of amniotic fluid performed as early as 15 wk GA Indications

-

• identification of genetic and chromosomal anomalies ( 15 16 wk GA ) as per indications above • confirmation of positive NIPT testing

-

• positive el TS/ 1PS/ MSS • assessment of fetal lung maturity ( T3) via the L/S ratio if >2:1, KDS is less likely to occur

.

Compared to CVS amniocentesis has a higher accuracy of prenatal cytogenetic diagnosis (99.8% vs 97.5%) and lower risk of spontaneous abortion 0.5% vs 1 2%)

.

(§>


35 yr, the risk of chromosomal anomaly ( 1/180) is greater than the risk of miscarriage from the procedure • more accurate genetic testing than CVS Disadvantages

• 1/ 200 to 1/900 risk of procedure-related pregnancy loss, depending on local experience • results take 14-28 d; QF- PCR or FISH can be done on chromosomes X, Y, 13, 18, 21, 22 to give preliminary' results in 48 h; chromosomal microarray also readily available CHORIONIC VILLUS SAMPLING

• biopsy of fetal- derived chorion using a transabdominal needle or transcervical catheter at 10-12 wk GA

GRIMM Genetics: family history of NTD ( risk of having second child with NTD is increased to 2 5%) consanguinity, chromosomal (characteristic of trisomy 13, 18, and 21) Race: Higher risk in Europeans and non- Hispanic whites than African Americans, 3 fold higher in Htspanics Insufficient vitamins: zinc and folate Maternal chronic disease (e.g. DM ) Maternal use of antiepileptic drugs

- .

-

General population risk for NTD is 0.1%

Advantages

• enables pregnancy to be terminated earlier than with amniocentesis • rapid karyotyping and biochemical assay within 48 h , including FISH analysis • high sensitivity and specificity Disadvantages

-

• 1% risk of procedure related pregnancy loss

• does not screen for ONTD • 1 2% incidence of genetic mosaicism “ false negative” results

-

ISOIMMUNIZATION SCREENING

Definition

• isoimmunization: antibodies ( Ab) produced against a specific RBC antigen ( Ag) as a result of antigenic stimulation with RBC of another individual Etiology • maternal-fetal circulation normally separated by placental barrier, but sensitization can occur and can affect the current pregnancy’, or more commonly', future pregnancies • anti-Rh Ab produced by a sensitized Rh-negative mother can lead to fetal hemolytic anemia • risk of isoimmunization of an Rh-negative mother with an Rh -positive ABO-compatible infant is 16% • sensitization routes

incompatible blood transfusions previous fetal- maternal transplacental hemorrhage (e.g. ectopic pregnancy, trauma, abruption ) invasive procedures in pregnancy (e.g. prenatal genetic diagnosis, cerclage, D &C ) any type of abortion labour and delivery trauma (e.g. car accident, fall, etc.)

Rh Antibody Titre A positive titre (21:16) indicates an increased risk of fetal hemolytic anemia

Investigations

• screening with indirect Coombs test at first visit for blood group, Rh status, and antibodies

• Kleihauer- Betke test used to determine extent of fetomaternal hemorrhage by estimating volume of fetal blood volume that entered maternal circulation • detailed U /S for hydrops fetalis • middle cerebral artery Dopplers are done to assess degree of fetal anemia; if not available, bilirubin is measured by serial amniocentesis to assess the severity of hemolysis • cordocentesis for fetal Hb should be used cautiously ( not first line)

-

Standard dose of 300 pg of Rhogam ' sufficient for 30 mL of fetal blood . Give additional 10 pg of Rhogam - for every ml of fetal blood over 30 mL

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LJ

Prophylaxis

• exogenous Rh IgG ( Rhogam* or WinRho*) binds to Rh antigens of fetal cells and prevents them from contacting maternal immune system • Rhogam* (120-300 pg) given to all Rh - negative and antibody screen negative women in the following

+

scenarios:

routinely at 28 wk GA (provides protection for ~12 wk ) within 72 h of the birth of a Rh-positive fetus with any invasive procedure in pregnancy (CVS, amniocentesis)

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Toronto Notes 2023

OBlO Obstetrics

as part of management of ectopic pregnancy

• with miscarriage or therapeutic abortion with an antepartum hemorrhage

• with trauma • Rhogam* 300 ug provides sufficient prophylaxis for 30 mL fetal Rh-positive whole blood •a Kleihauer-Betke test or flow cytometry can be used to measure the relative quantity of fetal blood in maternal circulation to determine if additional Rhogam* is indicated ( if >30 mL fetal blood ) •if Rh negative and Ab screen positive, follow mother with serial monthly Ab titres throughout pregnancy + U /S ± serial amniocentesis as needed ( Rhogam * has no benefit , as B cells/antibodies already in circulation )

-

Treatment •falling biliary pigment warrants no intervention ( usually indicative of either unaffected or mildly

affected fetus) •intrauterine transfusion between 18- 35 wk GA of O negative packed RBCs may be required for

-

severely affected fetus

•early delivery of the fetus for exchange transfusion following 35 wk GA

Complications •anti-Rh IgG can cross the placenta and cause fetal RBC hemolysis resulting in fetal anemia, CHF, edema, and /or ascites •severe cases can lead to hydrops fetalis (edema in at least two fetal compartments due to fetal heart failure secondary to anemia ) or erythroblastosis fetalis ( moderate to severe immune mediated hemolytic anemia )

-

Fetal Surveillance •patients will generally first notice FM ( “quickening” ) at 18-20 wk GA in primigravidas; can occur 1-2 wk earlier in multigravidas; can occur 1-2 wk later if placenta is implanted on the anterior wall of uterus •if there is concern about decreased FM, the patient is counselled to choose a time when the fetus is normally active to count movements ( usually recommended after 26 wk GA ) •all high - risk patients should be advised to do FM counts should experience >6 perceived movements in 2 h period if there is a subjective decrease in FM, time how long it takes to feel 10 discrete movements (laying on the left in a quiet setting may facilitate feeling subtle movements) if 10 movements take more than 2 h , further assessment is indicated , and patient should present to labour and delivery triage for assessment

DDx of Decreased Fetal Movements

DASH De ath of fetus Amniotic fluid decreased Sleep cycle of fetus Hunger.Thrrst

NON- STRESS TEST

Definition • FHR tracing > 20 min using continuous external fetal monitoring to assess FHR and its relationship to FM (see Gynaecology. l irst and Second Trimester Bleeding , GY 20 )

-

Normal NST: 2 accelerations, >15 bpm from baseline, lasting >15 s in 20 min

'

Indication •any suggestion of uteroplacental insufficiency or suspected compromise in fetal well-being

Table 5. Classification of Intrapartum EFM Tracings Normal Tracing (Category 1) Atypical Tracing (Category 2)

110 -160 bpm

Baseline

100 -110 bpm or >160 bpm for 30 - 80 min Rising baseline Arrhythmia

6 -25 bpm (moderate ) s5 (absent or minimal) for 40 - 80 80 min Erratic baseline s5 for >80 min >25 bpm for >10 min

Sinusoidal

Decelerations

None Non- repetitive uncomplicated variable Early decelerations

Acceleration

Interpret Clinically

.

Repetitive uncomplicated variables Non-repetitive complicated variables Intermittent late decelerations Single prolonged deceleration >2 min but 3 min but < 10 min

Spontaneous accelerations but not required Acceleration with scalp stimulation

Absence of acceleration until scalp Usually absent (accelerations, if present, do not change stimulation classification of tracing)

No evidence of fetal compromise

Physiologic response

Describing NSTs: baseline rate, absent' minimatmoderate/marked variability, accelerations present/not present decelerations early /late/variable

m

Reassuring BPP (8 8)

LAMB Limb ectension + flexion AFV 2 cm x 2 cm Movement P discrete) Breathing (one episode x 30 s)

ri j

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+

Possible fetal compromise

.

Adapted from: SOGC Fetal Heallfi Surveillance:Intrapartum Consensus Guideline March 2020

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Toronto Notes 2023

OBU Obstetrics

Operating Characteristics • false positive rate depends on duration; false negative rate = 0.2-0.3%

Interpretation

• normal, >32 wk GA: at least 2 accelerations of FHR >15 bpm from the baseline lasting > 15 s in 20 min • normal, 3), placenta previa after 28 wk GA, persistent T2 or 13 bleeding, uncontrolled T1 DM, uncontrolled thyroid disease, serious cardiovascular or respirator)' disease, and other systemic disorders • relative contraindications of physical activity • recurrent pregnancy loss, gestational HTN, history of spontaneous preterm birth, mild / moderate cardiovascular or respiratory disease, symptomatic anemia, malnutrition, eating disorder, twin '

pregnancy after 28 wk GA , and other significant medical conditions • weight gain: optimal gain depends on pre- pregnancy BM 1 (varies from 6.8-18.2 kg ) • work: strenuous work, extended hours, and shift work during pregnancy may be associated with

greater risk of low birth weight, prematurity, and spontaneous abortion • air travel: acceptable in T 2; airline cut off for travel is 36-38 wk GA depending on the airline, to avoid giving birth on the plane • sexual intercourse: may continue, except in patients at risk for: spontaneous abortion, PTL, or placenta previa; breast stimulation may induce uterine activity, and is discouraged in high-risk patients near term • smoking: assist /encourage to reduce or quit smoking (see Family Medicine, FM13) increased risk of decreased birth weight, placenta previa /abruption, spontaneous abortion, PTL,

Weight Gain in Pregnancy

BMI

Total Gain in T 2 4 T3

-

Weekly Gaia

18.5 18.5 24.9

-

28 40 lb 25 35 lb

1 lb%t

25-29.9 30

15251b 11-20 6

154JW 0.40.6 Itrtrk




U3Wrt

and stillbirth psychosocial interventions considered first-line, nicotine replacement therapy, and /or pharmacotherapy if counselling unsuccessful lowest effective dose to minimize fetal exposure, intermittent dosage preparations preferred • limited safety data for bupropion and varenicline use during pregnancy alcohol: no amount of alcohol is safe in pregnancy; encourage abstinence from alcohol during pregnancy; alcohol increases incidence of spontaneous abortion, stillbirth, and congenital anomalies fetal alcohol spectrum disorder (see Paediatrics P29) • cocaine: microcephaly, growth retardation, prematurity, and placental abruption • cannabis: associated with low birth weight infants and risk of neurobehavioural abnormalities in childhood • biopsychosocial considerations: discuss adjustment to pregnancy (e.g. mood , work, stress, family ) and birth plan, refer to counselling or community resources as necessary

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Toronto Notes 2023

OB13 Obstetrics

Medications • most drugs cross the placenta to some extent • very few drugs are teratogenic, but very few drugs have proven safety in pregnancy • use any drug with caution and only if necessary

• analgesics: acetaminophen preferable to ASA or ibuprofen Table 7. Documented Adverse Effects , Weigh Benefits vs. Risks, and Consider Medication Change Contraindicated Medication

Adverse Effect

ACE Inhibitor

Fetal renal defects, IUGR, oligohydramnios ONTO in 1 2%

Carbamaztpine

Chloramphenicol

lithium Misoprostol

NSAIDs Phcnytoin

-

Grey baby syndrome ( fetal circulatory collapse 2’to toxic accumulation) Ebstein's cardiac anomaly, goitre, hyponatremia Mobius syndrome (congenital facial paralysis with or without limb delects), spontaneous abortion P1l Premature closure ol the ductus arteriosus after 30 wk Gt (prior to that, indomelhacin used for tocolysis )

.

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.

.

Fetal hydantoin syndrome in 5 10% ( IUGR mental retardation , facial dysmorphogenesis congenital anomalies)

Retinoids (e.g. Accutane ' )

CNS, craniofacial , cardiac, and thymic anomalies

Sulpha drugs

Anti folate properties, therefore theoretical risk in T1; risk of kernicterus in T3

Tetracycline

Stains infant's teeth, may affect long bone development Congenital malformation (including ONTO) up to 9%

Valproate

Warfarin

Drug Resources During Pregnancy and Breastfeeding • Hale T. Medications and mothers' milk , 18th ed. Springer Publishing Company, 2019 • Lactmed: https:// toxnet.nlm.nih.gov / nowtoxnet/lactmed.htm

Increased incidence of spontaneous abortion , stillbirth , prematurity , IUGR. fetal warfarin syndrome ( nasal hypoplasia , epiphyseal stippling, oplic atrophy, mental retardation , intracranial hemorrhage)

Immunizations Intrapartum

• administration is dependent on the risk of infection vs. risk of immunization complications

• safe: tetanus toxoid, diphtheria, influenza, hepatitis B, and pertussis • avoid live vaccines ( risk of placental and fetal infection ): polio, measles/ mumps/ rubella, and varicella • contraindicated: oral typhoid • the Public Health Agency of Canada recommends: all pregnant women receive the influenza vaccine all pregnant women should be given Tdap every pregnancy irrespective of immunization history. Ideally between 27-32 wk GA but can be given at 13-26 wk GA if high-risk of PTL Postpartum

• rubella vaccine for all non - immune mothers. If they have had an adult booster and remain non immune, they should not be revaccinated and pregnancy should be deferred for at least 1 mo following vaccination

• hepatitis B vaccine should be given to infants within 12 h of birth if maternal status unknown or

-

-

positive or if father is known to have chronic hepatitis B infection follow up doses at I and 6 mo • any vaccine required / recommended is generally safe postpartum • delayed postpartum vaccination is recommended if patient receives immunoglobulin or blood products (e.g. Rhlg or packed red blood cells)

Radiation • ionizing radiation exposure is considered teratogenic at high doses if indicated for maternal health, should be done • imaging not involving direct abdominal/ pelvic high dosage radiation is not associated with adverse effects • higher dosage of radiation to fetus occurs with plain x ray of lumbar spine/abdomen /pelvis, barium enema, CT abdomen / pelvis / lumbar spine • radioactive isotopes of iodine are contraindicated • no known adverse effects from U /S or MKI ( long term effects of gadolinium unknown, avoid if possible)

-

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Toronto Notes 2023

OBM Obstetrics

Table 8. Approximate Fetal Doses from Common Diagnostic Procedures Examination

Plain Film Abdomen Pelvis Lumbar spine Thoracicspine Cbest |2 views)

Estimated Fetal Dose (cGy )

Number of Exams Safe in Pregnancy

014 0-11 0-17 0.009 5 cGy • Necessary amount to cause malformations: >20-30 cGy

2 20 833

.

Adapted from:Cohen Kefem et al. 2005 and Valentin 2000

-

Antepartum Hemorrhage •see Gynaecology, First and Second Trimester Bleeding, GY 20 Definition • vaginal bleeding from 20 wk GA to term

Differential Diagnosis •bloody show ( represents cervical changes/early stages of dilation ) - most common physiologic etiology in T3 • placenta previa • placental abruption - most common pathological etiology in T3 • vasa previa •cervical lesion ( cervicitis, polyp, ectropion , cervical cancer ) • uterine rupture •other: bleeding from bowel or bladder, abnormal coagulation Table 9. Comparison of Placenta Previa and Abruptio Placentae Placenta Previa

Abruptio Placentae

Definition

Abnotmal location of the placenta neat, partially, or completely over the internal cervical os

Premature separation of a normally implanted placenta after 20 wk GA

Etiology

Idiopathic

Idiopathic

Epidemiology

0.5 0.8 % of all pregnancies

1- 2% of all pregnancies

Risk Factors

History of placenta previa |4 - 8% recurrence risk ) Multiparity Increased maternal age Multiple gestation Uterine tumour (e.g. fibroids) or other uterine anomalies Uterine scar due to previous abortion, CO. D & C . myomectomy

Previous abruption (recurrence rate 5 - 16%) Maternal HIN (chronic or gestational HTN in 50% of abruptions) or vascular disease Cigarette smoking (>1 pack /d ), excessive alcohol consumption, cocaine Multiparity and/or maternal age >35 yr PPR 0 M Rapid decompression of a distended uterus ( polyhydramnios, multiple gestation) Uterine anomaly , fibroids Trauma ( e.g. motor vehicle collision , maternal battery)

Bleeding

PAINLESS

Usually PAINFUL

Placenta Previa Definition

• placenta implanted in the lower segment of the uterus covering the internal cervical os (either fully or partially ) • placental location is described in relation to the internal os as “ mm away" or “ mm of overlap" Clinical Features

• PAINLESS bright red vagina ) bleeding ( recurrent ), may be minimal and cease spontaneously but can become catastrophic • mean onset of bleeding is 30 wk GA , but onset depends on degree of previa • physical exam • do not perform digital vaginal exam until ruled out placenta previa (speculum and transvaginal probe are safe) • uterus soft and non - tender • presenting fetal part high or displaced • i HR usually normal shock /anemia correspond to degree of apparent blood loss

Do NOT perform a vaginal exam until placenta previa has been ruled out byU/S

+

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50 ng/mL) at 24 wk GA predicted spontaneous PTL at 30 mm has high negative predictive value for PTL before 34 wk GA ) • identification of bacterial vaginosis and Vrcaplasma ureatyticum infections • routine screening not supported by current data, but it is reasonable to screen high - risk women • family history of preterm birth • smoking • late maternal age • multiple gestation • cocaine

Prevention of Preterm Labour A. Cervical Cerclage • definition: placement of cervical sutures at the level of the internal os, usually at the end of T1 or in T2 and removed in T3 • indications: cervical incompetence ( i.e. cervical dilation and effacement in the absence of increased uterine contractility) • diagnosis of cervical incompetence • obstetrical Hx: silent cervical dilation, recurrent T2 losses, cervical procedures such as loop excisions ability of cervix to hold an inflated Foley catheter during a hysterosonogram • transvaginal U /S of cervical length is recommended only for high risk pregnancies and only

-

before 28 wk GA • proven benefit in the prevention of PTL in women with primary structural abnormality of the cervix (e.g. conization of the cervix, connective tissue disorders) B . Progesterone • progesterone thought to maintain uterine quiescence; however, exact mechanism of action is unclear • indicated if cervical length is < 25 mm at < 24 wk GA • if short cervix: 200 mg vaginally once daily from time of diagnosis to 36 wk GA • if risk factors or Hx of PTL present, give vaginally starting at 16-20 wk GA • superior to cerclage in preventing PTL of singletons not due to cervical incompetence C. Lifestyle Modification • smoking cessation, substance use reduction, treatment of GU infections ( including asymptomatic UT' Is ), and patient education regarding risk factors

Predicting Preterm Labour fetal fibronectin: a qlvcoprotein in amniotic fluid and placental tissue positive if >50 ng/ mL; SPV > PPV • done if one or more signs of PTL ( regular contractions >6/ h , pelvic pressure, low abdominal pain and /or cramps, low backache ) • done only if: 24 34 wk GA, intact membranes, < 3 cm dilated , established fetal well being contraindicated if: cerclage, active vaginal bleeding, vaginal exam , or sex in last 24 h • if negative, not likely to deliver in 7 14 d ( >95% accuracy ); if positive, increased risk of delivery, may need admission / transfer to centre that can do delivery ± tocolysis and /or corticosteroids

Ultrasooographic Cervical length Assessment in RietfKiiwg Preterm Birth in Singleton Pregnancies

J Ohstet Efaetnl Can 2018:40:154 -161 ieeoaaendations: t Irjrsajdo ~ ra ultrasonography should not he ati for cenrkal length assessnre nt to predict preterm beta (II-2D) 2 Tranvagral eltrasooograplty is the preferred rale for cervical assessment to identify worn en at f creased risk of spoirtan eo us preterm b irth end may he offeredlo non at mcreased risk of preterm bets (11-28) llraapenreel uSrasooographj may be offered to aomeo at increased risk of preterm birth

Itransvaipa! uitasKiography iseither unacceptable or cneratahle (11-28) 4.3ecaase of poor postve p redictive values Ed sens ti lies and lack of proven effective .nteneiDoss, rouine transvaginal cervical lenglb assessmea is not recommended in women at lenv-nsk (ll-2{) 5k wocnec presecing wits suspected PH iansvagaa sonograph.c assessment of cervical engtb may he used to help m determining who isat kgb -rsk of preterm delivery and may be helpful in preveaag unnecessary intervention. It is unclear whether Bis mformaion results in a reduced risk of ptea ra birth (H - 2B) 6.kr asymptomat ic women with a history of spontaneous preterm birth and an ultrasonograsbicalfy diagnosed short cemcal engtb («25 o m ) pror a 24 wk GA. cervical cerda ge shogfd he ctmsdered to reduce the risk of preterm

.

-

KAMI

J. hr al asymptomaic women who present with membranes at or protruding past the external cervical os. a:emergency cerclage should be cresiered a reduce the risk of pieterm delivery

'Hf

•

-

-

-

Clinical Features • regular contractions ( 2 in 10 min, >6/ h ) • cervix > 1 cm dilated, >80% effaced, or length 42 wk GA Epidemiology

• 41 wk GA: up to 27% • > 42 wk GA: 5.5% Etiology

• most cases are idiopathic

• anencephalic fetus with no pituitary gland • placental sulfatase deficiency ( X-linked recessive condition, incidence ranges from 1 in 2000 to 1 in 6000 births) • incorrect dates Management (for singleton, cephalic fetus, otherwise uncomplicated)

• labour induction is recommended at 41 +3 wk GA if no contraindications to vaginal delivery ( see Induction and Augmentation of Labour, OB3S )

Prognosis

• if > 42 wk GA , perinatal mortality 2-3x higher (due to progressive uteroplacental insufficiency ) • with increasing GA , higher rates of: intrauterine infection, asphyxia, meconium aspiration syndrome,

placental insufficiency, placental ageing and infarction, macrosomia, dystocia, fetal distress, operative deliveries, pneumonia, seizures, NICU admission, stillbirth • morbidity increased with gestational HTN, DM, placental abruption, 1UGR, advanced reproductive age, and multiple gestation

+

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Toronto Notes 2023

OB20 Obstetrics

s

Intrauterine Fetal Demise Definition • fetal demise in utero after 20 wk GA ( before 20 wk GA is called spontaneous abortion ) Epidemiology • occurring in 1% of pregnancies, increased in high - risk pregnancies

DIC: Generalized Coagulation and Fibrinolysis Leading lo Depletion ol Coagulation Factors

Etiology • 50% idiopathic • 50% secondary to HTN, DM, erythroblastosis fetalis, congenital anomalies, umbilical cord or placental complications, intrauterine infection, and APS

Obstetrical Causes • Placental abruption • Gestational HTN • Fetal demise PPH

Clinical Features • decreased perception of FM by mother • SFH and maternal weight not increasing • absent fetal heart tones on Doppler ( not diagnostic) • high MSAFP • on U /S: no FHR. Depending on timing of death, may see skull collapse, brain tissue retraction, empty fetal bladder, non-filled aorta, or poor visualization of midline falx Management • diagnosis: absent cardiac activity and FM on U /S ( required )

• determine secondary cause maternal: HbAk, fasting glucose, TSH, Kleihauer Betke, VDRL, ANA, CBC, anticardiolipins, antibody screens, 1NR/ PTT, serum / urine toxicology screens, cerv ical and vaginal cultures, and TORCH screen • fetal: karyotype, cord blood , skin biopsy, genetics evaluation, autopsy, amniotic fluid culture for CMV, parvovirus B19, and herpes placenta: pathology, bacterial cultures

-

DIC specific Blood Wort • CBC (platelets)

• aPIT and PT [prothrombin time ) • TOP

Fibrinogen Treatment • Treat underlying cause • Supportive • Fluids • Blood products • FFP, platelets, cryoprecipitate

-

• Consider anti coagulation as tfTEpropbplaiis

-

Treatment

• >20 wk GA:10L with vaginal misoprostol (Cytotec*) • monitor for maternal coagulopathy (10% risk of DIC) • parental psychological care/ bereavement support as per hospital protocol • comprehensive discussion within 3 mo about final investigation and post-mortem results, help make plans for future pregnancies

Intrauterine Growth Restriction Definition

• failure of a fetus to reach its biologically determined growth potential due to pathological factors Etiology/Risk Factors

• 50% unknown • maternal: malnutrition, smoking, drug misuse, alcoholism , cyanotic heart disease, T1 DM, SLE , pulmonary insufficiency', previous 1UGR (25% risk ), chronic HTN, gestational HTN, chronic renal insufficiency', prolonged gestation • placental: any disease that causes placental insufficiency • gross placental morphological abnormalities (infarction, hemangiomas, placenta previa, and abnormal cord insertion ) • fetal: TORCH infections, multiple gestation, and congenital anomalies/chromosomal abnormalities

TORCH To xoplasmosis Others: e.g. syphilis Rubella CMV HSV See Table 15 0B31

.

(10%)

Clinical Features

• symmetric/type 1 ( 25-30%); occurs early in pregnancy reduced growth of both head and abdomen • HC/AC ratio may be normal ( >1 up to 32 wk GA; =1 at 32-34 wk GA; < 1 after 34 wk GA ) • usually associated with congenital anomalies or TORCH infections • asymmetric/ type 11 (70%): occurs late in pregnancy fetal abdomen is disproportionately smaller than fetal head • brain is spared; therefore HC/AC ratio increased usually associated with placental insufficiency more favourable prognosis than type I • complications prone to meconium aspiration, asphyxia, polycythemia, hypoglycemia, hypocalcemia, hypophosphatemia, hyponatremia, and intellectual disability greater risk of perinatal morbidity and mortality

+

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Toronto Notes 2023

0B21 Obstetrics

Investigations •SFH measurements at ever)' antepartum visit ( ensure accurate GA ) •if mother at high - risk or SFH lags >2 cm behind GA • U /S for biparietal diameter, HC/AC ratio, FL, fetal weight, AFV (decrease associated with 1UGR), and decrease in the rate of growth ± BFP • Doppler analysis of umbil ical cord blood flow

.

Management • prevention via risk modification prior to pregnancy is ideal • modify controllable factors: smoking, alcohol, nutrition, and treat maternal illness •serial BPP (monitor fetal growth) and determine cause of 1UGR, if possible •deliver)' when extrauterine existence is less dangerous than continued intrauterine existence (abnormal function tests, absent grow'th, severe oligohydramnios) especially if >34 wk GA •optimize fetus with betamethasone valerate (telestone*), MgSO 4 for neuroprotection, early GBS swab, and paediatrics consult if anticipated preterm delivery • as 1 UGR fetuses are less likely to withstand stresses of labour, they are more likely to be delivered by

CD

Macrosomia Definition

• infant weight S90 th percentile for a particular GA or > 4000 g Etiology/Risk Factors maternal obesity, gestational and pre-gestational DM, past history of macrosomic infant, prolonged gestation, multiparity, excessive maternal weight gain during pregnane)'

-

Clinical Features • increased risk of perinatal mortality • CPD and birth injuries (shoulder dystocia, fetal bone fracture) more common • complications of DM in labour ( see Table 14, OB30 ) Investigations • serial SFH • U /S for EF W if mother at high - risk or SFH >2 cm ahead of GA Management

-

• prevent hyperglycemia in patients with DM, optimize pre pregnancy weight, and limit excessive pregnancy weight gain in patients with increased BM1 • planned CD is a reasonable option where EFW >5000 g in non -diabetic patients and EFW >4500 g in diabetic patients

n\

u

+

AL GRAWANY

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Toronto Notes 2023

OB22 Obstetrics

Polyhydramnios/Oligohydramnios Table 11. Polyhydramnios and Oligohydramnios Polyhydramnios

Oligohydramnios

Definition

AFI >25 cm U/S: single deepest pocket >8 cm

AM «S cm U S: single deepest pocket s 2 cm

Etiology

Idiopathic most common Maternal I10 M: abnormalities of transchorionic flow Maternal- fetal Chonoangiomas Multiple gestation Fetal hydrops (increased erythroblastosis) Fetal Chromosomal anomaly (up to 2/3 of fetuses have severe polyhydramnios) Respiratory: cystic adenomatoid malformed lung CNS: anencephaly hydrocephalus, meningocele fit: tracheoesophageal fistula, duodenal atresia, facial clefts (interfere with swallowing)

Idiopathic most common

Epidemiology

Occurs in 0.2-1.6% of all pregnancies

Occurs in 4.SN of all pregnancies Severe form in"0.7% Common in pregnancies >4t wk £A ('12 c)

Clinical Features and Complications

Uterus large for GA. difficulty palpating fetal parts and hearing FHR Maternal complications Pressure symptoms from overdistended uterus (dyspnea, edema, hydronephrosis) Obstetrical complications Cord prolapse, placental abruption, malpresentation. P1L uterine dysfunction. andPPH

Uterus smal for dates Fetal complications 15-25 c have fetal anomalies Amniotic fluid bands (11) can lead to Potter's facies, limb deformities, abdominal wall defects Obstetrical complications Cord compression Increased risk of adverse fetal outcomes Pulmonary hypoplasia (late- oosel) Marker for infants who may not tolerate labour well

Management

Determine underlying cause Screen for maternal disease/infection Complete fetal U /S evaluation Depends on severity Mild to moderate cases require no treatment If severe, hospitalize and consider therapeutic amniocentesis

Always warrants admission and investigation Rule out ROM fetal monitoring IBS!.BPP) U S Doppler studies (umb lical cord andutenne artery ) Maternal hydration with oral or IV fluids to help increase amniotic fluid Injection of fluid via amniocentesis will improve condition for «1wk - may be most helpful for visualizing any associated fetal anomalies Consider delivery if term Ammo - infusion may be considered during labour na intrauterine catheter

Prognosis

2- to 5 fold increase in risk of perinatal

.

.

-

mortality

Maternal Uteroplacental insufficiency (preeclampsia, nephropathy) Medications (ACEI)

Fetal Congenital urinary tract anomalies (renal agenesis, obstruction, posterior urethral uahres) Demise/chronic hypoiemia (blood shunt away from kidneys to perfuse brain) IUGR Ruptured membranes: prolonged amniobc fluid leak Amniotic fluid normally decreases after 35 wk CA

-

Poorer with early onset High mortality related to congenita! malformations and pulmonary hypoplasia when diagnosedduring 12

Antenatal Depression Definition • major depression occurring in a patient who is pregnant , onset may be prior to pregnancy

Epidemiology • occurs in 7- 9% of pregnancies Risk Factors • prior history of depression , anxiety, unintended or unwanted pregnancy, life stress, intimate partner

violence or history of abuse, poor social support, chronic general medical conditions (specifically hypothyroidism )

Clinical Features • comparable to symptoms of non - pregnant major depressive disorder (see Psvchiatrv . PS 12) • suspect if: prior history of depression, excessive anxiety about the fetus, poor self-esteem, despondency, anhedonia , non-adherence to antenatal care, poor weight gain due to decreased appetite or inadequate diet , suicidal ideation

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OB23 Obstetrics

Assessment

• Edinburgh Postnatal Depression Scale or others Treatment

• antidepressants, psychotherapy, supportive care, and electroconvulsive therapy if refractory or if features of psychosis, catatonia, high risk of suicide, and fluid or food refusal leading to dehydration and malnutrition

Prognosis • may be associated with altered fetal physiologic effects, adverse pregnancy and neonatal outcomes, abnormal infant and child development, or cognitive impairment and psychopathology in the offspring, leading to lasting long- term effects • increased risk of recurrence after pregnancy, and conversion of the diagnosis to bipolar disorder

Multi-Fetal Gestation and Malpresentation Epidemiology

• incidence of twins is 1 in 80 and triplets is 1 in 6400 in North America • 2/3 of twins are dizygotic ( fraternal ) risk factors for dizygotic twins: 1 V E, increased maternal age, newly discontinued OCP, and ethnicity (e.g. certain African regions ) • monozygous twinning occurs at a constant rate worldwide ( 1 in 250) • determine zygosity by number of placentas, thickness of membranes, sex, and blood type Clinical Features

Maternal

Uteroplacental

Fetal

Hyperemesis gravidarum

Increased PROM PTL Polyhydramnios Placenta previa Placental abrupbon PPH ( uterine atony) Umbilical cord prolapse Cord anomalies (velamentous insertion. 2 vessel cord)

Prematurity IUGB

Management

m

The Ps of Multiple Gestation Complications

Increased rates of: Puking Pallor (anemia ) Preedampsia / Pregnancy- induced HTN Pressure (compressive symptoms) PTL PROM ' PPROM Polyhydramnios Placenta previa /abruption PPHlAntepartum hemorrhage Prolonged labour Cord Prolapse Prematurity Malpresentation Perinatal morbidity and mortality Parental distress Postpartum depression

.

Table 12. Complications Associated with Multiple Gestation

GDM Gestational HTN Anemia Increased physiological stress on all systems Increased compressive symptoms CO Thrombosis

m

Malpresentation

Congenital anomalies Twin twin transfusion syndrome Increased perinatal morbidity and mortality Twin interlocking ( twin A breech, twin S vertex) Single fetal demise

-

-

• U /S determination of chorionicity must be done within T1 ( ideally 8 12 wk GA)

• increased antenatal surveillance • serial U /S q 2-3 wk from 16 wk GA ( monochorionic), q3-4 wk from 18-22 wk GA (uncomplicated diamniotic dichorionic) to assess growth Doppler flow studies weekly if discordant fetal growth ( >30%) • BPP • may attempt vaginal delivery ( if dichorionic diamniotic or monochorionic diamniotic) if twin A presents as vertex and growth discrepancy < 25%, otherwise CD ( 40-50% of all twin deliveries, 10% of cases have twin A delivered vaginally and twin B delivered by CD ) • all monochorionic monoamniotic twins need to be delivered by CD • mode of delivery depends on fetal weights, GA , chorionicity, and presentation of presenting twin

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OB24 Obstetrics

Monoamniotic Monochorionic (forked cord )

Monoamniutic Monochorionic *9-12 d

Monoamniotic Monochorionic (one cord)

Diamniotic Dichorionic ( fused) *0-72 h

Diamniotic Dichorionic ( separated )

Monochorionic * 4- 8 d

Diammotic

Figure 4. Classification of twin pregnancies •Indicates time of cleavage

Twin-Twin Transfusion Syndrome Definition

• formation of placental intertwin vascular anastomoses that can cause arterial blood from donor twin to pass into veins of the recipient twin Epidemiology

• 10% of monochorionic twins • concern if >30% discordance in EFW Clinical Features • donor twin: IUGR, hypovolemia, hypotension, anemia , and oligohydramnios • recipient twin: hypervolemia , HTN , CH1;, polycythemia , edema, polyhydramnios, and kernicterus in

neonatal period Investigations

• detected by U /S screening, Doppler flow analysis Management

• fetoscopic laser ablation of placental vascular anastomoses ( preferred between 16-26 wk GA) • therapeutic serial amniocentesis to decompress polyhydramnios of recipient twin and decrease pressure in cavity and on placenta

• intrauterine blood transfusion to donor twin if necessary

Breech Presentation Definition

• fetal buttocks or lower extremity is the presenting part as determined on U /S • complete ( 10%): hips and knees both flexed • frank (60%): hips flexed , knees extended , buttocks present at cervix • most common type of breech presentation most common breech presentation to be delivered vaginally • incomplete (30%): both or one hip partially flexed and both or one knee present below the buttocks, feet or knees present first ( footling breech , kneeling breech ) Epidemiology

-

• occurs in 3 4% of pregnancies at term ( 25% at < 28 wk GA )

Criteria for Vaginal Breech Delivery

.

.

• Frank or complete breech >36 wk GA EFW 2500 -3800 g based on clinical

-

and U/S assessment 15.5 8.5 lb)

• Fetal head flexed

• Continuous fetal monitoring • Two experienced obstetricians,

assistant, and anesthetist present

• Ability to perform emergency CD within 30 min if required • Mother motivated for vaginal breech delivery and understands risks and benefits

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OB25 Obstetrics

Risk Factors

• maternal: pelvis (contracted ), uterus (shape abnormalities, fibroids, previous breech ), pelvic tumours causing compression , and grand multiparity

• placental: placenta previa • fetal: prematurity, amniotic fluid ( poly /oligohydramnios), multiple gestation , congenital

-

-

malformations ( found in 6% of breeches; 2 3% if in vertex presentations), abnormalities in fetal tone and movement, aneuploidy, hydrocephalus, and anencephaly

Management

• pre- or early-labour U /S to assess type of breech presentation , fetal growth, estimated weight, placenta position, attitude of fetal head ( flexed is preferable ); if U /S unavailable, recommend Cl) • KCV and elective CD should be presented as options with the risks and benefits outlined; obtain informed consent • ECV: procedure that is performed with external pressure on the uterus to encourage a non -vertex fetus ( breech, transverse, or oblique ) to turn into vertex presentation overall success rate of 40-60% criteria: >36 wk GA , singleton, unengaged presenting part, reactive NST, intact membrane contraindications: absolute: where CD is required ( placenta previa, previous classical CD), previous myomectomy, PROM, uteroplacental insufficiency, non- reactive NST, multiple gestation relative: mild/moderate oligohydramnios, suspected 1 UGR, HTN , previous T3 bleed, nuchal cord risks: abruption, cord compression, cord accident, ROM, labour, fetal bradycardia requiring CD (< 1% risk ), alloimmunization, fetal death (1 /5000 ) method: tocometry, followed by U/S guided transabdominal manipulation of fetus with constant FHR if patient Rh negative, give Rhogam' after the procedure better prognosis if multiparous, good fluid volume, small baby, skilled obstetrician , and posterior placenta if unsuccessful, planned vaginal breech birth or planned CD • vaginal breech delivery : can be spontaneous or assisted method: encourage effective maternal pushing efforts at delivery of aftercoming head , assistant must apply suprapubic pressure to flex and engage fetal head delivery can be spontaneous or assisted ; avoid fetal traction apply fetal manipulation only after spontaneous delivery to level of umbilicus contraindications: cord presentation, footling breech, fetal factors incompatible with vaginal delivery (e.g. hydrocephalus, macrosomia, 1 UGR ), clinically inadequate maternal pelvis • CD recommended if: the breech has not descended to the perineum in the second stage of labour after 2 h, in the absence of active pushing, or if vaginal delivery is not imminent after 1 h of active pushing

A. Complete Breech

-

B. Frank Breech

C. Incomplete Breech

®

Figure 5. Types of breech presentation

Prognosis • regardless of route of delivery, breech infants have lower birth weights and higher rates of perinatal mortality, congenital anomalies, abruption, and cord prolapse

Hypertensive Disorders of Pregnancy Hypertension in Pregnancy

-

• hypertensive disorders of pregnancy arc classified as either pre existing or tie novo (gestational HTN or preeclampsia ) and exist on a spectrum PRE-EXISTING HYPERTENSION

Definition • sBP 140 mmHg or dBP S90 mmHg prior to 20 wk GA; BP should be elevated on S2 occasions at least 15 min apart on the same arm, seated with appropriate sized cuff essential HTN is associated with an increased risk of gestational HTN , abruptio placentae, 1 UGR, and •

Ominous Symptoms of HTN in Pregnancy Right upper quadrant pain Headache Visual disturbances

-

1U1 D rt

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GESTATIONAL HYPERTENSION

Definition • sBP > 140 mmHg or dBP >90 mmHg after 20 wk GA without proteinuria in a patient known to be normotensive before pregnancy

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OB26 Obstetrics

PREECLAMPSIA

Definition • pre existing or gestational HTN with new onset proteinuria ( urinary protein:creatinine ratio > 30 mg/ mmol ) or adverse conditions (end organ dysfunction )

-

ECLAMPSIA

Definition • the occurrence of > 1 generalized convulsion and / or coma in the setting of preeclampsia and in the

absence of other neurologic conditions Etiology •

Eclampsia prior to 20 wk 6A is rare and should raise the possibility of an underlying molar pregnancy or APS

placental malperfusion -» soluble factors released into circulation -> maternal vascular endothelial injury -> hypertension + multi-organ injury

Epidemiology of Eclampsia • an eclamptic seizure occurs in approximately 0.5% of mildly preeclamptic patients and 2-3% of severely preeclamptic patients

Clinical Manifestation of Eclampsia • eclampsia is a clinical diagnosis • typically tonic clonic and lasting 60-75 s • symptoms that may occur before the seizure include persistent frontal or occipital headache , blurred vision, photophobia , right upper quadrant or epigastric pain , and altered mental status • in up to one third of cases, there is no proteinuria or hypertension prior to the seizure • approx 25% of cases will present in the postpartum period • in general, women with typical eclamptic seizures who do not have focal neurologic deficits or prolonged coma do not require diagnostic evaluation, including imaging

-

Risk Factors for Hypertensive Disorders in Pregnancy • maternal factors: primigravida (80-90% of gestational HTN ), first conception with a new partner, PMHx or FMHx of gestational HTN, or preeclampsia /eclampsia • DM, chronic HTN, or renal insufficiency

obesity'

APS or inherited thrombophilia extremes of maternal age (35 yr)

• previous stillbirth or 1U FD

vascular or connective tissue disease • fetal factors:

lUGRorolieohvdramnios

• GTN multiple gestation

• fetal hydrops 'mirror syndrome" abruptio placentae

Clinical Evaluation of Hypertensive Disorders in Pregnancy • in general, clinical evaluation should include the mother and fetus • evaluation of mother • body weight

• central nervous system

presence and severity of headache visual disturbances ( blurring, scotomata ) tremulousness, irritability’, and somnolence

hyperreflexia hematologic (bleeding, petechiae ) hepatic ( right upper quadrant or epigastric pain , severe N / V )

• renal ( urine output, colour) • evaluation of fetus: FM FHR tracing - NST • U/S for growth BPP • Doppler flow studies Laboratory Evaluation of Hypertensive Disorders in Pregnancy • CBC • PIT , INR, fibrinogen if abnormal LFT's or bleeding • ALT, AST • creatinine, uric acid • 24 h urine collection for protein or albumin:creatinine ratio • may consider placental growth factor ( P1GF ) testing or sFlt-1:P1GF ratio as an early screening test for suspected preeclampsia

-

Hypertension in Pregnancy Adverse Maternal Conditions • sBP >160 mmHg • dBP '100 mmHg • HELIP • Cerebral hemorrhage • Renal dysfunction: oliguria 90 mmHg •Initial anti -hypertensive therapy for severe hTI (sBf >160 mmHg or dBP >110 nnHg|sho !d ne wrr

-

.

_

labetalol, nifedipine, methyidopa. orrydraaire •Initial antihypertensive therapy for non -serere HTN|BP 140-159/ 90 -109 mmH$ shoe: j ie wnh labetolol, nifedipine, or methyldopa • Antenatal carticosteroidsfor feta ring maturation should oe cors dered ‘ora l women with pro eclampsia Before 34 wk 6A 1« women with pie eclampsia, initiation ol dehrery is recommended at 37 wk GA •MgSOi is the recommended fcst lae treafeatfir eclampsia and eclampsia prophylaxis in the case of severe preeclampsia ,

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OB27 Obstetrics

Complications of Hypertensive Disorders in Pregnancy • maternal

liver and renal dysfunction seizure - “eclampsia” abruptio placentae • left ventricular failure/pulmonary edema D1C ( release of placental thromboplastin consumptive coagulopathy) HELLP syndrome hemorrhagic stroke ( 50% of deaths) • fetal (secondary to placental insufficiency ) • IUGR, prematurity, abruptio placentae, 1UED

HELLP Syndrome Hemolysis Elevated Liver Enzymes Low Platelets

Management of Hypertension

• for non -severe HTN ( BP 149-159/90 -109 mmHg ): target a BP of 130-155/80- 105 mmHg in patient without comorbidities or < 140/90 mmHg in patient with comorbidities antihypertensive therapy for both pre - existing and gestational HTN : labetalol 100 -400 mg PO BID -T1D, nifedipine XL preparation 20 60 mg PO once daily or BID, or a- methyldopa 250 500 mg

-

-

-

PO BID TID • for severe HTN ( BP>160/ 110 mmHg ): target sBP < 160 mmHg and dBP < 110 mmHg, give one of: • labetalol 20 mg IV, then 20 80 mg IV q30 min ( max 300 mg ), then switch to oral nifedipine immediate release 5-10 mg capsule q30 min • hydralazine 5 mg IV, repeat 5 10 mg IV q 30 min or 0.5 10 rng/ h IV, to a maximum of 20 mg IV (or 30 mg IM ) • no AGi I , AKBs, diuretics ( may be used in cases of pulmonary edema or cardiac failure), prazosin , or

-

-

-

atenolol

-

• pre existing HTN and gestational HTN without any deterioration can be followed until 37 wk GA, then decide to induce shortly thereafter Management of Preeclampsia

• if stable and no adverse conditions ( 24 - 33-16 wk GA ): expectant management ± delivery as approaching 34 36 wk GA( must weigh risks of fetal prematurity vs. risks of developing severe

-

preeclampsia /eclampsia ) antenatal corticosteroids should be considered if 35 wk GA • if >37 wk GA, delivery is recommended • for severe preeclampsia, stabilize and deliver, regardless of GA • if severe preeclampsia during labour,'increase maternal monitoring: hourly input and output, hourly neurological vitals, and continuous l HR monitoring • antihypertensive therapy ( regimen as above for severe H TN )

-

• seizure prevention :

MgSO t: 4 g IV loading dose, followed by lg/ h postpartum management risk of seizure highest in first 24 h postpartum continue MgSO* for 12 24 h after delivery vitals ql h consider HELLP syndrome most return to a normotensive BP within 2 wk

-

•

. roll

-

Management of Eclampsia

ABCs patient into LLDP to prevent aspiration • • supplemental O’ via face mask to treat hypoxemia due to hypoventilation during convulsive episode • aggressive antihypertensive therapy for sustained sBP >160 mmHg or dBP > 109 mmHg or with hydralazine or labetalol • prevention of recurrent convulsions: to prevent the possible complications of repeated seizure activity (e.g. rhabdomyolysis, metabolic acidosis, aspiration pneumonitis, etc.) • MgSO* is the first-line therapy for eclampsia (used for treatment and prophylaxis) • the definitive treatment of eclampsia is DELIVERY after maternal stabilization, irrespective of GA or fetal distress, to reduce the risk of maternal morbidity and mortality from complications of the disease mode of delivery is dependent on the clinical situation and fetal - maternal condition

Differential Diagnosis of Cause for Seizure in a Pregnant Woman Stroke Hypertensive disease ( hypertensive encephalopathy, pheochromocytoma) • Space occupying lesion of the CNS • Metabolic disorders (hypoglycemia

..

-

SIADH)

• • • • •

.

Infection ( meningitis, encephalitis)

TTP or thrombophilia Idiopathic epilepsy Use of illicit drugs

Cerebral vasculitis

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OB28 Obstetrics

Medical Complications of Pregnancy Iron and Folate Deficiency Anemia Table 13. Iron Deficiency and Folate Deficiency Anemia Iron Deficiency Anemia

Folate Deficiency Anemia

Etiology

See Hematology. H15

See Hematoloov. H26

Epidemiology

Responsible for 80% of non-physiologic anemia during

Incidencevanes from 0.5- 25% depending on region, population, and diet

pregnancy Clinical Features

See Hematology. H15

Investigations

See Hematology H15

See Hematology H26

Management

Prevention (non-anemic): 30 mg elemental iron daily (met by most prenatal vitamins) Treatment (anemic): 30 -120 mg elemental iron daily 325 mg ferrous fumarate - 106 mg elemental Fe:32S mg ferrous sulfate - 65 mg elemental Fe; 325 mg ferrous gluconate - 36 mg elemental Fe Polysaccharide-Iron Complex - 150 mg elemental Feicapsule

Prevention:0.4-1mg folic add P0 daily for 1-3 mo preconceplually and throughout II

Complications

Maternal: angina CHF infection, slower recuperation, and PTL Fetal: decreased oxygen carrying capacity leading to fetal distress IUGR low birth weight, and fetal neurodevelopment

Maternal:decreased blood volume H V and anorexia Fetal:neural tube defects in 11 low birth weight,and prematurity

Notes

Mother needs 1 g of elemental iron per fetus: this amount exceeds normal stores + dietary intake Iron requirements increase during pregnancy due to fetal/ placental growth ( 500 mg),increased maternal R 8 C mass (500 mg), and losses (200 mg) - more needed for multiple gestations

Minimum daily requirement is 0.4 mg Most often associated with iron deficiency anemia Folic acidis necessary for closure of neural lube during early fetal development (by 28 d GA)

.

. .

. .

See Hemalnisov. H 26

.

.

. .

Diabetes Meilitus Epidemiology • 2-6% of pregnancies are complicated by DM

Classification of Diabetes Meilitus • T1 DM and T 2 DM (see Endocrinology. E9 ) • GDM: onset of DM during pregnancy (usually tested for around 24-28 wk GA ) Etiology • pre-existing T1 DM and T2 DM • GDM: anti - insulin factors produced by placenta and high maternal cortisol levels create increased peripheral insulin resistance -> leading to GDM and /or exacerbating pre-existing DM Management A. T1DM and T 2DM

Preconception

pre- plan and refer to high - risk clinic for interprofessional care • commence folic acid (1.0 mg daily) 3 mo prior to conception • optimize glycemic control ( HbAlc < 7%), counsel and assess for risks and complications ( retinopathy, neuropathy, CKD, CVD), review medications ( discontinue ACE1, ARBs, statins) •

Pregnancy • for T2DM, switch to insulin therapy and discontinue non -insulin antihyperglvcemic agents continuing glyburide or metformin is controversial teratogenicity unknown for other oral antihvperglycemics

• tight glycemic control insulin dosage may need to be adjusted as pregnancy advances due to increased demand and increased insulin resistance • monitor as for normal pregnancy, plus initial 24 h urine protein and creatinine clearance, retinal exam , and HbAlc (aim for 38.0”C (>100.4"F) • Intrapartum nucleic-acid amplification test positive for GBS

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Toronto Notes 2023

Urinary Tract Infection Epidemiology • most common medical complication of pregnancy • asymptomatic bacteriuria in 2 7% of pregnant women, more frequently in multiparous women • note: asymptomatic bacteriuria should be treated in pregnancy due to increased risk of pyelonephritis and PTl

-

Etiology • increased urinary stasis from mechanical and hormonal ( progesterone ) factors • organisms include GBS as well as those that occur in non - pregnant women Clinical Features • may be asymptomatic

Treat asymptomatic bacteriuria In pregnancy because o( increased risk ot progression to cystitis, pyelonephritis, and probable Increased risk of PTl

Major organisms responsible for pyelonephritis: C.coli klebsiella. eiterobocter proleus

• dvsuria , urgency, and frequency in cystitis • fever, flank pain, and costovertebral angle tenderness in pyelonephritis

.

.

Investigations

• urinalysis , urine CSS • renal function tests in recurrent infections Management • uncomplicated U IT first line: amoxicillin ( 250 -500 mg PC) q8 h x 7 d ) alternatives: nitrofurantoin ( 100 mg PC) BID x 7 d ) or cephalosporins follow with monthly urine cultures

• pyelonephritis

• hospitalization and IV antibiotics

Prognosis • complications if untreated : acute cystitis, pyelonephritis, and possible PTL • recurrence is common

Infections During Pregnancy

-

• infant immunity begins to develop at 9 15 wk GA • initial response to infection is Ig.M production • transplacental IgG provides passive immunity Table 15 , Infections During Pregnancy Infection

Agent

Greatest

Source of Transmission

Diagnosis

Effects on Fetus

Effects on Mother

Congenital varicella syndrome (limb aplasia, chorioretinitis, cataracts, cutaneous scars, cortical atrophy IUGR , hydrops), PTl

Fever, malaise, Clinical, ± vesicle vesicular pruritic lesions fluid culture * serology

Varicella roster immunoglobulin (VZIG) for mother if exposed, decreases congenital varicella syndrome If maternal infection 5 d before delivery, give infant VZIG for passive immunity Note: donoladminister vaccine during pregnancy (live attenuated vaccine)

5-10 % develop CNS involvement (mental retardation, cerebral calcification, hydrocephalus, microcephaly,

Asymptomatic or flu-like (fever, pharyngitis,

No specific treatment: maintain good hygiene and avoid high- risk situations

Management

Transmission Risk to Fetus

Chicken Pox

Varicella roster To mother:direct, virus (herpes respiratory family) To baby: transplacental

13 - 30 wkGAand 5 d pre - to 2 d post delivery

.

.

’Cytomegalovirus DNAvirus (herpes family)

Erythema

Parvovirus 619

Infectiosum (Fifth Disease)

Hepatitis 6

DNA virus

Tomother: blood/ organ transfusion, sexual contact To baby: transplacental, during delivery, bieasl milk

T1- T 3

Tomother: respiratory infected blood products To baby: transplacental

10 - 20 v/ k GA

.

.

Tomother: blood saliva, semen, vaginal secretions fo baby: transplacental, bieasl milk

lymphadenopathy, polyarthritis)

deafness, chorioretinitis) Spontaneous abortion Flu-like, rash, arthritis: ISA), stillbirth, hydrops often asymptomatic in utero

T3 10% vertical transmission if asymptomatic and HBsAq * ve: 85 90% il HBsAgandH 6 eAg * ve

Prematurity, low birth weight , neonatal death

.

Fever N/ V, fatigue, jaundice, elevated liver enrymes

Serologic screen:isolate virus from urine or secretion culture

-

Serology, viral PCS, maternal AFP:if IgM present, follow fetus with U/S for hydrops

If hydrops occurs, consider fetal transfusion

Serologic screening for all pregnancies

fix neonate with HBIG and vaccine (at birth 1, 6 mo): 90 % effective

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OB32 Obstetrics

Table 15. Infections During Pregnancy Infection

Agent

Source of Transmission

Effects on Fetus Greatest Transmission Risk

DMA virus

To mother: intimate

Delivery (if genital lesions present):less commonly muieio

Effects on Mother

Diagnosis

Management

Fa nful vesicular lesions

Clinical diagnosis

Acyclovir for symptomatic women, suppressive therapy at 36 wk 6A controversial Suggested CD if active genital lesions, even if remote from vulva

to Fetus 'Herpes Simplex

Virus

mucocutaneous contact To baby: transplacental, during delivery

RNA retrovirus

HIV

.

To mother: blood, semen, vaginal secretions Tobabyrrffufero. during delivery, breast milk

1/3 in siltro V3 at delivery.1/3 breastfeeding

Disseminated herpes (20 %); CNS sequelae (3S%); self-limited infection

. .

See Infectious Diseases. Serology,viral PCR All pregnant women are 1027 offered screening

IUGR PIl PR0M

Triple antiretroviral therapy decreases transmission to'1% Elective CD: no previous antiviral Rx or monotherapy only, viral load unknown or >500 RNA copies/mL unknown prenatal care, pabent request

.

II

ssRHAtogavrrus To mother:

'Rubella

SA or congenital rubella syndrome (hearing loss, cataracts. CV lesions mitral regurgitation. IUGR hepatitis. CNS

respiratory droplets (highly contagious) To baby:

,

transplacental

.

.

Rash (50%) lever, posterior auricular

Serologic testing:all

No specific treatment:

or occipital lymphadenopathy,

pregnant women screened (immune if litre >1:16): infection if IgM present or

offer vaccine following pregnancy

arthralgia

>4 x increase in

IgG

Do not administer during pregnancy (live attenuated vaccine)

defects, osseous changes)

Spirochete ( Ireponemc pallidum)

Syphilis

T1- T3

Tomother: sexual contact To baby: transplacental

.

Risk of PTL multisystem involvement, fetal death

.

See Infectious Diseases 1024

VORL screening for all

.

pregnancies:if positive

requires confirmatory testing

Benzathine penicillin 6

2.4 million IU IMildose if early syphilis. 3 doses if late syphilis, monitor VDRl monthly

No approved alternatives in pregnancy:if 6-lactam allergy,recommend to desensitize then beat with penicillin 'Toxoplasmosis

Protozoa ( foxop/osmo gondii ]

.

To mother raw meat unpasteurized goal's milk, cat feces/urine To baby: bansplacental

13 (but most severe if infected in 11);only concern if primary infection during pregnancy

Congenital toxoplasmosis (chorioretinitis hydrocephaly intracranial calcification,mibal regurgitation.

Majority subdinical; may IgM and Ig6 serology: PCR have Du -like symptoms of amwotic fluid

Congenital possible N1D if exposed in early pregnancy as a result of high fevers

Cough,sore throat malaise, headaches,

.

.

microcephaly). NB: 75% initially asymptomatic at birth

ssRNA virus

Influenza

Tomother: respiratory droplets To baby:

Earty pregnancy

transplacental

.

myalgia Complications include pneumonia

Clinical diagnosis,viral swab

Self - limiting in mother; spiramycin decreases fetal morbidity bul not rate of transmission

Immunization with inactivated influenza vaccine If infected: symptomatic treatment, antivirals, supportive therapy

' Indicates TORCH infection

Venous Thromboembolism Epidemiology • incidence of 12.1 in lOOOO ( DVT ) and 5.4 in 10000 ( PE) • increased risk of V I E throughout pregnancy ( highest risk of DVT in T3) and postpartum period ( highest risk of PE postpartum first 6 wk )

Virchow's Triad for VTE • Hypercoagulable slate • Venous stasis • Endothelial damage

Risk Factors previous VTE, age >35, obesity, infection , bedrest/ immobility, shock/ dehydration, smoking, pre eclampsia, and thrombophilias (see Hematology H36)

.

r “i c. J

Table 16 . Risk Factors for VTE Specific to Pregnancy Hypercoagulability

Stasis

Endothelial Damage

Increased Factors: H V VII VIII IX X XII, fibrinogen Increased platelet aggregation Decreased protein S, tPA. factors XI. Till Increased resistance to activated protein C Anbthrombin can be normal or reduced

Increased venous distensibility Decreased venous tone 50 % decrease in venous flow in lower extremity by T3 Uterus is mechanical impediment to venous

Vascular damage at delivery (CD or SVD) Uterine instrumentation Perrpartum pelvic surgery

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OB33 Obstetrics

Clinical Features

• most DVTs occur in the iliofemoral or calf veins with a predilection for the left leg • signs of a PE are non -specific Investigations

• duplex venous Doppler sonography for DVT • CT angiography preferred for PE Management

• before initiating treatment , obtain a baseline CBC including platelets and aPTT • treatment with LMWH preferred dosing varies depending on specific LMW H used should he discontinued at least 24 h prior to delivery • unfractionated heparin 80 lU / kg bolus ( max 5000 IU ) followed by 18 lli /kg / h infusion • measure aPTT 6 h after the bolus maintain aPTT at a therapeutic level (1.5 2x normal ) repeat q 24 h once therapeutic • heparin induced thrombocytopenia ( HIT ) uncommon (3%), but serious complication • warfarin is contraindicated during pregnancy due to its potential teratogenic effects • poor evidence to support a recommendation for or against avoidance of prolonged sitting • VTE prophylaxis women on long-term anticoagulation: full therapeutic anticoagulation throughout pregnancy and for 6-12 wk postpartum • women with a non-active PMHx of VTE: unfractionated heparin regimens suggested • postpartum thromboprophylaxis should be considered if absolute risk is over 1.0%, defined as: any two of the following: BMI >30 at first antepartum visit, smoking >10 dgarettes/d, preeclampsia, IUGR, placenta previa, emergency CD, peripartum / postpartum blood loss >1 L, any low -risk thrombophilia, maternal cardiac disease/SLE/SCD/lBD/varicose veins/GDM, preterm delivery, stillborn any three or more of the following: age >35, parity >2, use of ART, multiple gestation, placental abruption, PROM, elective CD, maternal cancer current prophylaxis regimens for acquired thrombophilias (e.g. APS ) include low dose ASA in conjunction with prophylactic heparin

-

-

Normal Labour and Delivery Definition of Labour

• true labour: regular, painful contractions of increasing intensity associated with progressive dilatation and effacement of cervix and descent of presenting part, or progression of station preterm (20-36 + 6 wk GA) term (37- 41+ 6 wk GA ) postterm ( >42 wk GA) • false labour ( Braxton -Hicks contractions ): irregular contractions with unchanged intensity and long intervals, occur throughout pregnancy and not associated with any cervical dilatation, effacement, or

descent • often relieved by rest or hydration

-

The Cervix • see Bishop Score (see Table 20, OB3S ) • dilatation: latent phase (0 4 cm, variable time); active phase ( 4 10 cm ) • effacement: thinning of the cervix by percentage or length of cervix (cm) • consistency: firm , medium, or soft position: posterior, mid, or anterior • other consideration application: contact between the cervix and presenting part ( i.e. well or poorly applied )

-

Maternal Triage Assessment ID: Age. 6PA, EDD, GA, GBS, Rh , Serology Chief Complaint (CC) HPI: 4 key questions: • Contractions: Since when, how close (q x min), how long (x s), how painful Bleeding: Since when, how much ( pads), colour (pinky vs, brownish vs. bright red ), pain, last U/S, trauma/ intercourse Fluid (ROM): Since when, large gush vs. trickle, soaked pants, clear vs green vs. red continuous • FM: As much as usual, time since last movement, kick counts (lie still for 1 2 h , cold juice, feel FM should have 6 movements in 2 h ) PregHx: Any complications ( HTN, GDM infections) IPS/FTS last U /S ( BPP score, growth EFW, presentation ), last vaginal

-

The Fetus

.

-

exam

• fetal lie: orientation of the long axis of the fetus with respect to the long axis of the uterus ( longitudinal, transverse, or oblique ) • fetal presentation: fetal body part closest to the birth canal breech (complete, frank, footling and incomplete ) (see Figure 5, OB25) cephalic ( vertex /occiput, face, or brow) transverse (shoulder ) compound (fetal extremity prolapses along with presenting part) all except vertex are considered malpresentations (see Obstetrical Complications, OBI 7 )

.

.

.

.

.

-

.

POBHx: Every previous pregnancy and outcome: year, SVD/CD/miscarriage/ abortion , baby size, length of labour, use of vacuum or forceps, complications PMHx . Meds Allergies. SHx 0/E: Maternal vitals, fetal heart tracing

.

(baseline, variability, presence of accelerations/decelerations), Leopold 's, vaginal exam U/S

.

7

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OB34 Obstetrics • fetal position: position of presenting part of the fetus relative to the maternal pelvis OA: most common presentation ( “ normal" ) - left OA most common OP: most rotate spontaneously to OA; may cause prolonged second stage of labour OT: leads to arrest of dilatation

Reference Point for Describing Fetal Position • Occiput for cephalic presentation • Sacrum for breech presentation • Mentum for face presentation

normally, fetal head enters maternal pelvis and engages in OT position subsequently rotates to OA position (or OP in a small percentage of cases) • attitude: tlexion /extension of fetal head relative to shoulders • brow presentation: head partially extended ( requires CD ) face presentation: head fully extended mentum posterior always requires C.' D, mentum anterior can deliver vaginally • station : position of presenting bony part relative to ischial spines - determined by vaginal exam • at ischial spines = station 0 = engaged -5 to -1 cm above ischial spines • +1 to +5 cm below ischial spines • asynclitism: alignment of the sagittal suture relative to the axis of the birth canal • lateral tilt seen with either anterior or posterior asynclitism and may impact descent Frontal Fontanelle or Anterior Fontanelle

Biparietal Diameter 9.5 cm

Occipital Fontanelle or Posterior Fontanelle

Occiput Anterior

Right Occiput Transverse

Occiput Posterior

=

•

Left Occiput Anterior

Right Occiput Posterior

Figure 6. Fetal positions

Four Stages of Labour First Stage of Labour (0-10 cm cervical dilatation) • latent phase uterine contractions typically infrequent and irregular slow cervical dilatation ( usually to 4 cm ) and effacement • active phase • rapid cervical dilatation to full dilatation ( nulliparous > 1.0 cm / h, multiparous > 1.2 cm / h ) • phase of maximum slope on cervical dilatation curve • painful, regular contractions q 2-3 min , lasting 45-60 s • contractions strongest at fundus Second Stage of Labour (10 cm dilatation - delivery of the baby) • from full dilatation to delivery of the baby; duration varies based on parity, contraction quality, and

type of analgesia • mother feels a desire to bear down and push with each contraction • women may choose a comfortable position that enhances pushing efforts and delivery upright (semi-sitting, squatting) and LLDP are supported in the literature • progress measured by descent

Figure 7. Synditism and asynclitism

CO

o

Course of Normal Labour’

Stage

Nulliparous

Multiparous

First

6-181

MOh

Secure Th.d

30 tu-3 h 5-30 min

5-30 min 5-30 no

-

Signs of Placental Separation • Gush of blood Lengthening of cord • Uterus becomes globular • Fundus rises

.

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Third Stage of Labour (delivery of the baby - delivery of the placenta)

• from baby’s birth to separation and expulsion of the placenta • can last up to 30 min before intervention is indicated • demonstrated by gush of fresh blood, umbilical cord lengthening, uterine fundus changing shape (firm and globular ), and rising upward • active management: start oxytocin IV drip, or give 101U L\1 or 5 mg IV push, after delivery’ of anterior shoulder in anticipation of placental delivery, otherwise give after delivery of placenta • routine oxytocin administration in third stage of labour can reduce the risk of PPH by >40% Fourth Stage of Labour

• first postpartum hour • monitor vital signs and bleeding, repair lacerations • ensure uterus is contracted ( palpate uterus and monitor uterine bleeding ) • inspect placenta for completeness and umbilical cord for presence of 2 arteries and 1 vein • 3rd and 4th stages of labour most dangerous to the mother ( i.e. hemorrhage)

Coa'jcioos Support for Women During Childbirth Codira:* DB Sjst Rev 201 /:?:CO 003766 SMr Systematic review ot 2? trials front 17 countries snoring a total of 15158 women Htmtioa: Corneous support vs. usual cae feriwg labour Outcoae : Effects on notbers audtheir babies lesiltr Women receiving continuous support were sight!) note Eketjf ID have a spontaneous vaginal both it!108.95% Cl 1.08 to 1.12) a nd shorter laoow (mean d ffevence 0.69 h , 95% Cl 1.04 to 0 341 aed were less ike Ip to use intrapartum analgesia (It 000.95% Cl 0.84 to 0.961 report dissatisfaction with tteirchidbirth eioener ee| t 0.69. 95% 0.59 hi 0-751 and bavea baby with a low 5 min APUI store (U 0.52.95% CI 0.46 to 0.8S)

-

-

. .«

-

a

The Cardinal Movements of the Fetus During Delivery

1. Head floating, before engagement

5. Complete extension

2. Engagement descent, flexion

3. Further descent,

internal rotation

6. Restitution ( external rotationl

4. Complete rotation, beginning extension

8. Delivery ot posterior shoulder

Figure 8. Cardinal movements of fetus during delivery Adapted from illustration in Williams Obstetrics, t9th ed

Analgesic and Anesthetic Techniques in Labour and Birth • pain or anxiety leads to high endogenous catecholamines, which produce a direct inhibitory' effect on uterine contractility Non-Pharmacologic Pain Relief Techniques • reduction of painful stimuli • maternal movement, position change, counter-pressure, and abdominal compression • activation of peripheral sensory receptors

• superficial heat and cold • immersion in water during labour

touch and massage, acupuncture, and acupressure

• TENS

intradermal injection of sterile water aromatherapy • enhancement of descending inhibitory pathways • attention focusing and distraction w hypnosis music and audio analgesia • biofeedback

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OB36 Obstetrics

Pharmacologic Methods (see Anesthesia. A 26) • nitrous oxide ( e.g. self-administered Entonox') • narcotics (usually combined with anti- emetic)

• pudendal nerve block • perineal infiltration with local anesthetic • regional anesthesia ( epidural block , combined spinal -epidural , and spinal )

Fetal Monitoring in Labour • see online Fetal Heart Kate Tutorial Vaginal Exam • membrane status, as indicated by amniotic fluid (clear, pink , bloody, and meconium ) • cervical etTacement ( thinning ), dilatation, consistency, position , and application • fetal presenting part, position , and station • bony pelvis size and shape • monitor progress of labour at regular intervals and document in a partogram Intrapartum Fetal Monitoring • intermittent fetal auscultation with Doppler device q 15-30 min for 1 min in active phase of first stage following a contraction , q5 min during second stage when pushing has begun • continuous electronic I HR monitoring reserved for abnormal auscultation , prolonged labour, labour which is induced or augmented, meconium present, multiple gestation /fetal complication, and concerns about the fetus tolerating labour • use of continuous electronic monitoring shown to lead to higher intervention rates and no improvement in outcome for the neonate when used routinely in all patients (i.e. no risk factors) techniques for continuous monitoring include external (Doppler ) vs. internal (fetal scalp electrode) monitoring • fetal scalp sampling should be used in conjunction with electronic FHR monitoring and contraction monitoring (CFG) to resolve the interpretation of abnormal or atypical patterns '

Electronic FHR Monitoring • FHR measured by Doppler; contractions measured by tocometer • described in terms of baseline FHR, variability ( short- term , long- term ), and periodicity (accelerations,

decelerations)

• see t able 5 , OB 10 • Baseline FHR

-

normal range is 110 160 bpm

• parameter of fetal well - being vs. distress

• Variability • physiologic variability is a normal characteristic of 1 HR • variability is measured over a 15 min period and is described as; absent , minimal ( 25 bpm ) • normal variability indicates fetal acid base status is acceptable • can only be assessed by electronic contraction monitoring (CFG ) variability decreases intermittently even in a healthy fetus • Periodicity • accelerations: increase of 15 bpm for 15 s (or 10 bpm for 10 s if < 32 wk GA ) • decelerations: 3 types, described in terms of shape, onset, depth , duration recovery, occurrence, and impact on baseline FHR and variability

-

-

Table 17. Factors Affecting Fetal Heart Rate Fetal Tachycardia ( FHR >160 bpm )

Fetal Bradycardia

Decreased Variability

(FHR tu4nCt)

Continuous Cardiotocography ( CTG ) is I form ol Electron it Fetal Monitoring|EFM ) for Felal Assessment Darin; labom CochraneOB Syst ter 201):$:CD 006066 Pnipose lo eur me the effectiveness of continuous electronic fetal monitoring or cardiotocography during labour Selection Criteria: Randorriiedand quasirandor red controlled trials comparing continuous CIC (with and without fetal blood sampling! to a ) no fetal monitoring. b) interrittertauscultation , or c) intermittent CIC Results: 13 trials.37000 women. Continuous CIG compared with intermittent auscultationshowed no difference in overall perinatal death rate oi cerebral palsy rates nonetheless, neonatal seizures ware hatred (HR 0.50.95% Cl 0.310.80) and there was a Significant increase in C0 ( RR 1.63, 95% Cl 1.29 2.07 ) and nstrmnental vaginal birth (RR 115.95% Cl 1.01-1.33) with CTG Conclusion : Cnobnuous CIG may reduce the incidence of neonatal seizures, but has no effect on cerebral palsy rates, infant mortality, or other measures of neonatal well ber. g. Continuous CIG was alsoassociated with an increase a CD and instrumental delvenes ,

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OB37 Obstetrics

Table 18 . Comparison of Decelerations Comparisons

Early Decelerations • Uniform shape with onset early in contraction , returns to baseline by end of contraction, mirrors contraction ( nadir occurs at peak of contraction ) • Gradual deceleration and return to baseline • Often repetitive; no effect on baseline f HR or variability • Benign , due to vagal response to head compression

Early Deceleration

BPM 180

Onset of deceleration

/

160

»

.

140

Nadir of

FHR (baseline )

s deceleration

120 100

I

"

/ AcmB ofN contraction

Onset of

nd of

contraction

. Most common typeonset ol

Uterine contraction ( baseline )

%

contraction

Variable Decelerations , and duration Variable in shape, periodicity seen during labour • • Often with abrupt drop In FHR >15 bpm below baseline|*15 s « 2 min ): usually no effect on baseline FHR or variability • Due to cord compression or, in second stage, forceful pushing with contractions

Variable Deceleration

.

FHR Variant,

.

in duration

.

mtansitY and timing

Uterine contraction

Complicated Variable Decelerations

.•

Rule of 60 s Suggesting Severe Variable

• FHR drop > 60 bpm lor >60 s loss of variability or decrease in baseline alter deceleration >

Decelerations Deceleration to 60 bpm below baseline

Slow return to baseline

>60 s in duration with slow return to

• Baseline tachycardia or bradycardia

baseline

• May be associated with fetal acidemia Late Decelerations • Uniform shape with onset, nadir, and recovery occurring alter peak of contraction , slow return to baseline • May cause decreased variability and change in baseline FHR • Due to fetal hypoxia and acidemia , maternal hypotension , or uterine

BPM

nset of deceleration

_

Nadir of deceleration /

140

Late Deceleration

FHR

120

hypertonus

100

• Usually a sign ol uteroplacental insufficiency (an ominous sign)

30 seconds 4 of lag time

> Recovery time

Acmu ol /contraction 4

Onset of contraction

Uterine contraction

\nd of contraction

Fetal Scalp Blood Sampling • cervix must be adequately dilated • indicated when atypical or abnormal FHR is suggested by clinical parameters including heavy meconium or moderately to severely abnormal FHR patterns ( including unexplained low variability, repetitive late decelerations, complex variable decelerations, and fetal cardiac arrhythmias)

• done by measuring pH or more recently fetal lactate • pH S7.25, lactate < 4.2 mmol / L: normal, repeat if abnormal FHR persists • pH 7.21-7.24, lactate 4.2 - 4.8 mmol/ L: repeat assessment in 30 min or consider delivery if rapid fall since last sample pH < 7.20, lactate > 4.8 mmol/ L indicates fetal acidosis, delivery is indicated • contraindications: known or suspected fetal blood dyscrasia ( hemophilia, VWD) maternal infection ( HIV, genital herpes Hep B ) active •

.

Fetal Oxygenation

• uterine contractions during labour decrease uteroplacental blood flow, which results in reduced oxygen delivery to the fetus • most fetuses tolerate this reduction in flow and have no adverse effects • fetal response to hvpoxia /asphyxia: decreased movement, tone, and breathing activities • anaerobic metabolism (decreased pH ) transient fetal bradycardia followed by fetal tachycardia • redistribution of fetal blood flow • increased flow to brain , heart, and adrenals • decreased flow to kidneys, lungs, gut , liver, and peripheral tissues • increase in blood pressure

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OB38 Obstetrics

Table 19. Factors Affecting Fetal Oxygenation Factor

Mechanism

Example

Maternal

Decreased maternal oxygen carrying capacity

Significant anemia (iron deficiency , hemoglobinopathies), carboxyhemoglobin {smokers)

Decreased uterine blood flow

Hypotension ( blood loss , sepsis), regional anesthesia , maternal positioning Vasculopathies (SLE , T1DM , chronic HTH ) , APS, cyanotic heart disease. COPD

Chronic maternal conditions Uterine hypertonus

Uteroplacental

Placental abruption , tachysystole secondary to oxytocin , prostaglandins, or normal labour Placental abruption , placental infarction (dysfunction marked by IUGR , oligohydramnios, abnormal Doppler studies) , chorioamnionitis, placental edema ( DM , hydrops) , placental senescence ( post -dates) Oligohydramnios , cord prolapse , or entanglement

Uteroplacental dysfunction

Fetal

Cord compression

Decreased fetal oxygen carrying capacity

Significant anemia (isoimmunization , fetomaternal bleed ), carboxyhemoglobin ( exposure to smokers)

Induction and Augmentation of Labour Induction of Labour Definition • artificial initiation of labour in a pregnant woman prior to spontaneous initiation to deliver the fetus and placenta

Prerequisites for Labour Induction • capability for CD if necessary • maternal: inducible/ ripe cervix: short , thin , soft, anterior cervix with open os if cervix is not ripe, use prostaglandin vaginal insert ( Cervidil*), prostaglandin gel ( Prepidil*), misoprostol (Cytotec*), or l oley catheter • fetal: • normal fetal heart tracing cephalic presentation adequate fetal monitoring available • likelihood of success determined by Bishop score: cervix considered unfavourable if 6 score of 9- 13 associated with high likelihood of vaginal delivery '

Table 20. Bishop Score Cervical Characteristic

0

1

2

Position Consistency

Poslerior firm

Mid Medium

Anterior Soft

Dilatation (cm )

030 0

12

Station of Fetal Head

•

Effaccmcnt ( „ ) "

3

4050

-

2

•

60 - 70 34

-

1.0

•

3

>

Induction is indicated when the risk of continuing pregnancy exceeds the risks associated with induced Labour and delivery

Induction vs. Augmentation Induction is the artificial initiation of labour Augmentation promotes contractions when spontaneous contractions are inadequate

Consider the Following Before

Induction • Indication for induction • Contraindications GA Cervical favourability Fetal presentation Potential for CPD Fetal wellbeing/FHR Membrane status

80

>5

- . -2. -3 1

Indications • late term and postterm pregnancy = most common reason for induction • 39 41 wk GA especially with risk factors such as advanced maternal age ( > 40 yr ): consideration should be given to 10 L due to increased risk of stillbirth • > 41 wk GA: offer l ( ) L if vaginal delivery is not contraindicated • 10 L shown to decrease CD, I HR changes, meconium staining, macrosomia, and death when compared with expectant management GA and expectant management elected: serial fetal surveillance • > 41 wk • h'M count by the mother BPP q 3 4 d • maternal factors: • DM = second most common reason for induction • gestational HTN 238 wk GA preeclampsia 237 wk GA • other maternal medical problems, ( e.g. renal or lung disease, chronic HTN , and cholestasis ) • significant but stable antepartum hemorrhage • labour induction may be offered to patients age 240 at 239 wk GA due to increased risk of

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OB39 Obstetrics

Toronto Notes 2023

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• maternal fetal factors:

• isoimmunization , PROM , and chorioamnionitis

• fetal factors: • suspected fetal jeopardy as evidenced by biochemical or biophysical indications • macrosomia, fetal demise, RJCiR, oligo/ polyhvdramnios, anomalies requiring surgical intervention, and twins previous stillbirth or low PAPP-A

Evidence loi Cervical Ripening Methods ( S 06 C Guidelines) • Meta -analysis of five trials has concluded that the use of ocytocin to ripen the term is not effect •Since the best dose and route of m isoprostot for labour induct on with a live fetus are not known and there are concerns regarding hyperstaolation.the use of misoprostol for lot should be in cases of IUFD to initiate labour

Risks • failure to achieve labour and /or vaginal birth • tachvsvstole with fetal compromise or uterine rupture • maternal side effects to medications • uterine atony and PPH if labour is prolonged

Vaginal Prostaglandin ( PGE 2 and PGI 2a) for

Contraindications

• maternal

Induction of labour at term Cochrane OS Syst Rev 2014.6 C 0003101 This analysis enam nedthe results ol TO RCIs (n IUS ) women ]. Use ol vaginal PGE 2 in creased the risk of uterine hy perstimulation with f HR changes|RR 3.16: 95% Cl 1.67- 5.98) aud likely reduces the CO rate slightly ( RR 0.91; 95% Cl 0.81 1.02) compared to placebo omo treatment, ( here were no detectable differences in effectiveness between gel or tablet forms of PGE2 or between sustained release pessaries end PGE 2 gel /tablets Theoretical advantages between mtreveginal PGE2 (Cervidil;) compared to Intravaginal Prostaglandin

-

-

prior classical or Inverted T lndslon CD or uterine surgery ( e.g . myomectomy) unstable maternal condition • active maternal genital herpes invasive cervical carcinoma pelvic structure deformities

• •

-

previous uterine rupture • maternal-fetal placenta previa or vasa previa cord presentation fetal fetal distress or malpresentation /abnormal lie

Gel: •Slow, continuous release • Ability to use oxytocin 30 mm after re moral vs.

fill lor gel • Abi lily to remove insect If required (e.g. etcessive uterine aclivityl

Methods for Induction of Labour CERVICAL RIPENING

Definition • use of medications or other means to soften , efface, and dilate the cervix ; increases likelihood of

Labouc Induction vs . Expectant Manageneot in Low Risk Multiparous Women NEJM 2018;379:513-523 Purpose: fo assess whether induction of labour between 39*0 wk GAand 40 6 wk GA implores perinatal and maternal outcomes Methods: 6106 low - risk nulliparous women were randomized to the elective indaction oc the expectant management groups. Ihe primary outcome wasa composite outcome of perinatal death or senre neonatal complications. The mam secondary outcome wasthe rale afCO Results: Ihe primary per natal outcome occurred in 4.3% ol neonales from Ihe elective induction group and 5.4% ol neonales from ihe eipectant management group ( RR : 0.80: 95% Ct 0.64 -1.00: P 0.049, P« 0.04 G lor sign 4i cancel This result was consistent after adjusting for other maternal facto is. CD occurred In 18.6% of Induction group mothers compared to 22.3% of eipectant management group mothers (RR: 0.84: 95% Cl: 0.76 0.93 P 1000 mL of blood after CD, >500 mL of blood after vaginal delivery, or bleeding associated with signs/symptoms of hypovolemia within 24 h of birthing process regardless of mode of delivery • primary within first 24 h postpartum • secondary after 24 h but within first 12 wk

-

-

Uterine atony is the most common cause ofPPH

Epidemiology • incidence 5-15% Etiology ( 4 Ts) 1. Tone (uterine atony) most common cause of PPH ( 70-80%) avoid with active management of 3rd stage of labour with 1) oxytocin administration; 2) uterine massage; and 3) umbilical cord traction for delivery of the placenta due to: overdistended uterus ( polyhydramnios, multiple gestations, and macrosomia ) uterine muscle exhaustion ( prolonged or rapid labour, grand multiparity, oxytocin use, and general anesthetic) uterine distortion ( fibroids ) intra amniotic infection ( fever or prolonged ROM ) bladder distension ( preventing uterine contraction ) 2. Tissue • retained placental products ( membranes, cotyledon, or succenturiate lobe) • retained blood clots in an atonic uterus

-

(§)

-

DDx of Early PPH 4 Ts To ne (atony) Tissue ( retained placenta, dots) Trauma (laceration, inversion ) Thrombin (coagulopathy)

DDx of Late PPH Retained products t endometritis Sub involution of uterus

-

GIN

• abnormal placentation (e.g. placenta accreta)

3. Trauma laceration (vagina, cervix, or uterus), episiotomv, hematoma (vaginal, vulvar, or retroperitoneal ), uterine rupture, and uterine inversion 4. Thrombin coagulopathy ( pre existing or acquired ) • most identified prior to delivery (low platelets increases risk )

-

• includes hemophilia , DIG, IIP. TIP, and VWD • therapeutic anti -coagulation

Investigations

• assess degree of blood loss and shock by clinical exam • explore uterus and lower genital tract for evidence of atony, retained tissue, or trauma • may be helpful to observe red- top tube of blood - no clot in 7-10 min indicates coagulation problem Management • ABCs, call for help • 2 large bore I Vs, run crystalloids wide open

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• CBC, coagulation profile, fibrinogen, cross and type packed RBCs • treat underlying cause • Foley catheter to empty bladder and monitor urine output

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OB47 Obstetrics

Medical Therapy for Atony

• oxytocin 10 III IM is preferred in low - risk vaginal deliveries, oxytocin IV infusion ( 20- 401U in 1000 mL crystalloid at 150 mL / h ) is an acceptable alternative; oxytocin 5 101U IV bolus ( 20 40 IU in 250 mL crystalloid ) can be used after vaginal birth , but not with elective CD • carbetocin , a long acting oxytocin, 100 pg IV bolus over 1 min for elective CD or 100 pg IM for vaginal deliveries with 1 risk factor for PPH (instead of a continuous oxytocin infusion ) • methylergonovine maleate ( Ergotamine* ) 0.25 mg IM /slow IV q 2 h up to 1.25 mg; can be given as IV bolus of 0.125 mg (contraindicated in HTN ) • carboprost ( Hemabate* ), a synthetic PGFia analog, 250 pg IM /1 MM ql 5 min to max 2 mg ( major

-

-

-

prostaglandin side effects and contraindicated in cardiovascular, pulmonary (asthma ), renal, and hepatic dysfunction ) • misoprostol (Cytotec*) 600 -800 pg PO/SL (faster ) or PR / PV (side effect: pyrexia if >600 pg ) • tranexamic acid (Cyklokapron* ), an antifibrinolytic, 1 g IV Local Control for Atony • bimanual massage: elevate the uterus and massage through patient’s abdomen • uterine packing ( mesh with antibiotic treatment ) • Bakri Balloon for tamponade: may slow hemorrhage enough to allow time for correction of coagulopathy or for preparation of an OR • manual removal if retained placenta (can also be used to treat PPH due to other causes) Surgical Therapy (Intractable PPH) for Atony

• D&C ( beware of vigorous scraping, which can lead to Asherman's syndrome) (can also be used to treat PPH due to other causes) • embolization of uterine artery or internal iliac artery by interventional radiologist • laparotomy with bilateral ligation of uterine artery ( may be effective ), or internal iliac artery ± compression sutures ( B Lynch or Cho sutures) (can also be used to treat PPH due to trauma and early

-

thrombus) • hysterectomy last option , with angiographic embolization if post hysterectomy bleeding

-

Retained Placenta Definition

• placenta undelivered after 30 min postpartum Etiology • placenta separated but not delivered • abnormal placental implantation ( placenta accreta, placenta increta, and placenta percreta )

Risk Factors • placenta previa, prior CD, post-pregnancy curettage, prior manual placental removal, and uterine

infection

Clinical Features • risk of PPH and infection

Investigations

• explore uterus

• assess degree of blood loss Management

• 2 large bore lVs, type and screen • Brandt maneuver ( firm traction on umbilical cord with one hand applying suprapubic pressure ccphalad to avoid uterine inversion by holding uterus in place)

• oxytocin 10 IU in 20 mL normal saline into umbilical vein • manual removal if above fails • D&C if required ( U / S guidance if available ) • cefazolin 2 g IV if manual removal or D&C

Uterine Inversion Definition

rn

• inversion of the uterus through cervix ± vaginal introitus

LJ

Etiology /Epidemiology • often iatrogenic (excess cord traction with fundal placenta ) • excessive use of uterine tocolytics • more common in grand multiparous women ( lax uterine ligaments ) • 1 in 1500 to 1 in 2000 deliveries

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OB 18 Obstetrics

Clinical Features • can cause profound vasovagal response with bradycardia, vasodilation, and hypovolemic shock • shock may be disproportionate to maternal blood loss Management • urgent management essential, call anesthesia • ABCs: initiate IV crystalloids • can use tocolytic drug (see Preterm Labour, OBIT ) or nitroglycerin IV to relax uterus and aid

replacement • replace uterus without removing placenta • remove placenta manually and withdraw slowly • IV oxytocin infusion (only after uterus replaced ) • re-explore uterus • may require general anesthetic ± laparotomy

Postpartum Pyrexia Definition

(§>

• fever >38°C on any two of the first 10 d postpartum , except the 1st day

Etiology of Postpartum Pyrexia

Etiology

• endometritis • wound infection (check CD and episiotomy sites) • mastitis/ breast engorgement • UT1 • atelectasis

-

B 5W Breast: engorgement, mastitis Wind: atelectasis, pneumonia Water: UTI Wound: episiotomy. CD site infection Walking: DVT. thrombophlebitis Womb: endometritis

• pneumonia • DVT or pelvic thrombophlebitis Investigations • detailed history and physical exam, relevant cultures • for endometritis: blood and genital cultures • serum lactic acid for early detection of sepsis Treatment • depends on etiology • infection: empiric antibiotics, adjust when sensitivities available • endometritis: clindamycin + gentamicin /tobramycin IV • mastitis: cloxacillin or cephalexin • wound infection: cephalexin + frequent sitz baths for episiotomy site infection DVT: anticoagulants • prophylaxis against post-CD endometritis: administer cefazolin 2-4 g IV ( based on BM1) 30 min prior to skin incision

ENDOMETRITIS

• definition: inflammation of the endometrium most commonly due to infection • clinical features: fever, chills, abdominal pain, uterine tenderness, foul smelling vaginal discharge, or lochia • treatment: depends on infection severity; oral antibiotics if well, IV antibiotics with hospitalization in moderate to severe cases

-

Risk Factors for Endometritis

.

CD intrapartum chorioamniomtis. prolonged labout prolonged ROM. and multiple vaginal examinations

. see

VENOUS THROMBOEMBOLISM Venous thromboembolism , OB32

Mastitis • definition: inflammation of mammary glands • must rule out inflammatory carcinoma, as indicated • differentiate from mammary duct ectasia: mammary duct (s) beneath nipple clogged and dilated ± ductal inflammation ± nipple discharge (thick, grey to green ), often postmenopausal women ri cJ

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OB19 Obstetrics

Table 22. Lactational vs. Non- Lactational Mastitis

-

Lactational

Non Lactational

Epidemiology

More common than non-lactational Often 2 3 wk postpartum

Periductal mastitis most common Mean age 32 yt

Etiology

S. aureus

May be sterile May be infected with S. aureus or other anaerobes Smoking is risk factor May be associated with mammary duct ectasia

Symptoms

Unilateral localited pain Tenderness Erythema

Subareolar pain

Treatment

Heat or ice packs Continued nursinglpumping Antibiotics ( clovacillim'cephalexin ) ( erythromycin if penidllin- allergic)

Broad-spectrum antibiotics and ISO Total duct eversion (definitive)

Abscess

Fluctuant mass Purulent nipple discharge Fever, leukocytosis Discontinue nursing,IVantibiotics (nafcillin/ oxacillin), ISD usually required

If mass does not resolve, fine -needle aspiration to exclude cancer and U/S to assess presence of abscess Treatmentindudes antibiotics, aspiration, or ISD (tends to recur) May develop mammary dud fistula Aminority of non-lactational abscesses may occur peripherally in breast with no associated periductal mastitis (usually S. aureus)

May haiesubareolar mass Discharge (variable colour) Nipple inversion

Postpartum Mood Alterations POSTPARTUM BLUES

• 40 - 80% of new mothers, onset 3-10 d postpartum; extension of the “ normal ” hormonal changes and ad justment to a new baby • self-limited, should resolve by 2 wk • manifested by mood lability, depressed affect, increased sensitivity to criticism, tearfulness, fatigue, irritability, poor concentration /despondency, anxiety, and insomnia POSTPARTUM DEPRESSION • definition: major depression occurring in a woman within 6 mo of childbirth (see Psychiatry, PS14 ) • epidemiology: 10-15%, risk of recurrence 50% • risk factors: personal or family history of depression ( including PPD) prenatal depression or anxiety • stressful life situation • poor support system

• unwanted pregnancy

• colicky or sick infant

• clinical features: suspect if the “ blues” last beyond 2 wk, or if the symptoms in the first 2 wk are severe (e.g. extreme disinterest in the baby, suicidal or homicidal / infanticidal ideation ) • assessment: Edinburgh Postnatal Depression Scale or others • treatment: antidepressants, psychotherapy, supportive care, and electroconvulsive therapy if

refractory • prognosis: interferes with

bonding and attachment between mother and baby, so it can have long-

term effects

POSTPARTUM PSYCHOSIS • definition: acute psychotic episode triggered by the complex psychosocial stressors and hormonal changes that occur following childbirth. Symptoms usually present within the first 2 wk but can last

for months • epidemiology: rare ( 0.2% ), but 50% risk of recurrence in next pregnancy if experienced in previous pregnancy. Increased risk in individuals with bipolar disorder, schizoaffective disorder,

schizophrenia, or other psychotic illness, or personal or family history of postpartum psychosis • treatment: psychiatric emergency as risk of infanticide. Typically requires hospitalization, mood stabilizer, and antipsychotics rT LJ

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OB50 Obstetrics

Postpartum Care Postpartum Office Visit at 6 Weeks

Care of Mother ( The 10 Bs ) • Be careful : do not use douches or tampons for 4 -6 wk post -delivery • Be fit: encourage gradual increases in walking , Kegel exercises • Birth control: assess for use of contraceptives • Breastfeeding is not as effective as other methods of birth control ( see Gynaecology, GY 15, for more detail about different contraceptive options postpartum ) lactational amenorrhea approved by WHO for up to 6 mo if meets criteria: l ) amenorrhea; 2) fully or nearly fully breastfeeding ( no interval of > 4 -6 h between breastfeeds); and 3 ) 000081. Chamberlain G, Zander L. Induction. BMJ 1999:318:995 - 998. Chamberlain G, Steer P. Labourinspecialcircumstances. BMJ 1999;318:1124-1127. Chamberlain G Steer P. Obstetric emergencies BMJ 1999:318:1342 -1345. Chamberlain G Steer P. Operative delivery. BMJ 1999:318:1260 1264. Chamberlain G Steer P Unusual presentations and positions and multiple pregnancy. BMJ 1999:318:1192-1194 Chan WS Rcy E Kent NE et al Venous thromboembolism and anlilhrombotic therapy in pregnancy SOGC Clinical Practice Guideline No 308 June 2014 J Obslet Gynaecol Can 2014;36:527 53. Chappell 1C Cluver CA, Kingdom J,etal Pre eclampsia, lancet 2021:398:341 354. Chodlrkcr BN Cadrin C Oavics GAL el al. Prenatal Canadian guidelines for prenatal diagnosis: techniques of prenatal diagnosis. SOGC Clinical Practice Guideline No 105 July 2001 J Obstet Gynaecol Can 2001:23:616 624. Chyu JK,Strassner HI.Prostaglandin E 2 for cervical ripening: a randomized comparison olcervidil vs. prepidil. Am J Obstet Gynecol 1997:177:606 611 Colgan R Williams M Johnson JR. Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician 2011:84:519 -526. Cohen -Kerem R Nulman I Abramow Newerly M etal. Diagnostic radiation in pregnancy: perception vs. true risks. J0GC 2005:28:43 - 48. Committee on Practice Bullelins- Obstelrics. Postpartum hemorrhage. ACOG Clinical Management Guidelines, No 183 October 2017. ObstetGynecol 2017:130:e168 - e186. Committee on Practice 8ulletins-Obstelrics. Use of Prophylactic Antibiotics in Labor andOelivery. ACOG Clinical Management Guidelines No 199, September 2018. Obstet Gynecol 2018:132:e103 - e119. Conde-Agudelo A. Romero R. Amniolic fluid embolism: an evidence- based review. Am J Obstet Gynecol 2009;201:445.e1-e13. Crane J, Amson A Brunner M.etal.Antenatal corticosteroid therapy for fetal maturation.SOGC Committee Opinion, No 122, January 2003. J Obstet Gynaecol Can 2003:25:45 - 48. Delaney M, RoggensackA.Guidelines for the management of pregnancy at 41*0 to 42*0 Weeks. SOGC Clinical Practice Guideline. No 214. August 2017. J Obstet Gynaecol Can 2017;39:e164- e174. Dore S, Ehman W. Fetal health surveillance:intrapartum consensus guideline.SOGC Clinical Practice Guidelines ND 396 March 2020. J Obstet Gynaecol Can 2020;42:316 -348. Emory EK Dieter JN. Maternal depression and psychotropic medication effects on the human fetus. Ann N V Acad Sci 2006;1094:287-291. Farrell S Chan MC Schulz JA. Midurethral minimally invasive sling procedures for stress urinary incontinence.SOGC Technical Update.No 213 August 2008. J Obstet Gynaecol Can 2008:30:728- 733. Fieg DS, Berger H Donovanl el al. Diabetes and pregnancy. Can J Diabetes 2018:42:S2S5 - 282. Findley I,Chamberlain G. Relief of pain. ABC of labour care. BMJ 1999;318:927 930. Ford HB Sc bust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009:2:76 83 Gagnon A Wilson RD . Obstetrical complications associated with abnormal maternal serum maikers analytes SOGC Technical Update No 217 October 2008. J Obslet Gynaecol Can 2008:30: 918 932 Gavin Nl, Gaynes BN Lohr KN et al. Perinatal depression: a systematic review of prevalence and incidence ObstetGynecol 2005;106:1071-1083. Goldcnberg Rl Culhanc JF lams JD et al Epidemiology and causes of preterm birth, lancet 2008:371:75 84 Grootscholton K, Kok M, Oei SG et al. External cephalic version-related risks: a mela analysis Obslet Gynecol 2008;112:1143 -1151 Gruslin A Sleben M, Halpenn S et al Immunization In pregnancy SOGC Clinical Practice Guideline No 236 November 2009. J Obstet Gynaecol Can 2009:236:1086 - 1092. Guise JM Berlin M, McDonagh M cl al. Safety of vaginal birth after cesarean: a systematic review. Obslet Gynecol 2004;103:420 429. Hahn M, Sheran N Weber S et al.Providing patient - centered perinatal carefor transgender men and gender- diverse individuals: a collaborative multidisciplinary team approach. ObstetGynecol 2019:134:959 963. Hajenius PJ Mol F, Mol BW etal.Interventions for tubal ectopic pregnancy. Cochrane OB Syst Rev 2007;1:CD 000324. Hamilton P.Care of the newborn in the del every room. BMJ 1999;318:1403 -1406. Heine RP Puopolo KM Beigi R etal. Intrapartum managementof inlraamniotic infection.ACOG Committee Opinion No 712,August 2017.Obstet Gynecol 2017;130:e95 e101. Hennessey MH Rayburn WF. Stewart JD.et al. Preedampsiaand induction of labour:a randomized comparison of prostaglandin E2 as an inlracervical gel with oxytocin immediately, or as a sustained-release vaginal insert. Am J ObstetGynecol 1998:179:1204 -1209. Hod M, Bar J Peled Y, et al. Antepartum management protocol. Timing and modeof delivery in gestational diabetes. Obstet Gynecol 2009:113:206 -217. Hodnelt ED Gates S Hofmeyr GJ el al. Continuous support for women during childbirth. Cochrane DB Syst Rev 2011;2:CD003766. Howarth GR. Botha DJ. Amniotomy plus intravenous oxytocin for induction of labour.Cochrane DB Syst Rev 2001;3:CD003250. Kelly A J Ian B. Intravenous oxytocin alone lor cervical ripening and induction of labour. Cochrane DB Sysl Rev 2001;3:CD003246. Kent N. Prevention and treatment ol venous thromboembolism |V1E) in obstetrics. SOGC Clinical Practice Guideline, No 95 September 2000. J Obstet Gynaecol Can 2000:22:736 - 742. Koren G. Caffeine during pregnancy ? In moderation Can Fam Physician 2000:46:801 803. Korcvaar II SteegeisEA de Rrjkc Y 8 etal Reference rangesand defer mi nants of total hCG levels during pregnancy: the Generation R Study EurJ Epidemiol 2015:30:1057- 10 66. Kolaska A Menticoqlou S. Management of breech presentation at term SOGC Clinical Practice Guideline No 284 August 2019. J Obstet Gynaecol Can 2019:41:1193 -1205. Langlois S, Ford J, Chitayat D Carrier screening for thalassemia and hemoglobinopathies in Canada Joint S0GC- CCMG Clinical Practice Guidcknc No 218 Octobei 2008. J Obslet Gynaecol Can 2008:30:950 -959. Langlois S Wilson R. Carrier screening for genetic disoiders In individuals of Ashkenazi Jewish descent . SOGC Clinical Practice Guideline No 177 Apiil 2006. J Obstet Gynaecol Can 2006:28:324 332. Leduc D Biringer A, Lee L et al. Induction of labour SOGC Clinical Practice Guideline No 296 September 2013. J Obstet Gynaecol Can 2013:35:840 - 857. Leduc D Bir inger A Lee L et al Induction of labour: revrevr. SOGC Clinical Practice Guideline No 296 September 2013 J Obstet Gynaecol Can 2015:37:380- 381 Leduc D, Senikas V Lalonde AB. et.al. Active managementof the third stage of labour: prevention and treatment of postpartum hemoirhage. SOGC Clinical Practice Guideline, Ho 235 October 2009. J Obstet Gynaecol Can 2009:31:980- 993. Ling F Duff P.Obstetrics and gynecology: principles for practice. 2nd ed.Hew York:McGraw Hill Professional; 2002. Liston R,Sawchuck 0, Young D.Fetal health surveillance:antepartum and intrapartum consensus guideline.SOGC Clinical Practice Guideline No 197,September 2007. J Obstet Gynaecol Can 2007:29:S1-60. Lowder JL, Burrows LJ Krohn MA. et al. Risk factors for primary and subsequent anal sphincter lacerations: a comparison of cohorts by parity and prior mode of delivery. Am J Obstet Gynecol 2007:196:344e1- e5. Luckas M, Bricker L. Intravenous prostaglandin for induction of labour.Cochrane DB Syst Rev 2000:4:CD002864. Mackeen AD, Packard RE. Ota E et al. Antibiotic regimens for postpartum endometribs.Cochrane DB Syst Rev 2015:2:CD001067. Mackeen AD, Seibel-Seamon J Muhammad J, et al. Tocolytics for preterm premature rupture of membranes. Cochrane DB Syst Rev 2014;2:CD007062. Magee LA, De Silva DA Sawchuck D et al. Magnesium sulphate lor fetal neuroprolection. SOGC Clinical Practice Guideline No 376 April 2019. J Obstet Gynaecol Can 2019:41:505 -522. Magee LA Pels A Helewa M etal. Diagnosis, evaluation, and management of the hypertensive disorders ol pregnancy: executive summary. SOGC Clinical Practice Guideline No 307 May 2014. J Obslet Gynaecol Can 2014:36:416 438. Maxwell C Gaudetl Cassir G el al Pregnancy and maternal obesity part 1: pre conception and prenatal care. SOGC Clinical Practice Guideline, No 391, November 2019 J Obslet Gynaecol Can 2019:41:1623 -1640

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OB53 Obstetrics

Toronto Notes 2023

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McAllister- Williams RH Baldwin DS. Cantwell Roch et al. British association for psychopharmacology consensus guidance on the use of psychotropic medication preconception,in pregnancy and postpartum 2017. J Psychopharmacol 2017;31:219 -52. Mcneies (V Yakoob MV SoomroI el al Reducing stillbirths: prevention and management of medicaldisorders and infections during pregnancy. BMC Pregnancy Childbirth 2009:9:54 Ministry ol Health and Long Term Care and Canadian Medical Association. Antenatal record 1. Ontario Ministry ol Health and Long Term Care and Canadian Medical Association Antenatal record 2 Ontario Money 0 Allen V the prevention of eaify - onset neonatal group 8 streptococcal disease. SOGC Clinical Practice Guideline No 298 August 2018. J Obstet Gynaecol Can 2018:40:e665 674. Money 0 luloch K. 8oucoiranI et al.Guidelines for the care ol pregnant women living with HIV and interventions to reduce perinatal transmission. SOGC Clinical Practice Ho 310 August 2014. J Obstet Gynaecol Can 2014:36:721-734. Morgan S Koren G.Is caffeine consumption safe during pregnancy? Can Fam Physician 2013:59:361-362. Morinl LimK. Ultrasound in twin pregnancies. SOGC Practice Guideline No 260, October 2017. J Obstet Gynaecol Can 2017:39:e 39B - 411. Motlola MF Davenport MH RuchatS el al. 2019 Canadian guideline for physical activity throughout pregnancy. Joint SOGC CSEP Clinical Practice Guideline . No 367, November 2018. J Obstet Gynaecol Can 2018:40:1528 1537. Mount Sinai Hospital. First trimester combined screening program.|lnlernel| Toronto: Sinai Health: c 2018 |cited 2020 Jun 22'. Available from: http:/ / womcnsandlnfanlshealth.ca /tesls / fir st liimester combinedscreening-ltsl Nicolaides KH Syngelaki A Ashoor G et al. Nonmvasive prenatal testing for fetal trisomies in a routinely screened first- trimester population.Am J Obstet Gynecol 2012:207:374. North YorkGeneral Hospital Genetics Program. Integrated prenatal screening.1999. Ordean A. WongS Graves L.Substance use in pregnancy. SOGC Practice Guideline, Ho 349 October 2017. J Obstet Gynaecol Can 2017;39:922-37.e2. Otlinyer WS, Menara MK Brost BC. Arandomized control trial of prostaglandin E2 intracervkal gel and a slow release vaginal pessary for preindudion cervical ripening. Am J Obstet Gynecol 1998;179:349 -353. Park CK Isayama T McDonald SO. Antenatal corticosteroid therapy before 24 weeks of gestation: a systematic review and meta - analysis. Obstet Gynecol 2016;127:715 - 725. PetkcrC Goldberg JD EI -SaycdYY etal Methods for eslimating the due dale AC 0G Committee Opinion No 700 May 2017. Obstet Gynecol 2017;129( 5):e150 c154. Prevention and Management ol Postpartum Hemorrhage. SOGC Clinical Practice Guidelines No. 88 April 2000. Revicky V Muralidhai A Mukhopadhy S et al. A case series of uterine rupture: lessons to be learned ior future clinical practice J Obstet Gynecol India 2012:62:665 -673. Robert M Ross S Conservative managemenlol urinary incontinence. SOGC Practice Guideline No 196 Oecember 2006.J Obstet Gynaecol Can 2018:40:e119- e125. Roberts 0 Brown J. Ned ley N et al.Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane OB Syst Rev 2017:3 X0004454. SitO Rothschild AJ Yfisner KL.A review of postpartum psychosis.J Womens Health (Larchmt|2006:15:352-368. SchragSJ Zell ER, Lynfiefd R. etal.A population-based comparison of strategies to prevent earty- onset group Bstreptococcal disease in neonates. NEJM 2002:347:233 -239. Schuurmans N Gagne G Ectat A, el al. Healthy beginnings: guidelines lor care during pregnancy and childbirth. SOGC Clinical Practice Guideline No 71 Oecember 1998. J Obstet Gynaecol Can 1998. Schuurmans N MacKinnon C lane C et al Prevention and management of postpartum hemorrhage SOGC Clinical Practice Guidelines Ho 88 April 2000. J Obstet Gynaecol Can 2000:22:271 281. Sharma 0, Shastri S Sharma P. Intrauterine giowth restriction: antenatal and postnatal aspects Clin Med Insights Pediatr 2016:10:67 - 83 Skoll A Boutin A Buiold E et al. Antenatal corticosteroid therapy for improving neonatal outcomes. SOGC Practice Guideline No 364, September 2018. J Obstet Gynaecol Can 2018:40:1219 1239 Society for Maternal - Fetal Medicine Simpson LL. Twin - twin transfusion syndrome. SMFM Clinical Guideline Am J Obstet Gynecol 2013:208:3- 18. Society of Obstetricians and Gynaecologists of Canada (Internet!. Ottawa ( Canada): The Society:c1994 [ cited 2020 Jun 22]. Available from: www.sogc.org. SOGC Clinical Practice Guideline.Immunization in Pregnancy. 2009: 236:1086 -1092. Soma - Pi Jay P Nelson -Piercy C, Tolppanen H. et al. Physiological changes in pregnancy.Cardiovasc J Afr. 2016;27:89 - 94. Soma Pillay P Nelson-Piercy C Tolppanen H. Mebazaa A. Physiological changes in pregnancy: review articles. Cardiovascular journal of Africa. 2016:27(2):89- 94. Statistics Canada. Table 13 -10 0395 - 01 leading causes of death, infants (Internet ]: c 2022 [cited 2022 Jun 20'. Available from: https:// www150.statcan.gc.ca /t1/lblVen/ tv.aclion7pid -1310039501. Staykova SY Slancva R StamenovG ctal. Preimplantation genetic testing: method and two case studies ol familial three - way complex translocations. Biolechnol Biolcchnot Equip 2019:33:1663 1670. StecrP FlintC Physiology and managemenlol normallabour. 8MJ 1999:318:793 - 796. Steer P Flint C Preterm labour and premature rupture olmembranes BMJ 1999: 318:1059 1062. Stewart 0. A broader context for maternal mortality CMAJ 2006:74:302- 303. Stewart DL. Barfield WD. Updates on an at-risk population: late - preterm and early - term infants. Pediatrics 2019:144e 20192760. Stewart JO Rayburn WF, Farmer KC etal. Effectiveness of prostaglandin E2 intracervical gel (pcepidil) with immediate oxytocin vs.vaginal insert (cervidil) for induction of labour.Am J Obstet Gynecol 1998;179:1175-1180. Van den Hoi M. Crane J.Ultrasound cervical assessment in predicting preterm birth. SOGC Clinical Practice Guideline No 102 May 2001. J Obstet Gynaecol Can 2001;35:418 - 421. Verani JR McGeel Schrag SJ Prevention of perinatal group B streptococcal disease. MMWR Recomin Rep 2010:59:1- 36. Wilson RD Audibert F Brock JA et al. Pre - conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic add sensitive congenital anomalies SOGC Clinical Practice Guideline No 324 May 2015. J Obstet Gynaecol Can 2015:37:534 - 552. Zander L Chamberlain G. ABC of labour care: place of birth. BMJ 1999:318:721- 723.

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Ophthalmology Michael Balas, Josh Herman , and Michelle Lim , chapter editors Vrati M Mehra and Chunyi Christie Tan , associate editors Arjan S Dhoot, EBM editor Dr Asim AH, Dr. VVat Ching Lam, and Dr. Jonathan Micieli, staff editors

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Acronyms

OP2

Basic Anatomy Review Differential Diagnoses of Common Presentations Loss of Vision Red Eye Ocular Pain Floaters Flashes of Light (Photopsia) Photophobia (Severe Light Sensitivity) Diplopia (Double Vision) Ocular Problems in the Contact Lens Wearer

.

Ocular Emergencies

The Ocular Examination

OP2 ,

OP3

OP5 OP5

.OP7

Optics The Orbit Globe Displacement Preseptal Cellulitis Orbital Cellulitis

.

Lacrimal Apparatus Dry Eye Syndrome (Keratoconjunctivitis Sicca) Epiphora (Excessive Tearing) Dacryocystitis Dacryoadenitis

OP9

OP10

Lids and Lashes Lid Swelling Ptosis Trichiasis Entropion Ectropion Flordeolum (Stye) Chalazion Blepharitis Xanthelasma

OP12

Conjunctiva Pinguecula Pterygium Subconjunctival Hemorrhage Conjunctivitis

OP14

Sclera Episcleritis

OP16

Sderitis Cornea Foreign Body Corneal Abrasion Recurrent Erosions Corneal Ulcer Herpes Simplex Keratitis Herpes Zoster Ophthalmicus

OP17

Keratoconus Arcus Senilis Kayser-Fleischer Ring The Uveal Tract Uveitis

OP20

Lens Cataracts Dislocated Lens (Ectopia Lentis)

OP 21

.

Vitreous Posterior Vitreous Detachment Vitreous Hemorrhage Endophthalmitis and Vitritis

OP22

Retina Central/Branch Retinal Artery Occlusion Central/Branch Retinal Vein Occlusion Retinal Detachment Retinitis Pigmentosa Age-Related Macular Degeneration

OP23

Glaucoma Primary Open-Angle Glaucoma Normal Tension Glaucoma Secondary Open-Angle Glaucoma Primary Angle-Closure Glaucoma Secondary Angle- Closure Glaucoma

OP26

Pupils Pupillary Light Reflex Pupil Abnormalities Dilated Pupil (Mydriasis) Constricted Pupil (Miosis) Relative Afferent Pupillary Defect

OP29

Malignancies Lid Carcinoma Uveal Melanoma Metastases

OP33

Ocular Manifestations of Systemic Disease HIV/ AIDS Other Systemic Infections

OP33

Diabetes Mellitus Hypertension Multiple Sclerosis Transient Ischemic Attack /Amaurosis Fugax Graves’ Disease Connective Tissue Disorders Giant Cell Arteritis/Temporal Arteritis Sarcoidosis

.OP37

Paediatric Ophthalmology Strabismus Amblyopia Leukocoria Retinoblastoma Retinopathy of Prematurity Nasolacrimal System Defects Ophthalmia Neonatorum Congenital Glaucoma

Ocular Trauma Blunt Trauma Penetrating Trauma Hyphema Blow- Out Fracture Chemical Burns

OP41

Ocular Drug Toxicity

OP43

Common Medications

OP44

Landmark Ophthalmology Trials

OP46

References

OP48

rn

+ OP 1 Ophthalmology

Toronto Notes 2023

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Toronto Notes 2023

0P2 Ophthalmology

Acronyms anterior ischemic optic neuropathy age - related macular degeneration best- corrected visual acuity branch retinal artery occlusion branch retinal vein occlusion cup - to- disc ratio

AJON

AMD BCVA BRAO BRVO CDR CMV CRAO CRVO D DR

cytomegalovirus

central retinal artery occlusion central retinal vein occlusion diopter diabetic retinopathy

EBV EOM FML GAT GCA GPA GPC HRT INO I0L IOP

Epstein- Barr virus extraocular movement fluorometholone Goldmann applanation

laser - assisted in situ keratomileusis MS multiple sclerosis optical coherence tomography OCT ocular hypertension OHT tonometry PACG giant cell arteritis primary angle-closure glaucoma proliferative diabetic retinopathy granulomatosis with polyangiitis PDR photodynamic therapy PDT giant papillary conjunctivitis Heidelberg retinal tomography PERRLA pupils equal, round, and reactive internudear ophthalmoplegia to light and accommodation POAG primary open - angle glaucoma intraocular lens intraocular pressure PRK photorefractive keratectomy posterior vitreous detachment PVD

LASIK

rheumatoid arthritis relative afferent pupillary defect retinal detachment retinopathy of prematurity retinal pigment epithelium superficial punctate keratitis thyroid eye disease transient ischemic attack visual acuity vascular endothelial growth factor yttrium aluminum garnet

RA RAPO RD ROP RPE SPK TED TIA VA VEGF

YAG

Basic Anatomy Review Lateral View

.. -Tendon of superior rectus muscle

Superior View

.

Meibomiai gland

_

mi, .

^3»

1 Ciliary muscle

Jr

Retina

Eyelash. l

and body

.\Choroid 5

and body

Cornea-, Ciliary muscle Lens

Anterior chamber Iris Bulbar . conjunctiva

_ .

Tendon of lateral

k Sclera

A Tendon of medial

rectus muscle

rectus muscle

ens

,

Cornea

— Optic nerve Palpebral w conjunctiva

Bulbar

Ai

conjunctiva '

-4

'"W

Choroid

lyfCtinaTbloDd vessels CM

a

7

.Tendon of inferior rectus muscle

f

Retinal blood vessels

t>

Conjunctival fornix

Rgure 1. Anatomy of the eye

RETINAL LAYERS (10 ) 1. Inner limiting membrane 2. Nerve fibre layer

3. Ganglion cell layer

LIGHT RAYS

CELL TYPES - Vitreous humour Optic nerve fibres Ganglion cells

4. Inner plexiform layer

—Amacrine cells 5. Inner nuclear layer

- Bipolar cells

— Horizontal cells G. Outer plexiform layer

7. Outer nuclear layer

8. Outer limiting membrane 9. Photoreceptor

—Rod nuclei

—Cone nuclei Rod cells Cone cells

layer

10. Retinal pigmented epithelium

Figure 2. Layers of the retina

Pigmented cells

Bruch's membrane Choroid

*> Motion PhachanNa 2016. alter Sarah A. Kirn 2006 Activate Windows Go to Settings to activate Wind'

+

0P3 Ophthalmology

Toronto Xotcs 2023

Lacrimal gland Superior lacrimal punctum iuperior canaliculus nferior canaliculus

-

Meibomian JS ff 3 gland

Inferior lacrimal punctum

r

undus of lacrimal sac

Nasolacrimal duct Valve of Hasner Inferior concha

30

Figure 3. Tear drainage from the eye ( lacrimal apparatus)

Differential Diagnoses of Common Presentations Loss of Vision Loss of Vision I

i Transient

Chronic ( weeks to months )

Acute ( seconds todays )

( seconds to hours )

• TIA/

i

I

Vitreous/Relina/ Cornea/ Anterior Optic Nerve amaurosis Segment lugax • Corneal edema • Vitreous • Migraine • Hyphema hemorrhage with auia (blood in anteriot • RD chamber ) • Retinal artery/ vein occlusion • Acute angle-

closure

• Acute macular

glaucoma

lesion • Optic neuritis • GCA • AION

• Trauma/loreign body

i

Cortical/Other Cornea/Anterior Vitreous/Retina/ Cortical/Other Segment Optic Nerve • Occipital • Pituitary adenoma infarction/ • Corneal • AMO hemorrhage dystrophy/ • DR • Medication scarring/edema • Retinal vascular induced • Conical ( sildenafil, blindness * Refractive error insufficiency amiodarone) • Functional * Cataract * Compressive (non organic, * Glaucoma optic neuropathy • Nutritional (intracranial mass, deficiency diagnosis of exclusion) orbital mass) • Papilledema • Intraocular

-

-

neoplasm

* Retinitis pigmentosa

Figure 4. Loss of vision

Red Eye Table 1. Common Causes of Red Eye Common Causes

Lids/Orbit/ Lacrimal System Hordeolum /chalazion Blepharitis Entropion/ectropion Foreign body/laceration Dacryocystitis / da cryoadenitis

Cornea Foreign body (including contact lens) Keratitis Abrasion, laceration Ulcer

Conjunctiva /Sclera Subconjunctival hemorrhage Conjunctivitis Dry eyes Pterygium Episderitis/sderitis Preseptal/ orbital cellulitis

Anterior chamber Anterior uveitis (iritis, iridocyclitis) Acute glaucoma Hyphema ( blood in anterior chamber) Hypopyon (pus in anterior chamber )

Other Trauma Postoperative endophthalmitis Pharmacologic (e.g. prostaglandin analogues)

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OPl Ophthalmology

Table 2. Common Differential Diagnoses of Red Eye Conjunctivitis

Acute Iritis

Acute Glaucoma

Keratitis (Corneal Ulcer )

Discharge

Bacterial: purulent Viral: serousimucoid Allergic: mucoid

No

Pain

i

" (dull'achy)

"(nausea)

" (sharp)

Photophobia

No

Smaller Ciliary flush (peri-liobal)

fued mmid- dilation

Same or smaller Possible conjunctival

Blurred Vision

No

Pupil

Normal

Injection

Diffuse conjunctival

Clear

Bacterial:’purulent

Varies Conjunctival injection

injection

injection involving the bulbar conjunctiva for 360' •palpebral or tarsal conjunctiva

Cornea

Normal (subepithelial infiltrates in adenoviral conjunctivitis)

Iterate precipitates

Cloudy

Infiltrate, edema, and may have keratic precipitates

I0P

Normal

Varies

Increased markedly

Normal or slightly decreased

Anterior Chamber

Normal

*** CeOs and flare

Shallon

Cells and flare or normal, and may have hypopyon

Nausea and Vomiting

No

No

Other

Large, tender pre-auricular Posterior synechiae nodejs) if viral

No

Coloured haloes

Ocular Pain differentiate from eye fatigue (asthenopia ) ocular surface disease herpes zoster prodrome trauma /foreign body blepharitis keratitis corneal abrasion/ulcer acute glaucoma acute uveitis

scleritis episcleritis optic neuritis

Floaters • PVD (often secondary to age-related vitreous svneresis ) • vitreous hemorrhage • retinal tear/detachment • intermediate uveitis ( pars planitis )

• posterior uveitis ( chorioretinitis )

Flashes of Light (Photopsia) • PV D (often secondary to age - related vitreous svneresis ) • retinal tear /detachment •

migrainous visual aura

Photophobia (Severe Light Sensitivity) •

corneal abrasion , corneal ulcer

• keratitis • acute angle -closure glaucoma

r ~t

• iritis meningitis/encephalitis • migraine • subarachnoid hemorrhage ( SAH )

uJ

+

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0 P5 Ophthalmology

Toronto Notes 2023

Diplopia (Double Vision) Table 3. Common Causes of Diplopia Binocular Diplopia

Monocular Diplopia Definition

Occurs with both eyes open, eliminated with occlusion o ( either eye Decompensated congenital strabismus Ocular motor nerve dysfunction: III IV VI nerve palsy

..

Neuromuscular junction disease: myasthenia gravis, botulism

Occurs with one eye open , remains with occlusion of unaffected eye Causes Optical factors: refractive error / astigmatism

Mechanical process: dislocated lens, postoperative sequelae (cataract surgery , peripheral laser iridotomy ) Other: strands of mucus in tear film , keratoconus

.

Mechanical process: muscle reslriction /enlrapmcnl HD

Supranuclear causes: skew deviation , dorsal midbrain syndrome

Ocular Problems in the Contact Lens Wearer

Example 1

sc

• solution hypersensitivity • tight lens syndrome

V

• corneal abrasion • GPC/contact lens allergy

Example 2

• SPK from dry eyes • limbal stem cell deficiency • corneal neovascularization • sterile corneal infiltrates ( immunologic) • infected ulcers ( Pseudomonas , Acanthamoeba )

CF 3 yj HM

CC

Note: RIGHT EYE visual acuity always listed on top.

Ocular Emergencies

V SC CC 20/40 - 1

Vision Without correction With correction

CF

Counting fingers Hand motion

All except one letter of 20/40 20/80+2 All of 20/80 plus two letters of 20/70 PH Visual acuity with pinhole

These require urgent ophthalmology consultation for management

Sight-Threatening

lid laceration globe rupture chemical burn corneal ulcer gonococcal conjunctivitis

20/40 - 1 20/80 + 2 -» 20/ 25 PH

correction

HM

Figure 5. Ophthalmology nomenclature for visual acuity

acute iritis acute glaucoma

CRAO intraocular foreign body RD (especially when macula threatened ) endophthalmitis GCA Life-Threatening

• proptosis ( rule out cavernous sinus fistula or thrombosis ) • cranial nerve (CN ) 111 palsy with dilated pupil ( rule out intracranial aneurysm or externally compressive neoplastic lesion) • papilledema (elevated or increased 1CP workup) • orbital cellulitis • leukocoria: white pupillary reflex (absent red reflex: rule out retinoblastoma in children )

00 - oculus dexter - right eye OS - oculus sinister - left eye OU - oculus uterque both eyes

-

The Ocular Examination VISUAL ACUITY Visual Acuity - Distance • Snellen VA = smallest line patient can read on the chart at the testing distance ( usually 20 ft or 6 m ). e.g. 20/40 = what the patient can see at 20 feet away ( numerator ) is what a “ normal ” person can see at 40 feet away (denominator ) • distance VA should he tested with distance glasses on in order to obtain BCVA • testing hierarchy for low vision: Snellen VA ( 20/ x ) > counting fingers at a given distance (Cl' ) -> hand motion ( HM ) -> light perception with projection ( LP with projection ) -> light perception ( LP ) -> no light perception ( NLP)

Snellen VA of 20/20 equates fo "normar vision

ri LJ

Normal Infant and Child Visual Acuity Equivalent 6-12 mo: 20/120 1-2 yr: 20/80 2- 4 yr: 20/20

.

. .

+

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0P6 Ophthalmology

• minimum visual requirements to operate a non -commercial automobile in Ontario are: 20/ 50 BCVA with both eyes open and examined together, 120° continuous horizontal visual field , and 15° continuous visual field above and below fixation

Visual Acuity - Near

• use pocket vision chart ( Rosenbaum Pocket Vision Screener)

• record jaeger ( j) or Point Number and testing distance ( usually 30 cm ) e.g. J 2 QP 30 cm • conversion to distance VA possible (e.g. immobile patient, no distance chart available) Visual Acuity for Infants, Children, Non-English Speakers, and Dysphasics

• newborns

VA cannot be tested conventionally •3 mo-3 yr: can usually only assess visual function, not acuity test each eye for fixation symmetry using an interesting object normal function noted as “CSM " = central, steady, and maintained •3 yr until alphabet known • pictures or letter cards/charts such as HOTV or Sheridan-Gardiner test (children point to optotypes on a matching card )

m

Test pupils using an ophthalmoscope focused on the led reflex; this will provide a better view than using a penlight

4 Ps of Inspection Pu pit shape, size, symmetry Position: esotropia, exotropia, central Ptosis Primary nystagmus

tumbling “ E" chart COLOUR VISION

• test with Ishihara pseudoisochromatic plates • record number of correctly identified plates presented to each eye ( usually 14 plates) • important for testing optic nerve function and identifying an optic neuropathy (e.g. optic neuritis ) • note: red -green colourblindness is sex-linked and occurs in 7-10% of males VISUAL FIELDS

• estimation of visual field loss: test by confrontation ( 4 quadrants, each eye tested separately ) • accurate, quantifiable assessment: automated visual field testing ( Humphrey or Goldmann ) or Tangent Screen • AMD monitoring: Amsler grid (each eye tested separately) to check for central or paracentral scotomas ( blind spots ) and distortion •see Neurology, N 15 for visual field defects PUPILS • use reduced room illumination with patient focusing on distant, fixed object to prevent near reflex • examine pupils for shape, size, symmetry, and reactivity to light ( both direct and consensual

CF CF CF CF

jj

CF CF|

^

RIGHT EYE fields drawn on right side; LEFT EYE Helds drawn on left side ( as if seen through patient's eyes) CF Able to count fingers in specified quadrant with peripheral vision

W/. Gross visual field deficit in specified quadrant using peripheral vision

Figure 6. Ophthalmology nomenclature for visual fields by confrontation

response) • test for RAPD with swinging flashlight test, check by reverse RAPD test if one pupil is non - reactive • test pupillary constriction portion of near reflex by bringing object close to patient 's nose • “ normal " pupil testing often noted as PERRLA ( pupils equal, round , reactive to light and accommodation ) ANTERIOR CHAMBER DEPTH

•shine light tangentially from temporal side • if > 2 /3 of nasal side of iris in shadow > shallow anterior chamber • gonioscopy is the gold -standard for assessing anterior chamber depth The Van Herick Method (Slit- Lamp technique) shine thin -angled slit beam onto the peripheral cornea of each eye, view at a 60“ angle from the beam • estimate anterior chamber depth using the ratio of corneal slit beam thickness to the space between the posterior cornea and the iris

-

EXTRAOCULAR MUSCLES

Shallow

source &

Alignment

• Hirschberg corneal reflex test

examine in primary position of gaze ( i.e. straight ahead ) with patient focusing on distant object shine light into patient’s eyes from ~ 30 cm away • corneal light reflex should be at the same position on each cornea •strabismus testing as indicated (cover test, cover - uncover test , prism testing ) (see Strabismus , OP37)

Movement • examine movement of eyeball through six cardinal positions of gaze • identify if there is limitation of eye movement in each position of gaze • observe for horizontal, vertical, or rotatory nystagmus ( rhythmic, oscillating movements of the eye) • resolving horizontal nystagmus at end -gaze is usually normal

Figure 7. Estimation of anterior chamber depth

r

L

j

+

Diplopia •see Neurology, N 16

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0P7 Ophthalmology

Toronto Notes 2023

SLIT-LAMP EXAMINATION

SR 10

Ocular Adnexa

•lids, lashes, and lacrimal system

s

IRSO

Anterior Segment •conjunctiva /sclera

MR MR

\

'

/

SOIR

\

© Sherry H. Lai Z006

>

•cornea

-

•

fluorescein dye: stains de cpithelialized cornea; dye appears fluorescent green with cobalt blue Altered light • Rose Bengal dye: stains devitalized corneal epithelium; dye appears red •anterior chamber (cells, flare) and angle ( Van Herick method ) • iris/ pupil •lens (assess for cataract ) •anterior vitreous

Figure 8. Diagnostic positions of gaze for isolated primary actions of extraocular muscles

(§>

Extraocular Muscle Innervations

LR6 S04 AE3 Lateral Rectus via CN VI Superior Oblique via CNIV All Else via CN III (superior, medial, and inferior rectus, inferior oblique)

Posterior Segment (requires 78 D or 90 D lens)

•vitreous

•optic disc (colour, CDR ratio, sharpness of disc margin ) • macula ( 1.5 2 disc diameters temporal to disc), fovea ( foveal light reflex )

-

10 SR

\ / LR S0s: blurring of distance vision due to severely decreased accommodation Astigmatism

Light rays not refracted uniformly in all meridians due to non- spherical surface of cornea or non- spherical lens (e.g. football- shaped) Two types Regular - curvature uniformly different in meridians at right angles to each other Irregular - distorted cornea caused by injury, keraloconus (cone - shaped cornea), cornealscar or severe dry eye

-

.

Affects 30% of population with prevalence increasing with age Mild astigmatism unnoticeable Higher amounts of astigmatism maycauseblurryvision, squinting, asthenopia,or headaches

Myopia Correct with cylindrical lens (if regular ) Try contact lens (if irregular ) Refractive eye surgery

Hyperopia F - focal point

^ Figure 11. Emmetropia and refractive errors

.

Presbyopia

Structures Responsible for Refractive Power

Normal aging process If initially emmetropic, person Correct with positive begins to hold reading material dioptci/convcx / "plus" (» 40 yt) Hardening,1reduced farther away, but distance lenses for reading deformability of lens results vision remains unaffected in decreased accommodative If initially myopic, person ability removes distance glasses Accommodative power is 140 loread at age 10 diminishes to 3.50 If initially hyperopic, symptoms of presbyopia occur earlier by age 40 Near images cannot be focused onto the retina ( focus is behind the retina as in hyperopia )

• Cornea (2/3) • lens (1/3)

.

Anisometropia

Difference in refractive errors between eyes

Myopia corrected with negative diverging lens Second most common cause of amblyopia in children

_

r "i i J

Hyperopia corrected with positive converging lens F ^ focal point

+

Figure 12. Correction of refractive errors

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The Orbit

§

Globe Displacement Table 5. Exophthalmos (Proptosis) and Enophthalmos Exophthalmos ( Proptosis)

Enophthalmos

Definition

Anterior displacement (protrusion) of the globe Exophthalmos generally refers to an endocrine etiology or protrusion of >18 mm (as measured by a Nertel exophthalmometer) Proptosis generally refers to other etiologies (e.g. cellulitis) or protrusion of reduces risk of blindness intravitreal injection of corticosteroids or anti - VEGT for fovea - involved diabetic macular edema • macular photocoagulation laser for clinically significant macular edema ( when not involving centre of macula ) vitrectomy for non -clearing vitreous hemorrhage + tractional RD in PDR vitrectomy before vitreous hemorrhage does not improve the visual prognosis LENS CHANGES • earlier onset of senile nuclear sclerotic and cortical cataracts • may get hyperglycemic cataract due to sorbitol accumulation ( rare ) • changes in blood glucose levels ( poor control ) can suddenly cause refractive changes by 3 1 diopters due to induced osmotic changes of the lens

-

Aflibercept , Bevaciiumab , or Ranibiiumab for Diabetic Macular Edema : 2 Vear Result Irom a Comparative Effectiveness Random iicd Clinical

trial Ophthalmology 2016:123:1351 1359 All 3 anti -VEGF agents showed improvement of VA and decreased numbev of injections in yr 2. Among eyes mtb worse baseline VA aflibercept bad superior 2 yr VA compared with hevacuumab , butsuperiority over lambitumab in yr 1 was no longer identified.

-

Effects of Medical therapies on Retinopathy Progression in T 2 DM

OPTIC NEUROPATHY • VA loss due to infarction of optic disc/ nerve

REJM 2010 ;363:233-244 See tandmaik Ophthalmology Ihalstiblelor more information on Effects of Med cal Iberapies on Retinopathy Progression in I 20 M. which details

Inner limiting mumbrnno

whether intensive glycemic control. combination therapy for dyslipidenia and intensive blond pressure control can limit the progression of OR.

Flame shaped

.

hemorrhage

Ganglion cell layor

Inner ploxiform Inyor

-

.

EXTRAOCULAR MUSCLE PALSY

• usually CN 111 infarct • pupil usually spared in diabetic CN 111 palsy, hut ptosis is observed • may involve CN IV and VI • usually recover within a few months

Nerve fibre layer

Anti Vascular Endothelial Growth Factor loi Diabetic Macular Oedema: A Network Meta Analysis Cochrane DB Syst Rev 2018:10 0007419 Purpose: la compare the effectiveness and safety of the afferent anti - VEGF drugs using network meta analysis methods. Results : included 24 studies with 6007 patients with delete macular edema (DM £|ard noderate vision loss. Aftibercept. bevacejmab. hndianibiuimab were all more effective than laser therapyfor improving vision by 3 or move lines after one yr. Aflibercept may confer some advantage over ran buumab and hevacuumab. there were nodifferences in adverse events Conclusions: Anti - VEGF drugsaie effective at improving vision m people with 0ME with three to four in every 10 pe op le likely to evper ience an improvement of 3 or more lines VAat one yr. More evidence on the long - term (greater than two yr ] comparative effects of these anti VEGF agents is needed .

Cotton wool spots

Hypertension retinopathy

Inner nuclear layer Optic disc

Outor ploxiform layor Outer nuclear layor External limiting membrane Rod and cono outer sogmonts

Pigmontod epithelium

Dot and blot hemorrhage

Hard oxudate

Diabetes mcllitus retinopathy

Figure 24. DM vs . HTN retinopathy

l

L r1

Hypertension retinopathy is the most common ocular manifestation • acute HTN retinopathy: retinal arteriolar spasm, superficial retinal hemorrhage, cotton wool spots, •

+

optic disc edema • chronic HT N retinopathy: arteriovenous ( AV ) nicking, flame/dot / blot retinal hemorrhages, cotton wool spots • increases risk for many other ocular diseases ( DR, BRVO, CRAO/ BRAO)

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OP36 Ophthalmology

Table 10. Modified Scheie Classification Classification Grade 0

No changes

Grade 1

Mild arterial narrowing

Grade 2

Obvious arterial narrowing with local irregularities

Grade 3

Grade 2 ^ retinal hemorrhages andfor exudate

Grade 4

Grade 3 swollen optic nerve Imalignanl HIN|

Multiple Sclerosis • see Neurology, N55 Clinical Features • blurred vision and decreased colour vision secondary to optic neuritis • central scotoma due to damage to papillomacular bundle of retinal nerve fibres • diplopia secondary to 1 N 0 • RAPD, ptosis, nystagmus, uveitis, optic atrophy, optic neuritis • white matter demvelinating lesions of optic nerve on MR1 Treatment

Corticosteroids lorlreating Optic Neuritis Cochrane OB Syst Dev 201S ;8:CD 001430 S ummary : No conclusve evidence of benefit in ter ms ol recovery to normal VA visual held. « contrast sensitvity sm mo after Initiation of IV or oral corticosteroids. Results: After renew of 6 RCIs evaluating systemic corticosteroids for treatment of acute optic neuritis, all meta -analyses show sim ilar outcom es for placebo vs. corticosteroid group lor VA, contrast sensitivity,

.

and visual held .

• IV steroids with taper to oral form for optic neuritis

DO NOT treat with oral steroids in isolation due to increased risk of developing MS

Transient Ischemic Attack /Amaurosis Fugax • sudden , transient blindness from intermittent vascular compromise • ipsilateral carotid most frequent embolic source • typically monocular, lasting < 5-10 min

• Hollenhorst plaques (glistening microemboli seen at branch points of retinal arterioles) sometimes seen

Graves’ Disease • ophthalmopathy occurs despite control of thyroid gland status

• ocular manifestations occur mainly due to increased fibroblast proliferation and accumulation of hydrophilic glycosaminoglycans (mostly hyaluronic acid) in the extraocular muscles and orbital tissues

Clinical

• initial inflammatory phase is followed by a quiescent cicatricial phase

Treatment

• treat hyperthyroidism • monitor for corneal exposure and maintain corneal hydration • manage diplopia , proptosis, and compressive optic neuropathy with one or a combination of: steroids ( during acute phase) • orbital bony decompression • external beam radiation of the orbit • consider strabismus and /or eyelid surgical procedures once acute phase subsides

Connective Tissue Disorders

The most common cause of unilateral or bilateral proptosis in adults is Graves' disease

*

Progression of Signs and Symptoms of Graves' Ophthalmopathy NO SPECS No signs/ symptoms Only signs (lid retraction, lid lag) Soft tissue swelling (periorbital edema) Proptosis (exophthalmos) Extraocular muscle weakness (causing diplopia) Corneal exposure

Sight loss

• RA , juvenile idiopathic arthritis, SIT , Sjogren 's syndrome, ankylosing spondylitis, polyarteritis nodosa • most common ocular manifestation: dry eyes (keratoconjunctivitis sicca )

Giant Cell Arteritis/ Temporal Arteritis rt

• see Rheumatology, RH 22 Clinical Features • more common in women > 60 yr • sudden loss of vision, pain over the temporal artery, jaw claudication, scalp tenderness, constitutional symptoms, and PMHx of polymyalgia rheumatica • ischemic optic neuropathy or, less commonly, CRAO often preceded by transient monocular vision

loss

u

ESR in GCA/Temporal Arteritis Males >agc/2 Females >(age 10)/ 2

+

• very high risk of vision loss in contralateral eye if untreated

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OP37 Ophthalmology

Diagnosis

• CBC ( thrombocytosis), elevated ESR and CRP • temporal artery biopsy Treatment

• high dose corticosteroids to prevent further ischemic complications and improve systemic symptoms • if diagnosis of GCA is suspected clinically: start STAT treatment + perform temporal artery biopsy to confirm diagnosis within 2 wk of initial presentation

Sarcoidosis Clinical Features • granulomatous uveitis with large “ mutton fat” keratic precipitates and posterior synechiae • complications include glaucoma, cataracts, retinal hemorrhages, peripheral retina neovascularization,

and dry eye • neurosarcoidosis: optic neuropathy, oculomotor abnormalities, visual field loss Treatment

• topical/systemic steroids and mydriatics

Paediatric Ophthalmology Strabismus • ocular misalignment in one or both eyes, can be found in up to 3% of children •classification manifest (constant ) vs latent ( hidden ) alignment comitant (deviation equal in all positions of gaze, also known as non - paralytic or concomitant )

.

vs. incomitant (deviation worse in certain positions, also known as paralytic or restrictive) described in direction of deviation relative to the fixating eye • distinguish from pseudostrabismus ( prominent epicanthal folds, hypertelorism ) • complications: amblyopia, cosmesis

Heterotropia • manifest deviation •deviation not corrected by the fusion mechanism ( i.e. deviation is apparent when the patient is using both eyes)

Strabismus in children under 4 mo o< age sometimes resolves , particularly if the deviation is intermittent , variable , or

measures 24 h after open globe injury) increases risk for post traumatic endophthalmitis in the absence of an intraocular foreign body (IOFB) • If IOFB present, early vitrectomy and IOFB removal must be performed within 24 h of injury • Extreme pain with hypopyon and vitritis indicate endophthalmitis until proven otherwise, and samples must be obtained for culture • Treat with empirical intravitreal and intravenous antibiotic guided by nature of trauma, and adjust based on culture

-

• sleep with head upright

• may need surgical drainage if hyphema persists or if re-bleed Complications • risk of re-bleed highest on day 2 -5, and may result in secondary glaucoma , corneal staining, and iris necrosis

• never prescribe Aspirin* (increases risk of re- bleed )

Blow- Out Fracture

.see Plastic

Surgery, PL34

Definition • blunt trauma causing fracture of orbital floor and herniation of orbital contents into maxillary sinus •orbital rim remains intact •inferior rectus and /or inferior oblique muscles maybe incarcerated at fracture site

Shaken Baby Syndrome Syndrome of findings characterized by absence of external signs of abuse with respiratory arrest seizures, or coma. Ocular exam findings are important diagnostically for Shaken Baby Syndrome These findings include extensive retinal and vitreous hemorrhages that occur during the shaking process and are extremely rare in accidental trauma. A detailed fundoscopic exam or an ophthalmology referral should be conducted for all infants in whom abuse is suspected.

.

•infraorbital nerve courses along the floor of the orbit and may be damaged

Clinical Features •pain and nausea at time of injury •diplopia, restriction of EOM

•infraorbital and upper lip paresthesia or anesthesia (CN V 2 ) •enophthalmos (sunken eye) and periorbital ecchymosis

-

Classic Signs of Blow Out Fracture • Enophthalmos • Decreased upgaze (inferior rectus trapped)

• Cheek anesthetized (infraorbital

nerve trapped )

L J

Investigations •CT: anteroposterior and coronal view of orbits

+

Treatment •avoid coughing, blowing nose, and Valsalva maneuvers •systemic antibiotics may be indicated •surgery if fracture > 50% orbital floor, diplopia not improving, or enophthalmos >2 mm

• may delay surgery if the diplopia improves

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OP13 Ophthalmology

Chemical Burns •alkali burns have a worse prognosis than acid burns because acids coagulate tissue and inhibit further

corneal penetration • poor prognosis if cornea opaque , likely irreversible stromal damage •even with a clear cornea initially, alkali burns can progress for weeks - thus, very guarded prognosis Treatment • immediately irrigate with water or balanced saline solution ( BSS ) • irrigate with eyelids retracted in emergency department with IV drip to physiologic pH ( test with litmus paper) • swab upper and lower fornices to remove possible particulate matter •do not attempt to neutralize an acid with a base, or vice versa • topical antibiotics and patching • topical cycloplegics to decrease iris spasm ( pain ) and prevent secondary glaucoma (due to posterior

synechiae formation ) steroids ( prescribed by ophthalmologist ) to decrease inflammation , use for < 2 wk in the case of a persistent epithelial defect

• topical

Ocular Drug Toxicity Table 12 . Drugs with Ocular Toxicity Drugs

Corneal microdeposits and superficial keratopathy ( vortex keratopathy ) Rate: Ischemic optic neuropathy Pupillary dilation ( risk of angle closure glaucoma )

Amiodaronc

-

Atropine , benrtropine

.

Bisphosphonates ( Fosamax Actonol )

Inflammatory eye disease (iritis, sderilis, episcleritis)

Chlotoqulno , hydroxychloroquine

Bull's eye maculopathy Vortex keratopathy

Chlorpromazine

Anterior subcapsular cataract

Contraceptive pills

Decreased tolerance to contact lenses Migraine Optic neuritis Retinal vein occlusion Benign increase in ICP

Digitalis

Yellow vision Blurred vision

Ethambutol

Optic neuropathy

Halopcridol ( Haldol )

Indomethacin

Oculogyric crises Blurred vision Superficial keratopathy

Interferon

Relinal hemorrhages and cotton wool spots

Isoniaiid

Optic neuropathy

Nalidixic acid

Papilledema

Steroids

Posterior subcapsular cataract Glaucoma Papilledema (systemic steroids ) Increased severity of NSV infections (geographic ulcers) Predisposition to fungal infections

.

-

Sulfonamides NSAIDs Tamsulosin ( Flomax )

Stevons Johnson syndrome

Tetracycline

Papilledema (associated with pseudotumour cerebri )

Thioridazine

Pigmentary degeneration ol retina Relinal deposition with macular sparing, peripheral visual field loss

Vigabatrin

Vitamin Atoxicity Vitamin D toxicity

Intraoperative floppy iris syndrome (can complicate cataract surgery)

Papilledema

Band keralopalhy

ri

LJ

+

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OP 11 Ophthalmology

Common Medications TOPICAL OCULAR DIAGNOSTIC DRUGS

Fluorescein Dye • water-soluble orange-yellow dye • green under cobalt blue light (ophthalmoscope, slit lamp ± applanation tonometry ) • absorbed in areas of epithelial loss ( ulcer , abrasion , laceration ) • stains mucus, contact lenses, foreign bodies

-

Rose Bengal Stain • stains devitalized epithelial cells and mucus to indicate tear film abnormalities (e.g. mucin deficiency)

Anesthetics

.

• e g. proparacaine HC10.5%, tetracaine 0.5%

• indications: removal of foreign body and sutures, tonometry, and examination of painful cornea • toxic to corneal epithelium ( inhibit mitosis and migration ) and can lead to corneal ulceration and scarring with prolonged use, therefore NEVER prescribe

Mydriatics • dilate pupils • two classes

cholinergic blocking (e.g. tropicamide - Mvdriacyl*) dilation plus cycloplegia (loss of accommodation ) by paralysis of iris sphincter and the ciliary body indications: refraction, ophthalmoscopy, therapy for iritis • adrenergic stimulating (e.g. phenylephrine HC) 2.5%) stimulate pupillary dilator muscles, no effect on accommodation usually used with tropicamide for additive effects side effects: HTN, tachycardia, arrhythmias Table 13 . Mydriatic Cydoplegic Drugs and Duration of Action Duration of Action

Drugs tropicamide (Mydriacyl ) 0.5%, 1%

45h

Cydopentolate HCI 0.5%,1%

3-6 h

-

3 -7 d

HomatropineHBr 1%, 2%

.

.

Atropine sulfate O S% 1%

1- 2 wk

Scopolamine H Bi 0 25%, 5%

1- 2 wk

GLAUCOMA MEDICATIONS Table 14 . Glaucoma Medications Drug Category

Dose

Effect

Comment/Side Effects

o- Agonist a2 -selcctivc • brimonidine 0.2 % (Alphagan I • apradonidine 0.5% (lopidine - )

1 git 0S /0D BID/ tID

Non selective: reduced aqueous production * increased TM outflow Selective:reduced aqueous production * increased uveosderal outflow

Non - selective: mydriasis,macular edema, tachycardia Selective: contact allergy, hypotension/ apnea in children

P - Blockcr Non- sclcctive • timolol (Ilmoptic 'l • levobunolol ( Bclagan |

1 gtt 0S / 0 D once dailyl8 IO

p 1- sclectivc

• belaxolol ( Betoptic

Reduced aqueous production

Bronchospasm (caution in

asthma / COPD) Increased CNF Bradycardia, hypotension, depression, heart block,

)

impotence

Carbonic Anhydrase Inhibitor • doreolamide ( Trusopt ) • briniolamidc |Aiopl '| • oral: ucetaiolamide (Dianio * ) methacolamide (Neptaiane )

1 gtt OS ,’0 D 1ID Diamo« : 500 mgP0 BID

Parasympathomimetic (cholinergic stimulating) • pilocarpine (Pilopine ) • carbachol (Isopto Carbachol )

1- 2 gits OS / OD TIDJOIO

Prostaglandin Analogues • latanoprost ( Xalatan ) • travaprost ( Travatan: ) • bimatoprost (Lumigan1)

1 gtt 0S /0D OHS

Reduced aqueous production

Must ask about sulfa allergy Generally local side effects with topical preparations Oral: diuresis, laliguc paresthesia, Gl upset

Ophthalmic Drop Cap Colours Cholinergics Red Anticholinergics White Anesthetics, antibiotics artificial tears, steroids (3-blockers Yellow (3- blocker combinations Blue Purple a-agonists Prostaglandins Teal Orange Carbonic anhydrase inhibitors Fluoroquinolones Tan Grey NSAIDs Anti-inflammatories, Pink steroids

Green

.

.

.

-

Increased TM outflow

-

-

Increased uveosderal outflow (uveosderal responsible for 20% of drainage)

Miosis Reduced night vision Increased Gl motility, brow ache, headache Reduced heart rale

rT LJ

Iris colour change Periorbital skin pigmentation Lash growth Conjunctival hyperemia

+

Cosopt = timolol douolamide; Xalacom = timolol lantanoprost: Combigan * = timolol brimonidine; DuoTrav = timolol travaprost: gtt = drop, gtts drops

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OP 15 Oplnhalmology WET AGE- RELATED MACULAR DEGENERATION MEDICATIONS

VEGF Inhibitors (Anti-VEGF) • anti-VEGF agents prevent ocular angiogenesis and development of choroidal neovascularization • administered via intravitreal injections • aflibercept ( Eylea*) is a VEGF “ trap" agent that binds VEGF A, B, and placental growth factor • ranihizumab ( Lucentis*) is a monoclonal l ab fragment and non selective anti VEGF agent • brolucizumab ( Beovu* ) is a humanized monoclonal single- chain variable fragment antibody directed

- -

-

-

against human VEGF A • bevacizumab (Avastin*) is recombinant humanized monoclonal IgG antibody and non -selective antiVEGF agent • FDA approved only for treatment of metastatic breast cancer, colorectal cancer, and non small cell lung cancer; therefore, its widespread ophthalmologic use is off label

-

-

Intravitreal Bevacizumab vs . Ranibizumab for Treatment of Neovascnlar Age - Related Macular Degeneration: findings from a Cochrane Systematic Review Ophthalmology 2016; Q 1|:)0 W Summary: In 6 RCIsmth 2009 participants, there were no important differences in effectiveness or safety between bevacirnmob and ranibirnmab. despite a significant cost difference.

« -

-

Antiplatelet and Anticoagulant Drugs Do Not Affect Visual Outcome in Neovascular Age -Related Macular Degeneration in the BRAMD Trial

TOPICAL OCULAR THERAPEUTIC DRUGS

NSAIDs

• used for less serious chronic inflammatory conditions

• e.g. ketorolac ( Acular*), diclofenac ( Voltaren* ), nepafenac ( Nevanac* ) drops Anti-Histamines

• used to relieve red and itchy eyes, often in combination with decongestants

AmJ Ophthalmol 2018:187:130137 Summary : In 330 MVAMO patients receiving edbev bevacizumab or ranibtnunab treatment, use o! anti-coagulantand anti-platelet agents was not associated with visual decline or occurrence of ocular hemorrhages.

• sodium cromoglycate - stabilizes membranes • olopatadine ( Patanol*, Pataday * ) Decongestants

• weak adrenergic stimulating drugs (vasoconstrictor) • e.g. naphazoline, phenylephrine ( Isopto Frin*) • rebound vasodilation with overuse; rarely can precipitate angle closure glaucoma

-

Antibiotics

• indications: bacterial and hyperpurulent conjunctivitis, corneal abrasions and ulcers, endophthalmitis, keratitis, blepharitis, globe rupture, cellulitis, lacrimal sac, and lacrimal gland

infections • commonly as topical drops or ointments, may give systemically • e.g. sulfonamide (sodium sulfacetamide, sultisoxazole), aminoglycosides (gentamicin ( Garamycin* ), tobramycin (Tobrex*)), erythromycin, tetracycline, bacitracin, polymyxin B, fluoroquinolones

(ciprofloxacin (Ciloxan*), ofloxacin (Ocuflox*), moxifloxacin ( Vigamox*), gatifloxacin ( Zymar*))

Corticosteroids

• e.g. fluorometholone (FML*), betamethasone, dexamethasone (Maxidex*), prednisolone ( Predsol* 0.5%, Pred Forte* 1% ), rimexolone ( Vexol*), loteprednol etabonate 0.5% ( Lotamax*), and difluprednate ( Durezol*) • primary care physicians should avoid prescribing topical corticosteroids due to risk of glaucoma, cataracts, and reactivation of HSV keratitis complications • potentiates HSV keratitis and fungal keratitis as well as masking symptoms increased 10P, more rapidly in steroid responders (within weeks) • posterior subcapsular cataract (within months )

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Toronto Notes 2023

OP 16 Ophthalmology

Landmark Ophthalmology Trials Trial Name

Reference

Clinical Trial Details

AGE -RELATED MACULAR DEGENERATION

AREDS 2

JAMA 2013:3091191:2005 - 2015

Title: lutein Tcaxanlhin and Omega - 3 fatly Adds lor AMO: The Age - Related Eye Disease Study 2 ( AREDS2) Randomired Clinical Trial Purpose: to determine whether adding lutein * zeaxanthin. OHA EPA or both to the AREDS formulation (vitamins C and E. 3 - carotene, zinc,and copper) decreases the risk of developing advanced AMD and lo evaluate the effect of eliminating 3 carotene, lowering zinc doses, or both in the AREDS formulation. Methods: Patients at risk for progression to advanced AMD were randomized to receive lutein * zeaxanlhrn DHA * EPA. lutein •zeaxanthin and DHA EPA, or placebo, In addition lo taking the AREDS formula. Results: Comparison with placebo (ARE 0 S formula alone) in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD. There was no apparent effect of 3- carotene elimination or lower- dose zinc on progression lo advanced AMD. More lung cancers were noted in the 3 carotene, mostly in former smokers. Conclusions: Addition of lulein'zeaxanthin OHA EPA, or both lo the AREDS formulation did not further reduce risk

.

-

.

-

.

’

of progression to advancedAMD. Because ol the potential increased incidence of lung cancer with high doses of 3- carotene, Iutein 112* in diameter

IV

Frosion of cartilage down to bone

Treatment • individualized • patient factors (age, skeletal maturity, activity level, etc.)

• defect factors ( Outerbridge Classification, subchondral bone involvement, etc.) • non operative • rest, COX2 inhibitors, NSAIDs, bracing, physiotherapy, intra -articular corticosteroids • operative • microfracture, osteochondral grafting ( autograft or allograft ), autologous chondrocyte implantation

-

Orthopaedic X-Ray Imaging General Principles - “Rule of 2s” • x- ray 1 joint above and 1 below • obtain at least 2 orthogonal views ± specialized views • 2 sides, as needed for comparison When reading a radiograph consider

• open or closed fracture ( air/gas seen in the soft tissue) • the view • anatomical location • laterality ( right vs. left ) • skeletally mature vs. immature • intra-articular vs. extra-articular

Sample radiograph description: “There is a simple transverse fracture of the proximal right humerus diaphysis. There is 1cm of shortening. The distal fragment is medially angulated 70 degrees"

• joint congruent, subluxed or dislocated • rotation • angulation

• displacement • shortening Table 5. Orthopaedic X- Ray Imaging Site

Injury

X- Ray Views

Shoulder

Anterior dislocation Posterior dislocation AC separation

AP Axillary t stress mew with 10 lb in hand Trans-scapular Tanca view (10-15 cephalic tilt)

Arm

Humerus A

AP Lateral

Elbow/Forearm

Supracondylar A Radial head A

AP Lalecal

Monteggia A Nightstick A Galeazzi A

Wrist

Colies' A Smith A Scaphoid A

AP

lateral Clenched Fist (foe scaphotunate dissociation)

Pelvis

Pelvic A

AP pelvis Inlet and outlet views Judet mews (obturator and iliac oblique for acetabular A )

Hip

Femoral head 'neck A Intertrochanteric A Arthritis SCFE FAI

AP lateral Frog-leg lateral Ounr False profile

Knee

Knee dislocation Femur /tibia A Patella A Patella dislocation Patella femoral syndrome

AP standing,lateral Skyline (tangenbal new with knees flexed at 45° to see patellofemoral joint)

Leg

Tibia shaft A Fibula shaft A

AP lateral

Developmental dysplasia of the hip ( DDH|

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0R9 Orthopaedic Surgery

Table 5. Orthopaedic X- Ray Imaging

-

Site

Injury

X Ray Views

Ankle

Ankle S

AP Lateral Mortise view (ankle at 15° of internal rotation)

Talar t Calcaneal t

Foot

MTI lisftanc injuries Spine

Compression i

Burst t Cervical spine A

AP lateral Oblique lateral. Karris, anal AP spine AP odontoid lateral Oblique Swnmmec'jnew (lateral view with arm abducted 180' to evalua te C7- I1 junction if lateral view is inadequate ) lateral Reuorv’eilension new: evaluate subluxation of cervical vertebrae

Orthopaedic Emergencies Trauma Patient Workup Etiology • high energy trauma (e.g. MVC, fall from height ) • may be associated with spinal injuries or life-threatening visceral injuries Clinical Features • comminuted, open fractures with significant soft tissue injury • local swelling, tenderness, deformity of the limbs, and instability of the pelvis or spine • decreased level of consciousness, hypotension, hypovolemia • consider involvement of EtOH or other psychoactive substances Investigations • trauma survey ( see Emergency Medicine. ER2 ) • x- rays: lateral cervical spine, AP chest, AP pelvis, AP and lateral of all bones suspected to be injured CT is also utilized to inspect for musculoskeletal injuries in the trauma setting • other views of pelvis: AP, inlet, and outlet; )udet views for acetabular fracture ( see Table 19, OR30 )

Treatment • ABCDEs: initiate resuscitation for life- threatening injuries ( ATLS protocol ) • assess genitourinary injury ( rectal exam / vaginal exam mandatory ) • external or internal fixation of all fractures • if patient unstable then Damage Control Orthopaedics - use of external fixation for fractures initially and then bring patient back to OR for definitive fixation (1M nail or OR1E ) once hemodynamically

stable • DVT prophylaxis once stable Complications

-

• hemorrhage - life threatening ( may produce signs and symptoms of hypovolemic shock ) • fat embolism syndrome - SOB, hypoxemia, petechial rash, thrombocytopenia, and neurological symptoms • venous thromboembolism - DVT and PE • bladder/ urethral/ bovvel injury • neurological and vascular damage • persistent pain /stiffness/ limp/ vveakness in affected extremities • post traumatic OA of joints with intra -articular fractures • sepsis and /or tetanus infection especially if missed open fracture

Orthopaedic Emergencies

VON CHOP Vascular compromise Open fracture Neurological compromise/cauda equina syndrome Compartment syndrome Hip dislocation Osteomyelitis/septic arthritis Unstable Pelvic fracture

Controversies in Initial Management of Open Fractures Scar,dJSurg 2014;103( 2):132-137 Study: Literaturereview exam icing the initial management of open fractures. 40 studies ir.duded. Findings: • A first -generation cephalosporin ( or clindavlyda} should be administered upon arnvaL In general. 24 h of antibiotics after each debridement is sufficient to reduce infection rates. •Although cultures ate taken from delayed (»24 h| or infected injuries, it may not be necessary to routinely take post -debridenent cultures open fractures. • Open fractures should be debrided as soon as possible , although the '6 h rule' is not generally valid. • Wo undo should be closed w.thi.n 7 d once soft tissue has stood red and all non - nob e tissue removed . • Negative pressure wound therapy ( HPWT) has been shown to decrease infectkm totes in open

froctores.

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ORIO Orthopaedic Surgery

Open Fractures • fractured bone and hematoma in communication with the external or contaminated environment Emergency Measures

• ABCs, primary survey, and resuscitate as needed • remove obvious foreign material once in a controlled hospital environment • irrigate with normal saline if grossly contaminated • cover wound with sterile dressings • immediate IV antibiotics • tetanus toxoid or immunoglobulin as needed (see Plastic Surgery. PL28) • N PO and prepare for OR ( blood work, consent, ECC>, CXR) operative irrigation and debridement within 6 8 h to decrease risk of infection OKI I traumatic wound may be left open to drain with vacuum assisted closure if necessary re examine with repeat irrigation and debridement in 18 h if necessary

-

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-

-

Table 6. Gustilo Classification of Open Fractures Gustilo Grade

Length of Open Wound

Description

Prophylactic Antibiotic Regimen

I

«1 cm

Minimal contamination and soft tissue injury Simple or minimaly comminuted fracture

First generation cephalosporin (cefa zolin) 2 g IV q8 h for 2 d If allergy use clindamycin 300 mg IV q8 h If MRSA positive use vancomycin 15 mgi'kg IV q12 h

Moderate contamination Moderate soft tissue injury

As per Grade I

II

1-10 cm

III*

>

10 cm

33% of patients with open fractures have multiple injuries

Antibiotic Prophylaxis in the Management of Open Fractures J8JS Reviews: 2019 Feb:7(2|:e1 Purpose: Provide current practice recommendations on prophylaxis for patients with open fractures of the extremities Methods: Systematic survey of plications from January 200) to June 201),andsearch of WohdCat for textbooks and websites for institutional guidelines. Results: Most recommendationssuggested Cram - positive antibiotics up to 3 d postxnjury for less severe injuries. For more severe injr es. most recommendations included broad spectrum anti biotics for 2-3 d. A s well,most sources

.

recommend immediately administration of

antibiotics. Conclusions: Current practice recommendations supportear lysystemx prophylaxis for patents

with open fractures of the extremities. However, differences are seen across antibiotic regimens, doses, and duration of administration.

IIIA:Extensive soft tissue mjury with adequate First generation cephalosporin (cefazolin) for 2 ability of soft tissue to cover wound d plus Gram - negative coverage Igentamidn or IIIB:Extensive soft tissue injury with periosteal ceftriaxone) for at least 3 d For soil or fecal contamination, metronidazoleis stripping and bone exposure: inadequate soft tissue to cover wound added for anaerobic coverage r penicillin G NIC: Vascular injury- compromise If MRSA positive use vancomycin 16 mgi'kg IV q12 h

.

.

'Any high energy,comminuted fracture,shot gun tarmysnt soil water contemirstjor exposure to oral flora,or fracture >8 hold is immediately classified as Grade III

Cauda Equina Syndrome

.

• see Neurosurgery NS32

Compartment Syndrome • increased interstitial pressure in an anatomical compartment (forearm , calf ) where muscle and tissue are bounded by fascia and bone ( fibro-osseous compartment), with little room for expansion • interstitial pressure exceeds capillary perfusion pressure, leading to irreversible muscle necrosis ( in 4-6 h ) and eventually nerve necrosis

Etiology • intracompartmental

• fracture ( particularly tibial shaft or paediatric supracondylar and forearm fractures) • reperfusion injury, crush injury, or ischemia

• extracompartmental: constrictive dressing (circumferential cast ), poor position during surgery,

Most important sign is increased pain

with passive stretch. Most important symptom is pain out of proportion to

injury

circumferential burn

Increased pressure from blood and intracompartmental swelling"

*

1

*

Decreased venous drainage Transudation into tissue Decreased lymphatic drainage surrounding compartment Intracompartmental pressure greater than perfusion pressure

Acidosis 4-

Muscle and nerve anoxia

Figure 8. Pathogenesis of compartment syndrome

Leaky basement

membranes

^

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Musc and nerve necrosis

^

"

5 Ps of Compartment Syndrome Pa in: out of proportion for injury and not relieved by analgesics • Increased pain with passive stretch of compartment muscles Pallor: late finding Paresthesia Paralysis: late finding Pulselessness: late finding

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0R11 Orthopaedic Surgery

Toronto Notes 2023

Clinical Features

• pain out of proportion to injury ( typically first and most significant symptom ) • pain with active contraction of compartment • pain with passive stretch ( most sensitive sign ) • swollen, tense compartment • suspicious history • 5 Ps: late sign - do not wait for these to develop to make the diagnosis!

Plain Film Findings of Osteomyelitis • Soft tissue swelling • Lytic bone destruction" • Periosteal reaction (formation of new bone, especially in response to •)"

-

'Generally not seen on plain films unU 10 12 d after

onset olinlection

Investigations • compartment syndrome is a clinical diagnosis; investigations usually not necessary • in children, unconscious patients, or associated peripheral nerve injury where clinical exam is unreliable, compartment pressure monitoring with catheter ( normal = 0 mmHg; elevated >30 mmHg or [dBP - measured pressurej 80 yr), prosthetic joint, recent joint surgery, skin infection / ulcer, IV drug use, recent intra articular corticosteroid injection, immunocompromised ( cancer, DM , alcoholism , RA )

-

used to monitor response to therapy

Docs This Adult Patient Have Septic Arthritis? JAMA 2007:297(13|:1478 -t488 Purpose: To review the accuracy and pretss:- of : e clinical evaluatin'! for the diagnosis of nongrscocca bacterial arthritis. Methods: Devew of t4 studies me hiling 6242 patients of which 653 had positive srnov a: cu tire (gold standard diagnostic tnol forseptx afnts). Results: Age, diabetes nelStos. rbearztod arthritis, joint surgery , hip or knee prosthesis, sc r infection , and human immunodeficiency eras type t infection significantly increase the proPati ity of septic arthritisJoint pain, history of joct swtfrg. and fever are found m >50 of cases. The presence ol inoeased WBC increases the Iiielzood rano for counts 25000/pL LR 2.9:95 0.2J 3.4: foe counts elOOOOOipL: IR. 2 B.0: 95 0, C.0-66.C|. A polymorphonuclear cell count of ?90 mueases oe IR of septic arthritis hy 3.4.* !e a PMI cel coat of 50000 with > 90% neutrophils, protein level >4.4 rng /dL, joint glucose level Posterior

.

shoulder

• Posterior hip > Anterior hip • The glenohumeral joint is the most commonly dislocated joint in the body since stability is sacrificed for

motion

Table 8. Anterior and Posterior Shoulder Dislocation Anterior Shoulder Dislocation (>90%)

Posterior Shoulder Dislocation (5 %)

Abducted externally rotated/hyperextended arm Blow to posterior shoulder Involuntary, usually Iraumalic; voluntary, atraumatic

Adducted, internally rotated, flexed arm

Symptoms

Pain, arm slightly abducted and externally rotated with inability to internally rotate

Pain,arm is held in adduction and internal rotation; external rotation is blocked

Shoulder Exam

" Squared off shoulder

Anterior shoulder flattening, prominent coracoid, palpable mass posterior to shoulder Positive posterior apprehension (“ jerk ") test: with patientsupine flex elbow 90° and adduct,internally rotate the arm while applying a posterior force to the shoulder;patient will “jerk* back with the sensation of subluxaton Note: the posterior apprehension test is used to test for recurrent posterior instability NOT lor acute injury

MECHANISM

FOOSK 3 Es (epilepticseizure. EtOH. electrocution) Blow to anterior shoulder

CLINICAL FEATURES

Positiveapprehension test : palientlooks apprehensive with gentle shoulder abduction and external rotation to 90” as humeral head is pushed anteriorly and recreates feeling of anterior dis' ocation Positive relocation test: a posteriorly directed force applied durmgthe apprehension test relieves apprehension since anterior subluxation is prevented Positive sulcus sign: presence of subacromial indentation with distal traction on humerus indicates inferior shoulder instability

.

.

These tests are more commonly used for chronic recurrent instability Neurovascular Exam

Including

Axillary nerve: sensory patch over deltoid and deltoid contraction Musculocutaneous nerve: sensory patch on lateral

. . . . 7. Humerus 8. Glenohumeral joint ,9. Scapula

1 Manubrium 2 Sternoclavicular joint 3 Clavicle 4. Coracoid process 5 AC joint 6. Acromion

Coracoid

Humeral head is anterior

Humeral head is posterior

Trans scapular 'Y° View

Humeral head is anterior to the center of the "MercedesBent "sign

Humeral head is posterior to center of "Mercedes- Bent * sign

AP View

Sub- coracoid lie of the humeral head is most common

Partial vacancy of glenoid fossa (vacant glenoid sign) and >6 mm space between anterior glenoid rim and humeral head (positive rim sign), humeral head may resemble a lightbulb due to internal rotation (lightbulb sign)

humeral head due to forceful impaction of an anteriorly dislocated humeral head against the glenoid rim Bony Bankart lesion: avulsion of the anterior glenoid labrum (with attached bone fragments) from the glenoid

-

rim

process

V

Axillary View

- Sachs lesion: compression fracture of posterior

§ e

Full Renovascular exam as per anterior shoulder dislocation

RADIOGRAPHIC FINDINGS

? Hill

er

Figure 9. Shoulder joints

forearm and biceps contraction

Hill -Sachs and Bony Bankart Lesions

:

t Reverse Hill

-Sachs lesion (75% of cases): divot in

anterior humeral head * Reverse bony Bankart lesion: avulsion of the posterior glenoid labrum from the bony glenoid rim

/

Acromion

2

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OR 13 Orthopaedic Surgery

Toronto Notes 2023

Table 8 . Anterior and Posterior Shoulder Dislocation

Bankart

Anterior Shoulder Dislocation (>90%)

Posterior Shoulder Dislocation (5%)

Closed reduction with IV sedation and muscle relaxation Traction - countertraction : assistant stabilizes torso with a folded sheet wrapped across the chest while the surgeon

Closed reduction with IV sedation and muscle relaxation Interior traction on a Hexed elbow with pressure on the back of the humeral head Obtain post -reduction x - rays Check post - reduction NVS Sling in abduction and external rotation x 3 wk followed by shoulder rehabilitation [dynamic stabilizer strengthening)

TREATMENT

applies gentle steady traction Stimson: while patient lies prone with arm hanging over table edge, hang a 5 lb weight on wrist lor 15 - 20 min Hippocratic method: place heel into patient’s axilla and apply traction to arm Cunningham 'smethod: gentle longitudinal support and traction of the arm at the patient's side, massage/ relaxation of deltoid, trapezius, and biceps to allow atraumatic shoulder reduction, low -risk, low pain;if not successful try above methods Obtain post -reduction x- rays Check post - reduction MVS Sling x 3 wk (avoid abduction and external rotation), followed by shoulder rehabilitation (dynamic stabilizer strengthening)

.

Hill- Sachs

Figure 11. Posterior view of anterior dislocation causing Hill-Sachs and Bankart lesions

Prognosis • recurrence rate depends on age of first dislocation • < 20 yr 65 - 95%; 20 - 40 yr = 60- 70%; > 40 yr 2- 4%

Specific Complications • recurrent dislocation ( most common complication ) • unreduced dislocation

• shoulder stiffness • rotator cuff or capsular or labral tear ( Bankart / SLAP lesion ) • injury to axillary nerve / artery, brachial plexus

-

u>

I

§

I

-

-5s

—

a r

«

.

O

Antorior apprehension sign

Sulcus sign

s

I s

S

s

>-

5

4

a

i

e

Posterior apprehension sign

Traction- countertraction

Figure 12. Shoulder maneuvers

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OR! l Orthopaedic Surgery

Rotator Cuff Disease

—

Supraspinatus

\

Acromion L

Table 9. Rotator Cuff Muscles (SITS )

Supraspinatus

Muscle Attachments

Proximal

Distal

Scapula

Greater tuberosity ol

Nerve Supply

Muscle Function

Suprascapular nerve

Abduction

Eitemal rotation

Coracoid

4k

• rotator cuff consists of 4 muscles that act to stabilize the humeral head within the glenoid fossa

Muscle

ligament

process

humerus Infraspinatus

Scapula

Greater tuberosity of humerus

Suprascapular nerve

Teres Minor

Scapula

Greater tuberosity ol humerus

Axillary nerve

filer nalrotation

Subscapularis

Scapula

lesser tuberosity of humerus

Subscapular nerve

Internal rotation and adduction

1-

ASubscapularis

Clinical Features • insidious onset, but may present as an acute exacerbation of chronic disease, night pain, and difficulty sleeping on affected side • pain worsens with active motion (especially overhead ); passive movement generally permitted • weakness and loss of ROM , especially between 90-130° (e.g. trouble with overhead activities ) • tenderness to palpation over greater tuberosity • rule out bicep tendinosis ( Speed ’s test ) and SLAP lesions ( O' Brien’s test )

Investigations • x ray: AP view may show sclerosis of the undersurface of the acromion or greater tuberosity, high riding humerus relative to glenoid, indicating large tear, evidence of chronic tendonitis • MR1: coronal / sagittal, oblique, and axial orientations are useful for assessing full / partial tears and tendinopathy ± arthrogram : geyser sign ( injected dye leaks out of joint through rotator cuff tear) • arthrogram: not commonly used but can assess full thickness tears, difficult to assess partial tears • ultrasound: may be a useful adjunct but limited ability to evaluate other intra-articular pathology

-

Treatment

• non-operative first line treatment, rotator cuff injury treatment begins with physiotherapy ( regardless of severity on MR 1 findings ) • physiotherapy, activity modification, non- narcotic analgesia ± steroid injection • mild or moderate cases frequently improve • progression to surgery if necessary • operative severe tear or impingement that is refractory to 2 -3 mo physiotherapy and 1 -2 corticosteroid injections arthroscopic or open surgical repair ( i.e. acromioplasty, rotator cuff repair )

Joint capsule

Infraspinatus

capular body

Teres minor

SPECTRUM OF DISEASE: IMPINGEMENT. TENDONITIS, MICRO OR MACRO TEARS

Etiology • narrowing of subacromial space • most commonly due to a relative imbalance of rotator cuff and larger shoulder muscles, allowing for superior translation and subsequent wear of the rotator cuff muscle tendons • glenohumeral ( rotator cuff ) muscle weakness leading to abnormal motion of humeral head scapular muscle weakness leading to abnormal motion of acromion - poor posture • acromial abnormalities, such as congenital narrow space or osteophyte formation or Type Ill acromion morphology 1. outlet / subacromial impingement: “ painful arc syndrome,” compression of rotator cuff tendons ( primarily supraspinatus) and subacromial bursa between the head of the humerus and the undersurface of acromion, AC joint, and CA ligament 2. bursitis and tendonitis 3. rotator cuff thinning and tear if left untreated

I j 5

Figure 13. Lateral view of the muscles of the rotator cuff

Bigliani Classification of Acromion Morphology

• Type I - flat • Type II - curved • Type III - hooked

Screening Out Rotator Cuff Tears No night pain (SN 87.7%) No painful arc (SN 97.5%) No impingement signs (SN 97.2%) No weakness Returning to the bedside; Using the history and physical examination to identify rotator cuff tears

• • • •

« -

J Am eeriatr Sac 2m :K33 K37

-

Ruling in Rotator Cuff Tears 98% probability of rotator cuff tear if all 3 of the following are present: • Supraspinatus weakness • External rotation weakness • Positive impingement sign(s) Diagnosis of rotator cuff tears. Uriel 2001:357:765-770

Does this Patient with Shoulder Faia have Rotator Cull Disease’ The Rational Clinical Euniaation Systematic Review JAMA 2013:310:837 847 Study: 5 studies of suficien:gcalty netd ‘ 3 30-203 shoulders and a peeve e te of ICO ranging from 33 81%.

-

*

-

Results / Condosions: Jmong pan prpvocatiotesis, a positive pairfal ait test fad the gaetes: specificity aid sensitnrty (SP 81%.SI 21%). Amrg strength tests, a positveeftrael rotetion lag as: and internal rotation lag as!were the nnstamiraa

fnr fidl-thickness tears $P 47%.SI 94%:SP 92%. SH 83% respectively ). The Menal rotation legtesJ was therefore also the mast accs aa far Meutdywg patients without a ful-tticksess aar. A positive drop arm test is helpful to ; dertify patients with RCD (SN 24%. SP 93 %L

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0R15 Orthopaedic Surgery

Toronto Notes 2023

Table 10. Rotator Cuff Special Tests Examination

Positive Test

Supraspinatus: place the shoulder in 90’of adduction and 30’of horizontal flexion (from the scapular plane) and internally rotate the arm so that the thumb is pointing toward the floor

Weakness with actnre resistance suggests a supraspinatustear

lift- off Test

Subscapularis: internally rotate arm so dorsal surface of hand rests on lower back;patient instructed to actively lift hand away from back against examiner resistance (use Belly Press Test if too painful)

Inability to actively lift hand away from back suggests a subscapularis tear

Posterior-Cuff Test

Infraspinatus and teres minor; arm positioned at patient's side in 90 " of flexion:patient instructed to externally rotate arm against the resistance of the examiner

Weakness with active resistance suggests posterior cuff tear

fleer's Test

Rotator cuff impingement;passive shoulder flexion

Pam elicited between 130-170" suggests impingement

Hawkins -Kennedy Test

Rotator cuff impingement: shoulder flexion to 90’and passive internal rotation

Pain with internal rotation suggests impingement

Painful Arc Test

Rotator cuff tendinopathy: patient instructed to actively abduct the shoulder

Pain with abduction >90’suggests

Speed's Test

Apply resistance to the forearm when the arm is in forward flexion with the elbows fully

Pam in the bicipital groove

Test

..

Jobe's Test (i e

Empty Can Test)

tendinopathy

extended Pain or clicking in the glenohumeral joint in SLAP lesion: forward flexion of the arm to 90’while keeping the arm extended. Arm is internalrotation but not external rotation adducted 10-15" Internally rotate the arm so thumb is facing down and apply a downward force. Repeat the test with arm externally rotated

O'Brien's Test

r

\

/

Jobe s test

Lift- off test

)

Posterior cuff test

2

s

Neer's test

r

Ur

£

130-170"

Hawkins- Kennedy test

i 0

I CM

1 Z.

I© Figure 14. Rotator cuff tests n LJ

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0R 16 Orthopaedic Surgery

Acromioclavicular Joint Pathology •subluxation or dislocation of AC joint • 2 main ligament groups attach clavicle to scapula: AC and CC ligaments Mechanism • fall onto shoulder with adducted arm or direct trauma to point of shoulder ( usually fall onto the posterosuperior aspect of the lateral shoulder )

Pneumothorax or pulmonary contusion are potential complications of severe clavicle fracture and rarely severe AC joint dislocation

Clinical Features • pain with adduction of shoulder and /or palpation over AC joint • palpable step deformity between distal clavicle and acromion (with dislocation ) i.e. piano key sign • limited ROM Investigations

• x - rays: bilateral AP, Zanca view ( 10-15° cephalic tilt ), axillary Treatment • non - operative sling 1 -3 wk, ice, analgesia, early ROM, and rehabilitation •operative » indication: Rockwood Class IV-VI ( 111 if labourer or high level athlete) • number of different approaches involving AC/ CC ligament reconstruction or screw /hook plate insertion Table 11. Rockwood Classification of Acromioclavicular Joint Separation Grade

Features

I

Joint sprain, absence of complete tear of either ligament Non - operative

II

Complete tear of AC ligament,incomplete tear of CC ligament, without marked elevation of lateral clavicular head

Non - operative

Complete tear of AC and CC ligaments, >5 mm elevation at AC joint, superior aspect of acromion is below the inferior aspect of the clavicle

Most non-operative, operative if labourer or high level athlete Will heal with step deformity, although most fully funcbonalin 4-6 mo

IV -VI

Based on the anatomical structure the displaced clavicle is in proximity to (posterior,very superior, inferior)

Operative in most cases

Treatment

Grade

AC Ligament

CC Ligament

Reducible

Treatment

I

Sprained

Normal

N, A

Non operative

II

lorn

Sprained

Yes

Non- operative

III

lorn

Torn

Yes

Most non-operative, operative if labourer or high-level athlete Will heal with step deformity. alLhough most fully functional in 4- 6 mo

IV - VI

lorn

Torn

No

Operative in most cases

-

Rockwood separations IV- VI are determined based on direction ot displacement IV: Distal clavicle displaced posteriorly into trapezius (seen on axillary XR) V: Distal clavicle herniated through dellotrapezial fascia into subcutaneous tissue VI: Distal davide displaced interior to acromion or coracoid under conjoined tendon (rare)

Clavicle Fracture • incidence: proximal (5%), middle ( 80% ), or distal ( 15%) third of clavicle • common in children ( unites rapidly without complications)

Mechanism

• fall on shoulder (87% ), direct trauma to clavicle ( 7%), 100SH (6%) Clinical Features • pain and tenting of skin • arm is clasped to chest to splint shoulder and prevent movement

Investigations • evaluate N VS of entire upper limb • x ray: AF, 45" cephalic tilt (superior/ inferior displacement ), 45° caudal tilt ( AP displacement ) • C l : useful for medial physeal fractures and sternoclavicular injury

-

Opea iedictioi aid litenalFiiati:a vs. iMsirgical Treataeitii Displaced Midshaft Qavide Fra dares:A Meta -dialysis J (top Irac=a 203J2(7)a2)5 -e2!3 Purpose: Compare c.icotes frpn DBF ard »eperane treaheeats a ispacednd-shaft dander fradires. Methods Keta aa'ysis ittSKIs reportag xpuini toctxuai outcomes, and ssbsegoei: surgeres pateds older thas K yr. Destlts: 9 ia:dp= zed dital trialsniI02) ata patents iere ".ded. OJLF lasassocated a sgahcadly loaer toe ® rate of LTV compared to H 5'« ‘or ae Mt -ope-avre teat ect gtozps (M 0.8 95% CL 0.0S-0-31).Fatctozal ooica ces rated by ether DASH or Coestad set res mere s 3 cScact y better it Olf gp to 6 wo.lies eidodeg elect re pate reoovaL de rate ot szbsegsett szrger es«s sgaScaatly lower i«ie ODD cohort (Aft is. W% M 0-36.95% C10.2A-0.5SL Coidisiots OBf isassocatediisgtocao: redochoos « ootswes aadeerier fsscboual octtoses n dspaced dstaftdatdi fradres.

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0R17 Orthopaedic Surgery

Treatment

Toronto Notes 2023

-

• medial and middle third clavicle fractures

• for nondisplaced fractures, simple sling for I -2 wk pm

early ROM and strengthening once pain subsides » if fracture is shortened >2 cm , consider ORIF • distal third clavicle fractures • undisplaced ( with ligaments intact ): sling for 1-2 wk • displaced (CC ligament injury): ORIF

-

Associated Injuries with Clavicle Fractures • Up to 9% ol clavicle fractures are associated with other fractures (most commonly rib fractures) • Majority of brachial plexus injuries

are associated with proximal third fractures

Specific Complications ( see General Fracture Complications, OR7 ) • cosmetic bump ( most common complication ) • shoulder stiffness, weakness with repetitive activity • pneumothorax, brachial plexus injuries, and subclavian vessel (all very rare )

Frozen Shoulder (Adhesive Capsulitis) •disorder characterized by progressive pain and stiffness of the shoulder, usually resolving spontaneously within 18 mo

Mechanism •primary adhesive capsulitis

idiopathic, often associated with DM usually resolves spontaneously in 9-18 mo •secondary adhesive capsulitis • due to prolonged immobilization • shoulder- hand syndrome: CRPS/ RSD characterized by arm and shoulder pain, decreased motion , and diffuse swelling • following Ml, stroke, shoulder trauma • poorer outcomes Clinical Features • gradual onset ( weeks to months) of diffuse shoulder pain with: • decreased active AND passive ROM • pain worse at night and often prevents sleeping on affected side increased stiffness as pain subsides: continues for 6-12 mo after pain has disappeared Investigations •x- ray: AP ( neutral, internal/external rotation ), scapular Y, and axillary views of the shoulder may be normal, or may show demineralization from disease

Stages of Adhesive Capsulitis 1. Freezing phase: gradual onset, diffuse pain (lasts 6-9 mo) 2. Frozen phase: decreased ROM impacts function (lasts 4-9 mo) 3. Thawing phase: gradual return of motion (lasts 5- 26 mo)

ft Conditions Associated with an Increased Incidence of Adhesive Capsulitis • Prolonged immobilization (most significant) • Female gender • Age >49 • DM (Sx) • Cervical disc disease • Hyperthyroidism Stroke Ml • Trauma and surgery • Autoimmune disease

.

Treatment

-

•freezing phase maintenance of active and passive ROM (physiotherapy)

NSAlDs and steroid injections if limited by pain

• thawing phase

aggressive physiotherapy, possible manipulation under anesthesia and early physiotherapy

• arthroscopy for debridement/decompression

Humerus Proximal Humeral Fracture Mechanism

• young: high energy trauma (MVC) • elderly: l 'OOSH from standing height in osteoporotic individuals Clinical Features

• proximal humeral tenderness, deformity with severe fracture, swelling, painful ROM, bruising extends down arm and chest • physical exam usually reveals diminished forward elevation, with or without disuse atrophy of deltoid and periscapular musculature Investigations • test axillary nerve function (deltoid contraction and skin over deltoid ) • x-rays: AP, trans-scapular, and axillary views of the shoulder are essential • CT’ scan: to evaluate for tuberosity or articular involvement and fracture displacement, and if the diagnosis of non - union is unclear

-

Necr Classification Based on 4 parts of humerus • Greater tuberosity • Lesser tuberosity • Humeral head Shaft One- part fracture: any of the 4 parts with none displaced Two-part fracture: any of the 4 parts with 1displaced Three-part fracture: displaced fracture of surgical neck + displaced greater tuberosity or lesser tuberosity Four-part fracture: displaced fracture of surgical neck + both tuberosities

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Toronto Notes 2023

OR18 Orthopaedic Surgery

Classification

• Neer classification is based on 4 fracture locations or ‘parts' • displaced: displacement >1 cm and /or angulation > 45° • the Neer system regards the number of displaced fractures, not the fracture line, in determining classification • ± dislocated /subluxed: humeral head dislocated /subluxcd from glenoid Treatment

• assess for and treat osteoporosis if needed • non - operative

nondisplaced and minimally displaced (85% of patients): broad arm sling immobilization , begin ROM within 14 d to prevent stiffness • most displaced fractures in low-demand elderly patients • operative • OR1F (anatomic neck fractures, displaced, associated irreducible glenohumeral joint dislocation ) or 1M nail (surgical neck) hemiarthroplasty or reverse TSA may be necessary, especially in elderly minimally invasive percutaneous pinning and intramedullary nail fixation are indicated in rare instances Specific Complications ( see General Fracture Complications, OR7 ) • AVN, nerve palsy ( 45%; typically axillary nerve ), malunion , post-traumatic arthritis, persistent pain and weakness, frozen shoulder

'Greater tuberosity Lesser tuberosity

Humeral Shaft Fracture

v

11

Mechanism • young: high energy trauma (direct blows/ M VC ) • elderly: FOOSH , twisting injuries, mctastascs

' Anatomical neck

Surgical neck t

Clinical Features

• pain , swelling, weakness ± shortening, motion /crepitus at fracture site • must test radial nerve function before and after treatment: look for drop wrist , sensory impairment in

1 .

;

dorsum of hand Investigations

• x- ray: AP and lateral views of the humerus, including the shoulder and elbow joints Treatment • in general, humeral shaft fractures are treated non-operatively • non -operative ± reduction; can accept deformity due to compensatory ROM of shoulder hanging cast ( weight of arm in cast provides traction across fracture site) with collar and cuff

sling immobilization until swelling subsides, then Sarmiento functional brace, followed by ROM • operative

indications: see NO CAST sidebar, OR6 , pathological fracture, “floating elbow” ( simultaneous unstable humeral and forearm fractures) ORIF: plating ( most common ), IM rod insertion, external fixation ( rare )

Specific Complications ( seeGeneral Iracture Complications, OR7) • failure of functional bracing ( seen in up to 30% of patients) • radial nerve palsy: expect spontaneous recovery in 3 4 mo, otherwise send for EMli • non union: most frequently seen in middle 1 /3

• decreased ROM

-

Figure 15. Fractures of the proximal humerus

Acceptable Humeral Shaft Deformities for Non Operative Treatment • 10° angulation

Galeazzi Fracture

Figure 20. Nightstick fracture

•fracture of the distal radial shaft with disruption of the DRU| • most commonly in the distal 1 /3 of radius near junction of metaphysis/diaphysis Mechanism

•FOOSH with axial loading of pronated forearm or direct wrist trauma •forceful axial loading of radial shaft (e.g. direct trauma to distal 1 /3 of radius ) Clinical Features •pain, swelling, deformity, and point tenderness at fracture site

For all isolated radius fractures assess DRUJ to rule out a Galeazzi fracture

rh LJ

(§) Monteggia vs. Galeazzi Fractures Remember the mnemonic 'MUGGER': Monteggia Ulnar fracture Galeazz Radial fracture

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Toronto Notes 2023

OR23 Orthopaedic Surgery

Investigations

-

Fracluro ol distal radius

• x ray: AP, and lateral views of the elbow, wrist, and forearm

shortening of distal radius > 5 mm relative to the distal ulna

• widening of the OKU ) space on AP • dislocation of radius with respect to ulna on true lateral Treatment

• all cases are operative ( “ fracture of necessity") OR1P of radius; afterwards, assess DRU|stability by balloting distal ulna relative to distal radius if DRU ) is stable and reduced, splint for 10-14 d with early ROM encouraged if DRU ) is unstable, OR1P or percutaneous pinning with long arm cast in supination x 2-3 wk

Wrist

Dislocation of ulna

Figure 21. Galeazzi fracture

Colles’ Fracture • extra -articular transverse distal radius fracture ( ~2 cm proximal to the radiocarpal joint ) with dorsal displacement ± ulnar styloid fracture • most common fracture in those > 40 yr, especially in women and those with osteoporotic bone Mechanism

. KOOSH

Clinical Features • “dinner fork " deformity • swelling, ecchymosis, tenderness Investigations • x- ray: AP and lateral ± oblique views of wrist

Indications for Direct Surgical Management of Codes' Fracture • Displaced intra - articular fracture • Comminuted • Severe osteoporosis • Dorsal angulation >5‘ or volar tilt >20" • >5 mm radlal shortening

Features of Inadequate Closed Reduction that Require ORIF Radial shortening >3 mm or Dorsal tilt >10“ or Intra- articular displacement/step-off >2 mm

--

Treatment

• goal is to restore radial height (13 mm), radial inclination (22°), volar tilt (11°), as well as DRU ) stability and useful forearm rotation • non -operative closed reduction (think opposite of the deformity ) hematoma block (sterile prep and drape, local anesthetic injection directly into fracture site ) or conscious sedation • closed reduction: traction with extension (exaggerate injury ); traction with ulnar deviation , pronation , flexion ( of distal fragment not at wrist ) dorsal slab/ below elbow cast for 5 6 wk • obtain post reduction Aims immediately; repeat reduction if necessary • x ray at 1 wk, 3 wk, and at cessation of immobilization to ensure reduction is maintained

•

operative

-

-

-

Lateral View

indication: failed closed reduction, or loss of reduction percutaneous pinning, external fixation, or ORIF

Smith’s Fracture • volar displacement of the distal radius (i.e. reverse Colies’ fracture) Mechanism • fall onto the back of the flexed hand

Investigations

• x- ray: AP and lateral ± oblique views of wrist Treatment

• if non - displaced / stable: closed reduction and splinting in wrist extension with hematoma or regional nerve block; long arm cast in supination x6 wk • if displaced / unstable: ORIF

AP View 1. Dorsal tilt 2. Dorsal displacement 3. Radial shortening 4. Ulnar stylold fracture

5 Radial tilt 6. Radial displacement

Figure 22. Colles’ fracture and associated bony deformity

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Toronto Notes 2023

0R21 Orthopaedic Surgery

Complications of Wrist Fractures • most common complications are poor grip strength, stiffness, and radial shortening • distal radius fractures in individuals < 40 yr of age are frequently high energy/comminuted and are more likely to require ORU' 80 • % have normal function in 6-12 mo

-

.

Table 13 Early and Late Complications of Wrist Fractures Early

Late

Difficult reduction t loss ol reduction

Malunion, radial shortening Painful wrist secondary to ulnar prominence Froren shoulder (“shoulder hand syndrome") Post traumatic arthritis Carpal tunnel syndrome CRPS/ RSD

Compartment syndrome Extensor pollicis longus tendon rupture Acute carpal tunnel syndrome Finger swelling with venous block Complications ot a tight cast/ splinl

-

-

AP view A. Radial inclination B. Radial length

Scaphoid Fracture Epidemiology • most common carpal bone injured • common in young men; not common in children or in patients beyond middle age • may be associated with other carpal or wrist injuries (e g. Colies’ fracture)

.

Mechanism • FOOSH : impaction of scaphoid on distal radius, most commonly resulting in a transverse fracture through the waist (65%), distal (10%), or proximal ( 25%) scaphoid Clinical Features • pain with resisted pronation • tenderness in the anatomical “snuffbox”, over scaphoid tubercle, and pain with long axis compression into scaphoid

• usually nondisplaced Investigations • x ray: AP, lateral, and scaphoid views with wrist extension and ulnar deviation

-

• ± Q’ or MRI: detect occult fracture and prevent AVN • bone scan rarely used • note: a fracture may not be radiologically evident up to 2 wk after acute injury, so if a patient complains of wrist pain and has anatomical snuffbox tenderness but a negative x ray, treat as if positive for a scaphoid fracture and repeat x ray 2 wk later to rule out a fracture: if x ray still negative, order CT or M R1

- -

-

Treatment

Lateral view

.

C Volar tilt Effect ol Colics’ Iracturo on distal radius

1 o

.

Figure 23 Normal wrist angles * wrist angles in Codes’ fracture Note the relative shortening of the radius relative to the ulna on AP view in Codes’ fracture

Scaphoid Fracture Special Tests Tender snuff box: 100% sensitivity, but 29% specific, as it is also positive with many other injuries of radial aspect of wrist with FOOSH

• early treatment critical for improving outcomes • non -operative

non - displaced (< 1 mm displacement / 5° angulation ): long-arm thumb spica cast x 4 wk, then short arm cast until radiographic evidence of healing is seen ( 2 3 mo) • operative • displaced: OR It with headless/countersink compression screw is the mainstay treatment

•

^

-

Specific Complications (seeGeneral Fracture Complications, OR7 ) • most common: nonunion /malunion ( use bone graft from iliac crest or distal radius with fixation to heal ) • AVN of the proximal fragment • delayed union ( recommend surgical fixation ) • scaphoid nonunion advanced collapse (SNAC) - chronic nonunion leading to advanced collapse and arthritis of wrist

The proximal pole of the scaphoid receives as much as 100% of its arterial blood supply from the radial artery that enters at the distal pole. A fracture

through the proximal third disrupts this blood supply and results In a high incidence of AVN/nonunion

Prognosis • proximal pole: proximal fifth fracture, AVN rate 100%; proximal third fracture: AVN rate 33% • waist: middle of the scaphoid fractures have healing rates of 80 -90% • distal pole: distal third fractures have healing rates close to 100%

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Figure 24 ORIF left scaphoid

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Toronto Notes 2023

OR25 Orthopaedic Surgery

Hand

Ulna

Radius

'Scaphoid

Lunate

• sec Plastic Surperv. PL 24

Trapezium

Triquetrum

Spine

•Trapezoid

Pisiform ^ Hamate

** Capitate

^

process

Neural arch

n Metacarpal bones ( 1 5)

-

-

. 1

Lamina

Transverse Pedicle

3 ;

Spinous process

u

Superior

-

u

articular process

© Hisheva Merci

Figure 25. Carpal bones

1/

V-

V- iVertebral

'

•

/

y

Order of Carpal Bones

-1M

.

So Long To Pinky Here Comes The

Transverse - - - r i:

Pedicli

body

•

ir

.

Vertebral foramen

Inferior articular process

Vertebral

Spinous process

body

Left Lateral View

Thumb Proximal Row: Scaphoid . Lunate Triquetrum. Pisiform ( Lateral to Medial) Distal Row: Hamate. Capitate. Trapezoid Trapezium ( Medial to Lateral )

8 s ' .

.

* J

1 a.

Superior View

Figure 27. Schematic diagram of vertebral anatomy

Adapted fron: Moore KL Agi.r AMR. Essential Clinical Anatomy, 3rd ed . Philadelphia: Lippincott Williams and Wilkins. 2007. p274

Fractures of the Spine • see Neurosurgery. NS 39

Compression

Cervical Spine General Principles • Cl (atlas): no vertebral body, no spinous process • C2 (axis): odontoid = dens • 7 cervical vertebrae; 8 cervical nerve roots • nerve root exits above vertebra ( i .e. C4 nerve root exits above C 4 vertebra ), C8 nerve root exits below

C7 vertebra

= impingement of nerve root myelopathy = impingement of spinal cord

• radiculopathy •

Burst

Special Testing • compression test: pressure on head worsens radicular pain • distraction test: traction on head relieves radicular symptoms • Valsalva test: Valsalva maneuver increases intrathecal pressure and causes radicular pain • Lhermitte Sign: electric shock sensation radiating to back upon forward flexion of the neck, some etiologies include multiple sclerosis, cervical myelopathy, and B 12 deficiency • occiput-wall distance ( OW' D ): patient stands against a wall with erect posture and distance between the occiput and the wall is measured, value greater than 2 cm is abnormal, indicative of thoracic

hyper-kvphosis

Fracture- dislocation Figure 26. Compression, burst, and dislocation fractures of the spine

Table 14 . Cervical Radiculopathy/Neuropathy Root

C5

C6

a

C8

Motor

Deltoid Biceps

Biceps Brachioradialis

triceps Wrist flexion Finger extension

Interossei Digital flexors

Sensory

Axillary nerve (patch over lateral deltoid )

Index and middle finger

Bing and little finger

Reflex

Biceps

triceps

Finger jerk

Wrist extension thumb Biceps

Brachioradialis

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Toronto Notes 2023

OR26 Orthopaedic Surgery

X- Rays for C-Spine • AP spine: alignment • AP odontoid: atlantoaxial articulation • lateral vertebral alignment: posterior vertebral bodies should be aligned ( translation >3.5 mm is abnormal ) • angulation: between adjacent vertebral bodies (> 11° is abnormal ) disc or facet joint widening anterior soft tissue space (at C3 should be S3 mm: at C4 should be 90%) • degenerative (disc, facet, ligament ) • nerve root compression (e.g. disc herniation ) spinal stenosis (congenital, osteophyte, central disc) 2. others ( L4-5 > L3-4 • M:F=3:1 • only 5% become symptomatic • usually a history of flexion -type injury Clinical Features • back dominant pain (central herniation ) or leg dominant pain (lateral herniation ) • tenderness between spinous processes at affected level • muscle spasm i loss of normal lumbar lordosis

i

Cauda equina syndrome and ruptured aortic aneurysms are causes of low back pain that are considered surgical emergencies

Disc Prolapse Annulus librusjs

\ Nucleus

NYpulposus

Nerve '// //1 root

Vertebra

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nerve root compression

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Toronto Notes 2023

OR2 H Orthopaedic Surgery

• neurological disturbance is segmental and varies with level of central herniation • motor weakness ( L 4, L5, SI ) • diminished rellexes ( 1.4 , SI ) • diminished sensation ( 1.4 , L5, SI ) • positive straight leg raise • positive contralateral SLU • positive Lasegue and Bowstring sign • cauda equina syndrome ( present in l - 10%): surgical emergency

Neurogenic claudication Is position dependent; vascular claudication is exercise dependent

Investigations • x - ray, MRI, consider a post -void residual volume to check for urinary retention; post -void > 100 mL should heighten suspicion for cauda equina syndrome Treatment • non - operative symptomatic extension protocol physiotherapy program

NSAlDs • operative • indication ; progressive neurological deficit , failure of symptoms to resolve within 3 mo, or cauda equina syndrome due to central disc herniation • surgical discectomy

MRI abnormalities (e.g. spinal stenosis, disc herniation) are quite common in both asymptomatic and symptomatic individuals and are not necessarily an indication for intervention without clinical correlation

• prognosis

90 % of patients improve in 3 mo with non -operative treatment

Table 17. Types of Low Back Pain Mechanical Back Pain

Direct Nerve Root Compression

Disc Origin

Facet Origin

Spinal Stenosis

Root Compression

Pain Dominance

Back

Back

Leg

Leg

Aggravation

Flexion

Extension, standing, walking

Exercise, extension, v/ al king, standing

flexion

Onset

Gradual

More sudden

Congenital or acquired

Acute leg t back pain

Duration

Long ( weeks, months)

Shorter (days, v/ eeks)

Acute or chronichistory ( weeks to months)

Constant and severe pain, lasting weeks)

Treatment

Relief of strain, physiotherapy and exercise, weighlloss. NSAlDs, acetaminophen

Relief of strain, physiotherapy and exercise, weighlloss. NSAlDs acetaminophen

Belief of strain, physiotherapy ( flexion back program), surgical decompression if progressive or severe deficit NSAlDs. acetaminophen

Relief of strain, physiotherapy ( extension back program for disc

.

herniation), surgical decompression il progressive or severe delieit NSAlDs.

.

.

acetaminophen

Back Pain

*

Constant

*

T Constant

Intermittent

Mechanical

BACK PAIN Bowel or bladder dysfunction Anesthesia (saddle) Constitutional symptoms/malignancy Khronic disease Paresthesias Age >50 yr IV drug use Neuromotor deficits

Sciatica • Most common symptom of radiculopathy ( L4 - S3) • Log dominant , constant , burning pain • Pain radiates down leg i foot • Most common cause - disc herniation

Ley Dominant

Back Dominant

Inflammatory

Red Flags for

Disc Herniation ( lateral)

Intermittent Spinal Stenosis

T

Disc Herniation ( central)

Facet Joint

Figure 29. Approach to back pain

K

.-

f

i

SPONDYLOLYSIS

[Spondylolysis

Definition • defect in the pars interarticularis with no movement of the vertebral bodies

Mechanism

• trauma; gymnasts, weightlifters, backpackers, loggers, labourers

t

Spondylolisthesis

( anterioi displacement )

Clinical Features

-

• activity related back pain , pain with unilateral extension Investigations • oblique x- ray; “collar ” break in the “Scottie dog’s" neck • bone scan • CTscan

, h

.

f*

( Michelis "

test )

V

8 : V) a

1 y

+

Figure 30. Spondylolysis, Spondylolisthesis

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Toronto Notes 2023

OR29 Orthopaedic Surgery

Treatment • non -operative activity restriction, brace, stretching exercise

Superior articular

process (ear)

Fracture

ADULT ISTHMIC SPONDYLOLISTHESIS

Definition • defect in pars interarticularis causing a forward translation or slippage of one vertebra on another, usually at L5 S1, less commonly at L4 5

-

-

Mechanism

• degenerative (adults), traumatic, pathological, teratogenic

1

A

f

'

>

I

*

v

^

Inferior articular Transverse process (nose ) process

Eg

Figure 31. “Scottie dog ” fracture

Clinical Features • lower back pain radiating to buttocks relieved with sitting • neurogenic claudication

• L5 radiculopathy

• Meyerding Classification ( percentage of slip) Investigations

-

-

• x ray ( AP, lateral, oblique flexion extension views), MRI Treatment

• non -operative

activity restriction , bracing, NSAIDs

• operative Table 18. Classification and Treatment of Spondylolisthesis Class

Percentage of Slip

Treatment

1 2

0- 25\ 2S SO

Symptomatic operative lesion only lor intractable pain

3 4

sore re -ioo

Decompression lor spondylolisthesis end spinal fusion

s

»

100

Same ns above Same as above Same as above

Specific Complications

• may present as cauda equina syndrome due to roots being stretched over the edge of L5 or sacrum

Pelvis Pelvic Fracture Mechanism

• young: high energy trauma, either direct or by force transmitted longitudinally through the femur • elderly: low energy trauma, fall from standing height • lateral compression , vertical shear, or anteroposterior compression fractures Clinical Features • pain, inability to bear weight • local swelling, tenderness • abnormal lower extremity positioning: external rotation of one or both extremities, limb-length

-Anterior column

-

Posterior pr. column S

discrepancy

3.

• pelvic instability

Investigations • x-ray: AP pelvis, inlet and outlet views, ) udet views (visualizes obturator and iliac oblique when acetabular fracture suspected ) 6 cardinal radiographic landmarks of the acetabulum: ilioischial line, iliopectineal line, teardrop, weight bearing roof, posterior rim, anterior rim CT scan useful for evaluating posterior pelvic injury and acetabular fracture (if stable) may see contrast blush (indicating active bleeding ) • assess genitourinary injury (rectal exam, vaginal exam, hematuria, blood at urethral meatus) if involved, the fracture is considered an open fracture

i

V

A ©

Figure 32. Pelvic columns

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Toronto Notes 2023

OR30 Orthopaedic Surgery

Classification Table 19. Tile Classification of Pelvic Fractures Type

Stability

Description

A

Rotationally stable Vertically stable

A1: fracture not involving pelvic ring|i.e. avulsion or iliac wing fracture) A 2: minimally displaced fracture of pelvic ring je.g. ramus fracture) A3: transverse sacral or coccygeal fracture

6

Rotationally unstable Vertically stable

B1: open book (external rotation ) 62: lateral compression ipsilateral 62 1: with anterior ring rolation/displacemenl through ipsilateral rami 62 2: with anterior ring rolation/ displacemenl through non ipsilateral rami (bucket handle ) 63: bilateral

-

-

C

Rotationally unstable Vertically unstable

-

Cl: unilateral C1 1: iliac fracture C1 2: sacroiliac fracture dislocation C1 3: sacral fracture C2: bilateral with 1 side type 8 and 1 side type C C3: bilateral both sides type C

--

-

Possible Radiological Findings • Pubic rami fractures: superior/inferior • Pubic symphysis diastasis _ : common in AP compression (N 5 mm) • Sacral fractures: common in lateral compression • SI joint diastasis: common in AP compression (N M mm) • Disrupted anterior column (iliopectineal line) or posterior column (ilioischial line) • “Teardrop" displacement: acetabular fracture • Iliac, ischial avulsion fractures • Displacement of the major fragment superior (VS), open book (APC). bucket handle (LC) *

Treatment

• ABCDEs • emergency management IV fluids/ blood pelvic binder/sheet

± pre- peritoneal packing

externa ] fixation vs. emergent angiography/embolization ± laparotomy ( if EAST/ DHL positive) • non - operative treatment: protected \VB

indication: stable fracture (e.g. elderly patient with fracture sustained in fall from standing ) • operative treatment: OKIE

Stable avulsion fracture

• indications unstable pelvic ring injury symphysis diastasis > 2.5 cm open fracture Specific Complications ( see General Fracture Complications, 0 R7 ) • hemorrhage ( life - threatening) • injury to rectum or urogenital structures • obstetrical difficulties, sexual and voiding dysfunctions • persistent SI joint pain

Open book fracture

-

• post traumatic arthritis of the hip with acetabular fractures • high - risk of DVT/ PE

Hip Hip Dislocation • full trauma survey (see Emergency Medicine. Patient Asscssmcnt/ Managemcnt, FR 2 ) •examine for neurovascular injury prior to open or closed reduction • high index of suspicion for associated injuries • reduce hip dislocations within 6 h to decrease risk of AVN of the femoral head • hip precautions ( no extreme hip flexion, adduction, internal or external rotation ) for 6 wk postreduction •see Hip Dislocation Post Total Hip Arthroplasty, OR32

-

ANTERIOR HIP DISLOCATION

Typo C Unstable vertical fracture

-

Figure 33. Tile classification of pelvic fractures

Up to 50% of patients with hip dislocations suffer fractures elsewhere at the time of injury

• mechanism : posteriorly directed axial loading of the femur with hip widely abducted and externally rotated

3. External rotation 2. Internal rotation

•classified into inferior ( flexion , abduction, external rotation ) and superior (extension and external rotation ) •clinical features: shortened, abducted , externally rotated limb • treatment closed reduction under conscious sedation /GA post- reduction Cl to assess joint congruity

!

raction t

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© Janet SM Chan 2009

Figure 34. Rochester method

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0R31 Orthopaedic Surgery

Toronto Notes 2023

POSTERIOR HIP DISLOCATION • most frequent type of hip dislocation (90%) • mechanism: severe axial load to knee with hip flexed and adducted

• e.g. knee into dashboard in MVC

• clinical features: shortened, adducted, internally rotated limb • x- ray: affected femoral head will appear smaller than unaffected femoral head • Thompson and Hpstein classification posterior dislocation:

-

I - with no or minor posterior acetabular wall fracture II - with large posterior acetabular wall fracture III - with comminuted acetabular fracture IV - with acetabular floor fracture V - with fracture of femoral head • treatment • closed reduction under conscious sedation / GA only if no associated femoral neck fracture or

ipsilateral displacement

• GRIT if unstable, intra-articular fragments, or significant displacement post- reduct ion CT to assess joint congruity and fractures

COMPLICATIONS FOR ALL HIP DISLOCATIONS • post-traumatic OA • AVN of femoral head • associated fractures (e.g. femoral head , neck, or shaft ) • sciatic nerve palsy in 25% (10% permanent ) • HO • thromboembolism - DVT / PH

Hip Fracture General Features • acute onset of hip pain after a fall • unable to weight-bear • shortened and externally- rotated leg • painful ROM

X- Ray Features of Subcapital Hip Fractures • Disruption of Shenton’s line (a radiographic line drawn along the upper margin of the obturator foramen, extending along the inferomedial side of the femoral neck) • Altered neck- shaft angle (normal is 120 130")

-

IF -

-

-

Normal joint

Subcapital fracture

Intertrochanteric

fracture

Subtrochanteric fracture

Cl

m

0

.

Table 20. Overview of Hip Fractures Fracture Type

Definition

Mechanism

Investigations

Treatment

Femoral Neck ( Subcapital)

Intracapsulat

Young: MVC, fall from height Elderly: fall from standing , rotational force

X- Ray: AP hip , AP pelvis, cross fable lateral hip

See table 21 OH 32

Intertrochanteric posteromedial cortex Unstable: non - inlacl posteromedial cortex

Subtrochanteric

Exlracapsular fracture Same as femoral neck X - Ray: AP hip , AP pelvis, cross table fracture and lesser trochanters Oirect or indirect lateral hip and transitional bone force transmitted to between the neck the intertrochanteric and shall area between the greater

Fracture begins at or below the lesser trochanter and involves the proximal femoral shaft

Young: high energy trauma Elderly : osleopenic bone * fall,

Source: UptoDat •Prevention ol venous Ihrcmbcefnbcfam in adult orthopedic surgical pitienb. tnouparin (IOYHMM) US FIX approved product information https. vswrv.jccesvdatj rdi.gcrdrwgvatldj do(vilat>ei/20 T7D 20164s110IM.pdl

*

Figure 35. Subcapital, intertrochanteric , and subtrochanteric hip fractures

Stable: intact

DVT Prophylaxis in Hip Fractures LMWH (i.e. enoxaparin 40 mg SC once daily ), fondaparinux, low dose heparin on admission, do not give F 2:1, severity 1;>M

-

Physical Exam • examine for CAVE deformity • examine hips for associated DDH • examine knees for deformity • examine back for dysraphism ( unfused vertebral bodies) • diagnosis is often from physical exam findings alone, radiographs unnecessary

CAVE deformity Midfoot Cavu (tight intrinsics, FHL, FDL) Forefoot Adductus (tight tibialis posterior) Hindfoot Varus tight Achilles tendon, tibialis posterior, tibialis anterior) Hindfoot Equinus (Hindfoot Equinus (tight Achilles tendon)

n LJ

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Toronto Notes 2023

OR 19 Orthopaedic Surgery

Treatment

• largely non -operative via Ponseti Technique (serial manipulation and casting)

' Plantar flexion of ankle joint

• correct deformities in CAVE order

change strapping /cast ql -2 wk typically requires percutaneous Achilles tendon release after ~ 2 months of casting with another 3 weeks of casting in maximal dorsiflexion surgical release in refractory case ( rare ) • delayed until age 3-4 mo • 3 yr recurrence rate = 5 10% • mild recurrence common; affected foot is permanently smaller/stiffer than normal foot with calf

-

muscle atrophy

Scoliosis Definition • lateral curvature of spine with vertebral rotation • age: 10-14 yr • more frequent and more severe in females

Talus in equinus and varus

I

-

v,

I

0

[0

/ -j I1

Forefoot bones in

varus ,

Inversion of calcaneus

i

-

Figure 54. Club foot depicting the gross and bony deformity

Etiology

• idiopathic: most common (90%) • congenital: vertebrae fail to form or segment • neuromuscular: UMN or LMN lesion , myopathy • postural: leg length discrepancy, muscle spasm • other: osteochondrodystrophies, neoplastic, traumatic Clinical Features

• cosmetic concern ± back pain • primary curve where several vertebrae affected

• secondary compensatory curves above and below fixed primary curve to try to maintain normal position of head and pelvis • asymmetric shoulder height when bent forward • Adam’s test: thoracic or lumbar prominence on affected side with forward bend at the waist • prominent scapulae, creased flank, asymmetric pelvis • associated posterior midline skin lesions in neuromuscular scoliosis • cafe au lait spots, dimples, neurofibromas • axillary freckling, hemangiomas, hair patches • associated pes cavus or leg atrophy • apparent leg length discrepancy • Scoliosis Lenke Classification: guide to select curves to be included within the fusion construct

- -

.

-

Figure 55 Cobb angle used to monitor the progression of the scoliotic curve

Investigations

• x- ray: 3-foot standing, AP, lateral measure curvature: Cobb angle • may have associated kyphosis

Scoliosis screening is not recommended in Canada (Grieg A, et al. 2010; Health Canada.1994)

Treatment

• based on Cobb angle

•

< 25°: observe for changes with serial radiographs

• >25° or progressive: bracing ( many types, controversial ) that halt /slow curve progression but do not reverse deformity • > 45°, cosmetically unacceptable, or respiratory problems: surgical correction (spinal fusion )

In structural or fixed scoliosis, bending forwards makes the curve more obvious

Postural scoliosis can be corrected by correcting the underlying etiology

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OR50 Orthopaedic Surgery

Bone Tumours • primary bone tumours are rare after 3rd decade • metastases to bone are relatively common after 3rd decade Clinical Features • malignant ( primary' or metastasic ): local pain and swelling ( weeks to months), worse on exertion and at night, ± soft tissue mass • minor trauma can be the initiating event that calls attention to lesion

Red Flags • Persistent skeletal pain • Localized tenderness • Spontaneous fracture • Enlarging mass soft tissue swelling

-

Table 25. Distinguishing Benign from Malignant Bone Lesions on X - Ray Malignant

Benign

..

No periosteal reaction or benign appearing reaction (e g uniform smooth periosteal thickening as seen in a healing fracture)

Acute periosteal reaction •Codman’s triangle •"Onion skin" •"Sunburst ” Poorly defined borders, with a wide zone of transition,or infiltrative

Sharp,well-demarcated borders,narrow zone of transition (between lesion andnormal bone,suggesting slow - growing lesion)

(suggesting fast - growing lesion)

Well-developed bone formation

Varied bone formation

Intraosseous and even calcification

Eitraosseousand irregular calcification

No soft tissue mass

Soft tissue mass present

No cortical destruction or uniform cortical destruction in some low grade and locally aggressive benign lesions

Aggressive cortical destruction or tumour infiltration without cortical destruction

Adapted from Bucktioltz RW . Heckman JD. Rockwood and Green's Fractures in Adults. Volume 1. Philadelphia: Uppincotl Williams & Wilkins. 2001. p558

Diagnosis

• malignancy is suggested by rapid growth, warmth , tenderness, aggressive features on imaging • may be associated with constitutional symptoms such as fevers, night sweats, weight loss, or loss of

©

-

Describing Bone Tumours on X rays 1 Location (which bone and whether it is in the diaphysis. metaphysis. or epiphysis) 2 Size 3 Solitary vs. multifocal 4 Morphology: geographic, permeative, or moth-eaten margins 5 Presence of periosteal reaction 6 Presence of bony remodeling

7 Cortical involvement 8 Matrix: osteoid (cumulus cloud), chondroid (punctate or popcorn calcification ), or fibrous (ground glass appearance) 9 Presence of soft - tissue mass 10 Associated pathological fracture

appetite • staging should include:

• local full length radiographs of the affected bone ± CT and/or MR1 of affected bone

biopsy

should be referred to specialized centre for biopsy • systemic blood work (CBC, electrolytes, liver function assays, inflammatory markers, bone profile, extended electrolytes including calcium ) serum electrophoresis for older patients ± Bence ) ones protein CT chest /abdo/ pelvis Bone scan or bone marrow biopsy depending on preliminary diagnosis

Neoplasi

Periosteum

Benign Active Bone Tumours Codman's

BONE-FORMING TUMOURS

Osteoid Osteoma • benign bone tumour arising from osteoblasts; not known to metastasize • peak incidence in 2 nd and 3rd decades, M:F=2-3:1 • proximal femur> tibia diaphysis most common locations; spine ( can cause painful scoliosis) • radiographic findings: small, round radiolucent nidus (6 dB

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OTIO Otolaryngology

Toronto Notes 2023

Table 4. The Interpretation of Tuning Fork Tests Examples

Normal or bilateral SNHL

.

-

Right sided CHL normal left car

.

Weber

Rinne

Central

ACvBC (*) bilaterally

lateialnes right

SC AC (-) right

-

Right -sided SNHl normal left car

Lateralizes left

AOBC I*) bilaterally

Right - sided severe SNHL or dead right ear, normal left ear

Lateralizes left

BOAC I-) right *

-

-

'A vibrating tuningIoik on lilt. mastoid stimulates the cochlea bilaterally, then lore, In this case, the left cochlea Is stimulated by the Rinne test on the light (eg. a false negative test), these tests are not valid it the ear canals are obstructed with cerumen (eg. will cieate conductive loss)

Frequency ol Tuning Fork (Hz )

Minimum Hearing loss forRinneto Reverse|BC »AC, NEGATIVE Rinne) (dB )

256

15

512

30

1024

45

Pure Tone Audiometry • a threshold is the lowest intensity level at which a patient can hear the tone 50% of the time • thresholds are obtained for each ear at frequencies of 250, 500, 1000, 2000, 4000, and 8000 Hz • air conduction thresholds are obtained with headphones and measure outer, middle, inner ear, and auditory nerve function • bone conduction thresholds are obtained with bone conduction oscillators, which bypass the outer and middle ear

Range of Frequencies Audible to Human Ear • 20 to 20000 Hz • Most sensitive frequencies:1000 to 4000 Hz • Range of human speech: 500 to 2000 Hz

Degree of Hearing Loss

•determined on basis of the pure tone average ( PTA) at 500, 1000, and 2000 Hz FREQUENCY ( Hzl 250 500 1000 2000 4000 8000

Audiogram Legend for a Left Ear

x

250 500 1000 2000 4000 8000

- 10 0 10

-

AC Unmasked > v BC Unmasked - AC Masked ) = BC Masked

20 30 40 50

m

§ 2

Z>

+

2 *

C. Conductive Hearing Loss ( Otosclerosis )

10 0 10 20 30 40 50 60 70 60 90 100 110 120

.

-

M B. Conductive Hearing Loss ( Otitis Motlia )

A. Normal Audiogram 250 500 1000 2000 4000 6000

HL occurs most often at higher frequencies Noise induced (occupational) HL is classically seen at 4000 Hz (Boilermak er's notch). Ht associated with otosclerosis is seen at 2000 Hz (Carhart’s notch)

20 30 40 50 60 70 60 90

«| TO § W 5 90

10 0

< 10

250 500 1030 2000 4000 6003

10 20

250 500 1000 2000 4000 6000

-

/

10 0

10 20 30

•

41 ,

50 60 . 70 80 90 .

too

no D. Sensorineural

120

Hearing Loss ( Noise Induced )

—

20 30

>

40 50 60 70 SO

100

. -

10 0 10

E. Sensorineural

110 120

Hearing Loss ( Presbycusis)

.

Figure 16 Types of hearing loss and associated audiograms of a left ear

PURE TONE PATTERNS

1. Conductive Hearing Loss ( see Figures 16B and 16 C) • BC in normal range • AC outside of normal range • gap between AC and BC thresholds > 10 dB (an air-bone gap) 2. Sensorineural Hearing Loss ( see Figures 16D and 16 E ) • both air and bone conduction thresholds below normal • gap between AC and BC < 10 dB ( no air- bone gap)

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3. Mixed Hearing Loss

• both air and bone conduction thresholds below normal • gap between AC and BC thresholds > 10 dB ( an air- bone gap)

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0T11 Otolaryngology

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Speech Audiometry Speech Reception Threshold

• lowest hearing level at which patient is able to repeat 50% of two syllable words which have equal

emphasis on each syllable (spondee words) • speech reception threshold (SRT) and best pure tone threshold in the 500 to 2000 Hz range (frequency range of human speech ) usually agree within 5 dB; if not, suspect a retrocochlear lesion or functional HL

• used to assess the reliability of the pure tone audiometry Speech Discrimination Test • percentage of words the patient correctly repeats from a list of 50 monosyllabic words • tested at 40 dB above the patients SRT, therefore degree of HL is taken into account • patients with normal hearing or CHL score >90% • rollover effect: a decrease in discrimination as sound intensity increases; typical of a retrocochlear lesion (c.g acoustic neuroma ) • investigate further if scores differ more than 20 % between ears, as asymmetry may indicate a retrocochlear lesion • best predictor of hearing aid response: a poor discrimination score indicates significant neural degeneration and hearing aids may not be the best option for the patient

.

Impedance Audiometry Tympanogram • the Eustachian tube equalizes the pressure between the external and middle ear • tympanograms graph the compliance of the middle ear system against a pressure gradient ranging from 400 to + 200 mmH 20 • tympanogram peak occurs at the point of maximum compliance: where the pressure in the external

-

canal is equivalent to the pressure in the middle ear • normal range: -100 to + 50 mmHiO

(

High

Type B

Type A

s

Jl Low

0

D

Air Pressure

Air Pressure

• Normal pressure peakatOmmHO • Note: with otosclerosis, peak is still at 0 mmH ,0 but has a lower amplitude

• Poor TM mobility indicative of MEE or perforated TM

* No pressure peak

-

0

-

Air Pressure

• Negative pressure peak

• Indicative ol Eustachian tube dysfunction

or early stage otitis media without effusion

• Note: with ossicular chain discontinuity, peak is still at 0 mm Hi 0 but has a higher amplitude

Figure 17. Tympanograms

Static Compliance

• volume measurement reflecting overall stiffness of the middle ear system

-

• normal range: 0.3 1.6 cc • negative middle ear pressure and abnormal compliance indicate middle ear pathology • in a type B curve, ear canal volumes of >2 cc in children and >2.5 cc in adults indicate TM perforation or presence of a patent ventilation tube Acoustic Stapedial Reflexes

• stapedius muscle contracts in response to loud sound • acoustic reflex threshold = 70-100 dB greater than hearing threshold; if hearing threshold >85 dB, reflex likely absent stimulating either ear causes bilateral and symmetrical reflexes for reflex to be present, CN VII must be intact with no CHL in monitored ear • if reflex is absent without CHL or severe SNHL , suspect CN VII lesion • acoustic reflex decay test ability of stapedius muscle to sustain contraction for 10 s at 10 dB normally, little reflex decay occurs at 500 and 1000 Hz • with cochlear HL, acoustic reflex thresholds are 25-60 dB • with retrocochlear HL (acoustic neuroma ), absent acoustic reflexes or marked reflex decay (>50%) within 5 s

-

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0T12 Otolaryngology

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Auditory Brainstem Response • measures neuroelectric potentials ( waves) in response to a stimulus in live dilTerent anatomic sites (see Order of the Neural Pathway sidebar, OT 9; this test can be used to determine the site of lesion) • delay in brainstem response suggests cochlear or retrocochlear abnormalities • does not require volition or co- operation of patient (therefore , value retained in children and

malingerers)

Otoacoustic Emissions • objective test of hearing where a series of clicks is presented to the ear and the cochlea generates an

echo which can be measured • signals come from outer hair cells which are a proxy for the inner hair cells which facilitate hearing • often used in newborn screening • can be used to uncover normal nearing in malingering patients • absence of emissions can be due to HL, fluid in the middle ear, or narrow EACs

Prelingual deafness: deafness occurring before speech and language are acquired Postlingual deafness: dealness occurring after speech and language

are acquired

Aural Rehabilitation • dependent on degree of H L, communicative requirements, motivation, expectations, and physical and mental abilities • negative prognostic factors

• poor speech discrimination narrow dynamic range ( recruitment ) • unrealistic expectations • types of hearing aids • BTE: behind- the -ear ( with occlusive mould or open fit which allows natural sound to pass - for less severe hearing loss) 1TE: in-the-ear, placed in concha ITC: in - the - canal , placed entirely in ear canal • C1C: contained - in - canal . placed deeply in ear canal BAHA : bone - anchored hearing aid: attached to skull ( bone conduction ) • CKOS: contralateral routing of signals • assistive listening devices direct/ indirect audio output infrared, EM radio, or induction loop systems

telephone , television , or alerting devices • cochlear implants electrode is inserted into the cochlea to allow direct stimulation of the auditory nerve for profound bilateral SNHL refractory to conventional hearing aids • established indication: postlingually deafened adults, pre and postlingually deaf children

Prelingually deaf Infants are the best candidates for aural rehabilitation because they have maximal benefit from ongoing developmental plasticity

BAHAs function based on bone conduction and arc indicated primarily for patients with CHI unilateral HL and mired HL who cannot wear conventional hearing aids. BAHAs consist of an osseointegrated titanium implant an external abutment and a sound processor. The sound processor transmits vibrations through the external abutment to the titanium implant and then directly to the cochlea

.

.

Vertigo Evaluation of the Dizzy Patient • vertigo: illusion of rotational , linear, or tilting movement of self or environment produced by peripheral ( inner ear ) or central ( brainstem - cerebellum ) stimulation important to distinguish vertigo from other potential causes of “ dizziness" (see Pigure 11, OT6 ) Table 5. Peripheral vs. Central Vertigo Symptoms

Peripheral

Central

Imbalance

Moderate - severe

Mild - moderate

Nausea and Vomiting

Severe

Variable

Auditory Symptoms

Common

Rare

Neurologic Symptoms

Rare

Common

Compensation

Rapid

Slow

Nystagmus

Unidirectional

Bidirectional Horl to nlalor vertical

Horizontal or rotatory

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Table 6. HINTS (Head Impulse -Nystagmus- Test of Skew ) Exam Test

Central ( Infarct )

Peripheral ( Vestibular Neuritis)

Sattade present Unidirectional, horizontal nystagmus

Head Impulse

No saccades

Nystagmus

Nystagmus dominantly vertical, torsional or gaze- evoked directional

Test of Skew

Abnormal

Normal

Table 7. Differential Diagnosis of Vertigo Based on History Condition

Time Course

Benign Paroxysmal Positional Vertigo ( BPPV )

Seconds, recurrent

Menit re' s Disease

Mm to h, episodic

Hearing loss

Unifbilaleral. fluctuating Unilateral

Acoustic Neuroma

Progressive

Brainstem / cerebellar infarct

Aural Fullness

Other Features Onsetwith change in position

Labyrinthitis/ H tod Vestibular Neuronitis Chronic

Tinnitus

Prcssurc /watmlh t Whistling

Prolonged

May have recent AOM Ataxia

CN VII palsy Suspect if vascular risk factors

Benign Paroxysmal Positional Vertigo Definition • acute attacks of transient rotatory vertigo lasting less than I min , initiated hv certain head positions, accompanied by torsional ( i.e. rotatory) nystagmus ( geotropic = fast phase towards the floor) • most common form of positional vertigo (50% of patients with peripheral vestibular dysfunction have BPPV )

Etiology

BPPV is the most common cause of episodic vertigo: patients are often symptomatic when rolling over in bed or moving their head to a position of extreme posterior extension (such as looking up at a tall building or getting their hair washed at the hairdresser)

• due to canalithiasis ( migration of free floating otoliths within the endolymph of the semicircular canal ) or cupulolithiasis (otolith attached to the cupula of the semicircular canal ) • can affect each of the 3 semicircular canals, although the posterior canal is affected in >90% of cases caused by: head injury', viral infection ( URT1), degenerative disease, idiopathic results in slightly different signals being received by the brain from the two balance organs, resulting in sensation of movement Diagnosis • history ( time course, provoking factors, associative symptoms) • positive Dix Hallpike maneuver (sensitivity 82%, specificity 71% )

-

Dix -Hallpike Positional Testing ( see website for video and illustrations) • the patient is rapidly moved from a sitting position to a supine position with the head hanging over the end of the table, turned to one side at 45°, and neck extended 20" holding the position for 20 s • onset of vertigo and rotatory nystagmus indicate a positive test for the dependent side • other diagnostic testing is not indicated in posterior canal BPPV Treatment

-

Signs of BPPV Seen with Dix Hallpike Maneuver • latency of 20 s • Crescendo/decrescendo vertigo lasting 20 s • Geotropic rotatory nystagmus ( nystagmus MUST be present for a positive test) • Reversal of nystagmus upon sitting

-

up

• Fatigability with repeated stimulation

• reassure patient that process resolves spontaneously • particle repositioning maneuvers • Epley maneuver ( performed by physician or by patient with the help of devices such as the DizzyllX") Brandt- Daroff exercises ( performed by patient ) • anti -emetics for N / V • posterior semicircular canal occlusion or singular neurectomy for refractory cases • drugs to suppress the vestibular system delay eventual recovery and are therefore not used

Meniere’s Disease (Endolymphatic Hydrops) Definition

• episodic attacks of tinnitus, HL, aural fullness, and vertigo lasting min to h Proposed Etiology •

inadequate absorption of endolymph leads to endolymphatic hydrops (over accumulation ) that distorts the membranous labyrinth

Diagnostic Criteria for Meniere's Disease Definite Meniere's Disease • Two or more spontaneous episodes of vertigo lasting from 20 min to 12 h • Audiometric confirmation of SNHL (low to mid frequency) • Fluctuating tinnitus and/or aural

rT

LJ

fullness

Probable Meniere's Disease • Two or more spontaneous episodes of vertigo or dizziness lasting from 20 min to 24 h • Fluctuating tinnitus and /or aural

+

fullness

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Toronto Notes 2023

OTM Otolaryngology

Epidemiology • peak incidence 40-60 yr • bilateral in 35% of cases

Clinical Features • episodic vertigo, fluctuating low frequency SNHL, tinnitus, and aural fullness, ± drop attacks ( Tumarkin crisis), ± N / V • vertigo disappears with time ( min to h ), but HL remains • early in the disease: fluctuating SNHL • later stages: persistent tinnitus and progressive HL • attacks come in clusters and can be debilitating to the patient • triggers: high salt intake, caffeine, stress, nicotine, and alcohol Treatment

• acute management may consist of bed rest, antiemetics, antivertiginous drugs (e.g. betahistine (Sere*), meclizine, diphenhydramine), and anticholinergics (e.g. scopolamine ) • long term management may include medical low salt diet, diuretics (e.g. hydrochlorothiazide, triamterene, amiloride ) Sere’ prophylactically to decrease intensity of attacks « inlratympanic gentamicin to destroy vestibular end organ , results in complete SNHL intratympanic glucocorticoids (e.g. dexamethasone) may improve vertigo symptoms surgical selective vestibular neurectomy or laby rinthectomy potential benefit for endolymphatic sac decompression or sacculotomy must monitor opposite ear, 35% of cases are bilateral

-

-

Vestibular Neuronitis (Labyrinthitis) Definition • acute onset of disabling vertigo often accompanied by N / V and imbalance without HL that resolves over days, leaving a residual imbalance that lasts d to wk • vestibular neuronitis: inflammation of the vestibular portion of CN VIII

• labyrinthitis: inflammation of both vestibular and cochlear portions Etiology

• thought to be due to a viral infection (e.g' . measles , mumps, herpes zoster ) or post -viral syndrome • only ~30% of cases have associated URT I symptoms • labyrinthitis may occur as a complication of acute and chronic otitis media, bacterial meningitis, cholesteatoma, and temporal bone fractures

Clinical Features • acute phase severe vertigo with N / V and imbalance lasting 1-5 d irritative nystagmus ( fast phase towards the offending ear) ataxia: patient tends to veer towards affected side tinnitus and HL in labyrinthitis • convalescent phase imbalance and motion sickness lasting d wk spontaneous nystagmus away from affected side gradual vestibular adaptation requires wk mo

Drop Attacks (Tumarkin's Otolithic Crisis) are sudden falls occurring without warning and without loss ol consciousness, where patient experiences feeling of being pushed down into the ground

-

-

Treatment

• acute phase

bed rest, antivertiginous drugs corticosteroids (methylprednisolone) ± antivirals bacterial infection: treat with IV antibiotics, drainage of middle ear, ± mastoidectomy

• convalescent phase

progressive ambulation, especially in the elderly vestibular exercises: involve eye and head movements, sitting, standing, and walking

Before proceeding with gentamicin treatment, perform a gadolinium enhanced MRI to rule out CP A tumour as the cause of symptoms

-

_

rt t

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0T15 Otolaryngology

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Acoustic Neuroma ( Vestibular Schwannoma) Definition

O

• schwannoma of the vestibular portion of CN VIII Pathogenesis

• tumour starts in the internal auditory canal and expands into CPA, compressing cerebellum and

Acoustic neuroma is the most common intracranial tumour causing SNHL and the most common CPA tumour

brainstem • when associated with type 2 neurofibromatosis: bilateral acoustic neuromas, juvenile cataracts, meningiomas, and ependymomas

Clinical Features

• usually presents with unilateral SNHL (chronic) or tinnitus • dizziness and unsteadiness may be present, but true vertigo is rare as tumour growth occurs slowly,

allowing for compensation to occur • facial nerve palsy and trigeminal ( V1) sensory deficit (corneal reflex) are late complications • risk factors: exposure to loud noise, childhood exposure to low dose radiation , history of parathyroid adenoma

-

In the elderly, unilateral tinnitus or SNHL is acoustic neuroma until proven otherwise

Diagnosis

• M RI of internal auditory canal with gadolinium contrast ( gold standard ) • audiogram ( to assess SNHL ) • poor speech discrimination relative to the HL • stapedial reflex absent or significant reflex decay • ABR: increase in latency of the 5th wave • vestibular tests: normal or asymmetric caloric weakness (an early sign ) Treatment • expectant management if tumour is very small or in elderly • definitive management is surgical excision • other options: gamma knife, radiation

K

Tinnitus Definition • an auditory perception in the absence of an acoustic stimuli, likely related to loss of input into neurons in central auditory pathways, that results in abnormal firing History

• subjective vs. objective (see I ' igurc 14, 0 /7) • pulsatile vs. nonpulsatile • unilateral vs. bilateral

• associated symptoms: HL, vertigo, aural fullness, otalgia , otorrhea Investigations • physical examination: cranial nerve examination, otoscopy, auscultate for bruits over the neck, mastoid , and preauricular areas for pulsatile tinnitus

• audiology

• if pulsatile

CT or magnetic resonance angiogram and venogram of the H & N to rule out vascular abnormalities • if nonpulsatile and unilateral • non contrast MRI

-

Treatment

• if a cause is found , treat the cause (e.g. drainage of middle ear effusion , embolization , or excision of arteriovenous malformation ) no treatable cause: 15% will resolve, 20% will improve, 15% will worsen, 50% will remain the with • same • primary and secondary prevention for SNHL (e.g. avoid high-volume music through headphones, ototoxic meds, smoking, high glvcemic load , and hypercholesterolemia ) • conservative management (e.g cneck zinc levels, Improve sleep, reduce stress, reduce caffeine and alcohol consumption ) • if cause is deemed benign, recognize distress that patient may be experiencing and provide

n

.

reassurance

• sound amplification (e.g. hearing aids, white noise, tinnitus instrument ) • pharmacotherapy ( e.g. melatonin )

+

consider tricyclic antidepressants and SSR1 if comorbidities include anxiety and depression • tinnitus retraining therapy • surgical management ( rare )

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Diseases of the External Ear Cerumen Impaction Is the most common cause of CHL for those 15 50 y/o

Cerumen Impaction Etiology • ear wax: a mixture of secretions from ceruminous and pilosebaceous glands, squames of epithelium, dust, and debris

Risk Factors

• hairy or narrow ear canals, in - the -ear hearing aids, cotton swab usage, osteomata Clinical Features

• CHL, tinnitus, fullness, itching, otalgia, discharge, odour, and cough

Syringing

Indications • Totally occlusive cerumen with pain , decreased hearing, or tinnitus Contraindications • Active Infection • Previous ear surgery • Only hearing car

• TM perforation

. OETM ..• Trauma

Complications

Treatment

-

• observation , cerumenolytic agents ( water dissolves cerumen better than over- the counter medications), irrigation, or manual removal

Exostoses Definition • bony protuberances in the EAC composed of lamellar bone

Etiology

• possible association with swimming in cold water

perforation

Pain

• Vertigo • Tinnitus

Otitis media Method • Establish that TM is intact • Gently pull the pinna superiorly and posteriorly • Using lukewarm water, aim the syringe nozzle upwards and posteriorly to irrigate the car canal

•

Clinical Features

• usually an incidental finding

• can cause cerumen impaction or OE, if large Treatment

• no Tx unless symptomatic (e.g. frequent OE, CHL )

Otitis Externa Definition • inflammation of EAC or auricle

Etiology

• bacterial (90% of OE ): Pseudomonas aeruginosa, Pseudomonas vulgaris, Escherichia coli, Staphylococcus aureus • fungal: Candida albicans, Aspergillus niger Risk Factors

• anatomic abnormalities: canal stenosis, exostoses, hairy ear canal • canal obstruction: cerumen , foreign body, sebaceous cyst • epithelial integrity: cerumen removal, earplugs, hearing aids, instrumentation / itching • dermatologic conditions: eczema, psoriasis, seborrhea • water in ear canal: swimming, other prolonged water exposures Clinical Features • acute

otalgia, itching, fullness, ± HL, ± ear canal pain on chewing tenderness aggravated by traction of pinna or pressure over tragus ear canal edema, erythema, ± otorrhea , ± regional lymphadenitis, ± cellulitis of the pinna • chronic pruritus of external ear ± excoriation of ear canal atrophic and scaly epidermal lining, ± otorrhea, ± HL wide meatus, but no pain with movement of auricle TM appears normal

Pulling on the pinna is extremely painful in OE , but is usually well tolerated in otitis media

j

Treatment

• microdebridement • topical antimicrobials, topical antibiotics ± topical corticosteroids antipseudomonal agents (e.g. ciprofloxacin ) or a combination therapy (e.g. Ciprodex* ) ototoxic topical agents (e.g. gentamicin, neomycin, neomycin/ polymyxin B/ hydrocortisone ) should not be used in a perforated TM

+

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Toronto Notes 2023

0T17 Otolaryngology • keep the EAC dry

• oral antibiotics if the infection has spread beyond the ear canal • ± analgesics for pain management • chronic OE: treat the underlying cause (e.g. dermatologic conditions )

Malignant (Necrotizing) Otitis Externa (Skull Base Osteomyelitis) Definition

• osteomyelitis of the mastoid or temporal bone Epidemiology

• occurs in elderly patients with DM and immunocompromised patients Etiology

• rare complication of OE • most commonly caused by Pseudomonas aeruginosa Clinical Features

Gallium and Technetium Scans 6allium scans are used to show sites of active infection. Gallium is taken up by PMN . and therefore only lights up when active Infection is present. It will not show the extent of osteomyelitis. Technetium scans provide information about osteoblastic activity and, as a result are used to demonstrate sites of osteomyelitis. Technetium scans help with Dx, whereas gallium scans are useful in follow up

-

• otalgia and purulent otorrhea that is refractory to medical therapy • granulation tissue or necrotic tissue on the floor of the auditory canal Complications

• cranial nerve palsy ( most commonly CN V11>CN X>CN XI ) • systemic infection, death Management

• imaging: high resolution temporal bone CT scan, gadolinium - enhanced MR!, technetium scan • medical emergency: hospitalization , debridement, IV antibiotics • may require OR for debridement of necrotic tissue/ bone

Diseases of the Middle Ear Acute Otitis Media and Otitis Media with Effusion • see Paediatric Otolaryngology, OT39

Chronic Otitis Media Definition

• an ear with TM perforation in the setting of recurrent or chronic ear infections Benign • dry TM perforation without active infection Chronic Serous Otitis Media

• continuous serous drainage ( straw -coloured ) Chronic Suppurative Otitis Media

• persistent purulent drainage through a perforated TM

Cholesteatoma Definition

• a cyst composed of keratinized desquamated epithelial cells occurring in the middle ear, mastoid , and temporal bone • two types: congenital and acquired

n LJ

Congenital • presents as a “small white pearl ” behind an intact TM (anterior and medial to the malleus) or as CHL • believed to be due to aberrant migration of external canal ectoderm during development • not associated with otitis media/Eustachian tube dysfunction

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0T18 Otolaryngology

Toronto Notes 2023

Acquired (more common)

• primary cholesteatoma

frequently associated with retraction pockets in the pars (laccida, pars tensa, or both a sequela of the dysfunction of the regulation of middle ear pressure often has crusting or desquamated debris on lateral surface • secondary cholesteatoma “ pearly mass" evident behind TM , frequently associated with marginal perforation may appear as skin that has replaced the mucosa of the middle ear • the associated chronic inflammatory process causes progressive destruction of surrounding bony

Mechanisms of Cholesteatoma Formation • Epithelial migration through TM perforation|2“ acquisition ) • Invagination of TM (1“ acquisition ) • Metaplasia of middle ear epithelium or basal cell hyperplasia (congenital)

structures Clinical Features

• history of otitis media (especially if unilateral ), ventilation tubes, ear surgery • symptoms

progressive HL ( predominantly conductive, although may get SNHL in late stage ) otalgia, aural fullness, fever

• signs

•

retraction pocket in TM, may contain keratinous debris TM perforation granulation tissue, polyp visible on otoscopy

malodourous, unilateral otorrhea

Complications

Table 8. Complications of Cholesteatoma Intracranial

Local Ossicular erosion: CHL

Meningitis

.

Inner ear erosion: SNHl dizziness, and/or labyrinthitis

Sigmoid sinus thrombosis

Temporal bone infection: masloidilis, pelrosilis Facial paralysis

Intracranial abscess (subdural, epidural, cerebellar )

Investigations • audiogram and non -contrast CT of temporal bones

Treatment

• surgical: mastoidectomy ± tympanoplasty ± ossicular reconstruction

Mastoiditis Definition

• infection (usually subperiosteal ) of mastoid air cells, most commonly seen approximately two wk after onset of untreated or inadequately treated AOM (suppurative) • more common in children than adults Etiology

.

• acute mastoiditis is caused by the same organisms as AOM: S'. pneumoniae, H. influenzae , M. catarrltalis , S. pyogenes , S. aureus , P aeruginosa , etc.

.

Classic Triad • Otorrhea • Tenderness to pressure over the mastoid • Retroauricular swelling with protruding ear

Clinical Features

• otorrhea • tenderness to pressure over the mastoid • retroauricular swelling with protruding ear • fever, HL, ± TM perforation ( late ) • CT radiologic findings: opacification of mastoid air cells by fluid and interruption of normal trabeculations of cells (coalescence) Treatment

Complications of AOM are rare due to rapid and effective treatment of AOM

with antibiotics

-

• IV antibiotics with myringotomy and ventilation tubes usually all that is required in acute cases • may require additional incision and drainage of postauricular abscess

• cortical mastoidectomy debridement of infected tissue allowing aeration and drainage • indications for surgery failure of medical treatment after 48 h symptoms of intracranial complications aural discharge persisting for 4 wk and resistant to antibiotics

rT LJ

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0T19 Otolaryngology

Toronto Notes 2023

Otosclerosis Definition

• fusion of stapes footplate to oval window such that it cannot vibrate Etiology • autosomal dominant, variable penetrance approximately 40% • T> M, progresses during pregnancy (hormone responsive)

Otosclerosis is the 2 nd most common cause of CHL in 15 50 y/o (after cerumen impaction )

-

Clinical Features

• progressive CHL first noticed in teens and 20s ( may progress to SNHL if cochlea involved )

• ± nonpulsatile tinnitus • TM normal ± pink blush (Schwartz’s sign ) associated with the neovascularization of otosderotic bone

-

• characteristic dip at 2000 Hz (Carhart’s notch ) on audiogram (see l igure 16C , OT 10 ) Treatment

• monitor with serial audiograms if coping with loss

• hearing aid ( AC, BC, BAHA ) • stapedectomy or stapedotomy (with laser or drill ) with prosthesis is definitive treatment

Diseases of the Inner Ear Congenital Sensorineural Hearing Loss Hereditary Defects • non syndrome associated ( 70%) often idiopathic, autosomal recessive connexin 26 (GJB2) most common • syndrome associated ( 30%)

-

•

Waardenburg: white forelock, heterochromia iridis (each eye different colour ), wide nasal bridge,

and increased distance between medial canthi Pendred: euthyroid goiter, SLC26A4 gene, enlarged vestibular aqueducts Treacher-Collins: first and second branchial deft anomalies Alport: hereditary nephritis

Risk Factors for Neonatal Sensorineural Hearing Loss • family history of permanent HL • craniofacial abnormality • prenatal infections TORCH: toxoplasmosis, other (syphilis, varicella zoster, parvovirus B 19), rubella , CMV, HSV

Zika

-

• postnatal infections bacterial meningitis, mumps, measles • neonatal intensive care unit stay >2 d • extracorporeal membrane oxygenation at birth • assisted ventilation at birth / perinatal anoxia, birth trauma ( hemorrhage into inner car ) • ototoxic drug use • hyperbilirubinemia requiring exchange transfusion Treatment

• presence of any risk factor: ABR study performed before leaving NICU and at 3 mo adjusted age • early rehabilitation improves speech and school performance

Presbycusis Definition

• SNHL associated with aging (starting in 5th and 6th decades ) Presbycusis is the most common cause of SNHL

Etiology

• hair cell degeneration • age- related degeneration of basilar membrane, possibly genetic etiology • cochlear neuron damage • ischemia of inner ear

n LJ

+

Clinical Features

• progressive, bilateral hearing deterioration initially at high frequencies, followed by middle and lower

frequencies

-

• loss of discrimination of speech, especially with background noise present patients describe people as mumbling

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OT20 Otolaryngology •recruitment phenomenon: inability to tolerate loud sounds •tinnitus

Treatment • hearing aid if patient has difficulty functioning, HL >30 -35 dB, and good speech discrimination •± lip reading, auditory training, auditory aids (doorbell and phone lights)

Sudden Sensorineural Hearing Loss Etiology

• usually idiopathic (80-90% of cases ); rule out other causes

autoimmune infectious (e.g. EBV, group A Streptococcus, HSV, herpes-zoster virus, HIV, Lyme disease, meningitis, syphilis)

• trauma

vascular (e.g. cerebrovascular disease) neoplastic (e.g. angioma, meningioma, neurofibromatosis 2, schwannoma) other (e g. ototoxins, pregnancy)

Sudden SNHL may easily be confused with ischemic brain events It is important to leep a high index of suspicion especially with elderly patients presenting with sudden SNHL as well as vertigo

.

.

.

Clinical Features • presents as a sudden onset of significant SNHL (usually unilateral ) ± tinnitus, vertigo, aural fullness Treatment

• treat the underlying cause • MRI to rule out tumour and/or Cl' to rule out ischemic/ hemorrhagic stroke if associated with any other focal neurological signs (e.g. vertigo, ataxia, abnormality of CN V or VII , weakness) • if idiopathic, intratympanic or oral corticosteroids ( prednisone I mg/ kg/d for 7 14 d ). Start within 3 d (most ideal ) up to 14 d after onset

-

Prognosis

• depends on degree of HL

• 70% resolve within 10-14 d • 20% experience partial resolution • 10% experience permanent HL

Clinical Practice Cnideline: Sudden Hearing toss Otolaryngol Head Keek Surg 201$ »ug:1H ( commendations Based on Findings • Confirm HL is sensorineural wilt aadioMlrit testing (loss of at least 30 dB affecting three

^

consecutive frequencies) . Cl or HRI not required unless indicated by history and physical • Initiate steroid treatment within 14 d ol symptom

. .

onset

Autoimmune Inner Ear Disease Etiology

• idiopathic

• may be associated with systemic autoimmune diseases (e.g. RA, SLE), vasculitides (e.g. GPA, polyarteritis nodosa), and allergies Epidemiology • most common between ages 20 -50

Clinical Features

• rapidly progressive or fluctuating bilateral SNHL • ± tinnitus, aural fullness, vestibular symptoms ( e.g. ataxia, disequilibrium, vertigo) Investigations

• autoimmune workup: CBC, ESR, ANA, rheumatoid factor Treatment

• high - dose corticosteroids; treat early for at least 30 d • consider cytotoxic medication for steroid non - responders

Drug Ototoxicity Aminoglycosides • streptomycin and gentamicin (vestibulotoxic), kanamycin , and tobramycin (cochleotoxic) • toxic to hair cells by any route: oral, IV, and topical (if the TM is perforated ) • destroys sensory hair cells: outer first , inner second ( therefore, otoacoustic emissions arc lost first )

n LJ

• high frequency HL develops earliest • ototoxicity occurs d-wk post-treatment • must monitor with peak and trough levels when prescribed , especially if patient has neutropenia and / or history of ear or renal problems • q24 h dosing recommended ( with amount determined by creatinine clearance)

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Toronto Notes 2023

• aminoglycoside toxicity displays saturable kinetics, therefore, once daily dosing presents less risk than divided daily doses

•duration of treatment is the most important predictor of ototoxicity

treatment: immediately stop aminoglycosides Analgesics and Antipyretics

• acetaminophen, NSA 1DS, and salicylates • HL with tinnitus, reversible if discontinued Others

•antineoplastic agents (e.g. bleomycin )

•loop diuretics (e.g. furosemide) and antimalarials (e.g. quinine) reversible by decreasing or stopping medications

Noise- Induced Sensorineural Hearing Loss Pathogenesis • 85-90 dB over mo or yr, single sound impulses >135 dB, or repetitive vibratory insults (e.g. jackhammer) can cause cochlear damage • bilateral SNHL initially and most prominently at 4000 Hz ( resonant frequency of the temporal bone), known as “ boilermaker's notch" on audiogram, extends to higher and lower frequencies with time (see Figure 16 D, 0770) • speech reception not altered until HL >30 dB at speech frequency, therefore considerable damage may occur before patient complains of HL • difficulty with speech discrimination, especially in situations with competing noise Phases of Hearing Loss • dependent on: intensity of sound and duration of exposure temporary threshold shift when exposed to loud sound, decreased sensitivity or increased threshold for sound may have associated aural fullness and tinnitus hearing returns to normal with removal of noise permanent threshold shift hearing does not return to previous state Treatment

• hearing aid • prevention ear protectors: muffs, plugs limit exposure to noise with frequent rest periods regular audiologic follow- up

Temporal Bone Fractures Table 9. Features of Temporal Bone Fractures Otic Capsule Involving (1)

Otic Capsule Sparing (2)

Extension Incidence

Into hony labyrinth and internal auditory meatus 10 20%

Into middle ear 70 90%

Etiology

Fronla l / occipital trauma

Laleral skull trauma

CN Pathology Hearing Loss

CN VII palsy|50%) SNHL due to direct cochlear injury

CN VII palsy (10 20%) CHL 2° to ossicular injury

Vestibular Symptoms

Sudden onset vestibular symptoms due lodirect semicircular canal injury (vertigo, spontaneous nystagmus) Intact external auditory meatus,1M t hemotympanum Spontaneous nystagmus CSF leak In Eustachian tube to nasopharynx t rhinorrhea (risk ol meningitis)

Rare

Other Features

-

-

-

TornTM or hemotympanum Bleeding from EAC Step formation in EAC CSF otorrhea Battle's sign' mastoid ecchymosis Raccoon eyes periorbital ecchymosis

-

• characterized as longitudinal or transverse relative to the long axis of the petrous temporal bone • temporal bone fractures are rarely purely transverse or longitudinal (often a mixed picture)

'

S Teddy Cameron 2002

Figure 18. Types of temporal bone

fractures

^ iJ

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OT22 Otolaryngology Diagnosis

• otoscopy

•

do not syringe or manipulate external auditory meatus due to risk of inducing meningitis via TM perforation • CT of temporal bones • audiology, facial nerve tests (for transverse fractures), Schirmer's test (of lacrimation ), stapedial reflexes if CN VII palsy • if suspecting CSF leak: look for halo sign, send fluid for P -2 transferrin or p-trace protein ( prostaglandin D synthase )

Signs ol Basilar Skull Fracture • Battle’s sign ( bruising over mastoid ) • Racoon eyes ( periorbital ecchymosis)

• CSF rhinorrheafotorrhea • Cranial nerve involvement: • facial palsy CN Vll:

-

• nystagmus » CN VI; • facial numbness » CN V

.Treatment ABCs

• medical: expectant, prevent otogenic meningitis • surgical: explore temporal bone; indications:

• CN Vll palsy ( immediate and complete) •

gunshot wound depressed fracture of external auditory meatus early meningitis ( mastoidectomy ) bleeding intracranially from sinus CSF otorrhea ( may resolve spontaneously)

Complications

• AOM ± labyrinthitis ± mastoiditis • meningitis /epidural abscess / brain abscess • post traumatic cholesteatoma

-

Facial Nerve (CN Vll) Paralysis Central Facial Paralysis

• (see Neurology. N 4) Peripheral Facial Paralysis (PFP) • mononeuropathy of the facial nerve characterized by weakness in the muscles of facial expression • classified as primary if idiopathic or secondary if ascribed etiology Etiology • congenital • infection (e.g. otitis media , mastoiditis, HSV, varicella zoster virus) • idiopathic ( Bell 's Palsy) • trauma • toxins/drugs

-

7 d • clinical diagnosis requiring > 2 major symptoms, and at least one of the symptoms is either nasal obstruction or purulent /discoloured nasal discharge • can confirm diagnosis with CT of paranasal sinuses and /or endoscopically

.

Major Symptoms (at least 2 of PODS 1 must be 0 or D )

Minor Symptoms

P

Facial Pain/Pressure/ fuHness

Headache

0

Nasal Obstruction

Halitosis

D

Purulentfdiscoloured nasal Discharge

Fatigue

S

Hyposmia/anosmia (Smell)

Dental pain Cough

Ear pam. fullness

Etiology • bacteria: S pneumoniae (35%), H. influenzae (35%), M catarrhalis, S. aureus , anaerobes (dental ) • children are more prone to a bacterial etiology, but viral is still more common • the maxillary sinus is the most commonly affected sinus • must rule out fungal causes ( mucormycosis ) in immunocompromised hosts (especially if painless black or pale mucosa on examination )

.

.

Acute Rhinosinusitis Complications Consider hospitalization if any of the following are suspected:

Orbital (Chandler's classification ) • I Preseptal cellulitis • II Orbital cetluftis • III Subperiosteal abscess • IV Orbital abscess • V Cavernous sinus thrombosis Intracranial • Meningitis Abscess

.

Bony

• Subperiosteal frontal bone abscess ("Pott's puffy tumour") • Osteomyelitis Neurologic

LJ

• Superior orbital fissure syndrome (CN Ill/lVrVI palsy, immobile globe, dilated pupils, ptosis. VI hypoesthesia ) • Orbital apex syndrome (as above plus neuritis, papilledema, decreased visual acuity)

.

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OT26 Otolaryngology

Toronto Notes 2023

Clinical Features • sudden onset of: nasal blockage/ congestion and /or purulent nasal discharge/ posterior nasal drip • ± facial pain or pressure, ihyposmia, ±sore throat • persistent symptoms >10 d or worsening symptoms > 5 d or presence of purulence for 3- 4 d with high fever (>39°C) • speculum exam: erythematous mucosa , mucopurulent discharge, pus originating from the middle meatus • predisposing factors: viral URT' l, allergy, dental disease, anatomical defects • differentiate from acute viral rhinosinusitis (course: ophthalmic -> anterior / posterior ethmoidal

2. posterior septum external carotid -> internal maxillary -> sphenopalatine 3. lower anterior septum external carotid > facial artery > superior labial artery -> nasal branch • external carotid -> internal maxillary -> descending palatine -> greater palatine • vessels anastomose to form Kiesselbach’s plexus, located in Little's area ( anterior inferior portion of the cartilaginous septum )

-

-

90% of nosebleeds occur in Little's area

-

Table 14 . Etiology of Epistaxis

Special Cases

Type

Causes

• Adolescent male with unilateral

Primary Epistaxis Secondary Epistaxis

Idiopathic or spontaneous

local

Trauma (most common ) Fractures: facial, nasal Sell induced: digital, lorcign body

Tumours

Iatrogenic: nasal, sinus, orbit surgery

Inflammation Rhinitis: allergic , non allergic Infections: bacterial, viral, fungal

Benign : polyps, inserting papilloma , angiofibroma Malignant: SCC esthesioncuroblastoma (olfactory neuroblastoma )

.

-

•

recurrent epistaxis: consider juvenile nasopharyngeal angiofibroma (JNA): this is the most common benign tumour of the nasopharynx Thrombocytopenic patients: use resorbable packs to avoid risk of re bleeding caused by pulling out (he removable pack

-

-

Nasal dryness: dry air, supplemental nasal oxygen Structural abnormalities: septal deviation , chronic septal perforation

Chemical: nasal cocaine , nasal sprays, etc Systemic

.

Coagulopathies Medications: anticoagulants, NSAIDs Hemophilias, von Willobrand disease Hematological malignancies liver failure, uremia Vascular: KIN atherosclerosis, Osler Weber Rendu disease ( hereditary hemorrhagic telangiectasia )

.

.

-

-

Others:OPA SIE

Investigations

• CBC, PT/ PTT/ INR / platelet function assay (if suspicious ofbleeding disorder) • CT as needed Treatment

• locate bleeding and achieve hemostasis 1. ABCs

• lean patient forward to minimize swallowing blood and avoid airway obstruction • apply constant firm pressure for 15 to 20 min on cartilaginous part of nose ( not bony pyramid ) while the head is in neutral position • if significant bleeding, assess vitals for signs of hemorrhagic shock ± IV NS, cross match blood

-

2. Determine Site of Bleeding • anterior / posterior hemorrhage defined by location in relationship to bony septum • visualize nasal cavity with speculum • use cotton pledget with topical lidocaine ± topical decongestant (Otrivin*) to help identify area of bleeding (often anterior septum ) 3. Control the Bleeding • first-line: topical decongestant (Otrivin*) if first-line fails and bleeding source adequately visualized, cauterize with silver nitrate • do not cauterize both sides of the septum at one time due to risk of septal perforation from loss of

septal blood supply

A. Anterior hemorrhage treatment if failure to achieve hemostasis with cauterization place anterior pack with expandable nasal tampons (Merocel*) or fabric sponges ( Rapid Rhino Riemann )* consider lubricated absorbable packing (e.g. Gelfoam wrapped in Surgicel*) for patients with coagulopathy or on anticoagulation medication to prevent recurrent epistaxis from packing

n LJ

removal

+

alternatively, use a half inch Vaseline*-soaked ribbon gauze strips layered from nasal floor toward nasal roof and extending to posterior choanae can also apply l-'loseal* ( hemostatic matrix consisting of topical human thrombin and crosslinked gelatin ) if other methods fail

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OT28 Otolaryngology

B. Posterior hemorrhage treatment • if unable to visualize bleeding source, the source is likely posterior • place posterior pack* using a Foley catheter, gauze pack, or Epistat* balloon • subsequently, layer anterior packing bilaterally • admit to hospital with packs in for 3 d • watch for complications: hypoxemia ( nasopulmonary reflex ), toxic shock syndrome ( remove packs immediately), pharyngeal fibrosis/stenosis, alar/septal necrosis, aspiration C. If anterior/ posterior packs fail to control epistaxis transnasal endoscopic sphenopalatine artery ligation + /- anterior ethmoid artery ligation by otolaryngology or embolization of culprit arterial supply by interventional radiology

± septoplasty

'antibiotics for any posteri or pack or any pack left for >48 hduetorid[ of Irak shock syndrome

4. Prevention

•prevent drying of nasal mucosa with humidifiers, saline spray, or topical ointments •avoidance of irritants • medical management of HTN and coagulopathies

Hoarseness Definitions • change in voice quality, ranging from voice harshness to voice weakness • reflects abnormalities anywhere along the vocal tract from oral cavity to the lungs • dvsphonia: a general alteration in voice quality • aphonia: no sound emanates from vocal folds

Acute Laryngitis

If hoarseness is present for >2 wk in a smoker, laryngoscopy must be done to rule out malignancy

Vocal Cord Paralysis

• Unilateral: Affected cord lies in the

Definition

paramedian position, inadequate

• hoarseness • environmental: toxic fume inhalation

-

Clinical Features

• URTI symptoms, hoarseness, aphonia, cough attacks

• true vocal cords erythematous/edematous with vascular injection and normal mobility Treatment

• usually self-limited, resolves within 1-2 wk • voice rest • humidification • hydration • avoid irritants (e.g. smoking, caffeine ) • treat with antibiotics if there is evidence of coexistent bacterial pharyngitis • treat with proton pump inhibitors if there is evidence of reflux

-

glottic closure during phonation weak, breathy voice. Usually medializes with time, whereby phonation and aspiration improve. Treatment options include voice therapy, injection laryngoplasty (Radiesse). mediatization using silastic block, recurrent laryngeal nerve reinnervation (RUf anastomosis to ansa cervicalis) • Bilateral: Cords rest in midline, therefore voice remains unchanged but respiratory function is compromised and may present as stridor. If no respiratory issues, monitor closely and wait for improvement. If respiratory issues, try CPAP or intubate if necessary. The patient will likely require vocal cord lateralization, arytenoidectomy posterior costal cartilage graft, or tracheotomy.Selective nerve reinnervation (Marie technique) in the proper hands may reestablish

.

movement

Chronic Laryngitis Definition

• >3 wk inflammatory changes in laryngeal mucosa Etiology

-

repeated attacks of acute laryngitis • infectious: chronic rhinosinusitis with postnasal drip • mechanical: chronic voice strain • environmental: chronic irritants (dust, smoke, chemical fumes), chronic alcohol use • esophageal disorders: GERD, Zenker's diverticulum, hiatus hernia • systemic: allergy, hypothyroidism, Addison's disease

n u

Clinical Features • chronic dvsphonia • cough, globus sensation, frequent throat clearing 2° to GERD • laryngoscopy: erythematous and thickened cords with ulceration/granuloma formation and normal mobility, rule out malignancy

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OT29 Otolaryngology Treatment

• remove offending irritants • treat related disorders (e.g. antisecretory therapy for GERD) • speech therapy with vocal rest

• ± antibiotics ± steroids to decrease inflammation

Vocal Cord Polyps Definition

• structural manifestation of vocal cord irritation • acutely, polyp forms 2 ” to capillary damage in the subepithelial space during extreme voice exertion

.

Vocal Cords: Polyps vs Nodules

Etiology • most common benign tumour of vocal cords • voice strain (e.g. muscle tension dysphonia ) • laryngeal irritants (e.g. GERD, allergies, tobacco )

Unilateral

Acute onset

Gradual onset

Epidemiology

May resolve spontaneously

Often follow a chronic course

.

• ages 30-50 y/o M>E

Nodules

.

BJaleral

asymmetric

Subepithelial capillary Acute: submucosal hemorrhage or edema

Clinical Features • primary symptom is dysphonia ± dyspnea ( if polyps are large) • other symptoms: hoarseness, aphonia, cough attacks • pedicled or sessile polyp on free edge of vocal cord • typically, polyp is asymmetrical, soft, and smooth • more common on the anterior 1/3 of the vocal cord Treatment

• avoid irritants • voice therapy may improve voice • vocal fold steroid injections ( percutaneous or transoral ) • endoscopic laryngeal microsurgical removal if persistent or if high - risk of malignancy

Soli,smooth, fusiform

.

pedunoiated mass

Acute:small, discrete nodules Chronic:hard, while, thickened, fibrosed nodules

Proton pump inhibitor Vocal rest with whispering, hydration, voice therapy

Surgical enision if

Surgical excision as

persistent or in the presence of risk factors for laryngeal cancer

last resort

Vocal Cord Nodules Definition

• vocal cord callus, bilateral by definition and symmetric

• also known as “screamer’s" or “singer’s" nodules Etiology

• early nodules occur secondary to submucosal hemorrhage

• mature nodules result from hyalinization, which occurs with long- term voice abuse

• chronic voice strain • frequent URT1, smoking, alcohol consumption Epidemiology

• frequently in singers, children , bartenders, and school teachers • I >M Clinical Features

• hoarseness worst at end of day • on laryngoscopy • bilateral symmetric nodules at the junction of the anterior 1/ 3 and posterior 2 /3 of the vocal cords ( point of maximal cord vibration ) • chronic nodules may become fibrotic, hard, and white Treatment

• primary treatment is voice rest and voice therapy • hydration • avoid irritants • surgery rarely indicated for refractory nodules

i

n LJ

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OT30 Otolaryngology

Recurrent Respiratory Papillomatosis Definition • small, benign wart like growths ( papillomas ) in the respiratory tract

-

Etiology

• most commonly HPV types 6, 11, but can be caused by types 16, 18, 31, 33 • possible hormonal influence, possibly acquired during delivery through birth canal Epidemiology

• biphasic distribution birth to puberty ( most common laryngeal tumour) • adult onset (age >12 y)

-

Clinical Features

• progressive hoarseness, stridor, and respiratory distress; less commonly wheezing, chronic cough , recurrent pneumonia, dyspnea, hemoptysis, dysphagia , failure to thrive, apneic events • can seed into tracheobronchial tree • highly resistant to complete removal, high tendency of recurrence • some juvenile papillomas resolve spontaneously at puberty • may undergo malignant transformation to squamous cell carcinoma Investigations • flexible nasolaryngoscopy shows wart-like lesions with vascular core in supraglottic larynx and

trachea • bronchoscopy with biopsy to confirm diagnosis and rule out malignancy • chest x- ray followed by CT chest if indicated, findings of pulmonary involvement require referral to respirology • for high risk patients, rule out TB, HIV

-

Treatment

• prevention using quadrivalent HPV recombinant vaccine • suspension microlaryngoscopy with laser removal and preservation of normal mucosa is gold standard ( not curative, goal is improvement in voice and /or breathing) preferably with CO:or KTP laser

• other options include microdebridement and cold steel

• consider systemic adjuvants if requiring > 4 surgeries/ yr. These include quadrivalent HPV recombinant vaccine, bevacizumab, cidofovir, interferon, indole-3-carbinol • PP1 if concomitant GERD

Laryngeal Carcinoma • see Neoplasms of the Haul < uni Neck , 0735

Salivary Glands Sialadenitis

Bilateral enlargement of the parotid glands may be a manifestation of a systemic disease , such as mumps HIV, Sjogren 's, or an eating disorder (Le. anorexia, bulimia )

.

Definition

• inflammation of salivary glands Etiology

• viral most common ( mumps) • bacterial causes: S. aureus, S. pneumoniae, H . influenzae • obstructive vs. non obstructive • obstructive infection involves salivary stasis and retrograde bacterial flow

-

.•

Predisposing Factors HIV anorexia / bulimia • Sjogren’s syndrome • Cushing’s syndrome, hypothyroidism , DM • hepatic/ renal failure • medications that increase stasis: diuretics, tricyclic antidepressants, (5-blockers, anticholinergics, antibiotics • sialolithiasis (can cause chronic sialadenitis)

Mumps usually presents with bilateral parotid enlargement SNHl t orchitis *

2 wk should be investigated for possible neoplastic causes Table 15. Prevalence of Acquired Causes of Neck Lumps According to Age Age |yr )

Possible Causes of Neck Lump

•40 > 40

1 Inllammalory

. .

. .

2 Congenllal/Develepmentii! 2 Inflammatory

1 Neoplastic

.

3 Neoplosllc 3, Congenital

Differential Diagnosis

• congenital

• lateral ( branchial cleft cyst, laryngocele, plunging ranula, lymphatic / venous / venolymphatic malformation )

• midline ( thyroglossal duct cyst , dermoid cyst, teratoma , thyroid / thymus anomaly, vascular malformation )

• infectious/inflammatory

• reactive lymphadenopathy ( 2° to tonsillitis, pharyngitis) • infectious mononucleosis

-

-

Kawasaki, Kikuchi Fujimoto, Kimura, Cat scratch, Castleman, Rosai - Dorfman disease

• HIV

• sialolithiasis, sialadenitis thyroiditis

• granulomatous disease

mycobacterial infections

• sarcoidosis

• neoplastic lymphoma salivary gland tumours thyroid tumours metastatic malignancy (“ unknown primary") lipoma, fibroma , hemangioma, nerve or nerve sheath tumour

n LJ

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OT33 Otolaryngology

Evaluation Investigations

• history and physical (including nasopharynx and larynx) • all other investigations and imaging are dependent upon clinical suspicion following history and physical congenital: CT with contrast, excisional biopsy inflammatory/infectious: W BC (infection vs. lymphoma), trial of antibiotics, chest radiograph, Mantoux TB test, CT with contrast, FNA neoplasms: thyroid function tests and scans, CT with contrast, FNA ( histologic examination ), panendoscopy ( identification of possible primary tumour) panendoscopy: nasopharyngoscopy, laryngoscopy, esophagoscopy, bronchoscopy with washings, and biopsy' of suspicious lesions primary identified 95% of time -> stage and treat primary occult identified 5% of time: excisional biopsy of node for histologic diagnosis -> manage with radiotherapy and /or neck dissection (SCC)

Congenital Neck Masses

Inflammatory vs. Malignant Neck Masses Inflammatory Neoplastic History

Painful

Y

H £N infection Y Fever Y N Weight loss Ct risk factors H

YiN H

Y Y

Younger

Older

lender

Y

H

Rubbery

Y

H

Rock hard Mobile

N Y

r (bed

Age Physical

Y

Branchial Cleft Cysts/Sinuses/Fistulae Embryology • at 4th wk of embryonic development, there are 4 pairs of branchial arches and 2 rudimentary arches, which are separated internally by pouches and externally by clefts • branchial anomalies form when pouches and clefts persist and fall into 3 types: 1. branchial fistula: persistent communication between skin and G1 tract 2. branchial sinus: blind-ended tract opening to skin 3. branchial cyst: persistent cervical sinus with no external opening Clinical Features

• 2nd branchial cleft malformations most common • sinuses and fistulae present in infancy as a small opening anterior to the SCM muscle cysts present as a smooth, painless, slowly enlarging lateral neck mass, often following a URT'I • 1st branchial cleft malformations present as sinus/fistula or cyst in preauricular area (Type I ) or on face over angle of mandible ( T ype 11) • 3rd branchial cleft malformations present as recurrent thyroiditis or thyroid abscess and have a tract which usually leads to the left pyriform sinus. Air on CT scan in or near the thyroid gland is pathognomonic for this anomaly • there is controversy whether 4th branchial cleft anomalies exist, as they may be remnants of the thyrothymic axis Treatment

• surgical removal of cyst or fistula tract • if infected: allow infection to settle before removal (antibiotics may be required )

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Toronto Notes 2023

External carotid a. Internal carotid a . ;

Middle constrictor m. Hyoid

Thyrohyoid membrane

Type I anomaly

Thyroid cartilage

Type II anomaly

Common carotid a.

A. First Branchial Anomaly

B. Second Branchial Anomaly

Thyroid cartilage

Internal carotid a . External carotid a Hyoid

Cricoid cartilage

^

XII

Left common carotid a . Right common carotid a .

A

-

i

Thyroid cartilage

Cricoid cartilage

P

Left subclavian a. Brachiocephalic trunk

Arch of aorta

I £

C. Third Branchial Anomaly

D. Fourth Branchial Anomaly

s

Figure 19. Branchial cleft anomalies

Thyroglossal Duct Cysts Embryology vestigial remnant of tract made by thyroid gland as it travels from its origin as a ventral midline diverticulum at the base of the tongue, caudal to the junction of 3rd and 4th branchial arches (foramen cecum ), and migrates to the inferior aspect of the neck ( see Figure 19 )

•

Clinical Features • most common congenital cervical anomaly • usually presents in childhood or from ages 20 - 40 as a midline cyst that enlarges with URT1 and elevates with swallowing and tongue protrusion • location can he suprahyoid or infrahyoid • may have fibrous cord, dysphagia, globus sensation

Thyroglossal duct cysts are the most common congenital neck mass found in children

Treatment • preoperative antibiotics to reduce inflammation ( infection before surgery is a well-described cause of

rT

recurrence ) • small potential for neoplastic transformation, so complete excision of cyst and tissue around tract up to foramen cecum at base of tongue, with removal of central portion of hyoid bone ( Sistrunk

c

j

procedure ) recommended

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OT35 Otolaryngology

Lymphatic, Venous, or Mixed Venolymphatic Malformations Definition

• lymphatic malformation arising from vestigial lymph channels of neck Clinical Features

• commonly identified in many fetuses, but regress before birth and never cause a clinical problem • usually present by age 2 • macrocystic: soft , painless compressible mass ( lymphatic dilation ) with skin discolouration • microcystic: soft , noncompressible masses with mucosal or skin vesicles • may have dysphagia , dyspnea, possible pain with acute infection • infection or trauma causes a sudden increase in size Treatment

• can regress spontaneously after bacterial infection , therefore do not plan surgical intervention until several mo after infection • macrocystic lesions can be treated by surgical excision or sclerotherapy (doxycydine ) • microcystic lesions are difficult to treat, but can be debulked if it will not cause loss of function of normal structures, or injected with sclerotherapy ( bleomycin ) in surrounding tissues

Neoplasms of the Head and Neck

All patients presenting with a H&N mass should be asked if they are experiencing the following obstructive, referred, or local symptoms Oropharyngeal; Odynophagia, dysphagia, non healing oral ulcers Otologic Otalgia HL Laryngeal; Dyspnea or stridor ( positional vs. non positional). hoarseness, dysphonia positional vs. non positional Nasopharyngeal: Recurrent epistaxis, unilateral nasal obstruction, persistent ihinorrhea or sinusitis Hemoptysis, hematemesis

-

-

Pre Malignant Disease

• lichen planus lacy white lines of oral mucosa + /- erythema exact cause unknown, thought to be immune- mediated treatment: topical corticosteroids (first-line), topical calcineurin inhibitors (second-line) risk of malignant transformation 5-10%, follow-up every 6-12 mo • leukoplakia white keratotic plaque/ patch of oral mucosa that cannot be rubbed off treatment; surgery, cryosurgery, laser ablation, retinoids risk of malignant transformation 5-20%, follow- up every 3-12 mo • ervthroplakia • red mucosal plaque adjacent to normal mucosa • commonly associated with epithelial dysplasia associated with carcinoma in situ or invasive tumour in 40% of cases • treatment: similar to leukoplakia • dysplasia (a feature of pre malignant lesions) • histopathologic presence of mitoses and prominent nucleoli involvement of entire mucosal thickness carcinoma in situ • associated progression to invasive cancer 15 30%

.

-

-

Detection of cervical lymph nodes on physical exam False negative rate:15 30% False positive rate; 30 40%

-

-

-

=

Investigations

-

-

• initial metastatic screen includes chest x ray • scans of liver, brain , and bone only if clinically indicated • CT scan superior to MK1 for the detection of pathologic nodal disease and bone cortex invasion

.•• ±

Pathological lymphadenopathy defined radiographically as A jugulodigaslric node >1.5 cm in diameter, or a retropharyngeal node >1 cm in diameter A node of any sire which contains central necrosis

MKI superior for discriminating tumour from mucus and detecting bone marrow invasion PET scans endoscopy with biopsy

Treatment

• treatment depends on: • histologic grade of tumour, stage

physical and psychological health of patient facilities available, expertise and experience of the medical and surgical oncology team • in general: 1° surgery for malignant oral cavity tumours with radiotherapy reserved for salvage or poor prognostic indicators 1° radiotherapy for nasopharynx, oropharynx, hypopharynx, and larynx malignancies with surgery reserved for salvage, although laser endoscopic surgery for early stage larynx cancer is an option and 1° surgery for advanced (T4) pharyngeal and laryngeal cancer is the standard of care there is a growing interesting in studying 1° surgery (transoral surgery (TOS)) for OPC palliative chemotherapy for metastatic or incurable disease concomitant chemotherapy increases survival in advanced disease chemotherapy has a role as induction therapy prior to surgery and radiation panendoscopy (bronchoscopy, esophagoscopy, laryngoscopy and pharyngoscopy) to detect 1° disease when lymph node metastasis is identified anti-epidermal growth factor receptor treatment (cetuximab, panitumumab) has a role as concurrent therapy with radiation for SCC of the H & N (for advanced local and regional disease)

o

Common sites of distant metastases for H& N neoplasms ( most common to least common ) lungs > (ver > bones

Risk Factors for H& N Cancer

• Smoking • EtOH (synergistic with smoking) • Radiation

• Occupational/environmental

exposures • Oral HPV infection (independent of smoking and EtOH exposure) Family history of cancer Previous cancer

..

n

LJ

+ The smaller the salivaiy gland, the greater the likelihood that a mass in the gland is malignant

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OT36 Otolaryngology

Toronto Notes 2013

Prognosis

synchronous tumours occur in 0.8 - 18% of patients late development of second primary is most common cause of post- treatment failure after 36 mo

• •

Table 16 . Quick Look - Up Summary of H & N Malignancies - Etiology and Epidemiology Etiology

Epidemiology

Risk Factors

Mean age: 50 - 60 yr M> f Most common site of HtH cancers 50 % on anterior 213 of tongue

Smoking.' EtOH Poor oral hygiene leukoplakia, erythroplakia Lichen planus, chronic inflammation Sun eiposure - lip HPV infection Plummer-Vinson syndrome GeneticfEtlmic

Oral Cavity

95% SCC Others: sarcoma, melanoma, minor salivary gland tumour

HPV nd Snrvival ot Patients with OPC KLItl 2010:363(1) 4- 35 ItProds te- jsoedve araysa of oatesis with stage 111 or IK o optaryogea SCC er: ed is a KI comja-ng acctoaSd ot standard rectoatos ‘ radolherapy.eacS c traced wiS CBfhato ttfraoy. Results:;;- ar 3 yt oxeraCsumal rate - bob! HPV-josibie treour treaties aras.Pabeds had Setter - ass of ore -a il ssnua I at 3 yr (823% is. 57.1%) a -d a 51' rad ct x n risk of death (Hazard Katie 0.42.55 % 0 017-0.561after a ssteg So- age. rate,honour andnodal stage.toSacco eiposu-e. a-rdteatseut. Siaaarj:I-etBMrHFIfstatzs mpatertsat; t>-orarpgaa SCC is a strj-g aod dependent prognostic Factor for s»mal.

-

^

.

Nose and Paranasal Sinus

75 - 80 % SCC Mean age: 50 -70 yr Adenocarcinoma (2nd most common) and Rare tumours mucoepidermoid incidence in last 5 -10 yr 99% in maxillary/ ethmoid sinus 10% of nose and paranasal sinus tumours arise from minor salivary glands

Woodi'shoe/teitile industry Hardwood dust (nasal'ethmoid sinus) Nickel, chromium (maxillary sinus) Air pollution Chronic rhinosinusitis

*

.

.

^

.

Carcinoma of the Pharynx - Subtypes (Nasopharynx Oropharynx Hypopharynx and Larynx)

Nasopharynx Mean age: 50 -59 yr M:F 2.4:1 Incidence 0.8 per 100000 100x increased incidence in Southern Chinese

90% SCC 10% lymphoma

-

~

EBV Salted fish Nickel eiposure Poor oral hygiene Genetic - Southern Chinese

Oropharynx

95% SCC - poorly differentiated Up to 70% of OPC attributable to HPV

Smoking EtOH Mean age: 50 -70 yr HPV patients with OPC are approximately 10 HPV 16 infection yryounger Prevalence of HPV OPC has increased by 225% from 1988 to 2004 M:F 4:1

-

-

Summary of Treatment for Head and Neck Masses Sage IN: single modality Stage UL1V: dual modality

-

Hypopharynx

95% SCC 3 sites 1. pyriform sinus ( 60%) 2. postcricoid (30%) 3. posterior pharyngeal wall (10%)

.

Mean age: 50 - 70 yr M> F 8-10 % of all HAN cancer

Smoking ' EtOH

Mean age: 45 -75 yr M:F-10:1 45% of all HAN cancer

Smoking ElOH

Mean age: 55 - 65 yr M- F 3 6% of all HAN cancer Percentage of malignant tumours in each gland: Parotid 15 -25% Submandibular 37- 43% Minor salivary >80%

Radiation eiposure

Children Adults 60 yr Nodules more common in females Malignancy more common in males

Radiation eiposure Family history - papillary CA or multiple endocrine neoplasia (MEN II) Older age Male Papillary - Gardner's syndrome Cowden syndrome, FAP

Larynx

SCC most common 3 sites 1. supraglotlic (30-35%) 2. glottic (60 - 65%) 3. subglottic (1%)

Salivary Gland

40% mucoepidermoid 30% adenoid cystic 5% acinic cell 5% malignant mixed 5% lymphoma

-

-

Thyroid (90% benign 10% malignant) >80% papillary

5-15% follicular 5% medullary < 5% anaplastic 1- 5% Hurthle cell 1 2% metastatic

-

.

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OT37 Otolaryngology

Table 17. Quick Look- Up Summary of H& N Malignancies - Diagnosis and Treatment Clinical Features

Investigations

Treatment

Prognosis

Biopsy

1“ surgery local resection * neck dissection t reconstruction 2" radiation

Syr overall survival 11/12: 75% 13/14: 30 - 35% Poor prognostic indicators Depth ol invasion, close surgical margins location (longue worse thanHoot ol moulh) Cervical nodes

Oral Cavity

Asymptomatic neck mass (30%) Non - healing ulcer « bleeding Oysphagia, sialorrhea,dysphonia Oral fetor , otalgia, leukoplakia, or crythroplakia ( pre malignant changes or clinically isolated syndrome)

Cl

Nose and Paranasal Sinus Early Symptoms Unilateral nasal obstruction Epistaxis, rhinorrhea

Cl/ MIII Biopsy

Surgery and radiation Chcmoradiolherapy

5 yr survival: 30 - 60% Poor prognosis 2o lo lale presentation

Late Symptoms

V lo invasion ol nose, orbit, nerves, oral cavity, skin, skull base, cribriform plate

Nasopharynx

Cervical nodes ( 60 -90%) Hasal obstruction, epistaxis

Hasopharyngoscopy

Unilateral otitis media t HL CN III to VI IX toXII (25%) Proptosis, voice change, dysphagia

CT/ MRI

.

1° radiation t chemoradiation Surgery for limited or recurrent disease

5 yr survival 11: 79% 12:72% 13:50-60% 14:36 -42%

1” radiation,consider therapy de- intensification for HPV* patients 2" surgery local resection tneck dissection reconstruction 1“ surgery emerging role of Iransoral Robotic Surgery

5 yr overall survival Stratified byTNM stage (I II Ill, IV) HPV negative OPC (70% 58% 50% 30%) HPV positive OPC ( 92% 87%, 74% 40%) HPV positive OPC further stratified by stage, age and smoking pack years|PY) group I (I1- 3N 0 - H 2c, s20 PY|: 89% group II (T1-3N0 - N2c >20 PY): 64% group III (14 or N3 age s70): 57% group IVA (14 or N3, age >70): 40%

1“ radiation 2" surgery

5 yrsuivtval 11: 53% 12/ 13: 36 39% 14: 24%

Biopsy Ct / MRI

Early stage: single modality (radiation or surgery) lale singe: rnultimodalily (surgery, radiotherapy, chemotherapy)

5 yr survival 14: >40% (surgery with radiation) Control rale early lesions: >90% (radiation) 10 to 12% of small lesions fail radiotherapy

FNA MRI /CI/U / S

1° surgery * neck dissection

Parotid 10 yr survival: 85.69 43 and 14% for stages 111014 Submandibular 2 yr survival: 82% 5 yr: 69% Minor salivary gland 10 yr survival: 83.52. 25.23% for stages 11 to 14

Biopsy

Oropharynx

Odynophagia, otalgia Ulcerated/enlarged tonsil Fixed tongueflrismus/dysarthria Oral fetor, bloody sputum HP 1/ OPC predominantly arises at base of tongue or tonsillar region Cervical lymphadenopathy (60%) Distant mets: lung/bone /liver |7%)

-

Biopsy Determine HPV status via RT-PCR: positive if presence of HPV DNA and p16 over expression Cl

.. . . . . .

.

.

.

Hypopharynx Dysphagia, odynophagia Otalgia, hoarseness Cervical lymphadenopathy

Pharyngoscopy Biopsy

Cl

-

larynx

.

Oysphagia odynophagia, globus Otalgia, hoarseness Oyspnea / slridor Cough / hemoptysis Cervical nodes (rare with glottic CA|

laryngoscopy

Salivary Gland

Painless mass (occ. pain is possible) CN VII palsy Cervical lymphadenopathy Rapid growth Invasion of skin Constitutional signs/ symptoms

Postoperative radiotherapy Chemotherapy if unresectable

. .

.

Thyroid Thyroid mass, cervical nodes Vocal cord paralysis,hoarseness Hyper/hypothyroidism Dysphagia

FNA U/ S

1” surgery

Recurrences occur within Syr Need long- term follow -up:clinical exam, thyroglobulin

Sestamibi

Wide surgical excision Postoperative monitoring of serum Ca2’

Recurrence rates 1 yr: 27 % 5 yr: 82% 10 yr:91% Mean survival: 6 - 7 yr

I trfor intermediate and high-risk well differentiated thyroid cancer

'

Parathyroid Symptoms of hypercalcemia Neck mass Bone disease, renal disease Pancreatitis

r

.t

CT imaging (or Head and Neck Malignancies are done with contrast for the neck and chest. CT head is not routinely order.

I J

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OT38 Otolaryngology

Thyroid Carcinoma Table 18 . Bethesda Classification of Thyroid Cytology Diagnostic Category

Risk of Malignancy

Non -diagnostic or unsatisfactory

1 - 4%

Benign

0 3%

follicular lesion of undetermined significance or atypia ofundetermined significance Follicular neoplasm or suspicious fora follicular neoplasm

5-15%

-

15 - 30%

60 - 75% 97 99%

Suspicious for malignancy

-

Malignant

The Bethesda System lot ftopoiting ThyioldCytopathology fTBSRTCIisa repotting system lot thyroid FNA .

Table 19. Thyroid Carcinoma Papillary

Incidence|% of all thyroid cancers)

Follicular

-

-

4 6%

90 92 %

Medullary

Anaplastic

Lymphoma

1-2%

3 4 cm in sice Hyperthyroidism not amenable to medical therapy

-

Paediatric Otolaryngology Acute Otitis Media Definition

• both presence of MEE/ M FI and acute onset of MEE/ MEl symptoms Epidemiology • most frequent diagnosis in sick children visiting clinicians’ offices and most common reason for

antibiotic administration

-

• peak incidence between 6-15 mo: 85% of children have > 1 episode by 3 yr old • seasonal variability: peaks in winter

Etiology • primary defect causing AOM : Eustachian tube dysfunction /obstruction > stasis/colonization by

pathogens

-

.

.

• bacterial: S. pneumoniae , non typeable H . influenzae, M catarrhalis , group A Streptococcus , S aureus • viral: RSV, influenza, parainfluenza, adenovirus • commonly due to bacterial/viral co-infection

Predisposing Factors

• Eustachian tube dysfunction / obstruction • swelling of tubal mucosa

.

URTT

allergic rhinitis

chronic rhinosinusitis obstruction /infiltration of Eustachian tube ostium tumour: nasopharyngeal carcinoma (adults ) adenoid hypertrophy ( by maintaining a source of infection rather than obstruction ) barotrauma ( sudden changes in air pressure ) • inadequate tensor palati function: cleft palate (even after repair ) • abnormal Eustachian tube Down syndrome ( horizontal position of Eustachian tube), Crouzon syndrome, cleft palate, and Apert syndrome • aberrant function of: cilia of Eustachian tube: Kartagener’s syndrome mucus secreting cells • capillary network that provides humoral factors, PM Ns, phagocytic cells • immunosuppression / deficiency due to chemotherapy, steroids, DM, hypogammaglobulinemia , cystic fibrosis

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Toronto Notes 2023

OT IO Otolaryngology Risk Factors

• non -modifiable: young age, family history of OM, prematurity, orofacial abnormalities, immunodeficiencies, Down syndrome, race, and ethnicity : lack of breastfeeding, daycare attendance, household crowding, exposure to cigarette modifiable • smoke or air pollution , pacifier use Protective Factors

• breastfeeding • xylitol

Clinical Assessment of SOM in Paediatrics JAMA 2010:304 : 2161 69 In assessment ot AOM in pedulrks, tar pain is Die most useful symptom with an It between 3.0 -7.3. Useful otoscopic signs include erythematous (It 8.4. 95% Cl Ml ), ttoudy (It 34.95% Cl 28-42 ). bulging (It 51, 95% Cl 38-73).and immobile tympanic membrane ltd 31, 95% Q 26 -37) on pneumatic otoscopy.

Pathogenesis

• obstruction of Eustachian tube -> air absorbed in middle ear -> negative pressure (an irritant to middle ear mucosa ) -> edema of mucosa with exudate/clTusion -> infection of exudate from nasopharyngeal

secretions Clinical Features • triad of otalgia, fever (especially in younger children ), and CHL • rarely tinnitus, vertigo, and /or facial nerve paralysis • otorrhea if TM perforated

expectant obseruatioo.

• infants/ toddlers

•

Antibiotics lot AON la Children Cochrane D 6 Systtev 2013:1X0000219 Study: Meta - analysis ol Kardonired Controlled trials (dCIs) on children (1-15 mo) with acute otitis media comparing any antibiotic regime to placebo and

ear- tugging ( this alone is not a good indicator of pathology ) HL , balance disturbances ( rare ) irritable, poor sleeping

Data Sources: Cochrane Central Register ol Controled trials ( 2012 issue 10). MEDLINE (1966 to October 20)2) . 010ME0 UNE (1958 to 1965|. EMBASE (January 1990 to November 2012) Cu n ent Contents 11966 to November 2012) CINAHl (2000 lo November 20121 and UlACS (2008 to November 2012) without language restrictions. Main Outcomes:t) Pam at 24 h, 2 3 d, and 4 7 d; 2| Abnormal tympanometry Endings:3|1M perforation ; 4) Contralateral otitis; 5|AOM recurrences; 6) Serious com plications from AOM; 7) Adverse eltects from antibiotics. Results: treatment with antibiotics had no significant Impact on pain at 24 h. However, pa n at 2 3 il and 4 7 d was lower in the antibiotic groups with a HHI of 20. Antibiotics had no significant effect on tympanometry Endings, number of AOM recurrences, or severity ol complications. Antibiotic treatment led toa significant reduction in IM perforations ( NHI 33) and halved contralateral AOM (NNT tl).Adverse events (vomiting, diarrhea, or rash ) occotred more olte n in children taking antibiotics. Conclusion: Hit role of antibiotics is largely restricted lo pain control at 2 7 d but mast (82 %) settle without antibiotics. Ihts can also be achieved by analgesics. However, antibiotic treatment can reduce nsk of IM perforation and contralateral AOM episodes. These benefits must be weighed against risks of adverse events from antibiotics.

.

vomiting and diarrhea

.

-

anorexia • otoscopy of TM

hyperemia bulging, pus may be seen behind TM loss of landmarks: handle and long process of malleus not visible

-

-

Diagnosis

• history acute onset of otalgia or ear tugging in a preverbal child, otorrhea, decreased hearing unexplained irritability, fever, upper respiratory symptoms, poor sleeping, anorexia, N / V, and

diarrhea

• physical

febrile MEE on otoscopy: immobile TM, acute otorrhea , loss of bony landmarks, opacification of TM , air fluid level behind I ' M MEI on otoscopy: bulging TM with marked discolouration ( hemorrhagic, red, grey, or yellow)

-

Management

-

- .

• supportive care and symptom management: maintain hydration, analgesic, and antipyretic (acetaminophen, ibuprofen ) • watchful waiting: in a generally healthy child >6 mo of age with unilateral, non severe, suspected AOM without MEE or with MEE but non bulging or mildly erythematous TM • consider viral etiology • reassess in 24 -48 h if not clinically improved (or earlier if worsening ) mildly ill (alert, responsive, no rigors, mild otalgia, fever 48 h of symptoms immunocompromised, craniofacial abnormalities perforated TM with purulent drainage • referral to otolaryngology for myringotomy and tympanostomy tubes may be warranted for recurrent infections

-

-

-

-

Treatment

• antimicrobial agents for AOM

rn

5 d course of appropriate dose antimicrobial recommended for most 22 yr with uncomplicated AOM; 10 d course for 6 24 mo, perforated TM, or recurrent AOM 1st line treatment (no penicillin allergy) t high -dose amoxicillin: 80-90 mg / kg /d divided BID

LJ

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0TI 1 Otolaryngology

Toronto Notes 2023

• 2 nd line treatment azithromycin: 10 mg/ kg (first line for penicillin allergy) clarithromycin: 15 mg / kg /d divided BID (first line for penicillin allergy ) cefprozil: 30 mg/ kg /d divided BID cefuroxime axetil: 30 mg / kg /d divided B1 D -TID ceftriaxone: 50 mg / kg IM (or IV ) x 3 doses • if initial therapy fails ( i.e. no symptomatic improvement after 2 3 d ) high - dose amoxicillin davulanate: 45 60 mg / kg /d (7: 1 formulation , 400 mg / 5 ml. suspension ) for 10 d for child weighing 235 kg or 500 mg tablets 'l lD for 10 d for child weighing >35 kg myringotomy and tympanostomy, if >4 AOM episodes ( with middle ear effusion ) within 12

-

-

-

mo Complications • extracranial HI. and speech delay ( secondary to persistent MEE ), TM perforation , extension of suppurative process to adjacent structures ( mastoiditis, petrositis, labyrinthitis ), cholesteatoma, facial nerve palsy, middle ear atelectasis, ossicular necrosis, vestibular dysfunction

• intracranial

meningitis , epidural / brain abscess, subdural empyema, lateral and cavernous sinus thrombosis, sigmoid sinus thrombophlebitis, carotid artery thrombosis, facial nerve paralysis • other postauricular abscess, Bezold’s abscess

•

Otitis Media with Effusion Definition

,

XMul prarbu guMnrt: lyinpinioilomv lube In War. Olotoiyng Head H«k 201J:1«:StS3$

• presence of fluid in the middle ear without signs or symptoms of ear infection

(

Epidemiology • most common cause of paediatric HL • not exclusively a paediatric disease • frequently follows AOM in children • MEE have been shown to persist following an episode of AOM for 1 mo in 40% of children, 2 mo in 20%, and >3 mo in 10% ( i.e. 90% of children clear the fluid within 3 mo observe for 3 mo before

considering myringotomy and tubes )

-

-

Risk Factors • same as AOM Clinical Features • CHL ± tinnitus

confirm with audiogram and tympanogram ( flat ) (see Figure 16 B, 0770 and Figure 17, 0777 ) • fullness - blocked ear • ± pain , low grade fever • otoscopy of tympanic membrane

-

discolouration amber or dull grey with “ glue" ear meniscus fluid level behind 'EM air bubbles

•

Indications for Myringotomy and Tympanostomy Tubes in Recurrent ADM and OME’ • Chronic bilateral OME and documented hearing difficulties >3 mo • Unilateral or bilateral OME >3 mo and symptoms likely attributable to OME (c.g. balance problems, poor school performance, car discomfort , etc.) • At- risk children (permanent HI, spcechdanguage delay, autismspectrum disorder, craniofacial disorders, blindness, cleft palate, developmental delay) with unilateral or bilateral OME with type B tympanogram or persistent effusion >3 mo • Recurrent AOM (>3 episodes in 6 mo or >4 in 12 mo) with unilateral or bilateral MEE

retraction pockets/ I M atelectasis most reliable finding with pneumatic otoscopy is immobility '

Effectiveness of Tympanostomy Tubesfor Otitis Media: A Meta - Analysis Paedatncs 2017;139|6|:e20170125 Study : Systematic review evaluating the effectiveness of lym pa nostomy tubes liuhildrr with chronic OM with effusion and lecuuent AOM compared to watchful waiting. Oata Sources MEDLINE , Cochrane Central Reg ster of Controlled Inals. EMBASE . CINAHl . Results: Children treated with tymparostoeny tubes compared with watchful waiting had a net decrease (improvement) in mean hearing threshold of 9.1 d3 et T3 moand 0.0 by 12-24 nD. Children with recurrent MM may have fewer episodes after tympanostomy

tut*. Conclusions Tympanostomy tubes improve heinng it 1 3 mo compartd with watchful willing, with noeidenceof benefit by 12 24 mo. Moreevidenc* is netded foi recurrent ROM. Ihe benefits ol tympanostomy tubes must be weighed agiinst i

-

variety ol associated adverse events.

Pharyngeal tonsil ( adenoid)

Treatment • expectant: 90% resolve by 3 mo

Upper midline in nasopharynx

\

• watchful waiting for 3 mo from onset or 3 mo from diagnosis if onset unknown • document HL with audiogram • recommend against intranasal or systemic steroids, systemic antibiotics, antihistamines,

A!

4

decongestants for OME treatment • surgery: myringotomy ± ventilation tubes to equalize pressure and drain ear ( tympanostomy tubes recommended ) ± adenoidectomy ( not recommended in 4 yr) Complications of OME • HL , speech delay, learning problems in young children

• chronic mastoiditis • ossicular erosion • cholesteatoma , especially when retraction pockets involve pars flaccida • retraction of tympanic membrane, atelectasis, ossicular fixation

-

Tubal

a i - tonsil 1x21

Around openings if Euslachion tubus ! ') — Palatine WM tonsil 1x21 law ' / Both sides 0

'

*

—

of oropharynx

^

Lingual tonsil Under mucosa of posterior 1/3 of tongue

5 CD

Figure 20. Waldeyer 's ring An interrupted circle of protective lymphoid tissue at the upper ends of the respiratory and alimentary tracts

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OT42 Otolaryngology

Adenoid Hypertrophy Definition • size peaks at age 5 and resolves by age 12 • increase in size with repeated URTT and allergies Clinical Features

• nasal obstruction

adenoid facies (open mouth , high arched palate, narrow midface, malocclusion ) history of hypernasal voice and snoring long term mouth breather; minimal air escape through nose

-

• choanal obstruction

chronic rhinosinusitis/ rhinitis OSA • chronic inflammation nasal discharge, post nasal drip, and cough

-

• cervical lymphadenopathy Diagnosis • enlarged adenoids on nasopharyngeal exam (usually with flexible nasopharyngoscope ) • enlarged adenoid shadow on lateral soft tissue x- ray ( palate elevation can make adenoid look larger)

Treatment

• self - resolving due to age- related adenoid atrophy

• antibiotics, if infectious uncomplicated: amoxicillin, clindamycin or azithromycin ( penicillin allergies) chronic or recurrent: amoxicillin -clavulanate adenoidectomy

.

Complications

• Eustachian tube obstruction leading to serous otitis media

• interference with nasal breathing, necessitating mouth breathing • malocclusion • sleep apnea/ respiratory disturbance

• orofacial developmental abnormalities

Adenoidectomy Indications for Adenoidectomy

• chronic upper airway obstruction with sleep disturbance/apnea ± cor pulmonale « chronic nasopharyngitis resistant to medical treatment • chronic serous OM and chronic suppurative OM (with second set of tubes ) • recurrent AOM resistant to antibiotics • suspicion of nasopharyngeal malignancy • persistent rhinorrhea secondary to nasal obstruction • persistent adenoiditis after two courses of antibiotics • hyponasal speech • dental malocclusion or orofacial growth disturbance documented by orthodontist or dentist Contraindications • uncontrollable coagulopathy • recent pharyngeal infection • conditions that predispose to velopharyngeal insufficiency (cleft palate, impaired palatal function, or enlarged pharynx) Complications

• bleeding, infection

• velopharyngeal insufficiency' ( hypernasal voice or nasal regurgitation ) • scarring of Eustachian tube orifice

Sleep - Disordered Breathing in Children Definition • spectrum of sleep- related breathing abnormalities ranging from snoring to OSA Epidemiology

+

• peak incidence between 2-8 yr when tonsils and adenoids are the largest relative to the pharyngeal airway

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OT43 Otolaryngology

Etiology

• due to a combination of anatomic and neuromuscular factors

• adenotonsillar hypertrophy

• craniofacial abnormalities ( neuromuscular hypotonia e.g. cerebral palsy, Down syndrome ) obesity • Clinical Features

• nighttime symptoms: heavy snoring, pauses or apnea , sleeping with neck hyperextended , enuresis • daytime symptoms: mouth breathing, excessive daytime sleepiness, behavioural / learning problems, symptoms of ADHD (e.g. inattention , hyperactivity), morning headache, failure to thrive Investigations • flexible nasopharyngoscopy for assessment of nasopharynx and adenoids • polysomnography (apnea-hypopnea index > l /h considered abnormal) children: mild OSA 1 - 5 - 10/ h adults: mild OSA 5.1-15/ h; moderate OSA 15.1-30/h; severe OSA >30.1/ h Treatment • nonsurgical: CPAP, BiPAP, sleep hygiene, weight loss in overweight /obese child with OSA • medication: topical nasal steroids and leukotriene- receptor antagonists for mild OSA or residual

sleep- disordered breathing post-adenotonsillectomy • surgical: bilateral tonsillectomy and adenoidectomy (T&A) is surgery of choice if persistent OSA following tonsillectomy and adenoidectomy, consider adenoid regrowth if these fail and patient not tolerant of positive airway pressure therapy, consider lingual tonsillectomy, midline posterior glossectomy, tongue suspension or other surgeries targeting areas of resistance as required; surgery may be guided by Drug Induced Sleep Endoscopy or cineradiography MRI to localize site of resistance

-

-

Peritonsillar Abscess (Quinsy) Definition

• cellulitis of space behind tonsillar capsule extending onto soft palate, leading to abscess Etiology

.

.

• bacterial: group A Streptococcus (GAS) (50% of cases), S pyogenes , S aureus, H . influenzae, and anaerobes

Epidemiology • can develop from acute tonsillitis with infection spreading into plane of tonsillar bed (see Paediatrics, P64 )

• unilateral • most common in 15-30 yr age group Clinical Features • trismus (due to irritation and reflex spasm of the medial pterygoid ) is the most reliable indicator of

peritonsillar abscess

• fever and dehydration • sore throat, dysphagia, odynophagia, and drooling • extensive peritonsillar swelling but tonsil may appear normal

Quinsy Triad

• Trismus

• Uvular deviation • Dysphonia (“ hot potato voice")

• edema of soft palate • uvular deviation • dysphonia ( edema -> failure to elevate palate ) 2" to CN X involvement • unilateral referred otalgia • cervical lymphadenitis Complications

• aspiration pneumonia 2° to spontaneous rupture of abscess • airway obstruction • lateral dissection into parapharyngeal and /or carotid space • bacteremia • retropharyngeal abscess LJ

Treatment • secure airway

• surgical drainage ( incision or needle aspiration ) with C&S

• warm saline irrigation

+

• IV penicillin G x 10 d if cultures positive for GAS • add PO/1V metronidazole or clindamycin x 10 d if culture positive for Bacteroides • consider tonsillectomy after second episode

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Toronto Notes 2023

OTlI Otolaryngology Other Sources of Parapharyngeal Space Infections • pharyngitis • acute suppurative parotitis (see Salivary Glands, OT30 )

.•

AOM

mastoiditis ( Bczold 's abscess) • odontogenic infection

Tonsillectomy Absolute Indications

• most common indication : sleep -disordered breathing • second most common indication: recurrent tonsillitis • tonsillar hypertrophy causing upper airway obstruction, OSA , severe dysphagia, or cardiopulmonary complications such as cor pulmonale • suspicion of malignancy (e.g. lymphoma, SCC ) • orofacial/ dental deformity • hemorrhagic tonsillitis Relative Indications (To Reduce Disease Burden)

• recurrent tonsillitis with a frequency of at least 7 episodes in the past yr, at least 5 episodes per yr for 2 yr, or at least 3 episodes per yr for 3 yr with documentation in the medical record for each episode

of sore throat, and I or more of the following: temperature >38.3*C, cervical adenopathy, tonsillar exudate, or positive test for group A P hemolytic Streptococcus ( Paradise Criteria ) • chronic tonsillitis with halitosis ( bad breath ) or sore throat ± tonsiliths/ tonsilloliths (clusters of

-

material that form in the crevices of the tonsils) • complications of tonsillitis: quinsy/ peritonsillar abscess, parapharyngeal abscess, retropharyngeal abscess • failure to thrive

Relative Contraindications

• velopharyngeal insufficiency: overt or submucous/covert cleft of palate, impaired palatal function due

to neurological or neuromuscular abnormalities • hematologic: coagulopathy, anemia • infectious: active local infection without urgent obstructive symptoms Complications

-

• hemorrhage: primary ( within 24 h ); secondary (within first 7 10 d ) • odynophagia and /or otalgia; dehydration 2* to odynophagia • infection • atlantoaxial subluxation (Grisel’s syndrome ) - rare

Airway Problems in Children DIFFERENTIAL DIAGNOSIS BY AGE GROUP

Neonates (Obligate Nose Breathers)

• extralaryngeal pyriform aperture stenosis septal deviation choanal atresia (e.g. CHARGE syndrome ) nasopharyngeal dermoid, glioma, encephalocoele glossoptosis: Pierre Robin sequence, Down syndrome, lymphatic malformation, hemangioma

• laryngeal

-

laryngomalacia: most common cause of stridor in children saccular cyst/ laryngocele vocal cord palsy (due to trauma or Arnold -Chiari malformation ) glottic web laryngeal cleft laryngeal papillomatosis

.

subglottic stenosis

• tracheal

TEF compression by vascular structure (e.g. left pulmonary artery sling, vascular ring ) tracheomalacia (anterior displacement of trachealis muscle ) complete tracheal rings

LJ

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Toronto Notes 2023

OT'IS Otolaryngology 2-3 Months • congenital laryngomalacia • vascular: subglottic hemangioma ( more common ), innominate artery compression, double aortic

arch

• laryngeal papilloma

• acquired

-

subglottic stenosis: post intubation tracheal granulation: post-intubation tracheomalacia: post-tracheotomy and TE1; repair Infants - Sudden Onset

• foreign body aspiration • croup • bacterial tracheitis • caustic ingestion • epiglottitis Children and Adults

• infection • Ludwig’s angina • peritonsillar/ parapharyngeal abscess retropharyngeal abscess • neoplastic • SCC ( larynx, hypopharynx ( adults)) • retropharyngeal: lymphoma, neuroblastoma nasopharyngeal: carcinoma, rhabdomyosarcoma • allergic angioneurotic edema

• polyps (suspect cystic fibrosis in children ) • trauma

•

laryngeal fracture, facial fracture burns and lacerations post intubation

-

caustic ingestion

• congenital li ngual thyroglossal duct cyst • lingual tonsil hypertrophy • lingual thyroid

Signs of Airway Obstruction Stridor • note quality, timing (suggests site of stenosis) inspiratory: vocal cords or above biphasic: subglottis and extrathoracic trachea expiratory': distal tracheobronchial tree • body position important lying prone: double aortic arch lying supine: laryngomalacia, glossoptosis Respiratory Distress

• nasal flaring • tracheal tug • supraclavicular and intercostal indrawing • sternal retractions • use of accessory muscles of respiration • tachypnea

• cyanosis

• altered LOC Feeding Difficulty and Aspiration

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• supraglottic lesion • laryngomalacia • vocal cord paralysis • laryngeal deft > aspiration pneumonia

LJ

• TEF

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0TI6 Otolaryngology

Toronto Notes 2023

Acute Laryngotracheobronchitis (Croup) Definition

• inflammation of tissues in subglottic space ± tracheobronchial tree • swelling of mucosal lining associated with thick, viscous, mucopurulent exudate which compromises upper airway (subglottic space is narrowest portion of upper airway) • normal function of ciliated mucous membrane impaired Etiology • viral: parainfluenzae 1 ( most common), 11, 111, influenza A and B, RSV

Clinical Features • age: 6 mo- 3 yr

• preceded by URT'I symptoms

• generally occurs at night • biphasic stridor and croupy cough ( loud, sea -lion bark ) • appear less toxic than epiglottitis • supraglottic area normal • rule out foreign body and subglottic stenosis • “steeple-sign" on AP x-ray of neck • if recurrent croup, think subglottic stenosis Treatment

-

Signs of Croup The 3 Ss St ridor Subglottic swelling Seal bark cough

-

• racemic epinephrine via metered dose inhaler ql 2 h PRN ( if severe croup, >2 Westley Croup Score ) • systemic corticosteroids (e.g. dexamethasone 0.5 mg / kg, prednisone) • adequate hydration • close observation for 3-4 h • positive pressure ventilation, nasal trumpet, laryngeal mask airway, intubation if severe (use smaller endotracheal tube than expected for age) • hospitalize if poor response to steroids after 4 h and persistent stridor at rest • consider alternate diagnosis if poor response to therapy (e.g. bacterial tracheitis) • if recurrent episodes of croup like symptoms, consider bronchoscopy for definitive diagnosis

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Acute Epiglottitis Definition • acute inflammation causing swelling of supraglottic structures of the larynx without involvement of

vocal cords

Acute epiglottitis is a medical emergency

Etiology

• H . influenzae type B

.

• relatively uncommon condition due to H influenzae type B vaccine • common causes now include S', pneumoniae and S. aureus Clinical Features • any age, most commonly 1-4 yr • rapid onset • toxic-looking, fever, anorexia, restlessness • cyanotic/ pale, inspiratory stridor, slow breathing, lungs clear with decreased air entry • prefers sitting up ("tripod " posture), open mouth , drooling, tongue protruding, sore throat , dysphagia

Investigations and Management

When managing epiglottitis, it is important not to agitate the child, as this may precipitate complete obstruction

-

Thumb sign: cherry shaped epiglottic swelling with loss of the normal air space of the vallecula seen on lateral neck radiograph

• examining the throat may lead to potential laryngospasm and airway compromise; ensure an anesthesiologist /otolaryngologist is present and make preparations for intubation or tracheotomy prior to any manipulation • WBC (elevated ), blood , and pharyngeal cultures after intubation • lateral neck radiograph (only done if patient stable ) shows " thumb sign" Treatment

• secure airway

• IV access with hydration

• antibiotics: IV cefuroxime, cefotaxime, or ceftriaxone (10-14 d course should be completed ) • moist air • extubate when leak around tube occurs and afebrile

n LJ

• watch for meningitis

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Toronto Notes 2023

OT47 Otolaryngology

Subglottic Stenosis Congenital

• diameter of subglottis 90% of cases • if severe, division of the aryepiglottic folds ( supraglottoplasty ) provides relief

Foreign Body Ingested

• usually stuck at cricopharyngcus muscle

• coins, toys, batteries (emergency ) • presents with drooling, dysphagia, stridor if very large

Foreign body inhalation is the most common cause of accidental death In

children

Aspirated

• usually stuck at right main bronchus

• peanuts, carrot , apple core, popcorn , balloons • presentation

stridor if lodged in trachea ( beware of the silent child as there may be complete obstruction ) unilateral “asthma” if bronchial, therefore often misdiagnosed as asthma if completely occluded airway: cough, lobar pneumonia, atelectasis, mediastinal shift, pneumothorax, death

Button batteries MUST be ruled out as a foreign body (vs. coins) as they are lethal and can erode through the esophagus. Batteries have a halo sign around the rim on AP x ray and a step deformity on lateral x ray

-

-

Diagnosis and Treatment • sudden onset, not necessarily febrile or elevated WBC • any patient with suspected foreign body should be kept NPO immediately • older patient: inspiratory-expiratory' chest x-ray (if patient is stable) • younger patient: right and left decubitus chest x- rays. Lack of lung deflation while resting on dependent side suggests foreign body blocking bronchus • bronchoscopy or esophagoscopy with removal

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Toronto Notes 2023

OT 18 Otolaryngology

Deep Neck Space Infection Definition

• most commonly arise from an infection of mandibular teeth , tonsils, parotid gland , deep cervical lymph nodes, middle ear, or the sinuses • often a rapid onset and may progress to fatal complications Etiology

• usually mixed aerobes and anaerobes that represent the flora of the oral cavity, upper respiratory tract, and certain parts of the ears and eyes Clinical Features • sore throat or pain and trismus

These investigations should be obtained carefully and the surgeon should consider accompanying the patient, as the worst place to lose an airway is during imaging

• dysphagia and odynophagia • stridor and dyspnea • late findings may include dysphonia and hoarseness • swelling of the face and neck, erythema • asymmetry of the oropharynx with purulent oral discharge • fever, lymphadenopathy Diagnosis • CBC with differential • lateral cervical view plain radiograph

Ludwig's angina is the prototypical infection of the submandibular and sublingual space

• cr

• MRI Treatment

• secure the airway • surgical drainage • maximum doses of IV systemic antimicrobials regimens according to the site of infection

Common Medications Table 22. Antibiotics Generic Name ( Brand Name )

Dose

Indications

amoxicillin (Amoxil ' . Amoxl®, Amox 5 )

Adult 500 mg PO TID Children: 75-90 mg /kg /d in 2 divided doses

Streptococcus Pneumococcus H. influenzae Proteus coverage

piperacillin with tarobadam

3 g TO qG h

Gram posilivcand negative aerobes and anaerobes plus

500 mg P0 BID

Pseudomonas , Streptococcus

Itosyn ®)

.

Notes

.

.

-

May cause rash in patients with infectious mononucleosis

May cause pseudomembranous colitis

Pseudomonos coverage ciprofloxacin (CiproCiloxan

-

.

methicillin resistanl Staphylococcus aureus ( MBSA ) , and most Gram negative: no anaerobic coverage

-

Animal studies suggest that systemic quinolones may cause cartilage necrosis in children

500 mgPOQID

Alternative to penicillin

Ototoxic

Generic Name ( Brand Name)

Dose

Indications

Notes

ciprofloxacin (Ciprodcx )

4 gtl In allotted car BID

for 0 E and complications of 0 M Pseudomonos , streptococci, MUSA , and most Gram - negative: no anaerobic coverage

neomycin , polymyxin 8 sulfate , and hydrocortisone ( Cortisporin Otic )

5 git in affected ear IID

forOE Used for inflammatory conditions which are currently infected or at risk of bacterial infections

May cause HI il placed in inner ear

hydrocortisone and acetic acid (YoSol HC ’ )

5 -10 git in affected ear TID

ForOM

Bactericidal by lowering pH

tobramycin and dciamethasone ( TobraDex - )

5 -10 gllinaflected ear BID

For chronic suppurative 0 M

Bisk ol vestibular or cochlear toxicity

2- 3 gtt in affected ear BID

ForOE , Otomycosis

erythromycin ( Erythrocin EryPed ®, Station3, Mat ®, Erybid ' , Hovorythro Encap ) '

Table 23. Otic Drops

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Locacorten Vioform Ear Drops

'

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0TI9 Otolaryngology

Toronto Notes 2023

Table 24. Nasal Sprays Generic Name (Brand Name)

Indications

Notes

Allergic rhinitis Chronic sinusitis

Requires up to 4 wk ol consistent use to have

Steroid flunisolide (Rhinalar budesonide (Rhinocort ), triamcinolone ( Nasacort ' ) beclomelliasonc ( Beconase ’ ) mometasone furoate, monohydratc (Nasonex ' fluticasone luroale ( Ayarnys ’ Flonase ' ) ciclesonide ( Omnaris }

. .

>.

.

effect longtermusc Dries nasal mucosa: may cause minor bleeding Patient should stoprf cpistams May sling Flonase’ and Nasonei' not absorbed syslemically

Antihistamine levocabastine (Livostin :)

Occongcslant

..

xylomelazoline ( Otrivin ' ) oxymelaaoline (Orislan ®) phenylephrine (Neosynephrlnc )

Allergic rhinitis

Immediate effect Discontinue if no effect by day 3 Use during allergy season

Acute sinusitis Rhinitis

Careful if patient has H1N Short term use ('5 d) II long term use cancausc decongestant addiction (i e.rhinitis medicamentosa)

-

.

.

Antibiotic!Decongestant framycetin, gramicidin, phenylephrine (Soframycin 5)

Acute sinusitis

Anticholinergic ipratropium bromide ( Atrovent " )

Vasomotor rhinitis

Careful not to spray into eyes as it can cause burning or precipitation ol narrow angle glaucoma

Increased ralcof epislaiis when combined with topical nasal steroids

lubricants

.

saline NeilMedRhinaris ®, Secaris !.Polysporin Vaseline ! Combination

’.

arelastine hydrochloride (antihistamine) and fluticasone propionate (steroid) ( Dymista ' )

Dry nasal mucosa

Use PRO Rhinaris: and Secaris may cause stinging '

Allergic rhinitis

Source: Dr. MM Carr

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OT 50 Otolaryngology

Landmark Otolaryngology - Head and Neck Surgery Trials Trial Name

Reference

Clinical Trial Details

Acute Otitis Media Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children

NEJM 2016:375:2446 -2466 Title: Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children Purpose: To study the potential of limiting the duration of antimicrobial treatment among children with acute otitis media to prevent antimicrobial resistance. Methods: Children with acute otitis media were assigned to 2 gioups.1 group received amoxicillin - clavulanale for 10 d the other group received a reduced duration of 5 d Rate of clinical response, recurrence, and nasopharyngeal colonisation were measured Results: Children treated with amoxicillin -clavulanale for 5 d had higher rates of clinical failure than those treated lor the full duration. Mean symptoms scores over Irom d 6 14 were 1.61 in the 5 d group and 1.34 in the 10 d group. Conclusions: 10 d of amoxlcillln clavulanate had more favourable outcomes and no increase in adverse events or antimicrobial resistance compared to a 5 d course in children ages 6 mo 2 yr.

.

.

-

Effect of Antimicrobial Treatment ol Acute Otitis Media on the Daily Disappearance on Middle Ear Effusion

.

-

JAMAPediatr. 2014;168( 7):635 - 641

Title: Meet ol Antimicrobial Treatment of Acute Otitis Media on the Daily Disappearance on Middle Tar Illusion Purpose: To study the effect of antimicrobial treatment on the duration ol middle ear effusion |MTE) and hearing impairment. Methods: Children were assigned to either have 40mg / kg of amoxicillin- clavulanale or a placebo miiture for 7 d. The primary outcome measure was time till disappearance of MET. Results:MEE disappeared 2 wk earlier in the antimicrobial group, than in the placebo group (2.7 wk vs. 4.7 wk, respectively). Conclusions: Treatment with amoxicillin-clavulanale reduced the duration of middle ear effusion compared to placebo in children vrith acute otitis media.

NEJM 2015: 373 (6):521-9

Title: Elective versus Therapeutic Neck Dissection n Node- Negative Oral Cancer Purpose: To evaluate survival after elective neck dissection vs. therapeutic neck dissection in patients with lateraliied stage 11 or 12 oval squamous - cell carcinomas Methods: Aprospedive, random ited, controlled trial that evaluated survival after elective node dissection vs therapeutic node dissection Overall survival and disease free survival were used asprimary and secondary endpoints, respectively Results: At 3 yr elective node dissection resulted in more survival (80%) than therapeutic neck dissection (67.5%) As well, at 3 yt elective node dissection patients had a higher rate of disease free survival compared lo those in the therapeutic surgery group (69.5% vs 45.9%) Conclusions: Among patients with early - stage OSCC elective neck dissection resulted in higher rates of overall and disease - free

Head and Heck Malignancy

Elective versus Therapeutic Neck Dissection in Node - Negative Oral Cancer

.

.

.

.

-

.

.

.

.

NEJM 2016; 374:1444-1454

.

.

survival.

PET-NECK

.

Title: PET- CT Surveillance versus Neck Oissection in Advanced Head and Neck Cancer Purpose: To compare the usefulness of planned neck dissection versus PET- CT - guided surveillance in patients with nodal stage N2 or N 3 SCC. Methods: Patients with N 2 or N 3 neck disease were randomly assigned to either a neck dissection (planned surgery group) or PET CT 12 weeks after chemoradiotherapy completion (surveillance group). The primary endpoint was overallsurvival. Results: The 2 yr survival rate was 84.9% (95% Cl 80.7 to 89.1) in the surveillance group and 81.5% (95% Cl 76.9 to 86.3 ) in the surgery group. The hazard ratio slightly favored PET CT - guided surveillance and indicated noninferiority (upper boundary of the 95% Cl lor the hazard ratio 1.50; P‘0.004). Conclusions: PET - CT -guided surveillance is noninferior to planned neck dissection for overall survival in N 2 or N 3 SCC of Ihe head and neck Title: Nivolumab for Recurrent Squamous - Cell Carcinoma ol the Head and Neck Purpose: To compare the overall survival of patients with plalinum -refiaclory SCC of the head and neck treated with nivolumab versus standard therapy. Methods: Patients with recurrent SCC of the head and neck and disease progression within 6 mo after platinum - based chemotherapy received either nivolumab or standard systemic therapy (methotrexate, docetaxel or celuximab). The primary endpoint was overall survival. Results:Median overall survival was 7.5 mo (95% Cl.5.5 to 9.1) in the nivolumab group compared to 5.1 mo (95% Cl, 4.0 to 6.0) in the standard therapy group. Survival is significantly longer with nivolumab (hazard ratio for death 0.70:97.73% Cl 0.51 to 0.96: P-0.01). Conclusions: Treatment with nivolumab resulted in longer overall survival than treatment with standard therapy in platinumrefractory recurrent squamous- cell carcinoma of the head and neck.

-

.

.-

.

-

.

Check Male 141

NEJM 2016: 375:1856 -1867

.

.

.

.

Sleep -Disordered Breathing

KATE

JAMA Otolaryngol Head Neck Surg. 2020;146|7|:647 654

.

Title: Effectiveness ol Ade no tonsillectomy vs Watchful Wailing in Young Children Willi Mild to Moderate Obstructive Sleep Apnea: A Randomized Clinical Trial Purpose: To determine whether adcnolonsillcclomy is more effective than watchful wailing for treatinghealthy children with mild lo moderate 0SA Methods: 60 children ages 2 to 4 with mild lo moderate 0SA were randomized to cither adonotonsilledomy or watchlul walling Ihe primary outcome was Ihe difference in mean obstructive apnea hypopnea index (0AHI) score change between the two gioups Results: Both gioups had a reduced mean 0AHI score with a small intergroup difference (-1.0: 95% Cl -2.4 to 0.5). Children with moderate 0SA showed a meaningful intergroup difference in mean 0AHI score change, favouring adenotonsilledomy (-3.1; 95% Cl, -5.71o -0.5). Conclusions: Otherwise healthy children ages 2- 4 with mild 0 SA may benefit from watchful waiting,while children with moderate OSA should beconsidered for surgical treatment.

.

.

.

CHAT

NEJM 2019: 20|9):12731285

Title: A Randomized Trial of Adenotonsilledomyfor Childhood Sleep Apnea Purpose: To investigate the benefits of adenotonsilledomy vs. supportive care on children with obstructive sleep apnea Methods: Children ages 5 -9 yr, with obstructive sleep apnea syndrome were randomized to adenotonsilledomy or a strategy of watchful waiting. Polysomnogiaphic, cognitive, behavioural, and health outcomes were assessed at baseline and again at 7 mo. Results: Attention and executive function scores from baseline did not change significantly in theadcnolonsilledomy group vs the watchful waiting group ( 7.1x13.9 vs. 5.1r13.4 respectively ) Signilican! differences from baseline in behavioural, and quality

.

.

.

.

.

of life were found in Ihe adenotonsilledomy group. Normalization ol polysomnogruphic findings were found in more of Ihe adenotonsilledomy than Ihe watchful waiting group ( 79% vs. 46%) Conclusions: Surgical treatment for obstructive slcepapnea in children ages 5 - 9 did not significantly improve attention or executive function but did improve behaviour, quality of life, and polysomnogiaphic findings compared to watchlul waiting.

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0T51 Otolaryngology

Toronto Notes 2023

References .

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Bailey BJ. Head and neck surgery -otolaryngology, 5th cd Philadelphia: lipplncott Williams and Wilkins 2013. Basura 0J Adams Ml Mofllared A cl al. Clinical practice guideline: Mdnibre's Disease. Ololaryng Head Neck Snrg. 2020:152 (2 suppl):$1 SSS Baugh Rf Aichei SM Mitchell R8 el al Clinical practice guideline: tonsillectomy in children Ololaryng Head Neck Surg 2011:144:51-S30. Becker W Haumann HH, Plaltr CD. Ear. nose, and throat diseases 3 rd ed. Hew York: Ihieme Medical Publishers, 2009. Berman S.Current concepts: olilis media in children. HUM 1995:332:1550 -1565. Bonner JA.Harari PM Giralt J el al.Radiotherapy plus cetuximab lor squamous-cell carcinoma of the head and neck.IIEJM 2006;354:567-558. Casey JR. PichicheroME . Changes infrequency and pathogens causing acute olilis in 1995-2003. Pedialr Infect Dis J 2004;23:824 - 828. Chan Y Goddard JC (editors). K. J.lee’s Essential Otolaryngology - Head and Neck Surgery 12th ed. New York: McGraw - Hill Education, 2019. Chang WH Iscng HC Chao IK etal. Measurement ol hearing aid outcome in the elderly: comparison between young and old elderly. Ololaryng Head Heck Surg 2008:138:730 734. Chan OA Chan OK. Diagnosis and Irealmcnt ol Congenital Sensorineural Healing loss Curt Otorhinolarynqol Rep 2017:5(1) 251 258. Cheng AW Mitchell 2 Foote J Can you hear inefSudden sensorineural hearing loss in the emergency department Can Earn Physician 2014:60( 101:907 909. Cho HJ. Mm HJ Chung HJ et al. Improved outcomes after low concentration hypochlorousacrd nasal irrigation in pediatric chronic sinusitis, laryngoscope 2016:126:791- 795. Cibas ES AIi SZ. Ihe 2017 Bethesda system for reporting thyroid cytopathology thyroid 2017:27:1341-1346. Coker fR. Chan IS Newberry SJ etal. Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review. JAMA 2010;304:2161-2169. Cooper DS. Doherty GI4 Haugen BR. etal. Revised American thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009:19:1167 -1214. Corvera Behar G, Garcia de la Cruz MA. Surgical Treatment for Recurrent Benign Paroxysmal Positional Vertigo. Int Arch Otorhinotaryngol 2017:21(2|:191-194. Crane RA Cam lion M Nguyen S et al. Steroids for treatment ol sudden sensorineural hearing loss: A meta - analysis ol randomized controlled trials. Laryngoscope 2015:125:209 - 217. de Almeida JR Guyalt GH, Sud S etal. Management of Bell Palsy: Clinical Practice Guideline CMAJ 2014:186(12);917 22. Oeschler 06 Richmon JO Khariwala SS et al. The "new" head andneck cancel patient • young, nonsmoker, nondrinker, and HPV positive Ololaryng Head Heck Surg 2014:151:375 380. Oesrosters M EvansGA Keith PK etal Canadian clinical practice guidelines for acute and chronic rhlnosinusitis All Aslh Clin Immun 2011:7(1) :! 38 . Dhillon RS East CA. Ear , nose, and throat, and head and neck surgery: an illustrated colour text 4 th cd. New York:Edinburgh: Elsevier 2013. D'Souza G Kreimer AR, Viscidi R.etal.Case-control study of human papillomavirus and oropharyngeal cancer. HEJM 2007:356:1944 1956. Eakhry C. Westra WH Ei S, et al.Improved survival of patients with human papillomavirus- positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancel Inst 2008:100:261- 269. Finn DG. Buchalter IH Sarti E et al.First branchial cleft cysts:clinical update. Laryngoscope 1987;97:136 -140. Einsleret J.Management of peripheral facial nerve palsy. Eur Arch Olorhinolaryngol 2008:265(7):743-752. Forastiere A Koch W, Trotti A, et al. Head and neck cancer. NEJM 2001;345:1890 -1900. Frisina A Piazza F Pasanisi E et at. Clelt palate and dysfunction of the Eustachian lube. Acta Biomcd Ateneo Parmense 1998:69:129-132. Fujisawa J Mutoh 1 KawamuraK cl al. Acute epiglottitis caused by community acquired melhicillin- icsislanl Staphylococcus aureus In a healthy infant , infect Drug Resist 2018:11:2063 - 2067 Furman JM, Cass SP Benign paroxysmal positional vertigo. NEJM 1999:341:1590 1596. Gillespie MB O'Connell BP Rawl JW et al Clinical and quality of lifc outcomes following gland preserving surgery for chronic sialadenitis, laryngoscope 2015:125:1340 1344. Grbgoire V Maignon P. Intensity modulated radiation therapy in head and neck squamouscell carcinoma: state of (heart and future challenges. Cancer Radiother 2005:9:42- 50. Haugen BR Alexander EK Bible KC.el al. 2015 American ThyroidAssociation management guidelines for adult patients with thyroid nodules and dilferentiated thyroid cancer: Ihe American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016:26:1-133. Hilton M. Pinder 0. The Epley (canalith repositioning) maneuver for benign paroxysmal positional vertigo. Cochrane D8 Syst Rev 2004:2:CD003162. Huang SH.Xu W. Waldron J et al. Refining American Joint Committee On Cancer/Union for International Cancer Control TMN stage and prognostic groups for Human Papillomavirus- related oropharyngeal carcinomas. JC0 2015:33:836 845. Isaacson JE Vora NM. Differential diagnosisand treatment of hearing loss Am Fain Physician 2003;68(6):1125 1132. Ivancic R Iqbal H deSllva 8 et al Current and future management ol recurrent rcspiraloiy papillomatosis, laryngoscope Invcslig Otolaryngol 2018:3|1):22 - 34. Jackson CG von Doeislen PG. Ihe facial nerve: current trends in diagnosis, treatment, and rehabilitation. Otolaryngol for Internist 1999:83:179 195. KaselasCH IsikopoulosG ChDrlrsCH ctal. Ihyroglossal dud cyst's inflammation When do we oper ate ? Pcdiatr Surg Int 2005:21:991 993. Kotecha S Bhatra P Rout PG. Diagnostic ultrasound in the head and neck region. Dent Update 2008:35:529 -530. Kumar It. Preciado D. Airway Papillomatosis: Newlreatmentsfor an Old Challenge. Front Pediatr 2019;7:383. layland MK (editor ). Washington manual otolaryngology survival guide. Philadelphia:lippincott Williams and Wilkins 2003. Le Saux N, Robinson JL. Management of acute otitis media in children six months of age and older. Canadian Paediatrics Society 2016. li X Gaol,li H, et al. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta - analysis. J Infect Dis 2013:207:479 - 488. Lieberthal AS Carroll AE Chonmailrcc T,cl al The diagnosisand treatment of acute olilismedia Pediatrics 2013:3:e964 c 999. lucente FE Har - Et G (editors) Essentials ol otolaryngology 5th ed Philadelphia: lippincott Williams and Wilkins, 2003. MacCatlum Pt, Paines 15 Sharpe M0 el al Comparison of open, percutaneous and translar yngeal tracheostomies. Otolaryngol Head Neck Surg 2000:122:686 690 Marcus Cl. BiooksU Draper KA etal.Clinical practice guideline: Diagnosis and management of childhoodobstructive sleep apnea syndrome. Ameiican Academy ol Pedialrics 2012;130|3):S76 - 584. Mdsaac WJ. Coyte PC Croxford R etal. Otolaryngologists' perceptions of the indications for tympanostomy tube insertion in children.CMAJ 2000:162:1285 -1288. McParland A.Elffers- Tan F AckeryA.Surfer ’s ear in a 29 -year - old man.CMAJ 2019:191|14):E 396. Mehanna H.Beech T, Nicholson T. et al. Prevalence of human papillomavirus in oropharyngeal and nonoro pharyngeal head and neck cancer - systematic review and meta -analysis of trends by time and region. Head A Neck 2013;35:747-755. Michels IC Duffy MT Rogers DJ. Hearing loss in adults: differential diagnosis and treatment. Am Fam Physician 2019:100(2):98 -108. Moore CA Staples JE Oobyns WB el al Characteriiing the pattern of anomalies in congenital zika syndrome for pediatric clinicians. JAMA Pediatr 2017:171:288 295 Muncic HI Sir mans SM James E.Dimness: Approach to Evaluation and Management Am Fam Physician 2017,95:154 162. Olstcwska E Rutkowska J Ozgirgm H Consensus- based recommendations on the definition and classification ol cholesteatoma.Int Adv Otol 2015 : 11( 1) 81 8 /. Orlandi RR Kingdom If Smith II et al International consensus statement on rhinology and allergy: rhlnosinusitis. Int Forum Allergy Rhinol. 20 " should be changed to "Orlandi RR Kingdom IT,Hwang PH et at. International consensus statement on allergy and rhinology: rhlnosinusitis Ininternational loium of allergy t rhinology 2016:6(Ho S1):S22-S209. Pasha R.Otolaryngology head and neck surgery clinical reference guide 5th ed. San Diego:Plural Publishing, 2017. Patel H Feldman M. Universal newborn hearing screening. Paediatr Child Health 2011:16(5):301-310. Patel HO. van Zantefl.Eisele DW. et al. Oncocytoma: the vanishing parotid mass.Am J Neuroradiol 2011:32:1703 -1706. Pohar S Gay H. Rosenbaum P, et al. Malignant parotid tumors: presentation, clinical/pathologic prognostic factors, and treatment outcomes.Int J Radial Oncol Biol Phys 2005:61:112-118. Prasad HK Bhojwani KM, Shenoy V el al HIV manifestations in otolaryngology. Am J Otolaryngol 2006:27:179 -185 Quesitcl AM Lindsay RW, Hadlock IA. When the bell tolls on Bell 's palsy: tindinq occult malignancy in acute - onset facial paialysis Am J Otolaryngol 2010:31:339 - 342. RomqvrstI Grun N Dalianis 1. Human papillomavirus and tonsillar and base of tongue cancer. Viruses 2015;7:1332- 1343. Rea P. Clinical anatomy of thecramal nerves. Academic Press 2014. RosenTield RM Schwartz SR Pynnonen MA. et al. Clinical practice guideline: tympanostomy lubes in children. Otolaryngol Head Neck Surg 2013:49:S1-S 33 RosenfeldRM Brown L Cannon CR etal. Clinical practice guideline: Acute otitis externa.Otolaryngol Head Neck Surg 2006:134(4):S4 -S23. Rosenfeld FM.Shin JJ, SchwartzSR. et aL Clinical practice guideline:Otitis media with effusion (update). Otolaryngol Head Neck Surg 2016;154:S1-S41. Sander R.Otitis Externa: A practical Guide to Treatment and Prevention. Am Fam Physician 2001:63(5):927-937. Schaefer P Baugh RF. Acute Otitis Externa: An Update. Am Fam Physician 2012;86(11):1055 -1061. Schularick HM Mowry SE Soken H et al Is eleclroneumgraphy beneficial in the management of Bell ' s palsy ? laryngoscope 2013:123:1066 -1067. Schwartz SR Magil AE Rosenfeld RM cl at Clinical Practice Guideline (Update ): Earwax (Cerumen Impaction) Otolaryngol Head Neck Surg 2017:156:51-529 Scholes MA Ramakiishnan VR (editors) EN 1 secrets 4th ed. Philadelphia:Elsevier 2016 Smalt P Keith PK Kim H Allergic rhinitis Allergy Asthma Clin Immunol 2018:14:51 Smith SS Terence EH Evans CT etal. Ihe prevalence of bacterial infection in acute rhlnosinusitis: a systematic review and mela analysis. Laryngoscope 2015;125:57- 69. Srafford IID. Wilde A. Parotid cancer.Surg Oncol 1997:6:209- 213. Sur DKC. Ptesa ML. Chronic nonallergic rhinitis.Am Fam Physician 2018:98(3):171-176. Tehrani AS, Kattah JC, Kerber KA. etal.Diagnosing stroke in acute dizziness and verb go:pitfalls and pearls.Stroke 2018:49(3):788 -795. Tesster FN Middleton WD Grant EG etal. ACR Thyroid Imaging.Reporting and Data System (TI- RADS): White Paper of Ihe ACR TI - RADS Committee. JACR 2017;14|5 ):587- 95

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OT52 Otolaryngology

.

Valencucla CV. Newbill CP. Johnston C cl at Proliferative laryngitis with airway obstruction In an adult: consider herpes laryngoscope 2016;126:945 -948. Vcnekamp HP SandetsS, Glasclou PP et at. Antibiotics lor acute otitis media in children. Cochrane DB Syst Rev 2013:1:C0000219. VenekampRP. Thompson MJ.Rovers MM.Systemic corticosteroid therapy lor acute sinusitis.JAMA 313:1258-1259. Wells SA. Henning Dralle SL.Elisei R.et al. Revised American Thyroid Association guidelines for themanagement of medullary thyroid carcinoma: the American Thyroid Association guidelines task force on medullary thyroid carcinoma. Thyroid 2015;25:567 610. Wheeler PW. Wheeler Sf. Vasomotor rhinitis. Am Fam Physician 2005;72|6):1075 -1082. Wu V Cooke B Eilulis S ctal. Approach to tinnitus management . Can Fam Physician 2018:64( 71 191 195. Wurdermann N Wagner S, Sharma SJ el al. Prognostic impact of A JCC / UICC 8th edition new staging rules In oropharyngeal squamous cell carcinoma. Front Oncol 2017:7:129.

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Paediatrics Onyinyechukwu Esenwa, Anna Jiang, Kahna Rasouli, Mary Xie, and Tingting Yan, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors Vijithan Sugumar, EBM editor Dr. Tanvi Agarwal, Dr. Jillian Baker, Dr. Tyler Groves, Dr. Joey Latino, Dr. Shazeen Suleman, and Dr. Janaki Vallipuram, staff editors Acronyms

P3

Paediatric Quick Reference Values

P3

Primary Care Visit Overview Routine Immunization Growth and Development Nutrition

P4

Circumcision Common Complaints Breath Holding Spells Crying/Fussing Child Infantile Colic Dentition and Caries

P10

Enuresis Encopresis Toilet Training Failure to Thrive Obesity Poison Prevention Rashes Sleep Disturbances Sudden Infant Death Syndrome

Pi Paediatrics

Adolescent Medicine

P17

Child Abuse and Neglect Physical Abuse Sexual Abuse Neglect

P18

Cardiology Congenital Heart Disease Acyanotic Congenital Heart Disease Cyanotic Congenital Heart Disease Congestive Heart Failure Dysrhythmias Heart Murmurs Infective Endocarditis

P 20

Development Global Developmental Delay Intellectual Disability Language Delay Specific Learning Disorder Fetal Alcohol Spectrum Disorder Attention Deficit Hyperactivity Disorder Autism Spectrum Disorder Motor Delay

P26

Endocrinology Antidiuretic Hormone Diabetes Mellitus Growth Hypercalcemia/Hypocalcemia/Rickets Hyperthyroidism and Hypothyroidism Disorders of Sexual Development

P30

Fluids and Electrolytes Approach to Infant/Child with Dehydration

P38

Gastroenterology Vomiting Gastroesophageal Reflux Tracheoesophageal Fistula Pyloric Stenosis Duodenal Atresia Malrotation of the Intestine Diarrhea

P40

Gastroenteritis Toddler's Diarrhea Lactase Deficiency (Lactose Intolerance) Irritable Bowel Syndrome Celiac Disease Cow's Milk Allergy Inflammatory Bowel Disease Cystic Fibrosis Constipation Abdominal Pain Chronic Abdominal Pain Abdominal Mass Upper Gastrointestinal 8leeding Lower Gastrointestinal Bleeding Genetics, Dysmorphisms, and Metabolism

P50

Hematology Approach to Anemia Physiologic Anemia Iron Deficiency Anemia Vitamin K Deficiency Anemia of Chronic Disease Sickle Cell Disease Thalassemia Hereditary Spherocytosis Glucose 6 -Phosphate Dehydrogenase Deficiency Bleeding Disorders Immune Thrombocytopenic Purpura Hemophilia von Willebrand's Disease

P50

Oncology Lymphadenopathy Leukemia Lymphoma Brain Tumours Wilms' Tumour (Nephroblastoma) Neuroblastoma Bone Tumours Cancer Predisposition Syndromes

P54

Infectious Diseases Fever Acute Otitis Media Otitis Media with Effusion Gastroenteritis HIV Infection Infectious Paediatric Exanthems Infectious Mononucleosis Infectious Pharyngitis / Tonsillitis Meningitis Mumps Pertussis Pneumonia Periorbital (Preseptal) and Orbital Cellulitis Sexually Transmitted Infections Sinusitis Urinary Tract Infection

P 58

-

.

Neonatology Gestational Age and Size Routine Neonatal Care Neonatal Resuscitation Common Conditions of Neonates Apnea Bleeding Disorders in Neonates Bronchopulmonary Dysplasia Cyanosis

P70

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^

Paediatrics Diaphragmatic Hernia Hypoglycemia Neonatal Hyperbilirubinemia

Necrotizing Enterocolitis Persistent Pulmonary Hypertension of the Newborn Respiratory Distress in the Newborn Retinopathy of Prematurity Sepsis in the Neonate Skin Conditions of the Neonate Nephrology Common Paediatric Renal Diseases Hemolytic Uremic Syndrome Nephritic Syndrome Nephrotic Syndrome Hypertension in Childhood

P82

Neurology Cerebral Palsy Febrile Seizures

P87

Hypotonia Neurocutaneous Syndromes Recurrent Headache Seizure Disorders Respirology Asthma Bronchiolitis Cystic Fibrosis Pneumonia Respiratory Distress

P 91

Rheumatology Growing Pains Juvenile Idiopathic Arthritis

P 95

Limb Pain Lyme Arthritis Reactive Arthritis Septic Arthritis and Osteomyelitis Systemic Lupus Erythematosus Transient Synovitis of the Hip

Vasculitides Common Medications

P99

Landmark Paediatric Trials

P100

References

P100

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Toronto Notes 2023

Activate Windows fin tn Settings tn artivatp Winrlnws

P 3 Paediatrics

Toronto Notes 2023

Acronyms AAP ABG ACE ACEI ADH AGA ALL ALPS AML ANA AOM ARB ARBO ARNO

ASD ASOT AIN AVM BRUE CAH CAS

COGP CF CFIR CHO CML CMV CP CPAP

CPS DAT DDAVP

American Academy o( Pediatrics arterial blood gas

01

angiotensin converting enzyme angiotensin converting enzyme inhibitor antidiuretic hormone appropriate for gestational age acute lymphoblastic leukemia autoimmune lymphoprolilerativc syndrome acute myelogenous leukemia antinuclear antibody acute otitis media angiotensin receptor blocker alcohol-related birth defects alcohol -related ncurodevclopmcntal disorder atrial septal delect antistreptolysin- o titre acute tubular necrosis arteriovenous malformation brief resolved unexplained events congenital adrenal hyperplasia Children's Aid Society constitutional delay of growth and puberty cystic fibrosis cystic fibrosis transmembrane conductance regulator congenital heart defect chronic myelogenous leukemia cytomegalovirus cerebral palsy continuous positive airway pressure Canadian Paediatric Society direct antiglobulin test 1- desamino - 8 - Darginine

coagulation diabetic ketoacidosis OKA DMARD disease modifying antirheumatic drug Down syndrome OS OSD disorder of sexual differentiation Epstcin - Barr virus EBV echocardiogram Echo FAS fetal alcohol syndrome FASD fetal alcohol spectrum disorder FISH fluorescent in situ hybridization FSS familial short stature failure to thrive FIT gestational age GA group A Streptococcus GAS G 8M glomerular basement membrane group B Streptococcus GBS GERD gastroesophageal reflux disease GN glomerulonephritis GSO glycogen storage disease GTPAL Gravidity Term Preterm Abortion Living HBsAg hepatitis B surface antigen hemorrhagic disease of the HDN8

vasopressin

QIC

diabetes insipidus disseminated intravascular

I6D IBW ICH IIP

inflammatory bowel disease ideal body weight intracranial hemorrhage immune thrombocytopenic purpura

IUGR IVH IVIg JIA

LAH LBW LGA LLSB LMN

LOC LP LRII LV LVH MAS MCAD

MOD

.

r ’ Li

MEE MSUO NCS newborn HEEADSSSHome Education / Employment NEC Eating Activities Drugs Sexuality NF Suicide/depression Safety/ NICU violence NS Haemophilus influenzae type b OOP Hib hepatobiliary iminodiacetic acid OME HIDA hypoxic ischemic encephalopathy ORT HIE HPA human platelet antigen OSA PAC human rotavirus HRV PCOS HSP Henoch - Schonlein purpura herpes simplex virus HSV PDA HUS PKU hemolytic uremic syndrome

intrauterine growth restriction intraventricular hemorrhage intravenous immunoglobulin juvenile idiopathic arthritis left atrial hypertrophy low birth weight large for gestational age lower left sternal border lower motor neuron level of consciousness lumbar puncture lower respiratory tract infection

left ventricle left ventricular hypertrophy meconium aspiration syndrome medium- chain acyl- CoA dehydrogenase minimal change disease metered dose inhaler middle ear effusion maple syrup urine disease nerve conduction study

necrotizing enterocolitis neurofibromatosis neonatal intensive care unit normal saline oral contraceptive pill otitis media with effusion oral rehydration therapy obstructive sleep apnea premature atrial contraction polycystic ovarian syndrome patent ductus arteriosus phenylketonuria

PPHN PPV PUVA RAD RAS RBB8

RDS RF

persistent pulmonary hypertension of newborn positive pressure ventilation psoralen * UVA right axis deviation renal artery stenosis right bundle branch block respiratory distress syndrome rheumatoid factor

Rh RL RSV RUS8 RVH RVOTO

Rhesus factor Ringer ’s lactate respiratory syncytial virus right upper sternal border right ventricular hypertrophy right ventricular outflow tract

SEM SGA SIAOH

systolic ejection murmur small for gestational age syndrome of inappropriate antidiuretic hormone sudden infant death syndrome Shiga toxin -producing E. coli

obstruction

SIDS STEC SVT

TEF 1M

TPN TIN UMN URTI UVA

VCUG VKDB VSD VUR WPW

supraventricular tachycardia tracheoesophageal fistula tympanic membrane total parenteral nutrition transient tachypnea of the newborn upper motor neuron upper respiratory tract infection ultraviolet A voiding cystourethrogram vitamin K deficiency bleeding ventricular septal defect

vesicoureteral reflux Wolff - Parkinson - White

Paediatric Quick Reference Values Table 1. Normal HR and RR at Various Ages Pulse (bpm)

Age (yr)

-

Respiratory Rate (br /min)

100 205 100-190

-

30 - 53

Toddler (1-2 yr )

98-140

22-37

Preschool (3-5 yr )

80 -120

20 -28

School-age ( 6-11 yr)

75-118

18 -25

Adolescent (12 -15 yr )

60100

12 - 20

Neonale ( 28 d )

-

Infant (1 12 mo)

Canadian Immunization Guide National Advisory Committee on Immunization. Canadian Immunization Guide (CIG). Last Modified 2021. Public Health Agency of Canada, 2006. Available at https://www.canada.ca/ en/public-health/services/canadianimmunization-guide.html

Table 2. Normal sBP at Various Ages Age

sBP (mmHg)

Birth 38

Ear

35.8”C to 38"C

>38 “ C

Oral Axillary

35.5”C 10 37.5’C 36.5"C to 37.5"C

>37.5VC

“C

+

>37.5“C

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Toronto Notes 2023

P I Paediatrics

Table 4 . Temperature Measurement Technique Recommendations Age

Suggested Technique

Birth to 2 yr

1. Rectal (definitive) 2. Axillary (screening low risk children)

Over 2 yr to 5 yr

1. Rectal (delinltive) 2. Axillary. Tympanic (or Temporal Artery if in hospital) (screening)

Older than

1. Oral (definitive) 2. Axillary, Tympanic (or Temporal Artery if in hospital) (screening)

5 yr

Primary Care Visit Overview •schedule of well - child visits

• newborn ( within 18 -72 h post -discharge), 2, 1, 6, 9, 12, and 18 mo
2 mo ( 2-4 doses given at least 8 vrk apart ) vrith booster every 5 yr thereafter • Canonirtroutine Men goccccal C Co .gate at 11 mo if received Men C - ACVWacd expected to receive a second dose wittier 8 « k • Pneumococcal polysaccharide vaccme ( Pneu P -23| at > 2 yr and single booster >5 yr alter first dose • Pneumococcal conjugate vaccine (Pneu C-tt ) 1 2 doses 8 wk a pa rl if >12 mo at ti me of diagnosis • Consider single booster Nib at >5 yr

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P 5 Paediatrics • social history

• who lives at home? Siblings? does the child attend daycare or school? Primary care givers?

• school adjustment , friends, activities, safety, stability, stressors • HEhADSSS history for adolescents

-

ITHELPS income, transportation , home, education , legal status, personal safety, support

Routine Immunization Table 5. Publicly Funded Immunization Schedule for Ontario

-

2 mo

DTaP TdaP IPV-Hib IPV MM

4 mo

-MM

-

-

6 mo

Rot 5

^IM

AO

-

-

4|M

^IM

12 mo

-

PneuC 13

Men' CC

MMR

^IM

-/SC

-

Var

MMRV

Men- CACYW

HepB

-

HPV 9

Inf

Tdap

Injection site Infants (1 yr

• main causes: motor vehicle crashes, burns, drowning, falls, choking, infanticide Table 11. Injury Prevention Counselling

-

0 6 mo

-

-

6 12 mo

.

Do not leave atone on bed on changing table, or in tub Keep crib rails up Check water temperature before

Install stair barriers Discourage use of walkers Avoid play areaswith sharp edged tables and corners bathing Cover electrical outlets Do not hold hot liquid and infant at Unplug appliances when not in use Keep small objects, plastic the same time bags, cleaning products, and Check milk temperature before feeding medications out of reach Appropriate car seats are required Supervise during feeding Appropriate car scats before leaving hospital Avoid co slecping with Infant

-

1 2 yr

25 yr

Hever leave unattended Keep pot handles turned to back of stove Caution with whole grapes, nuts, raw carrots, holdogs, etc due to choking hatard No running whileeating

Bicycle helmet Never leave unsupervised at home, driveway, or pool teach bike safety, stranger safely, and street safety Swimming lessons (>4 yr ), sunscreen (from 6 mo), fences around pools Appropriate car seats Ensure large devices ( such as TVs) secured to walls

.

Appropriate car seats

-

Note: This list is not exhaustive. For more details, see Rourke Baby Record (http://www.rourkebabyrecord.ca/downloads)

Circumcision • elective procedure CPS affirms that circumcision is not medically indicated, and does not recommend routine circumcision for every newborn male often done for religious or cultural reasons • benefits: prevention of phimosis and slightly reduced incidence of UTI, S'l'l, balanitis, cancer of the penis complications ( holds breath and becomes silent > spontaneously resolves or loses consciousness pallid type: child falls or is frightened > heart rate is reduced by vagal stimulation -> cerebral hypoperfusion -> loses consciousness • management usually resolves spontaneously and rarely progresses to seizure; median age of remission is 4 yr, and almost all children stop by 8 yr • help child control response to frustration and avoid drawing attention to spell may be associated with iron deficiency anemia, improves with supplemental iron if episodes prolonged /frequent, triggered by non - traumatic stimuli, or if there is a family history of syncope or sudden death -» in-depth cardiac evaluation indicated - check for prolonged QT syndrome

Crying/Fussing Child • common etiologies: functional (e.g. hungry', irritable), colic, trauma, illness

• history

description of baseline feeding, sleeping, crying patterns infectious symptoms: fever, tachypnea , rhinorrhea, ill contacts feeding intolerance: gastroesophageal reflux with esophagitis, N / V, diarrhea, constipation • physical injury ( unintentional or non-accidental ) recent immunizations (vaccine reaction ) or medications (drug reactions), including maternal drugs taken during pregnancy ( neonatal withdrawal syndrome) and drugs that may be transferred via breast milk «

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PU Paediatrics

inconsistent history, pattern of numerous emergency department visits, difficult social living conditions (e.g. parental substance use, precarious living circumstances) can raise concerns for

maltreatment consider broad array of possible underlying causes such as meningitis, sepsis, respiratory distress, constipation, etc

.

Infantile Colic • clinical features: unexplained paroxysms of irritability and crying for >3 h /d, >3 d/wk for >3 wk in an otherwise healthy, well-fed baby ( rule of 3s - Wessel criteria ) • epidemiology: 10% of infants; usual onset 10 d to 3 mo of age with peak at 6- 8 wk • etiology: unknown , 'theories: alterations in fecal microflora , cow's milk intolerance, Gl immaturity or inflammation, poor feeding, maternal smoking • diagnosis: diagnosis of exclusion after thorough history and physical exam to rule out identifiable causes such as otitis media, cow’s milk intolerance, Gl problem, fracture

• management parental relief, rest, and reassurance change breastfeeding or bottle-feeding technique hold baby, soother, car ride, music, vacuum , check diaper limited evidence for probiotics; further research required » breast fed infants: time limited trial ( typically 1 2 wk ) ofa hypoallergenic maternal diet ( i.e. no cow’s milk, eggs, nuts, wheat ) while monitoring baby’s behaviour formula-fed infants: time-limited trial (typically 1-2 wk ) of hydrolyzed formula prognosis: all resolve, most in the first 3-6 mo of life, no long-term adverse effects

-

-

-

Dentition and Caries Dentition

• primary dentition ( 20 teeth )

-

first tooth at 5 9 mo ( lower incisor), then 1 / mo 6-8 central teeth by 1 yr assessment by dentist 6 mo after eruption of first tooth and certainly by 1 yr of age (Grade B recommendation ) dentition (32 teeth ) secondary • first adult tooth is 1st molar at 6 yr, then lower incisors Caries

• early childhood caries: presence of one or more decayed , missing (due to caries), or filled tooth

surfaces in any primary tooth in a preschool -aged child • etiology: multifactoriai with biomedical factors (e.g. diet, bacteria, host ) and social determinants of

health

inappropriate feeding practices (e.g. frequent , prolonged bottle feeding, putting to bed with bottle, prolonged breastfeeding, and excessive juice consumption ) are important factors • prevention no bottle at bedtime, clean teeth after last feed minimize juice and sweetened pacifier dean gums with damp washcloth or soft bristle toothbrush ( no toothpaste ) when no teeth present 5 yr General Approach

• should be evaluated if: dysuria; change in colour, odour, or stream; secondary or diurnal; change in gait; or stool incontinence are present

Treatment for primary nocturnal enuresis should not be considered until 7 yr due to high rate of spontaneous cure

Primary Nocturnal Enuresis • clinical features: enuresis when bladder control has never been attained • epidemiology: 10% of children age 6, 3% of children age 12, 1% of children age 18, family history

rt LJ

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important

• etiology: developmental disorder or maturational lag in bladder control while asleep

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P12 Paediatrics

Toronto Notes 2023

• management • time, reassurance ( ~20% resolve spontaneously each yr), and avoidance of punishment or humiliation to maintain self esteem behaviour modification (limiting fluids and avoid caffeine- containing food before bedtime, void prior to sleep, ensure access to toilet, take out of diapers) conditioning: “wet" alarm wakes child upon voiding (70% success rate) • medications (for children >7 yr, considered second line, short term therapy, may be" used for sleepovers/camp): desmopressin (DDAVP) oral tablets (similar success rate as “wet alarm therapy but higher relapse rate), imipramine ( Tofranil") ( rarely used ; lethal if overdose; side effects: cardiac toxicity, anticholinergic effects)

-

-

Secondary Enuresis • clinical features: enuresis develops after child has sustained period of bladder control (>6 mo) • etiology: inorganic regression due to stress or anxiety (e g birth of sibling, significant loss, family discard, sexual abuse ), secondary to organic disease ( UTI, DM, Dl, sleep apnea, neurogenic bladder, CP, seizures, pinworms) • management; treat underlying cause, specialist referral as appropriate

..

Diurnal Enuresis • clinical features: daytime wetting (60-80% also wet at night) • etiology: micturition deferral ( holding urine until last minute) due to psychosocial stressor (e.g. shy ), structural anomalies (e.g. ectopic ureteral site, neurogenic bladder ) UT I constipation , CNS disorders,

Management andtreatment of Nocturnal Enuresis - An Updated Standardization Document f rom theInternational Children's Continence

Society J Pcdiati Urol 2020.10 19 Additional Investigations ere not warranted In aneisuretic child crith outcer tain waning signs. Key comorbidities to consider include psychiatric disorders, constipation, urinary tract infections, and snoring nr sleep apneas, floating constipation and daytime incontinence tan lead to symptom resolution. Irealing concomitant sleep disorder may alsu lead to symptom resolution and is indicated. If enuresn is non monosymptomatic treatment should begin with advice on eveningdrinklng and voiding habits. In monosymptomatic enuresis, treatment should begin with either desmopressin oi an enuresisalaim. Second line treatment includes anticholinergic medications. Antidepressants may be considered in rehactoiy enuresis though eipert opinion should

.

-

besought.

. .

DM • management: treat underlying cause, behavioural (scheduled toileting, double voiding, good bowel program, sitting backwards on toilet, charting /incentive system, relaxation / biofeedback ), good

constipation management, pharmacotherapy

Encopresis • clinical features: fecal incontinence in a child > 4 y r, at least once per mo for 3 mo • prevalence: 1-1.5% of school-aged children ( rare in adolescence); M:l'= 6:1 in school-aged children •causes: chronic constipation ( retentive encopresis), Hirschsprung disease, hypothyroidism, hypercalcemia, spinal cord lesions, CP, hypotonia , anorectal malformations, bowel obstruction

-

Retentive Encopresis • definition: child holds bowel movement, develops constipation, leading to fecal impaction and seepage of soft or liquid stool (overflow incontinence)

• etiology physical: painful stooling often secondary to constipation emotional: disturbed parent-child relationship, coercive toilet training, social stressors •clinical features

history

crosses legs or stands on toes to resist urge to defecate distressed by symptoms, soiling of clothes toilet training coercive or lacking in motivation

may show oppositional behaviour abdominal pain physical exam

-

digital rectal exam or abdominal x ray: large fecal mass in rectal vault anal fissures ( result from passage of hard stools ) palpable stool in LLQ abdomen (50% of children with fecal incontinence) staining of underwear with stool • management complete clean-out of bowel: PEG 3350 given orally is most effective and first line; enemas and suppositories may be second line therapies, but these are invasive, often less effective, and not recommended as first line maintenance of regular bowel movements (see Constipation , P46) assessment and guidance regarding psychosocial stressors behavioural modification • complications: recurrence, toxic ntegacolon ( requires >3 12 mo to treat ), bowel perforation

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Toilet Training • 90% of children attain bowel control before bladder control

• generally, females train earlier than males • 25% by 2 yr (in North America ), 98% by 3 yr have daytime bladder control • signs of toilet readiness ( usually 18 24 mo) ambulating independently, stable on potty, desire to be independent or to please caregivers ( i.e. motivation ), sufficient expressive and receptive language skills ( 2-step command level), can stay dry for several hours ( large enough bladder), can recognize need to go, able to remove clothing • stepwise approach used to familiarize child with the potty chair and create a connection between elimination and the potty chair; praise with use of potty chair

-

Failure to Thrive

s

• definition

• •

weight < 3rd percentile, falls across two major percentile curves on growth chart, or 2 yr: height, weight, BMI vital signs complete head to toe exam dysmorphic features or evidence of chronic disease upper to lower segment ratio sexual maturity staging

Clinical Signs of FTT SMALL KID Subcutaneous fat loss Muscle atrophy Alopecia

Lethargy Lagging behind normal

Kwashiorkor Infection ( recurrent) Dermatitis

signs of maltreatment or neglect • investigations (as indicated by clinical features)

.

CBC, blood smear, electrolytes, Tt, TSH urea , ferritin, Ca bone age x-ray

, celiac screen , and vitamins A , D, H

chromosomes/ karyotype chronic illness: chest (CXR, sweat Cl -), cardiac (CXR, ECG, echo), Gl (celiac screen , inflammatory markers, malabsorption ), renal ( urinalysis ), liver (enzymes, albumin ) Table 12. Failure to Thrive Patterns Growth Parameters

Suggestive Abnormality

Decreased Wt

Normal Ht

Normal HC

Caloric insufficiency Decreased intake

DecreasedWl

Decreased HI

Normal HC

Structural dystrophies Endocrine disorder

DecreasedWt

Decreased Ht

Decreased HC

Intrauterine insult

Upper to Lower Segment Ratio • Increased in achondroplasia , short limb syndromes, hypothyroidism, storage diseases • Decreased In Marfan’s Klinefelter’s, Kallman’s syndromes, and testosterone deficiency • Calculation: upper segment/lower segment • Upper segment: top of head to pubic symphysis • Lower segment: pubic symphysis to floor

.

-

BA bene age: CA » chronological age: HC * head circumference: Ht * height: Wl * weight

Etiology

• an interplay between pathophysiology and psychosocial influences • investigations should assess: 1. complex factors in the parent-child relationship dietary intake, knowledge about feeding, improper mixing of formula

feeding environment parent child interaction, attachment child behaviours, hunger /satiety cues postpartum depression social factors: stress, poverty, neglect , child /domestic abuse, parental substance misuse, restricted diets 2. inadequate caloric intake: inadequate milk supply/latching, mechanical feeding difficulty (cleft palate ), oromotor dysfunction , toxin -induced anorexia 3. inadequate absorption: biliary atresia, celiac, 1BD, CP, inborn errors of metabolism, milk protein allergy, pancreatic cholestatic conditions

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4. increased metabolism: chronic infection, CP, lung disease from prematurity, hyperthyroidism, asthma, 1BD, malignancy, renal failure 5. increased losses 6.increased utilization (e.g. chromosomal disorders) 7. prenatal factors: placental insufficiency, intrauterine infections, genetic, maternal Management

• most as outpatient using multidisciplinary approach: primary care physician , occupational therapist, dietitian, psychologist , social work, CAS • medical: oromotor problems, iron deficiency anemia, gastroesophageal reflux • nutritional: educate about age appropriate foods, calorie boosting, mealtime schedules, and environment; goal to reach 90 110% 1BW, correct nutritional deficiencies, and promote catch up growth /development •behavioural: positive reinforcement, mealtime environment, no distractions (e.g. toys, books, or TV ) during mealtime

-

-

Energy Requirements •see S utrition , P8 '

Obesity

Periaatal aid Eartj Cttdkood Factors for Overweight aad Obesity iw Young Canadian

-

C

• definition Age

-

0 2 yr 2 5 yr 5-19 yr

-

Overweight eight for length >97th percentile

Obese Weight lor length >995th percentile

BMI 97Ui percentile

BMI 99.9th percentile

BUI >1511! percentile

BMI > 97th percentile

>

>

• risk factors: genetic predisposition (e.g. both parents obese - 80% chance of obese child ), psychosocial/ environmental contributors • etiology increased intake (dietary, social /behavioural, and iatrogenic such as drugs and hormones) • decreased energy expenditure • organic causes are rare ( increased pulmonary blood flow -> increased pulmonary pressures • shunt volume is dependent upon three factors: (1 ) size of defect, ( 2) pressure gradient between chambers or vessels, and (3) peripheral outflow resistance • untreated shunts can result in pulmonary vascular disease, left ventricular dilatation and dysfunction, right ventricular HTN and RVH, and ultimately R to L shunts

Atrial Septal Defect

• 3 types: ostium primtim (common in DS, defect located at mitral or tricuspid valves), ostium secundum (most common type, 50 -70%, defect located at septum between left and right atria ), sinus venosus (defect located at entry of superior vena cava into right atrium ) • epidemiology: 6 - 8% of congenital heart lesions, common in patients with certain congenital disorders (e.g. DS, FAS) • natural history 80 100% spontaneous closure rate if ASD diameter 2 yr

3

Pulse

Normal , lull

Rapid

Rapid , weak

Blood Pressure

Normal

low to normal

Decreased in shock ( very lale finding in paediatrics and very dangerous)

Urine Output Oral Mucosa

Decreased Slightly dry

Markedly decreased Dry

Anuna

Anterior Fontanelle

Normal

Sunken

Markedly sunken

Eyes Skin Turgor

Normal Normal

Markedly sunken Tenting

Capillary Relill

Normal|* 3 s)

Sunken Decreased Normal to increased

*

'

Assessment of Severity of Dehydration

B

-

Anterior fontanelle Skin turgor Eyes sunken HR Oral mucosa Output of urine

'

Parched

Increased (>3 s)

-

Note that percentage* refer to percent to** ot pre illness body weight

2) Determine the likely electrolyte disturbance dependent on etiology of dehydration and type of fluid loss ( isotonic vs. hypertonic vs. hypotonic)

•

Table 18 . Electrolyte Content of Various Bodily Fluids

•

HCQ3-(mmol / L)

Bodily Fluid

Na" (mmol / L)

K (mmoiyi)

Ch (mmol/ L)

Saliva

20 15

70

30

Gastric Juice

30 30 GO 80

100

Pancreatic Juice

140

5 -10

60 90

0 40100

Bile

140

5 -10

Small Bowel

140

20

100 100

2550

Large Bowel

75

30

30

Sweat

20 - 70

5 -10

40 - 60

40 0 0

for moderate and severe dehydration , initial investigations should include urinalysis and blood work examining electrolytes ( Na *, K ', Cl ), glucose, acid - base disturbances ( blood pH , p(.0:, HCO.i -), and impaired renal function (creatinine, BUN )

3 ) Determine if the child requires PO or IV rehydration

• dehydrated child must receive adequate fluid management, including replacing deficits, ongoing losses, and maintenance fluids • oral rehydration therapy (ORT) indication: mild to moderate dehydration advantages: * cost, no IV needed, no increase in incidence of iatrogenic hyper/ hyponatremia, parental involvement in therapy • indications for IV rehydration therapy: severe dehydration requiring close monitoring and frequent assessment of electrolytes, inability to tolerate ORT (e.g. vomiting, alteration in mental status, ileus, monosaccharide malabsorption , etc.), inability to provide ORT, failure of ORT in providing adequate rehydration ( e.g. persistent diarrhea or vomiting )

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P‘IO Paediatrics 4) Return the child to a normal volume and electrolyte status by replacing current deficits and ongoing losses Degree of Dehydration

i

Mild dehydration

No dehydration

I

i 1 . Rehydrate with ORT at 50 mL/kg over 4 h 2. Replace ongoing losses with ORT 3. Age-appropriate diet after rehydration

1. Age-appropriate diet 2. Replace ongoing losses

Moderate dehydration 1. Rehydrate with ORT at 100 mL/kg over 4 h 2. Replace ongoing losses with ORT 3. Age-appropriate diet after rehydration

1 I 1 IV resuscitation with Severe dehydration .

NS 20 mlAg bolus 2. Reassess and repeat if necessary 3. Begin ORT when patient is stable 4. Replace ongoing losses with ORT 5. Age- appropriate diet after

Special Consideration - S1ADH • Clinical Signs: hyponatremia and excretion of concentrated urine • Risk Factors: certain medications (e.g. morphine), postoperative, pain. N'V. pulmonary disease (e.g. pneumonia). CNS disease (e.g. meningitis) • Caution: acute hyponatremia is associated with rapid administration of hypotonic IV fluids, this can lead to cerebral edema and brain herniation or central pontine myelinolysis

rehydration

Figure 10. Algorithm for deficit replacement and replacement of ongoing losses in the dehydrated child

5 ) Provide the appropriate fluid and electrolyte maintenance daily requirements

Table 19. Maintenance Fluid Requirements Body Weig ht

100:50:20 Rule ( 24 h maintenance fluids)

4:2:1 Rule (hourly rate of maintenance fluids)

I-10 kg II -20 kg

100 cc/kg /d 1000 cc 50 cc/ kg /d for every kg »10 kg

4 cc/kg/ h

40 cc 2 cci'kg / h for every kg »10 kg

20 kg

1500 cc + 20 cc/ kg /d for every kg »20 kg

60 cc 1 cc/kg/ h for every kg »20 kg

-

»

-

• prior to starting IV' fluids, serum electrolyte values should be measured • in children , all maintenance fluids should have a dextrose component due to their higher risk of hypoglycemia, especially if they are NPO • common IV’ fluid combinations used in paediatrics NS bolus for dehydration for maintenance: newborn: D10YV first mo of life: D5W /0.45 NS + KC120 mHq / L ( only add KC1 if voiding well) children without special considerations: D5W/ NS + KCI 20 mHq / L - decreased risk of

hyponatremia other options: D5 \V 0.45% NS + KG 20 mHq / L • most important thing to remember when correcting Na + aberrations due to fluid deficits risk of cerebral edema with rapid rehydration with hypotonic or isotonic solutions ( Le. NS ) therefore replace fluid slowly with close monitoring aim to adjust ( increase or decrease ) plasma [ Na i by no more than 12 mmol / L/d • management depends on etiology, severity of symptoms, and timing (acute vs. chronic) 6 ) Continue to monitor fluid and electrolyte status • accurate monitoring of daily fluid intake ( PO and IV' ) and ongoing losses ( urine output, diarrhea, emesis, drains) • if child receiving > 50% of maintenance fluids through IV, serum electrolyte values should be monitored daily and therapy adjusted accordingly • avoid iatrogenic hyper/ hvponatremia, keep the possibility of S1ADH in mind ( indicated by hyponatremia and concentrated urine)

Gastroenterology Vomiting History • characteristic of emesis (e.g. projectile, bilious, bloody, etc.) • pattern of emesis (e.g. association with feeds, cyclic, morning, prolonged, positional, etc.) • associated symptoms (e.g. anorexia , diarrhea, abdominal pain , hematochezia , fever, headache, etc.) • red flags: bilious or bloody emesis, projectile vomit, abdominal distension and tenderness, high fever, signs of dehydration, worse when lying down • remember that vomiting without diarrhea is not always gastroenteritis • post - tussive vomiting is also common with coughing fits in children

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P ll Paediatrics

Physical

• vital signs to determine clinical status and hydration state • abdominal examination for evidence of obstruction or focal tenderness • neurologic assessment for signs of increased 1CP Investigations • if child appears well and no worrisome features, often investigation is not required • CBC, electrolytes, BUN , Cr, amylase, lipase, glucose, liver enzymes, urinalysis done routinely • in sick child, add: HSR, venous blood gases, C&S ( blood , stool ), imaging ( x- ray, U/S)

Table 20. Common Differential Diagnosis , Associated Findings, and Diagnostic Approach Based on Age Suggestive Findings

Diagnostic Approach

Tracheoesophageal Fistula

Excessive secretions soon alter birth (e.g. drooling, choking, respiratory distress/ pneumonia), inability to feed, cyanosis (esp with feeds), emesis

Inability to advance NG tube. CXR. upper Gl series with water-soluble contrast

Pyloric Stenosis

Projectile non-bilious emesis within 30 min after feeding, fatigue, dehydrated, palpable “olive" in RUO. decreased stools, hunger

CSC. electrolytes Cr SUN. ASG (hypokalemic, hypochloremic metabolic alkalosis).U/S of pylorus,upper Gl study (if U /S nondiagnostic)

GERD

Fussiness after feeds, spit ups arching of back, poor weight gain

Empiric trial of acid suppression.pH monitoring study,upper Gl study,endoscopy

Sepsis

Fever, lethargy, tachycardia,tachypnea, widening pulse pressure

CBC. PT/PTT.electrolytes.Cr. BUN. tils, bilirubin, lactate,urinalysis, cultures (blood, urine.CSF) CXR

Inborn Error of Metabolism

Poor feeding FTT, jaundice, hepatosplenomegaly, cardiomyopathy, dysmorphia. developmental delay, neurologic manifestations

Electrolytes.ABG (hyponatremic.hyperkalemic metabolic acidosis) lactate, ammonia. LFTs. BUN. Cr.serum glucose,bilirubin. PT /PTT. CBC

Intestinal Obstruction - Malrotation with Volvulus Meconium Ileus, etc.

Bilious emesis, abdominal distension, pain, bloody stool,shock

AXR.upper Glseries contrast enema

Duodenal Alresia/Stenosis

Bilious emesis, abdominal distension, often seen in DS jaundice, polyhydramnios during pregnancy, hypokalemic, hypochloremic metabolic alkalosis

AXR.upper Glseries ('double bubble' sign)

Hirschsprung's Disease

Bilious emesis, abdominal distension, pain, failure to pass stool

AXR.contrast enema, rectal biopsy

Necrotizing Enterocolitis

Premature neonate,bilious emesis, bloody stools, abdominal distension, intolerance of feeds, electrolytes Cr BUN blood culture

AXR, CBC, electrolytes, Cr. BUN blood culture

Acute Viral Gastroenteritis

Diarrhea, fever, abdominal discomfort, myalgia, sick contact,recent travel

Generally clinical diagnosis: if severe: CBC. electrolytes,stool studies

Appendicitis

Periumbilical discomfort that later localizes to RLO fever, anorexia

Abdominal U/S

Intussusception

Colicky progressive abdominal pain, drawing ol legs up to chest,lethargy,bloody “red currant jelly " stool (Triad)

Abdominal U/S. AXR (rule out other etiologies and perforation)

Non - GI Infection (e.g. Meningitis, pyelonephritis, acute otitis media)

Fever, localized findings depending on cause

Cultures (CSF blood, urine), brain imaging CXR

IncreasedICP

Nocturnal wakening, progressive recurrent headache worse with Valsalva, focal neurologic deficits, gait disturbance

Brain CT without contrast Therapeutic LP in idiopathic intracranial HTN

Toxic Ingestion

Findings vary by substance - toxidrome often a Qualitative and sometimes quantitative levels (urine, blood) history of ingestion

Pregnancy

Amenorrhea, morning sickness, bloating breast tenderness

Urine jt -hCG

Cyclic Vomiting

At least 3 self - limited episodes of vomiting lasting 12 h 7 d between episodes, no organic cause of vomiting

Diagnosis of exclusion

Cause

NEONATES - NON - BILIOUS

.

.

..

.

.

NEONATES - BILIOUS

.

.

.

.

.. .

CHILDREN AND ADOLESCENTS

.

.

.

.

.

.

Management

r

• rehydration ( see Fluids and Electrolytes, P38 ) • treat underlying cause and correct metabolic/electrolyte abnormalities • antiemetic drugs can be used in older infants, children , and adolescents with severe vomiting: ondansetron , promethazine, prochlorperazine, metodopramide • not recommended when unknown etiology or anatomic abnormalities

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P 12 Paediatrics

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Gastroesophageal Reflux Epidemiology • extremely common in infancy ( up to 50%) but rarely causes pathology ( i.e. GERD) Clinical Features

• passage of stomach contents into esophagus, may cause regurgitation or vomiting typically soon after feeding, non bilious, rarely contains blood, small volume ( LJ

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P I I Paediatrics

Gastroenteritis History • non -specific: diarrhea, vomiting, fever, anorexia, headache, myalgias, abdominal cramps • viral causes most common, bacterial and parasitic agents more common in older children ( 2- 4 yr) • recent infectious contacts: symptoms usually begin 24- 48 h after exposure Physical Exam • febrile • dehydrated: must assess extent (see Approach to Infant/Child with Dehydration , P3S ) Investigations • not usually necessary in young children • CBC, electrolytes, and stool studies may be indicated in severe cases, if IV hydration required or atypical presentation • stool analysis: leukocytes /erythrocytes suggests bacterial or parasitic etiology

Complications • viral gastroenteritis usually self-limiting (lasts 3-7 d in most cases) • adverse effects related to hypovolemia , shock, tissue acidosis, and rapid onset and over-correction of

electrolyte imbalances • death in severe dehydration ( rare in developed countries ) Table 22. Gastroenteritis Viral Infection

Bacterial Infection

Etiology

Most common cause of gastroenteritis Commonly: rotaviruses (most common), enteric adenovirus, norovirus |typically older children)

Salmonella, Campylobacter, Shigella, pathogenic f. co// Yersinia C. difficile

Clinical Features

Associated with URTIs Resolves in 3- 7 d Slight fever, malaise, vomiting, vague abdominal pain

Severe abdominal pain High fever Bloody diarrhea

Risk Factors

Daycare. young age. sick contacts, immunocompromised BacteriaI infection: travel, poorly cooked meat, poorly refrigerated foods, antibiotics

Management

Prevention and treatment of dehydration most important (see Approach to lolaol /Child with Dehydration. P3S\ Early refeeding advisable, with age - appropriate diet upon completion of rehydralion Ondansetron for suspected gastroenteritis with mild to moderate dehydration or failed ORT and significant vomiting Antibiotic or anliparasitic therapy when indicated, antidiarrheal medications not indicated Notify Public Health authorities if appropriate Promote regular hand - washing and return to school 24 h after last diarrheal episode to prevent transmission Rotavirus vaccine

.

.

Toddler ’s Diarrhea Epidemiology • most common cause of chronic diarrhea during infancy • onset between 6 - 36 mo of age, resolves spontaneously between 2- 4 yr

Clinical Features • diagnosis of exclusion in thriving child • 4 - 6 bowel movements per d • diet history ( e.g. excess juice intake overwhelms small bowel resulting in disaccharide malabsorption )

• stool may contain undigested food particles • excoriated diaper rash

Management • reassurance that it is self- limiting • I Is (adequate Fibre, normal Fluid intake, lower dietary Fat ( 35 - 40% ), discourage excess Fruit juice)

Lactase Deficiency (Lactose Intolerance) Clinical Features • chronic, watery diarrhea and abdominal pain, bloating associated with dairy intake • primary lactose intolerance: crampy abdominal pain with loose stool ( older children, more common in Fast Asian and African descent) • secondary lactose intolerance: older infant , persistent diarrhea (decreased lactase production post viral /bacterial infection, celiac disease, or IBD)

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Diagnosis

• investigations usually not needed, trial of lactose- free diet • symptom assessment with validated questionnaire after oral lactose load • positive breath hydrogen test if >6 yr after oral lactose load with simultaneous symptom assessment • tests for lactase deficiency: small bowel biopsy, genetic testing • demonstration of lactose malabsorption should be combined with assessment of intolerance symptoms

Management

• lactose -free diet • lactase- containing tablets /capsules/drops (e.g. Lacteeze’, Lactaid*)

Irritable Bowel Syndrome • see Gastroenterology. G 26

Celiac Disease • Gastroenterology, G21 in children: presents at any age, often 6-24 mo with the introduction of gluten in the diet • poor weight gain, poor appetite, irritability, apathy, rickets, wasted muscles, flat buttocks, rarely distended abdomen • GI symptoms: N / V, edema, anemia, abdominal pain, diarrhea • non -(il manifestations: iron - deficiency anemia, dermatitis herpetiformis, dental enamel hypoplasia , osteopenia /osteoporosis, short stature, delayed puberty, behavioural changes • associated with other autoimmune disorders (e.g. Tl DM, thyroid disease)

Cow’s Milk Allergy

Celiac disease is associated with an increased prevalence of IgA deficiency. Since fTG is an IgA -detecting test you must order an accompanying IgA level

A Celiac disease diet must avoid gluten present in "BROW ” foods Barley

Oats (controversial) Wheat

Pathophysiology • cow’s milk allergy (CM A ) may be either an IgE mediated reaction or a non lgE mediated reaction, which is further classified as a food protein induced allergic proctocolitis ( EPIAP), food protein induced enterocolitis syndrome ( I ' PIES ), or food protein induced enteropathy

-

-

- -

-

-

Clinical Features

• IgE-mediated CM A reactions occur within hours of exposure and are present on the skin

(i.e. urticarial, pruritus, etc.), upper and lower resp tract symptoms (i.e. wheeze, cough, etc.), gastrointestinal symptoms ( i.e. abdominal pain, nausea /vomiting, diarrhea, etc.) • non -lgE - mediated CM A reactions occur hours following ingestion , within few mo, presents with: EPIAP: mild diarrhea, small amounts of bloody stools (common in young infant )

-

1 PIES:severe vomiting, and diarrhea, anemia, hematochezia food protein -induced enteropathy: FIT, chronic diarrhea, hypoalbuminemia • up to 50% of children intolerant to cow’s milk may be intolerant to soy protein as well Investigations

• food challenge ( gold standard ), skin prick test, serum measurement of allergen-specific IgE, patch testing Management

• IgE- mediated CMA: stop exposure, epinephrine for acute anaphylactic reactions • non - lgE - mediated CMA: stop, reintroduce milk at 6-8 mo, vast majority (> 90%) will outgrow by 1 yr • casein hydrolysate formula ( Nutramigen*, Pregestimil*) or mother may sequentially remove cow’s milk protein, all bovine protein , soy protein , legumes ( 7 d washout ), and continue breastfeeding ( with adequate calcium and vitamin D intake )

Inflammatory Bowel Disease • see ( itistroeiUerology. Ci 22

Cystic Fibrosis • see Respirolouv, KI 2

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P 16 Paediatrics

Constipation •decreased stool frequency ( < 3 stools/ wk ) and /or stool fluidity ( hard , pellet - like) FUNCTIONAL CONSTIPATION •99% of cases of constipation • Rome IV criteria for infants and toddlers 2 of the following for at least 1 mo: < 2 defecations/wk history of excessive stool retention history of large-diameter stools history of painful or hard bowel movements evidence of large fecal mass in rectum • in toilet- trained children, the following additional criteria may be used: at least 1 episode / wk of incontinence alter the acquisition of toileting skills history of large diameter stools that may obstruct toilet

-

Pathophysiology

• lack of fibre in diet or change in diet, poor fluid intake, behavioural • infants: often occurs when introducing cow's milk after breast milk due to high fat and solute

»

content , lower water content toddlers /older children: can occur during toilet training, starting school, or due to pain on defecation, leading to withholding of stool adolescents: often related to school stressors, anxiety/eating disorders

Management

•education: explanation of mechanism of functional constipation for parents/older children •clean out: PEG 3350 flakes ( 1-1.5 g / kg /d, max 100 g /d ), picosalax, PEGlyte* • maintenance: adequate fluid intake (if 38°C/ 100.4°1: oral or rectal • fever without a source/focus: acute febrile illness ( typically < 10 d duration ) with no identifiable cause of fever even after careful history and physical • fever of unknown origin: daily or intermittent fevers for at least 2 consecutive wk of uncertain cause after careful history and physical, and initial laboratory assessment

Etiology

• infectious: anatomic approach ( CNS, ears , upper and lower respiratory tract , (il , ( iU , skin , soft tissue, bones and joints, etc.) • inflammatory: mainly autoimmune ( Kawasaki disease ,|1 A, 1 BD, Sl. fi, etc.) • malignancy: childhood cancers ( leukemia, lymphoma , neuroblastoma, etc.) • miscellaneous: drugs and toxins, post immunization , familial dysaulonomia , factitious disorder, etc.

-

Diagnosis

• history: duration, height and pattern of fever, associated symptoms, exposures, constitutional symptoms, recent antipyretic use, ethnic or genetic background , daycare, sick contacts, travel, tick or other bug bites, age of child • physical exam: toxic vs. non - toxic, vitals, growth, complete head - to- toe exam to identify any focus of infection • investigations: guided by history, physical exam , and clinical suspicion Fever

£

i

-

-

Age: 37 vrk HomewiBi/beforeEoni No hosprtalizaboas No prior anbhiobcase No prior treatment for oneipla tired hyperbilirubinemia Noth tome disease j

considered high risk regardless of clinical features and laboratory findings

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Management

• admit to hospital if appropriate • treat the source if known • replace fluid losses (e.g. from vomiting, diarrhea ); maintenance fluid needs are higher in a febrile child • reassure parents that most fevers are benign and self-limited • antipyretics (acetaminophen and /or ibuprofen ) may be given if child is uncomfortable

Acute Otitis Media • all of:

1. presence of m iddle ear effusion

2. presence of middle ear inflammation 3. acute onset of symptoms of middle ear effusion and inflammation

.

Epidemiology • 60-70% of children have at least 1 episode of AOM before age 3 •6-24 mo is the most common age group commonly develops within a wk after a viral URI • one third of children have had S3 episodes hy age 3; peak incidence January to April Etiology

.

•bacterial - S pneumoniae (decreasing since the introduction of PCV 7 and PCV 13), H . influenza, M calarrhalis , group A Streptococcus (GAS) •less common - anaerobes ( newborns) , Gram negative enterics ( infants) •viral - more likely to spontaneously resolve

.

-

Risk Factors • Eustachian tube related: dysfunction /obstruction ( URT1, allergic rhinitis, chronic rhinosinusitis, adenoid hypertrophy, barotrauma ) inadequate tensor veil palatini function (deft palate ) genetic syndromes ( DS, Crouzon , Apert ) cilia disruption ( Kartagenger’s syndrome, CE) •genetic predisposition (family history, ethnicity - First Nations peoples and lnuit, low levels of secretory IgA , or persistent biofilm in middle ear ) • behavioural and environmental exposures ( not breastfed or shorter duration of breastfeeding, prolonged bottle feeding, bottle feeding laying down, pacifier use, second-hand smoke exposure, crowded living conditions/daycare, sick contacts ) • immunosuppression /deficiency ( chemotherapy, steroids, DM , hypogammaglobulinemia, Cl;) Pathogenesis • obstruction of Eustachian tube -» air absorbed in middle ear -> negative pressure (an irritant to middle ear mucosa) -> edema of mucosa with exudate/effusion -> infection of exudate from nasopharyngeal

secretions

Pneumococcal ConjugateVaccineslor Preventing Acnte OtitlsMedia inChildren Cochrane OBSyst He 2019:C00OU8O Purpose: lo syiterubully review the uu of pneumococcal conjugal vaccines in preventing AOU in children 39'C|

• Moderately to severely systemcilly III • Very severe olalgia

-

Significant rllnessfor 43 h Aotibiotic thevapj regime: • Amonicil n remains the clear drug ol choice • 10 d course for children 2 yr - :le ; ins, p aaNrtaSMSSIMIt at 48 Ir OR p wide an antibiotic prescription lo parents to 6II il the child does not improve in 48 h

-

•

-

.

Diagnosis • requires middle ear eflfusion and signs of inflammation ( most important is a bulging TM ) • accurate diagnosis of AOM is very important to prevent antibiotic overuse

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Management

• symptomatic therapy: antipyretics/analgesics ( e.g. acetaminophen or ibuprofen )

• watchful waiting if criteria met • antibiotic therapy if 39'C in absence of antipyretics such as bulging tympanic membrane OR >48 h of symptoms

4

Treat with anbmicrobials for 10 d if B mo-2 yr of age and for 5 d if 22 V

Figure 13. Management of acute otitis media

Flow diagram lor the management of children with suspected and confirmed acute otitis media - from CPS statement Feb 2016

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Otitis Media with Effusion Definition

• presence of fluid in the middle ear without signs or symptoms of ear infection Epidemiology • most common cause of conductive hearing loss in children • 90% of cases resolved by 3 mo • 80 90% of all children have one episode before 6 yr • 30 40% of affected children will experience recurrent episodes

-

Risk Factors • same as AOM

Clinical Features

• fluctuating conductive hearing loss t tinnitus • fullness in ear, balance problems • ± pain, low grade fever «

otoscopy of TM • discolouration - amber or dull grey meniscus fluid level behind TM air bubbles retraction pockets/TM atelectasis flat tympanogram most reliable finding with pneumatic otoscopy is immobility

Management

• expectant management appropriate if low risk for speech / language/ learning difficulties • ENT referral if unilateral OME >6 mo, bilateral OME >3 mo with hearing loss, or structural tympanic membrane damage • consider early ENT referral for children with craniofacial abnormalities or immunodeficiency • surgical options include myringotomy with tympanostomy ( ventilation ) tubes ± adenoidectomy (if tonsils enlarged or on insertion of second set of tubes after first set falls out) • no role for antibiotics, glucocorticoids, antihistamines, or decongestants Complications

• hearing loss, speech delay, learning problems in young children • chronic mastoiditis • ossicular erosion • cholesteatoma especially when retraction pockets involve pars flaccida • retraction of tympanic membrane, atelectasis, ossicular fixation

Gastroenteritis • see Gastroenterology. G 15

HIV Infection • see Infectious Diseases. IL) 27

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P62 Paediatrics

Infectious Paediatric Exanthems Table 27. Common Infectious Paediatric Exanthems Disease

Pathogen ( s)

Erythema Infecliosum (i e Fifth Disease/ Slapped Cheek)

..

Parvovirus B19

Incubation Period 4 - 14 d

Communicability

Mode of

Rash

Associated Features

Appearance:

Initial 7 -10 d of flu ltke illness and fever Rash maybe warm, non tender, and pruritic

Transmission

-

Low risk ol transmission once symptomatic

Respiratory secretions or infected blood

uniform,

-

.

erythematous maculopapular ‘lacy' rash

Management

Outcomes and Complications

Supportive

Rash fades over dtowk butmay reappear mo later with sunlight, exercise Transient Aplastic crisis (especially if chronic hemolytic anemia)

Supportive Pain control

Resolves in 3-12 wk

Supportive

Resolves in Iwk Mainly dehydration

Mainly supportive Consider oral or topical antivirals

Local: secondary skin infections, keratitis, gingivostomatitis CNS: encephalitis Disseminated hepatitis DIC Eczema herpeticum

-

liming: 10 -17 d less common presentations include after symptoms (immune response) ‘gloves and socks Distribution: syndrome' or STAR complex (sore throat, bilateral cheeks (‘slapped cheeks') arthritis, rash) with circurnoral sparing; may affect trunk and extremities Gianotti- Crosti Syndrome (i e. Papular

.

EBV and Hepatitis B virus (majority)

Variable

None

None

Asymptomatic or pruritic Appearance: symmetric papules

Acrodermatitis)

Distribution: lace,

Viral prodrome May have

.

lymphadenopalhy

and/or hepatosplenomegaly

cheeks, extensor

.

surfaces of the extremities, spares trunk

Hand Foot, and Mouth Disease

Coxsackie group A

Herpes Simplex

HSV 1.2

3 -5 d

Likely 1- 7 d after symptoms but may be up to months

1-26 d

Direct and indirect contactwith infected bodily fluids, fecal -oral

Appearance:

in the POSTERIOR pustules on an oral cavity (pharynx, erythematous base longue) Distribution:mouth, buttocks, acral, bul may extend up the extremity

Direct contact, often through saliva, vertical transmission at barlh or sexual contact

Grouped vesicles on Enanthem: vesicles/ erosions in the an erythematous ANTERIOR oral cavity base

Airborne

Appearance: erythematous maculopapular Timing: 3 d after start ofsymptoms Distribution: starts at hairline and spreads downwards with sparing of palms and soles

Ibuccal mucosa,

.

Kawasaki Disease

SeeP9S

Measles

Morbillivirus

8 13 d

4 d before and alter rash

Enanthem: vesicles

vesicles and

tongue) May present with herpetic whitlow ( autoinoculation)

.

Prodrome of cough, cotyra conjunctivitis

. )

PCs

Enanthem: Koplik’s spots 1 2 d before rash

-

Desquamation

Positive serology for measles IgM

Infected: supportive, some evidence for vitamin A. Unimmunized contacts: measles

vaccine within 72 hoi exposure or IgG within 6 d of exposure

Respiratory isolation, report to Public Health Prevention: MMR

Secondary bacterial infections: AOM. sinusitis, pneumonia Encephalitis Rare: myocarditis pericarditis thrombocytopenia Stevens-Johnson syndrome, GN subacute sclerosing panencephalitis

. .. .

vaccine Non -Specific

Enteroviruses

Variable

Variable

Direct and indirect contactwith infected bodily fluids

Polymorphous rash Systemic involvement (macules, papules, is rare,but possible vesicles, petechiae. urticaria)

Supportive Diagnosis confirmed using viral cultures (nasopharyngeal andrcclal swabs)

Self - limiting

Droplet transmission

Saliva

High grade lever 3 -5 d Common: maculopapular irritability, anorexia Timing: appears lymphadenopalhy, once fever subsides eiythcmalous IM and Distribution: starts pharynx Nagayama spots (erythematous at the neck and trunk and spreads papules on soft palate and uvula) to the face and extremities less common: cough,

Supportive

Self - limiting CNS: febrile seizures (10 - 25%),

Enteroviral Exanthems

Roseola

Human herpes virus S-15 d (HHV ) 6

Perinatal: transplacental infection, getmline cell integration

Appearance: blanching, pink,

.

.

.

coiyza

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aseptic meningitis Thrombocytopenia

+

bulging

fontanelles

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P63 Paediatrics

Table 27. Common Infectious Paediatric Exanthems Disease

Pathogen(s)

Incubation Period

Communicability

Mode of Transmission

Rash

Associated Features

Rubella

Rubivirus

14 - 21 d

7 d before and alter eruptions

Droplet

Appearance: pink , maculopapular Timing:1 5 d after

Prodrome of low grade Supportive Deport to Public fever and occipital/ Health retroauricular nodes STAR complex (sore Prevention: MM It throat , arthritis, rash ) vaccine Positive serology lor rubella IgM. Caution to

-

start ol symptoms Distribution: starts on lace and spreads to neck and trunk

Management

pregnanlwomenwith exposure

Scarlet Fever Varicella

Outcomes and Complications

Excellent prognosis with acquired disease Arthritis may last days to weeks Encephalitis

Irreversible defects in congenitally infected patients ( i.e. congenital rubella syndrome)

See «5 Varicella zoster virus

10 -21 d

-

-

1 2 d pre eruptions and 5 d post eruption

-

Direct contact, inhalation of lesion aerosols, aerosol!red respiratory secretions

Appearance: groups

of skin lesions, polymorphic, from macules lopapules to vesicles tocxusls Timing : 1 3 d after start ol symptoms Distribution: generalized

-

Significant pruritus Malaise, fever Enanlhcm : vesicular lesions which may become pustular or ulcerate Caution to pregnant women

.

Supportive Avoid salicylates (due to risk of Reye syndrome)

Skin: bacterial suptainfedion, necrotizing fasciitis CNS: acute Consider antivirals encephalitis and Respiratory and cerebellar ataxia Systemic: hepatitis. contact isolation , report lo DIC

Public Health Prevention: varicella vaccine

Congenital varicella syndrome if intrapartum

infection

Infectious Mononucleosis Definition

• systemic viral infection caused by EBV with multiviscera ] involvement; often called “ the great imitator" Epidemiology • peak incidence betss'een 15-19 yr • 50% of children in developed countries have a primary EBV infection by 5 yr, but < 10% of children

-develop clinical infection

Etiology • EBV: a member of herpesviridae • transmission is mainly through infected saliva ( “ kissing disease ” ) and sexual activity ( less commonly); incubation period of 1-2 mo Risk Factors • infectious contacts, sexually active, multiple sexual partners History • prodrome: 2 - 3 d of malaise, anorexia • infants and young children : often asymptomatic or mild disease • older children and adolescents: malaise , fatigue, fever, sore throat , abdominal pain (often LUQ ), headache, myalgia

Physical Exam • classic triad : febrile, generalized non - tender ly mphadenopathy, pharyngitis/tonsillitis (exudative) • ± hepatosplenomegaly • ± periorbital edema, ± rash ( urticarial, maculopapular, or petechial ) - more common after inappropriate treatment with (3-lactam antibiotics • any “ itis" ( including arthritis, hepatitis, nephritis, myocarditis, meningitis, encephalitis, etc.)

-

Investigations

• heterophile antibody test ( Monospot' test ) • 85% sensitive in adults and older children , but only 50% sensitive if age < l yr false positive results with HIV , SLE, lymphoma, rubella, parvovirus • EBV titres ( if negative heterophile test or clinical suspicion remains high ) • CBC and differential, blood smear: reactive lymphocytes, lymphocytosis, Downey cells ± anemia ± thromboc ytopen ia • throat culture to rule out streptococcal pharyngitis

-

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Management

• supportive: adequate rest, hydration, saline gargles, and analgesics for sore throat

• splenic enlargement is often not clinically apparent so all patients should avoid contact sports for 6-8 wk • if airway obstruction secondary to nodal and /or tonsillar enlargement is present (especially younger children ), admit for steroid therapy Prognosis

• most acute symptoms resolve in 1-2 wk, though fatigue may last for mo • short-term complications: splenic rupture, Guillain - Barre syndrome

Infectious Pharyngitis/ Tonsillitis Definition

• inflammation of the pharynx, especially the tonsils if present, causing a sore throat Etiology

• viral ( ~80%): adenoviruses, enteroviruses, coxsackie, upper respiratory tract viruses, HBV, CMV,

COV1D-19 • bacterial (~20%): mainly GAS, Af. pneumoniae (older children ), N. gonorrhoeae (sexually active), C. diphtheriae ( unvaccinated ), /•'. necrophorum (anaerobe causing Lemierre syndrome ) • fungal: Candida Epidemiology

• season: GAS pharyngitis more common in late winter or early spring; viral all year long • age: GAS pharyngitis peak incidence at 5-12 yr and uncommon 1 cm ) and tender anterior cervical lymph nodes, palatal petechiae, strawberry tongue, scarlatiniform rash • viral: sore throat (often mild ), conjunctivitis, cough, rhinorrhea, hoarseness, diarrhea, flu -like symptoms ( fever, malaise, myalgias ), absent/ mild tonsillar exudates, minor and non tender

adenopathy, viral exanthems

-

Investigations

• scores are used to predict if throat culture will be positive (e.g. m-CENTOR score ) » these score systems have not been found to be sensitive or specific enough to diagnose GAS in children and adolescents with sore throat • suspected diagnosis of GAS pharyngitis should be confirmed with a rapid streptococcal antigen test and a follow up throat culture if the rapid test is negative

-

Management

• antibiotics (for GASIS. pyogenes ) • penicillin V or amoxicillin or erythromycin ( if penicillin allergy ) x 10 d • can prevent rheumatic fever if given within 9 d of symptoms; does NOT alter risk of post streptococcal GN • supportive: hydration and acetaminophen for discomfort due to pain and/or fever • follow- up: if uncomplicated course, no follow- up or post-antibiotic throat cultures needed • prophylaxis: tonsillectomy may be considered for severe, recurrent streptococcal tonsillitis

-

Complications • preventable with antibiotics: AOM, sinusitis, cervical adenitis, mastoiditis, retropharyngeal / peritonsillar abscess, sepsis • immune- mediated complications: scarlet fever, acute rheumatic fever, post-streptococcal GN , reactive arthritis, paediatric autoimmune neuropsychiatric disorder associated with GAS ( PANDAS)

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SCARLET FEVER

• diffuse erythematous eruption

-

• delayed type hypersensitivity reaction to pyrogenic exotoxin produced by GAS • requires prior exposure to S. pyogenes • acute onset of fever, sore throat, strawberry tongue • 24 48 h after pharyngitis, rash begins in the groin , axillae, neck, antecubital fossa; Pastia’s lines may be accentuated in flexural areas • within 24 h , sandpaper rash becomes generalized with perioral sparing, non pruritic, non painful , blanchable • rash fades after 3-4 d, may be followed by desquamation • treatment is penicillin, amoxicillin, or erythromycin x 10 d

-

-

-

RHEUMATIC FEVER

• inflammatory disease due to antibody cross-reactivity following GAS infection • affects ~1 in 10000 children in developed world; much more prevalent in developing nations; peak incidence at 5-15 yr

m-CENTOR Score for Probability of

• clinical diagnosis based on|ones Criteria ( revised )

•

requires 2 major OR 1 major and 2 minor PLUS evidence of preceding strep infection ( history of scarlet fever, GAS pharyngitis culture, positive rapid Ag detection test, ASOIs) major: carditis and valvulitis, arthritis, CNS involvement (Sydenham chorea ), subcutaneous nodules, erythema marginatum minor: arthralgia, fever, tESR or CRP, prolonged PR interval treatment: penicillin or erythromycin for acute course x 10 d, prednisone if severe carditis

• secondary prophylaxis with daily penicillin or erythromycin • complications

acute: myocarditis, conduction system aberrations (sinus tachycardia, atrial fibrillation ), valvulitis (acute mitral regurgitation ), pericarditis chronic: valvular heart disease ( mitral and /or aortic insufficiency/stenosis ), infectious

»

endocarditis ± thromboembolic phenomenon onset of symptoms usually after 10 -20 yr latency from acute carditis of rheumatic fever

POST- STREPTOCOCCAL GLOMERULONEPHRITIS

• most common in children ages 4-8 yr; M >1; • antigen -antibody mediated complement activation with diffuse, proliferative GN • occurs 1 3 wk following initial GAS infection (skin or throat ) • clinical features vary from asymptomatic, microscopic and macroscopic hematuria ( cola coloured urine) to all features of nephritic syndrome (see Nephritic Syndrome, P83 ) • diagnosed upon clinical findings of acute nephritis and recent GAS infection. It can be confirmed with elevated serum antibody titres against streptococcal antigens ( ASOT, anti- DNAase B), low serum complement (C3) • management symptomatic: fluid and sodium restrictions; loop diuretics for HT' N and edema in severe cases, may require dialysis if renal function significantly impaired treat with penicillin or erythromycin ( if penicillin allergy) if evidence of persistent GAS infection 95% of children recover completely within 1-2 wk; 5- 10% have persistent hematuria

-

-

.

Streptococcal Pharyngitis For patients presenting with sore throat/ pharyngitis and URTI symptoms: Must be >3 yr Cough — no cough (+1) Exudates or Swelling — tonsillar exudates/swelling (+1) Nodes — anterior cervical adenopathy Ml Temperature - history of fever or temperature >38°C (+1) Only Young — patients 45 y/o (-1) Interpretation

-

m CENTOR Probability Recommendation Score ol strep pharyngitis 0 1

-

2

1 2.5% $•10% 11 17%

3

28 35%

»

4

-

51-53%

No further testing or antibiotics

Consider rapid

.

strep testing aod br culture

Consider rapid strep testing and/ or culture Empiric antibiotics nay be appropriate depending on scenario

.

Meningitis Definition

• inflammation of the meninges surrounding the brain and spinal cord Epidemiology

• peak age: < I yr; 90% of paediatric cases occur in children age 95%) have a single cause ( 70% U coli) • Gram negative bacilli: E coli, Klebsiella, Proteus, Enterobacter, Pseudomonas, Citrobacter • Gram-positive cocci: S. sapropliyticus, Enterococcus

.

-

Risk Factors

.

Bagged urine specimen not useful for ruling in UTI (high false positive rate >85%). but useful for ruling out UTI (high sensitivity)

• non -modifiable: female gender White, previous UTIs, FMHx

.

• modifiable: urinary tract abnormalities ( VUK neurogenic bladder, obstructive uropathy, posterior urethral valve), dysfunctional voiding, repeated bladder catheterization, uncircumcised males, labial adhesions, sexually active, constipation, toilet training History

-

• infants and young child: often just fever or non specific symptoms ( poor feeding, irritability, FIT, jaundice if < 28 d , vomiting ) • older child: fever, urinary symptoms (dysuria, urgency, frequency, incontinence, hematuria ), abdominal, and /or flank pain

Prophylasis Alter First febrile Urinary Tract Infection In Children!* Multicentre Randotaiied Controlled , Noninferiority Trial Pediatrics 2008:122:1064-107 Study: Randomized, controlled, open label 2 armed r or inferiority trial. Patients: 333 patients 2 rroto 50000 colony-forming units (CFUs)/mL in catheter specimen OR > 100000 Cl' Us/ mL in clean catch specimen

-

Management

• admit if: age < 2 mo, urosepsis, persistent vomiting, inability to tolerate oral medication , moderate severe dehydration, immunocompromised, complex urologic pathology, inadequate follow- up, failure to respond to outpatient therapy • supportive care: maintenance of hydration and adequate pain control • antibiotics base on local antimicrobial susceptibility patterns commence broad empiric therapy until results of urine C&S known, and then tailor as

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appropriate neonates: IV ampicillin and aminoglycoside infants and older children: oral antibiotics ( based on local t . coli sensitivity ) if outpatient; IV

ampicillin and gentamicin if inpatient duration 7 10 d

-

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P70 Paediatrics

• imaging • renal and bladder VIS for all febrile infants (< 2 yr ), recurrent febrile UT Is (any age ) looking for anatomical abnormalities, hydronephrosis, abscess VCUG not recommended after 1st febrile UT1 unless U /S reveals hydronephrosis, obstructive uropathies or other signs suggestive of high -grade VUR • follow up: outpatients to return in 24 - 48 h if no clinical response seek prompt medical evaluation for future febrile illnesses • prophylaxis: generally not recommended unless higher grades of VUR

-

Complications •long-term morbidity: focal renal scarring develops in 8% of patients; long-term significance unknown

Neonatology Gestational Age and Size Definitions • classification by CIA preterm: 42 wk • classification by birth weight • SGA: 2 SD < mean weight for GA or < 10th percentile • AGA: within 2 SD of mean weight for GA LGA: 2 SD > mean weight for GA or >90 th percentile • classification of preterm infants by birth weight • low birthweight ( LBW ) < 2500 g • very low birthweight ( VLBVV ) < 1500 g » extremely low birthweight ( liLBW ) < 1000 g

-

Dubowitz / Ballard Scares GA can be determined after birth using Dubowitz/8allard scores: • Assessment at delivery of physical maturity (c.g. plantar creases, lanugo, ear maturation) and neuromuscular maturity (e.g. posture, arm recoil ) translates into a score from -10 to +50 • Higher score means greater maturity (increased GA) • 10-20 wk; +5 - 44 wk • Ideal-35 40, which corresponds to GA 38 40 wk • Only accurate ± 2 wk • May be inaccurate in infants who are preterm , postterm , SGA infants

-

-

-

Table 30. Abnormalities of Gestational Age and Size Problems

Features

Causes

Preterm Infants

Spontaneous: cause unknown




Increased nskol slillbitlh or neonalaldealh Increased birthweight Fetal " postmaturity syndrome": impaired growth due to placental dysfunction Meconium aspiration

*10th

SGA Intants percentile Asymmetric ( head -sparing ): late onset, growth arrest

txtrinsic causes: placental insufficiency, poor nutrition. HTN multiple pregnancies , drugs, alcohol , smoking , familial (actors, fibroids

Perinatal hypoxia Hypoglycemia , hypocalcemia , hypothermia , hyperviscosity ( polycythemia ) , jaundice

SGA Intants Symmetric: early onset , lower growth

Intrinsic causes: maternal infections ( TORCH ) , congenital abnormalities, syndromal

PDA

.

idiopathic

LGA Infants 90th percentile

»

.

Maternal DM Racial or familial factors Increasing parity Previous LGA infant , high BMI . large pregnancy weight gain Certain syndromes

.

Birth trauma , perinatal depression ( meconium

r

aspiration )

RDS. TIN Jaundice, polycythemia Hypoglycemia , hypocalcemia

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Routine Neonatal Care • history taking

passage of meconium in 24 -48 h, urination /number of wet diapers feeding: breast milk or formula, route ( breast or bottle), duration , frequency and volume of feeds • issues: jaundice, poor feeding, difficulty breathing, cyanosis, seizures weight: discharge weight (close follow- up if >10% below birth weight), initial weight gain (goal 20-25 g /d ), number of days until birth weight regained (should regain by day 10-14 of life ) • erythromycin ointment: applied to both eyes for prophylaxis of ophthalmia neonatorum ( N .

gonorrhoeae); no longer recommended by Canadian Paediatric Society but required by law in some provinces/territories

• vitamin K 1M: prophylaxis against VKDB • newborn screening tests in Ontario • in Ontario, newborn screening tests for: metabolic disorders ( amino acid disorders, organic acid disorders, fatty acid oxidation defects, biotinidase deficiency, galactosemia ) blood disorders (sickle cell disease, other hemoglobinopathies ) endocrine disorders (CAH, congenital hypothyroidism ) others (CP, severe combined immunodeficiency) congenital hearing loss • if mother Rh negative: send cord blood for blood group and DAT (also consider sending DAT for O positive mothers) • if household contact is HBsAg positive: start hepatitis B vaccine series (and if mother is positive, give HBlg within 12 h of birth ); the US and some Canadian provinces give Hep B vaccine at birth routinely

Neonatal Resuscitation

i

Apgar Score

Appearance (colour) Pulse (heart rate) Grimace (Irritability) Activity (tone) Respiration (respiratory effort) Or: "How Ready Is This Child?"

• assess Apgar score at 1 and 5 min • if 7 • do not wait to assign Apgar score before initiating resuscitation

Table 31. Apgar Score Sign

0

1

Heart Rate

Absent

tOO /min

Active motion

Initial Resuscitation

• anticipation: know maternal history, history of pregnancy, labour, and delivery • steps to take for all infants » pre-delivery team debriefing including assigning roles, checking equipment, and discussing possible complications and management plan warm ( radiant heater, warm blankets) and dry the newborn ( remove wet blankets) stimulate infant: rub lower back gently or flick soles of feet o position airway ( “sniffing ” position ) and clear or suction if necessary

• assess breathing and HR

if apneic or ineffective respiration and HR < 100: bag and mask ventilation ( PPV ) with room air (or 30% if preterm infant ). Continue until HR > 100 and breathing spontaneously if HR 48 h of life ), prolonged glucose IV, severe symptomatic hypoglycemia (coma, lethargy, seizure), or no predisposing cause, send “critical blood work* during an episode of hypoglycemia: ABG , ammonia, p - hydroxybutyrate, cortisol, free fatty acids, GH , insulin , lactate, urine dipstick for ketones

Neonatal Hyperbilirubinemia Definition

-

• total serum bilirubin >95 th percentile ( high risk zone ) on Bhutani nomogram in infants >35 wk GA Clinical Features

• jaundice typically visible at serum bilirubin levels of 85 - 120 pmol / L • visual assessment is misleading, confirm jaundice with blood test

Hyperbilirubinemia T Unconjuyated

t

1

1

Pathologic

Physiologic

Always pathologic

1 Hemolytic

£

Intrinsic Membrane Spherocytosis Elliptocytosis Enzyme G6PD deliciency PK deficiency Hemoglobin

Thalassemia

Extrinsic Immune ABO incompatability Rh incompatability Kell, Dully, etc . Non-immune Splenomegaly Sepsis AVM

Jaundice is very common - 60N of term newborns develop visible jaundice

Conjugated

1 Non-Hemolytic Hematoma ( cephalohematoma ) Polycythemia Sepsis Hypothyroidism Gilbert syndrome Crigler-Najjar

Hepatic Infectious Sepsis Hep B, TORCH Metabolic Galactosemia

Post- Hepatic

Jaundice in the first 24 h of life and conjugated hyperbilirubinemia are always pathological

Biliary atresia

Choledochal cyst

Tyrosinemia a- 1- antitrypsin deliciency Hypothyroidism

CF Drugs

TPN Idiopathic neonatal hepatitis

Jaundice must be investigated if: • It occurs within 24 h of birth • Conjugated hyperbilirubinemia is present • Unconjugated bilirubin rises rapidly or is excessive for patient's age and

weight

• Persistent jaundice lasts beyond 1-2

wk of life

.

Figure 15 Approach to neonatal hyperbilirubinemia

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PHYSIOLOGIC JAUNDICE

Epidemiology • term infants: onset 3-4 d of life, resolution by 10 d of life • premature infants: higher peak and longer duration

Pathophysiology • increased hematocrit and decreased RBC lifespan • immature glucuronvl transferase enzyme system (slow conjugation of bilirubin )

• increased enterohepatic circulation Breastfeeding Jaundice • common: due to a lack of milk production -> dehydration > exaggerated physiologic jaundice Breast Milk Jaundice

• I in 200 breastfed infants • glucuronyl transferase inhibitor found in breast milk • onset 7 d of life, peak at 2 -3 wk of life, usually resolved by 6 wk Table 34 . Risk Factors for Jaundice Maternal Factors

Perinatal Factors

Neonatal Factors

Ethnic group|e.g. Asian , Indigenous)

Birth trauma (cephalohematoma. ecchymoses) Prematurity

Difficulty establishing breastfeeding

Complications during pregnancy (infant of diabetic mother. Rh or ABO incompatibility)

Infection (sepsis, hepatitis)

Breastfeeding

Genetic factors

FMHx/previous child required phototherapy

Polycythemia Drugs TPK

Table 35. Causes of Neonatal Jaundice by Age h 24 -72 h

< 24

ALWAYS PATHOLOGIC

Hemolytic

72 -96 h

Prolonged (>1 wk)

Physiologic polycythemia

Physiologic * breastfeeding

Breast milk jaundice

Dehydration

Sepsis

(breastfeeding jaundice)

Prolonged physiologic jaundice in preterm

,

Rh or ABO incompatibility

Hemolysis

Hypothyroidism

Sepsis Congenital infection ( TORCH )

G6PD deficiency

Severe bruising /hemorrhage

Spherocytosis

Neonatal hepatitis Conjugation dysfunction c.g. Gilbert syndrome.

Pyruvate kinase deficiency

hematoma

Bruising, hemorrhage,

Crigler - Najjar syndrome Inborn errors of metabolism

Sepsis/congenital infection

e.g. galactosemia

Biliary tract obstruction e.g. biliary atresia

PATHOLOGIC JAUNDICE • all cases of conjugated hyperbilirubinemia ; some cases of unconjugated hyperbilirubinemia are

pathologic

Investigations

unconjugated hyperbilirubinemia « hemolytic workup: CBC, reticulocyte count, blood group ( mother and infant ) , peripheral blood smear , Coombs test ( DAT ) if • babv is unwell or has fever: septic workup (CBC and differential, blood and urine cultures ± LP, CXR) other: G6PD screen (especially in males), TSH • conjugated hyperbilirubinemia must be investigated without delay • consider liver enzymes ( AST, ALT ), coagulation studies ( FT, P I T' ), serum albumin, ammonia , ISH , TORCH screen , septic workup, galactosemia screen (erythrocyte galactose 1 phosphate uridyltransferase levels), metabolic screen, abdominal U /S, H1DA scan , sweat chloride • predicting occurrence of severe hyperbilirubinemia measure either total serum bilirubin ( TSB) or transcutaneous bilirubin ( TcB) concentration in all infants between 24 h and 72 h of life and plot on appropriate hyperbilirubinemia treatment graph. If infant does not require immediate treatment , results should be plotted on predictive nomogram to determine the risk of progression to severe hyperbilirubinemia and need for repeat measurement ( refer to: http://www.cps.ca/ documents/ position / hyperbilirubinemia - newborn ) •

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TREATMENT OF UNCONJUGATED HYPERBILIRUBINEMIA

• to prevent kernicterus • breastfeeding does not usually need to be discontinued , ensure adequate feeds and hydration • lactation consultant support, mother to pump after feeds • treat underlying causes (e.g. sepsis) • phototherapy ( blue green wavelength, not U V light ); standard intensive or multiple intensive protocol depending on severity of hyperbilirubinemia insoluble unconjugated bilirubin is converted to excretable form via photoisomerization serum bilirubin should be monitored during and immediately after therapy ( risk of rebound because photoisomerization is reversible when phototherapy is discontinued ) contraindicated in conjugated hyperbilirubinemia ; results in “ bronzed '' baby side effects: skin rash , diarrhea, eye damage (eye shield used routinely for prevention ), dehydration use published guidelines and nomogram (see Figure 16) to determine appropriateness of phototherapy by stratifying infant risk and assessing if total scrum bilirubin level is above cutoff for respective gestational age • exchange transfusion indications: high bilirubin levels as per published graphs based on age, wk gestation most com monly performed for hemolytic disease and severe cases of G6 PD deficiency use of I Vlg in case of severe hyperbilirubinemia ( DAT+) becoming evidence based practice

-

-

KERNICTERUS

Etiology

“Bronzed ” Baby in Infants with

Conjugated Hyperbilirubinemia Phototherapy results In the production and accumulation of a lode metabolite which also imparts a bronze hue on the baby's skin

/Toni SxumR'iudt *

povl

>

P

—

Age Intents at lower nsk ( >38 wk and well - - Inter.ts at medium risk ( 28 wk t risk factors or 3M / V/ wt and well ) Intents at higher risk|3»3/ VI wk nsk factors)

—

--

j ^ Figure 16. Gold standard in deciding when to initiate phototherapy for unconjugated hyperbilirubinemia Licence number: 4601410094382

• unconjugated bilirubin concentrations exceed albumin binding capacity and bilirubin is deposited in the brain resulting in tissue necrosis and permanent damage (typically basal ganglia or brainstem ) • incidence increases as serum bilirubin levels increase above 340 pmol / L • can occur at lower levels in presence of sepsis, meningitis, hemolysis, hypoxia, acidosis, hypothermia, hypoglycemia, and prematurity Clinical Features • up to 15% of infants have no obvious neurologic symptoms • early stage: lethargy, hypotonia, poor feeding, emesis (acute bilirubin encephalopathy) • mid stage: hypertonia, high pitched cry, opisthotonic posturing ( back arching), bulging fontanelle, seizures, pulmonary hemorrhage • late stage (during first year and beyond ): hypotonia, delayed motor skills, extrapyramidal abnormalities (choreoathetoid CP), gaze palsy, mitral regurgitation, sensorineural hearing loss Prevention

• exchange transfusion, 1Vlg if indicated BILIARY ATRESIA

Definition

• atresia of the extrahepatic bile ducts which leads to cholestasis and increased conjugated bilirubin after the first wk of life • progressive obliterative cholangiopathy

. incidence I in

Epidemiology : 10000 -15000 live births • associated anomalies in 10 35% of cases: situs inversus, congenital heart defects, polysplenia

-

Clinical Features

• dark urine, pale stool, jaundice ( persisting for >2 wk ), abdominal distension, hepatomegaly Diagnosis

• conjugated hyperbilirubinemia , abdominal U /S, operative cholangiogram • HI DA scan ( may be bypassed in favour of biopsy if timing of diagnosis is critical ) • liver biopsy

Treatment

• surgical drainage procedure

• hepatoportoenterostomy ( Kasai procedure; most successful if age bacterial growth > bowel necrosis/gangrene/ perforation Risk Factors • prematurity (immature defenses) • asphyxia, shock ( poor bowel perfusion ) • hyperosmolar feeds • enteral feeding with formula (breast milk can be protective ) • sepsis

Influence ol EnteralMutrition on Occurrences of Recrotizing Enterocolitis in Very tow Birtli Ifcight Infants J Pedatr Gastroenterol Nutr 2015:61(4):445 450 Study: Case-control study of wry low -birth-weiglit (VlBI ) nlantsand occurrences of HECwrtlr in 30

-

-

-

.

dot Mi

Population: 1028 VLBW infants in neonatal intensive care unit Jan 2003 Hay 2008.

-

Primary Outcome: NEC defined using stage > 2 of modified Bell criteria. Resmlts: 55 infants developed MEC with in 30 d of life (5 4 % ) lltose mtii NEC had higher odds ol having been fed breast milk < 7 d (OS: 4.02|, not harmg achieved full enteral feeding during the first oin (OR: 3 S0) and having had parenteral feeding (Of : 2.10). Conclusions Occurience ol NEC can be reduced with breast nilk feeding beyond 7 d and early full enteral feeding.

. .

Clinical Features • usually presents at age 2 3 wk • distended abdomen, diminished bowel sounds, feeding intolerance • increased amount of gastric aspirate/ vomitus with bile staining • frank or occult blood in stool • signs of bowel perforation (sepsis, shock, peritonitis, DIC)

-

Investigations

• AXR: pneumatosis intestinalis (intramural air is a hallmark of NEC), free air, fixed loops, ileus, thickened bowel wall, portal venous gas CBC, ABG, lactate, blood culture, electrolytes • high or low WBC, low platelets, hyponatremia, acidosis, hypoxia, hypercapnia Treatment • NPO (7 10 d ), vigorous IV fluid resuscitation , decompression with NG tube, supportive therapy

.

-

TPN • antibiotics ( usually ampicillin, gentamicin ± metronidazole if risk of perforation x 7-10 d ) • serial AXRs detect early perforation (40% mortality in perforated NEC) • peritoneal drain /surgery if perforation • surgical resection of necrotic bowel and surgery for complications (e.g. perforation, strictures)

Persistent Pulmonary Hypertension of the Newborn Definition

• persistence of fetal circulation as a result of persistent elevation of pulmonary vascular resistance • classified as primary (absence of risk factors) or secondary Epidemiology

• incidence 1.9 in 1000 live births Clinical Features

• usually presents within 12 h of birth with severe hypoxemia /cyanosis; some may have only mild respiratory distress

Pathophysiology • elevated pulmonary pressures cause R -> L shunt through PDA, foramen ovale -> decreased pulmonary blood flow and hypoxemia -> further pulmonary vasoconstriction Risk Factors

• secondary PPHN: asphyxia , meconium aspiration syndrome, RDS, sepsis, pneumonia, structural abnormalities (e.g. diaphragmatic hernia, pulmonary hypoplasia ) • more common in term or post - term infants

rT

Investigations • measure pre and post ductal oxygen levels • hyperoxia test to exclude CHD EGG ( RV strain )

.

-

LJ

-

• echo reveals increased pulmonary arterial pressure and a R -> L shunt across PDA and patent foramen

+

ovale; also used to rule out other cardiac defects

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Treatment • maintain good oxygenation ( SaO * >95%) in at- risk infants • 02 given early and tapered slowly, minimize stress and metabolic demands, maintain normal blood

gases, circulatory support • mechanical ventilation, high frequency oscillation in a sedated muscle- relaxed infant • nitric oxide, surfactant • extracorporeal membrane oxygenation used in some centres when other therapy fails

Respiratory Distress in the Newborn Clinical Features tachypnea: RR >60/min; tachycardia: HR > 160/ min grunting, subcostal / intercostal indrawing, nasal flaring • duskiness, central cyanosis • •

• decreased air entry, crackles on auscultation

Differential Diagnosis of Respiratory Distress S'eonatal Resuscitation , P72

• see Table 33 under

Investigations • labs: CBC, blood gas, glucose, blood culture • imaging: CXR • if indicated: ECG, echo, LP (CSF cell count, culture, and chemistry )

Table 36 . Distinguishing Features of RDS , TTN , MAS Etiology

RDS Surfactant deficiency * pool lung compliance due to high alveolar surface tension » atelectasis » surface area for gas exchange * hypoxia acidosis * respiratory

Delayed resorption of fetal lung fluid •» accumulation offluid in peribronchial lymphatiesand vascular spaces < tachypnea * " Wet lung syndrome "

Preterm Maternal DM Preterm delivery

Usually term and late preterm Maternal DM Maternal asthma

Male sex

Male sex Macrosomia (> 4500 g) Elective Cesarean section or

*

-

-

TTN

MAS Meconium is sterile but causes airway obstruction, chemical inflammation, and surfactant inactivation leading lochemical pneumonitis

distress “Hyaline membrane disease*

Gestational Age Risk Factors

IBW Acidosis, sepsis Hypothermia Second born twin

Clinical Features

CXR Findings

Prevention

Treatment

Respiratory distress within first few hours ol life, worsens over next 24 - 72 It Hypoxia Cyanosis Homogenous infiltrates Airbronchograms Decreased lung volumes May resemble pneumonia |GBS) If severe,"white- out" with no differentiation of cardiac border Prenatal corticosteroids (e.g. Celcstone 12 mg q24 h x 2 doses) il risk of preterm delivery * 34 wk Monitor lecilhin:spliingomyehn IT'S) ratio with amniocentesis, L/S >2:1 indicates lung maturity Resuscitation

Oxygen Ventilation Surfactant (decreases alveolar surface tension, improves lung compliance, and maintains functional residual capacity) Complications

Prognosis

In severe prematurity and/or prolonged ventilation , increased risk of bronchopulmonary dysplasia

Dependent on GA at birth and severity of underlying lung disease:long- term

Term and post- term Meconium - stained amniotic fluid Post - term delivery

short labour late preterm delivery

Tachypnea within the first few hours of tile t retractions grunting,nasal flaring Often HO hypoxia or cyanosis Perihilar infiltrates "Wet silhouette;" fluid in

.

fissures

Respiratory distress within houis ol birth Small airway obstruction, chemical pneumonitis tachypnea, barrel chest with audible crackles Hypoxia Hyperinflation Patchy atelectasis Patchy and coarse Infillralcs 10 - 20% have pneumothorax

Where possible, avoidance of elective Cesarean delivery, particularly before 38 wkGA

If infant isdepressed at birth, intubate and suction below vocal cords Avoidance of factors associated with in utero passage of meconium (e.g. post - term delivery)

Supportive Oxygen if hypoxic Ventilator support |e g CPAP) IV fluids and HG lube feeds if too tachypneic to feed orally

Resuscitation Oxygen Ventilatory support Surfactant

..

Hypoxemia Hypercapnia Acidosis PPHN

Recovery usually expected in 24 -72 h

Inhaled nitric oxide Extracorporeal membrane oxygenation for PPHN

Hypoxemia Hypercapnia

Acidosis

r1

PPHN Pneumothorax Pneumomediastinum Chemical pneumonitis Secondary surfactant inhibition Respiratory failure Dependent on severity, mortality up to 20%

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risks of chronic lung disease

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P81 Paediatrics PNEUMONIA

• see Respirolog)' , P 93 • consider in infants with prolonged ( >18 h) or premature rupture of membranes, maternal fever or other signs and symptoms of chorioamnionitis, or if mother is GBS positive • suspect if infant exhibits respiratory distress, temperature instability, or WBC is low (30 x 109/ L), or left-shifted • symptoms may be non -specific (e.g. lethargy, apnea, tachycardia, poor perfusion, poor feeding ) • investigations: CXR ( hazy lung and /or distinct infiltrates, may be difficult to differentiate from KDS), blood and CSF cultures • neonates with pneumonia should be admitted to the NICU and given empiric antibiotics for management

Retinopathy of Prematurity

.

• see Ophthalmology OP40

Sepsis in the Neonate

(Sfy

Table 37. Sepsis Considerations in the Neonate Early Onset ( immunoglobulin deposition >

(§s Nephritic Syndrome

PHAROH Proteinuria ( glomerular inflammation and injury -> porous podocytes -> hematuria + RBC casts ± proteinuria • HTN secondary to fluid retention and increased renin secretion by ischemic kidneys Table 40, Major Causes of Nephritic Syndrome Primary (idiopathic)

Secondary (systemic disease)

Decreased C3

Normal C3

Post -infectious 611 (streptococcal infection is the most common) Membranoproliferathre Type I(SO -80%) Type II (>80%)

IgA nephropathy Idiopathic rapidly progressive GN Anti-EBM disease

SLE Bacterial endocarditis Abscess or shunt nephritis Cryoglobulinemia

HSP (very common) Polyarteritis nodosa Granu!omalos:s with polyangiitis Goodpasture's syndrome

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P81 Paediatrics

Toronto Notes 2023

Clinical Features • often asymptomatic; some overlap in clinical findings for nephritic and nephrotic syndrome • gross hematuria , mild moderate edema , oliguria , HTN • signs and symptoms suggestive of underlying systemic causes (e.g. fever, arthralgias, rash, dyspnea, pulmonary hemorrhage)

-

Investigations

• urine dipstick (hematuria, 0 to 2 + proteinuria) and microscopy (>5 RBCs per high-powered microscope field, acanthocytes, RBC casts) first morning urine protein /creatinine ratio ( 1;

-

Etiology • primary ( idiopathic): nephrotic syndrome in the absence of systemic disease ( most common cause in paediatrics) glomerular inflammation ABSENT on renal biopsy: MCD (85%), focal segmental glomerulosclerosis glomerular inflammation PRESENT on renal biopsy: membranoproliferative GN, IgA nephropathy • secondary': nephrotic syndrome associated with systemic disease or due to another process causing glomerular injury (300 mg/ mmol ) • blood work

diagnostic: hypoalbuminemia ( 5 mmol/ L) : electrolytes ( hypocalcemia, hyperkalemia, hyponatremia ), renal function (t BUN and secondary • Cr ), coagulation profile ( * PTT ) appropriate investigations to rule out secondary causes: CBC , blood smear, C3/C4, ANA, hepatitis B /C titres, ASOT, HIV serology, etc. • consider renal biopsy if: HTN, gross hematuria, * renal function, low serum C3/C4, no response to steroids after 4 wk of therapy, frequent relapses ( >2 in 6 mo ), presentation before first yr of life (high likelihood of congenital nephrotic syndrome ), presentation >12 yr ( rule out more serious renal pathology than MCD)

Daily protein excretion can be estimated from a random urine protein creatinine

'

ratio

-

Side Effects of Long Term Steroid Use

GOOD CUSHINGS Growth Impairment Obesity Osteoporosis Dorsal hump

Changes in behaviour Ulcers Striae Hypertension Immunosuppression: infection Need to eat Glucose elevation Salt and water retention

Management

• MCD: oral prednisone 2 mg/ kg/d (or equivalent ) for up to 12 wk -> varicella status should be known before starting • consider cytotoxic agents, immunomodulators, or high dose pulse corticosteroid if steroid resistant • symptomatic edema: salt and fluid restriction , possibly diuretic (avoid if significant intravascular depletion );

-

furosemide + albumin for anasarca

hyperlipidemia: generally resolves with remission; limit dietary fat intake; consider statin therapy if persistently nephrotic • hypoalbuminemia: IV albumin and furosemide not routinely given; consider if refractory edema abnormal BP: control BP; fluid resuscitation if severe intravascular depletion; AC HI or AKBs for persistent HIN • diet: no added salt; monitor caloric intake and supplement with Ca + and vitamin D if on corticosteroids • daily weights and BP to assess therapeutic progress • secondary infections: treat with appropriate antimicrobials; antibiotic prophylaxis not recommended; pneumococcal vaccine at diagnosis and varicella vaccine after remission; varicella Ig + acyclovir if exposed while on corticosteroids • secondary hypercoagulability: mobilize, avoid hemoconcentration due to hypovolemia, prompt sepsis treatment; heparin if thrombi occur

-

Prognosis

• generally good: 80% of children respond to corticosteroids • up to 2 /3 experience relapse, often multiple times; sustained remission with normal kidney function usually by adolescence • complications: t risk of infections (spontaneous peritonitis, pneumonia /empyema, cellulitis, sepsis); hypercoagulability due to decreased intravascular volume and antithrombin 111 depletion ( PH, renal vein thrombosis); intravascular volume depletion, leading to hypotension, shock, renal failure; anasarca; adverse effects on growth; drug side effects

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P86 Paediatrics

Hypertension in Childhood Definition

.

• HTN: sBP and /or dBP >95th percentile for sex age, and height on >3 occasions • elevated BP ( formerly pre- HTN ): sBP and/or dBP >90 th percentile but 120/80 irrespective of age, sex, and height

Table 41.95th Percentile Blood Pressures (mmHg) Female

Male

Age (Yr)

50th Percentile for Height

75th Percentile for Height

50th Percentile for Height

75th Percentile for Height

1

103/60

10461

103/55

10456

6

111/72

111/ 71

12

122/ 78 127/81

112/73 124.79

121/ 78

112/72 124.78

128 82

135/85

13786

17

-

.

Ftynn JT. Kaetbcr DC. Sahef Smitll CM et al. Clinical practice guideline tor screerirg and management of high blood pressure in children and adotescerts. Pediatrics 2017:140(3|:e20171904

Epidemiology

-

-

• prevalence: 3 5% for HTN, 7 10% for elevated BP; M>F

Etiology • primary HTN

diagnosis of exclusion

• most common in older children ( > 10 yr), especially if positive family history, overweight, and only mild HTN

-

• responsible for 90% of cases of HTN in adolescents, rarely in young children

• secondary HTN

identifiable cause of HTN ( most likely etiology depends on age )

• responsible for majority of childhood HTN

•

always consider white coat HTN for all ages

Table 42. Etiology of HTN by Age Group

-

-

System

Neonates

1 mo 6 yr

7 12 yr

>13 yr

Endocrine Metabolic

CAH

Wilms' tumour ( t renin) Neuroblastoma |t catecholamines)

Endoainopathies'

Endoainopathies' Essential hypertension

Essential hypertension

Renal

Congenital renal disease Renal artery thrombosis

Renal parenchymal drsease

Renal parenchymaldisease Renal parenchymal disease

Vascular

Coarctation of the aorta Renal artery thrombosis

Coarctation of the aorta RAS Corticosteroids

Renovascular abnormalities

Renovascular disease

Corticosteroids OCP

Corticosteroids 0CP Cyclosporine and

Drugs

Cyclosporine and tacrolimus

Cyclosporine and

tacrolimus

tacrolimus Recreational drugs (amphetamines, cocaine etc)

.

= -

.

.

.

.

Nat : r sy indi de hyperthyroidism hyperparathyroidism Cushing's syrdrone primary hyperaldosteronisnu’Conn's syndrome, pheochronocytoma

*

Risk Factors • primary HTN: obesity, male sex, African ethnicity, family history of HTN, LBW • secondary HTN: prepubertal age, no family history of HTN , history of renal disease, family history of autoimmune disease

Clinical Features • often asymptomatic, but can include ITT, fatigue, epistaxis • symptoms of hypertensive emergency • neurologic: headache, seizures, focal complaints, change in mental status, visual disturbances cardiovascular: symptoms of Ml or heart failure (chest pain , palpitations, cough, SOB ) • symptoms of secondary HTN: guided by etiology; ask about medications and recreational drugs (current and past ) Investigations • physical exam: upper and lower limb BP with correct cuff size, BM1, full neurologic exam, ophthalmoscopy, precordial exam, peripheral pulses, perfusion status

Signs of Secondary HTN • Edema ( renal parenchymal disease) • Abdominal or renal bruit (RAS) • Differential 4 limb BP/tSmaished femoral pulses (coarctation ) • Abdominal mass (Wilms', neuroblastoma ) • Goitre/skin changes ( hyperthyroidism ) • Ambiguous genitalia (CAH)

Paediatric BP Calculation sBP- age x 2 + 90 dBP- 2/3 x sBP

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P87 Paediatrics

Toronto Notes 2023

•laboratory • BUN , creatinine, electrolytes, urinalysis, fasting lipid profile obese patients: HbAlc* AST, ALT • further investigations based on history and physical • imaging: renal ultrasound ( with doppler ), echo (coarctation , LVH ) • 24 h ambulatory blood pressure monitoring ( if assessing white coat HTN ) Management

• treat underlying cause • non-pharmacologic: modify concurrent cardiovascular risk factors (e.g. weight reduction, exercise, salt restriction, smoking and drug cessation ) • pharmacologic: gradual lowering of BP using thiazide diuretics; no antihypertensives have been formally studied in children; if hypertensive emergency use hydralazine, labetalol, sodium nitroprusside • management of end-organ damage (e.g. retinopathy, LVH ) •consider referral to specialist Prognosis

-

•end organ damage (similar to adults) including LVH , CH1:, cerebrovascular insults, renal disease, retinopathy

Neurology Cerebral Palsy Definition

• non - progressive central motor impairment syndrome due to CNS anomaly or neural injury at the

prenatal, perinatal, or postnatal stage • incidence: 1.5 2.5 in 1000 live births (industrialized nations) • life expectancy is dependent on the degree of mobility and intellectual impairment, not on severity of

-

CNS lesion Etiology • no known cause identified in 1/3 of cases • prenatal causes: TORCH infections, maternal disorders (e.g. epilepsy), congenital CNS anomaly • perinatal causes: prematurity, LBNV, ischemic stroke • postnatal causes: infections (e.g. meningitis ), asphyxia, 1VH, trauma, severe jaundice

Clinical Features

• general signs: delay in motor milestones, developmental delay, learning disabilities, visual / hearing impairment, seizures, microcephaly, uncoordinated swallow (aspiration ) Table 43. Types of Cerebral Palsy Type

Characteristics

Spastic (70-80%)

Truncal hypotonia in first yr UMN ol pyramidal trad Increased lone, increased reflexes, clonus Hemiplegia most commonly caused by middle Can ailed one limb (monoplegia), one side ol body cerebral artery stroke (hemiplegia), both legs (diplegia), or both arms and Diplegia associated with periventricular leukomalacia

Area of Brain Involved

legs (quadriplegia )

in prematurebabies Ouadriplegia associated with HIE (asphyxia), higher incidence of intellectual disability

Athetoid/Dyskinetic (10-15%)

Athetosis t chorea or hypotonia Can involve face, tongue (results in dysarthria)

Basal ganglia (may be associated with kemiderus)

Ataxic ( F; age 6 mo 6 vr

-

-

Clinical Features • otherwise well, neurotypical child • fever often with associated illness ( source of fever), family history, past history of simple febrile seizures • no evidence of CNS infection/inflammation before or after seizure; no history of non-febrile seizures Table 44. Comparison of Typical and Atypical Febrile Seizures

-

Simple/Typical (70 80% ) All of the following: Duration 1 in 24 h period) Previous neurological impairment or neurological defidt after seizure Increased risk of developing epilepsy

population)

Investigations

• history : determine focus of fever, description of seizure, medications, trauma history, developmental history, FMHx • physical exam: LOC, signs of meningitis, neurological exam, head circumference, focus of infection • septic workup including LP if suspecting meningitis (strongly consider if child < 12 mo; consider if child is 12-18 mo; only if meningeal signs present in child >18 mo) • if typical febrile seizure, investigations only for determining focus of fever • EEG/CT/MRI brain not warranted unless atypical febrile seizure or abnormal neurologic findings Management • counsel and reassure patient and parents • febrile seizures do not cause brain damage • very’ small risk of developing epilepsy in simple febrile seizures 33% chance of recurrence ( mostly within 1 yr of first seizure and in children 1600 different mutations identified ) resulting in a dysfunctional chloride channel on the apical

-

membrane of cells • leads to relative dehydration of airway secretions, resulting in impaired mucociliary transport and airway obstruction Clinical Features

• neonatal: meconium ileus, prolonged jaundice, antenatal bowel perforation • infancy: pancreatic insufficiency with steatorrhea and ITT (despite voracious appetite), anemia, hypoproteinemia, hypo natremia

-

• childhood: heat intolerance, wheezing or chronic cough, recurrent chest infections ( S. aureus, P. aeruginosa , H . influenzae ), hemoptysis, nasal polyps, distal intestinal obstruction syndrome, rectal prolapse, clubbing of fingers • older patients: COPD, infertility ( males), decreased fertility' (female)

(§

>

CF Presenting Signs CF PANCREAS Chronic cough and wheezing F: 1 Pancreatic insufficiency (symptoms of malabsorption such as steatorrhea ) Alkalosis and hypotonic dehydration Neonatal intestinal obstruction (meconium ileus) /Nasal polyps Clubbing of fingors/Chest radiograph with characteristic changes Rectal prolapse Electrolyte elevation in sweat, salty

skin Absence or congenital atresia of vas deferens Sputum with S. aureus or P. aeruginosa (mucoid)

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P93 Paediatrics Investigations

• neonatal screening • sweat chloride test x 2 (>60 mEq / L )

false positive tests: malnutrition, atopic dermatitis, hypothyroidism, hypoparathyroidism, GSD, adrenal insufficiency, G6PD, Klinefelter syndrome, technical issues, autonomic dysfunction, familial cholestasis syndrome false negative tests: technical problem with test, malnutrition, skin edema, mineralocorticoids • Cl'TK gene mutation analysis: genetic screening panels or gene sequencing if clinically suspicious for rare mutation , useful when sweat chloride lest is equivocal • disease often detected during newborn genetic screening; positive result requires DNA testing and subsequent sweat chloride testing »

Management

• nutritional counselling: high calorie diet, pancreatic enzyme replacements, fat soluble vitamin supplements • management of chest disease: physiotherapy, postural drainage, exercise, bronchodilators, aerosolized DNase and inhaled hypertonic saline, antibiotics (e.g. cephalosporin, cloxacillin, ciprofloxacin, inhaled tobramycin depending on sputum C&S), lung transplantation • genetic counselling Complications

• respiratory failure, pneumothorax ( poor prognostic sign ), cor pulmonale ( late ), pancreatic fibrosis

with DM , gallstones, cirrhosis with portal HTN , infertility ( male ), recurrent respiratory infections • early death (current median survival in Canada is 46.6 yr)

Pneumonia Etiology

• inflammation of pulmonary tissue, associated with consolidation of alveolar spaces Clinical Features

• incidence is greatest in first year of life with viral causes being most common in children < 5 yr • fever, cough , tachypnea

• CXK: diffuse, streaky infiltrates bilaterally

• bacterial causes may present with cough , fever, chills, dyspnea , more dramatic CXR changes (e.g. lobar consolidation , pleural effusion ) Management

• supportive therapy: hydration, antipyretics, humidified O2 Table 45. Common Causes and Treatment of Community- Acquired Pneumonia Age

Bacterial

Viral

Treatment

Neonates

GBS f. eoli

HSV CMV Enterovirus

Ampicillin AND gentamicin

-

S omens S pneumoniae Chlamydia trachomatis H. influemae

RSV

Ampicillin OR ceftriaxone Azithromycin (il Chlamydia

listeria 1 3 mo

-

3 mo S yr

. .

S. pneumoniae i. aureus S pyogenes

.

> Syr

S. pneumoniae

Influenza Human metapneumovirus Adenovirus Parainfluenza virus RSV Influenza Human metapneumovirus Adenovirus

Parainfluenza virus Influenza

( roctomotosuspeded )

High dose amoxicillin OR ampicillin OR ceftriaxone

High dose amoxicillin OR ampicillin OR ceftriaxone Azithromycin OR clarithromycin (i I Uycaplasma'Chlomydophila pneumoniae suspected )

Hycaptasmo pneumoniae Chlamydophila pneumoniae S aureus H. influemae

.

Respiratory Distress

-

r >

APPROACH TO DYSPNEA

L

• determine if patient is sick or not sick; ABCs • history: onset, previous episodes, precipitating events, associated symptoms, past medical / family history of respiratory disease • physical exam: vitals, SpOz, evidence of cyanosis, respiratory, cardiovascular • investigations: CBC and differential, electrolytes, BUN Cr, NP swab, ABG, CXK, ECG ( based on clinical findings)

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P91 Paediatrics

Dyspnea I

I Pulmonary

I

£

Lower airway

Upper Airway Foreign body Croup Laryngeal edema Epiglottitis Retropharyngeal

;

I

Cardiac

Pleura Pulmonary ellusion Empyema

Bronchiolitis Pneumonia Atelectasis Asthma

CHF

Other tlCP

Cardiac tamponade Pulmonary edema

Ascites Scoliosis

Pulmonary embolus

Pneumothorax

abscess Tracheitis

Figure 18. Approach to dyspnea in childhood

APPROACH TO WHEEZING • caused by obstruction of airways below thoracic inlet

Differential Diagnosis of Wheezing • common: asthma ( recurrent wheezing episodes, identifiable triggers, typically >6 yr ), bronchiolitis (first episode of wheezing, usually < 1 yr), recurrent aspiration ( often neurological impairment ), pneumonia ( fever, cough, malaise) • uncommon : foreign body (acute unilateral wheezing and coughing ), CF ( prolonged wheezing,

unresponsive to therapy ), bronchopulmonary dysplasia ( often develops after prolonged ventilation in the newborn ) • rare: CHF, mediastinal mass, bronchiolitis obliterans, tracheobronchial anomalies APPROACH TO STRIDOR

• caused by obstruction above the thoracic inlet and may also present with hoarseness and suprasternal retractions • stridor at rest is an emergency • differential diagnosis of stridor: croup, bacterial tracheitis , epiglottitis, foreign body aspiration , subglottic stenosis (congenital or iatrogenic ), laryngomalacia / tracheomalacia (collapse of air way cartilage on inspiration ) , retropharyngeal abscess Table 46. Common Upper Respiratory Tract Diseases in Children Croup

Bacterial Tracheitis

Epiglottitis

trachea

Supraglottis

Choanal Atresia

(Laryngotracheitis )

Affected Site

Subglottis

Posterior nasal aperture(s)

Epidemiology

Common in children 6 -36 mo Increased incidence in fall and winter months

flare Usuallyseen in children 3 mo to 6 yr

Decreased incidence due to Hib vaccination Common in children 2- 6 yr

1in 7000 live births 2 in 3 are unilateral F> M

Etiology

Parainfluenza [75 %) Influenza A and 8 RSV

S. aureus 5. pneumoniae H. intluemae n- hemolytic Strep M. catarrtrolis

H. influenzae S. pneumoniae p hemolytic Strep S. aureus

Oronasal membrane persists preventing the nose joining the oropharynx

toxic appearance Rapid progression Cough 8iphasic stridor No response to corticosteroids and

Toxicappearance Rapid progression 4 Os: drooling, dysphagia, dysphonia, distress

Unilateral: diagnosed later in life, unilateral discharge or obstruction Bilateral: diagnosed during Infancy,noisy breathing, cyanosis that worsens with feeds and improves when crying Inability to pass NG tube through nates CTdelinitlve diagnosis

Adenovirus Clinical Presentation

Non- toxic appearance Barking cough

Stridor Viral prodrome (rliinorrhca pharyngitis, cough llow - grade lever ) Hoarseness

.

Investigations

nebulized epinephrine

Clinical diagnosis

Clinical diagnosis

CXR: " steeple sign" bom subglottic narrowing

Endoscopy: definitive diagnosis

-

Stridor Tripod position No cough Fever |»39 C|

"

Clinical diagnosis Perform physical exam cautiously to avoid exacerbating respiratory

distress Management

Mild to moderate: Intubation corticosteroids, supportive IV antibiotics care

Severe:corticosteroids, nebulized epinephrine, humidified oxygen, intubation if necessary

Intubation IV antibiotics

Acute (bilateral choanal atresia): place oral airway, initiate gavage feedings Long-term: relerral to otolaryngology

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Rheumatology Growing Pains Epidemiology

• age 2 -12 yr, M = F Clinical Features • diagnosis of exclusion • intermittent, non-articular pain in childhood with normal physical exam findings • pain at night, often bilateral and limited to the calf, shin, or thigh; typically short-lived • relieved by heat, massage, mild analgesics • child is well, asymptomatic during the day, no functional limitations • possible family history’of growing pains Management

• lab investigations not necessary if typical presentation; reassurance and supportive management

Juvenile Idiopathic Arthritis •a heterogenous group of conditions characterized by persistent arthritis in children < 16 yr •diagnosis: arthritis in 1 joint (s); duration S6 wk ; onset age < 16 yr; exclusion of other causes of arthritis; classification defined by features/ number of joints affected in the first 6 mo of onset Systemic Arthritis (Still 's Disease) •onset at any age, M F •once or twice daily fever spikes (>38.5®C) > 2 d /wk with temperature returning rapidly to baseline;

=

children usually acutely unwell during fever episodes

•extra-articular features: erythematous “salmon -coloured” maculopapular rash, lymphadenopathy, hepatosplenomegaly, leukocytosis, thrombocytosis, anemia, serositis, pericarditis •arthritis may occur wk to mo later • high tSR, CRP, WBC, platelet count

-

Oligoarticular Arthritis (1 4 joints) • most common type of|IA onset early childhood ( M • persistent affects no more than 4 joints during the disease course •extended: affects more than 4 joints after the first 6 mo typically affects large joints: knees ( most common ), ankles, elbows, wrists; hip involvement unusual • ANA positive 60 80%, RF negative •screening eye exams for asymptomatic anterior uveitis (occurs in 30%) •complications: knee flexion contracture, quadriceps atrophy, leg length discrepancy, growth disturbances, uveitis

.

-

-

--

Polyarticular Arthritis (5 or more joints) • ANA positive in 50%, uveitis in 10% • RF negative ( more common ) • onset: 2-4 yr and 6-12 yr, F>M • symmetrical involvement of large and small joints of hands and feet, TM|, cervical spine • RF positive onset: late childhood/early adolescence, F>M similar to the aggressive form of adult rheumatoid arthritis and has a similar course progressing into adulthood in most cases severe, rapidly destructive, symmetrical arthritis of large and small joints may have rheumatoid nodules at pressure points (elbow's, knees)

-

Enthesitis Related Arthritis

•onset late childhood/adolescence, M >F • RF negative arthritis and /or enthesitis (inflammation at the site where tendons or ligaments attach to the bone ) • weight bearing joints, especially hip and intertarsal joints, or sacroiliitis • risk of developing ankylosing spondylitis in adulthood •asymmetric involvement oflower limb joints, associated with HLA B27 and development of symptomatic uveitis/ iritis

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P96 Paediatrics

Toronto Notes 2023

Psoriatic Arthritis

-

• onset: 2- 4 yr and 9 11 yr, l;> M • arthritis and psoriasis OK arthritis and at least two of: • dactylitis, nail pitting or other abnormalities, or family history of psoriasis in a 1st degree relative asymmetric or symmetric small or large joint involvement ( usually knees and small joints in the hands and feet ) • erythematous, scaly lesions on scalp, post auricular area, peri umbilicus, or over extensor surfaces of

-

elbows and knees

-

Management

• goals of therapy: eliminate inflammation, prevent joint damage, promote normal growth and development as well as normal function , minimize medication toxicity • moderate- intensity exercise (aerobic fitness, flexibility and strengthening exercises) to maintain range of motion ( ROM ) and muscle strength • multidisciplinary approach: OT/ PT, social work, orthopaedics, ophthalmology, rheumatology • 1st line drug therapy: NSAIDs, intra-articular corticosteroids • 2nd line drug therapy: DMARDs ( methotrexate, sulfasalazine, leflunomide), corticosteroids (acute management of severe arthritis, systemic symptoms of J1A, topical eye drops for uveitis), biologic agents (1L-1/1L-6 inhibition for systemic arthritis, TNF antagonist for polyarticular J1A)

Limb Pain Evaluation of Limb Pain Table 47. Differential Diagnosis of Limb Pain 10 yr

Trauma

>

x

Infectious Septic arthritis Osteomyelitis

>

«

s

X

X

X

-

Cause

Inflammatory

Transient synovitis

I

JIA Spondyloarthritls SLE

X

X

x

Dermatomyositis

x x

HSP

x

Anatomic /Orthopaedic Legg Calve Perthes disease

- -

X

Slipped capital femoral epiphysis

X X

-

Osgood Schlatter disease

X

Neoplastic

leukemia

I

X

Neuroblastoma Bone tumour

X

X

X

X

Hematologic Hemophilia ( hemarthrosis)

x

x

x

Sickle cell anemia

X

X

X

Growing pains

X

X

Fibromyalgia

x

X

Pain Syndromes

Complex regional pain syndrome Must rule out infection , malignancy , and acute orthopaedic conditions

X

History

• pattern of onset and progression of symptoms ( including acuity and chronicity) • morning stiffness, limp/ weight-bearing status, night pain • joint involvement (type, distribution ) ± spine (axial ) involvement • extra -articular manifestations and systemic symptoms • functional status: activities of daily living • family history (arthritis, IBD, psoriasis, spondyloarthropathies, uveitis, bleeding disorders, sickle cell

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anemia) • past medical illness, intercurrent infection, travel, sick contact history, joint injury

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P97 Paediatrics

Physical Exam

• growth parameters • screening examination ( paediatric gait, arms, legs, spine exam ) • joint exam: inspection / palpation (swelling, erythema, warmth, tenderness, deformity), ROM

Red Flags for Limb Pain • Fever • Pinpoint pain/tendemess • Pain out of proportion to degree of inflammation • Night pain • Weight loss

• adjacent structures ( bone, tendon, muscle, skin ) • leg length • neurologic exam Investigations

• Erythema

• basic: CBC and differential, blood smear, ESR , CRP, x- ray

• as indicated: blood (ANA, RF, culture, viral/ bacterial serology, CK, PTT, sickle cell screen , immunoglobulins, complement ), urinalysis, synovial fluid (cell count, Gram stain, culture), TB skin test, imaging, bone marrow aspiration, slit lamp exam

• Unexplained fractures

Lyme Arthritis

.

• see Infectious Diseases 1D22

• caused by spirochete Borrelia burgdorferi • incidence highest among 5-10 yr • do not treat children 10, F:M =10:1 • childhood-onset SLE vs. adult-onset SLE: children have more active disease, are more likely to have renal disease, and receive more intensive drug therapy and have a poorer prognosis compared to

adults

Transient Synovitis of the Hip •benign , self-limited inflammatory joint disorder, usually occurs alter URT1, pharyngitis , ADM • key is to differentiate from septic arthritis Epidemiology •3-10 yr, M > F, more common on right side

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P98 Paediatrics

Clinical Features

• afebrile or low-grade fever; pain typically occurs in hips or knees (referred from hip) suddenly; painful limp but full ROM ( pain not as pronounced as in joint or bone infections); child does not look “toxic" pain is not disabling and gradually worsens over few days, can have sudden onset of symptoms • symptoms self-resolve over 7-10 d Investigations • WBC within normal limits; HSR and CRP may be mildly elevated • joint effusions maybe seen on ultrasound aspirate joint and examine synovial fluid if suspicious for septic arthritis MR1 if suspicious for osteomyelitis or periarticular pyomyositis

• diagnosis of exclusion Management • goal is to manage symptoms (anti-inflammatory medications and bedrest ) usually resolves within 24-48 h

Complications

• Legg-Calve- Perthes disease

Vasculitides HENOCH- SCHONLEIN PURPURA

• most common childhood vasculitis, peak incidence 4-10 yr, M:H =2:1 • vasculitis of small vessels • often have history of URT11-3 wk before onset of symptoms Clinical Features

• clinical triad: 1 ) palpable purpura, 2 ) abdominal pain, 3) arthritis • skin: palpable, non - thrombocytopenic purpura in lower extremities and buttocks, edema, scrotal swelling • joints: arthritis/arthralgia involving large joints associated with painful edema • GI: abdominal pain, G1 bleeding, intussusception • renal: microscopic hematuria, IgA nephropathy, proteinuria, HTN, renal failure in < 5% Investigations

• no routine investigations performed - diagnosis is mainly based on clinical features • urinalysis ( blood, protein creatinine ratio), serum ( urea /electrolytes, creatinine, albumin, elevated IgA ) skin/renal biopsy - IgA deposition • • ultrasound - intussusception /perforation, testicular pain /swelling • rule out other autoimmune conditions/ vasculitides Management

• mainly supportive (e.g. elevation for edema ) • anti- inflammatory medications for joint pain, corticosteroids for select patients • monitor for protein on urinalysis and hypertension every month for 6 mo to check for renal disease, which may develop late (immunosuppressive therapy if severe ) Prognosis

• self-limited, resolves within 4 wk

• recurrence in about one-third of patients • long-term prognosis dependent on severity of nephritis KAWASAKI DISEASE

• acute vasculitis of unknown etiology ( likely triggered by infection ) • medium -sized vasculitis with predilection for coronary arteries • most common cause of acquired heart disease in children in developed countries • peak age: 3 mo 5 yr; Asian people > Black peoploWhite people

-

Diagnostic Criteria

• fever persisting >5 d AND £ 4 of the following features

-

1. bilateral, non exudative conjunctival injection 2. oral mucous membrane changes ( fissured lips, strawberry tongue, injected pharynx ) 3. changes of the peripheral extremities acute phase: extremity changes including edema of hands and feet or erythema of palms or

Kawasaki Diagnostic Criteria Warm CREAM

Warm: >5 d fever Conjunctival injection Rash Edema of hands and feet Adenopathy Mucosal changes

soles subacute phase: periungual desquamation

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P99 Paediatrics

4 . polymorphous rash 5. cervical lymphadenopathy > 1.5 cm in diameter ( usually unilateral ) • exclusion of other diseases (e.g. scarlet fever, measles) • incomplete Kawasaki disease: fever persisting > 5 d and 2 -3 of the above criteria further evaluation dictated by CRP, ESR, and supplemental laboratory criteria Management therapy: lVlg ( 2 g/ kg ) and low dose of ASA (3-5 mg/ kg / d, max 325mg /d ) • lVlg within 10 d of fever onset reduces risk of coronary aneurysm formation • if fever persists 24-36 h after lVlg, repeat lVlg treatment at the same dose; if second dose fails, trial a third lVlg treatment, IV pulse methylprednisolone or consult rheumatology for next steps • baseline 2 D- echo and follow- up periodic 2 D -echo ( usually at 2 and 6 wk ) • initial

Complications

• coronary artery vasculitis with aneurysm formation occurs in 20 -25% of untreated children, < 5% if receive lVlg within 10 d of fever • 50% of aneurysms regress within 2 yr • anticoagulation for multiple or large coronary aneurysms

Common Medications Table 49. Commonly Used Medications in Paediatrics Drug Name

Dosing Schedule

acetaminophen

10 15 mg / kg /dose PO q 4 6 h PUN

amoxicillin

80 - 90 mg / kg /d P0 divided q8 h

Otilis media

dexamelhasonc

0.6 mqfkg PO x1 0.6 rncj / kgid P0 lor 2 d Moderate dose - 250 - 500 pg /d divided BID

Croup Acute asthma

llulicasone ( Movent )

-

-

Nigh dose BID

Indications

Comments

Analgesic, antipyretic

Not to exceed 60 mg ' kg /d in neonates or 75 mg / kg /d in older children to a max of 4 g /d Causes hepaloloxicily at high doses

- >500 pg /d divided

-

-

ibuprofen

5 10 mg / kg /dose P 0 q 6 8 h

iron

6 mg /kg/ d elemental iron P 0 once Anemia daily or divided TID

polyethylene glycol 3350 ( PEG )

Compaction:1 1.5 g /kg/d x3 d Maintenance:starling dose at 0.4 1 g /kg

prednisone / prednisolone

1 2 mg / kg /d P0 x5 d 3 4 mg /kg/dPO then taper to 1 - 2 mg / kq /d P0 once platelet count >30 x 109/1 60 mg/ml/d P 0 0.01 0.03 mt/ kg /dose in 3 ml NS via nebuliaer q 0.5 4 h PRN 100 200 pg /dose prn . max 4 - 8 puffs frequency q 4 h

Analgesic, antipyretic

Use cautiously in patients with liver impairment, history of Gl bleeding or ulcers

salbutamol (Ventolin ')

Side effects: dark stool, constipation , dark urine

-

-

-

-

-

Source: Leu E.(2009) The 2010-2011 Formulary

-

Asthma

IIP

Oral prednisone is bitter tasting , consider using prednisolone

Nephrotic syndrome

Acute asthma

Can cause tachycardia , hypokalemia, restlessness

Maintenance treatment for asthma

- The Hospital lot Sick Children

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Landmark Paediatric Trials Trial Name

Reference

Clinical Trial Details

NEJM 201S;372(9):803 - 813

Purpose: To assess the impact of peanut avoidance and consumption on the development of a peanut allergy in infants at high risk for the

NUTRITION LEAP

allergy.

Methods: RCT consisting of 640 infants aged between 4 and 11 mo with severe eczema, egg allergy, or both. Infants were randomized to consume or avoid peanuts until the age of 60 mo. The primary outcome was the proportion of infants that developed a peanut allergy. Results: The infants randomized to consume peanuts resulted in a smaller proportion of children developing peanut allergies (1.9%) when compared to the group that avoided peanut consumption (13.7%). Increased levels ol peanut - specific lgG 4 antibody was prevalent in the consumption group. Raised litres of peanut - specific IgE antibodies were prevalent in theavoidance group. Conclusion: Prevalence ol peanut allergy at 60 months of age was significantly reduced in the consumption group.

DIABETES

NEJM 2012;366|24):2247

10 DAY

Purpose:1o assess the efficacy of different treatment regimens in attaining glycemic control in youth with type 2 diabetes. Methods: RCT consisting of 699 patients between the ages of 10 and 17 yr with recent onsetI2 DM. Patients were assigned to continue metformin alone, or in conjunction with tosiglilazone, or a lifestyle modification focused on weight loss. Ihe outcome of interest was loss of glycemic control indicated by glycated hemoglobin level ol >8% for at least 6 mo. Results: Metformin alone resulted in a 61.7% failure rale, metforminnosiglitazonc resulted in a failure rate ol 38.6% and melfotmuHifoslylc intervention resulted in a failure rate of 46.6% Conclusion: Metformin plus rosiglitarone was significantly belter than metformin alone in achieving glycemic control within youth. Metformin plus lifestyle intervention did not have a signilicant impact on glycemic control when compared to metformin alone

.

.

.

NEJM 2019:381|7):637

ELLIPSE

Purpose: To assess Ihe efficacy ol liraglutlde in combination with metlormin as a treatment for type 2 diabetes in youth Methods: RCT consisting ol 134 patients between the ages ol 10 and 17 yr with a BMI greater than Ihe 86th percentile and a glycated hemoglobin level between 6.5 and 11%. Patients were randomized to receive metformin alone or metlormin in combination with

liraglutide. The outcomeol Interest was the change In glycatedhemoglobin level alter 26 wk ol treatment. Results: Alter 26 wk treatment with metlormin alone resulted in a 0.42% inciease in glycated hemoglobin levels and treatment with metlormin and liraglutide in combination resulted in a 0.64% decrease in glycated hemoglobin levels. Youth taking liraglutide reported Increased overall adverse events and gastrointestinal adverse events. Conclusion: Metlormin liraglutide combination therapy demonstrated increased elticacy in maintaining glycemic control compared to metlormin monotherapy

.

-.

RESPIRATORY SYNCYTIAL VIRUS N Engl J Med. 2022; 386|9):837

MELODY

Title: Nirsevimab lor Prevention of RSV in Healthy Late Preterm and Term Infants.

-

.

.

-

Purpose: To study the efficacy and safety ol Nirsevimab, a monoclonal antibody against RSV in late preterm and full term babies Methods: RCT consisting of 1490 Infants born at gestational age of 35 wk were randomized in a 2:1 ratio to receive nirsevimab or a placebo, respectively. The outcome of interest is the presence of RSV infection within 150 d of treatment dosage. Results: RSV Inlections occurred within 1.2% of intanls in the nirsevimab group and 5% ol patients In the placebo group Conclusion: Use ol nirsevimab results in effective protection ol preterm and full term infants from RSV infection.

.

-

ASTHMA

-

N Engl J Med 2022: 386:2071

MANDALA

2083

Titlc: Albuterol - Budesonide Fixed - Dose Combination Rescue Inhaler for Asthma Purpose: To assess the efficacy ol budesomde (corticosteroid) in combination with albuterol ( bronchodilator ) as a rescue medicine lor asthmatic patients Methods: RCT consisting of 3132 patients aged 4 11 yr with uncontrolled moderate to severe asthma. Patients were randomized to receive inhaled albuterol ( 180 pg ) and budesonide |160 pg), albuterol (180 pg) and budesonide (80 pg) or 180 pg ol albuterol alone for 24 wk of rescue treatment The outcome of interest was the presence of a severe asthma exacerbation Results: In the higher dose combination- treated group the risk of severe exacerbation was lowered by 26% when compared to the albuterol monotherapy. Conclusion: Use of albuterol in combination with budesonide as a rescue therapy reduces the risk of severe asthma exacerbation compared to albuterol monotherapy

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Pi 02 Paediatrics

Ng 1, loewy AD . Guidelines lor vitamin K prophylaxis in newborns. Paedialt Child Health 2018:23:394 - 397. Nicholson JF. Nelson 's essentials ol pediatrics. 4 th ed. Philadelphia : WB Saunders 2002. Inborn errois ol metabolism , p. 153 178. Niermcycr S Kallwinhcl J Van Receipts P. etal . International guidelines lor neonatal resuscitation: an excerpt ( torn the guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care: international consensus on science . Pediatrics 2000:106:120. Olson JC. Nelson's essentials of paediatrics 3rd ed . Philadelphia: WB Saunders:1908. Rheumatic diseases ol childhood , p 290 314. Oitir Alvarez 0 Mikrogianakisft . Canadian Paediatric Society Acute Care Committee. Managing the paediatric patient with an acute asthma exacerbation. Paediatr Child Health 2012:17( 51:251 255 Palmer! MR Dunkel l Delayed puberty . NFJM 2012: 366|5):445 453. Panagiotou l , Rourke U , Rourke JI, et al . Evidence based wel baby care. Part 2: education and advice section of the next generation of the Routke Baby Record. Can Fam Physician 1998; 44:568 572. Panagiotopoutos C Riddell MC Sellers EAC . Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management ol Diabetes in Canada: type 2 diabetes in children and adolescents. Can J Diabetes 2013:37(suppl 1):S163 S167. Parashette KR. Crollie J . Vomiting. Pediatr in Rev 2013:34( 7):307 3I9. Pearce JM Sills RH . Childhood leukemia . Pediatr Rev 2005:26:96 102. Provan D Stasi R , Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010:115:168-186. Publicly funded immunization schedules for Ontario. Augusl 2011. Purugganan O. Intellectual disabilities. Pediatr Rev 2018:39:299 - 309. Rastogi MV LaFranchi SN . Congenital hypothyroidism. Orphanet J Rare Dis 2010:5:11. Rimrodt SL, Lipkin PH. Learning disabilities and school failure. Pediatr Rev 2011:32|8):315 324. Robinson JL, Finlay JC. Lang ME. etal. Urinary tract infection in infants and children: Diagnosis and management. Paediatr Child Health. 2014:19 (6|:315-319. Rosa Olivares J , Porro A , Rodriguez Varela M. et al. Otitis Media: To Treat To Refer. To Do Nothing: A Review for the Practitioner. Pediatrics in Review. 2015:36(11):481. Rose SR , Vogiatzi MG. Copeland KC. A general paediatric approach to evaluating a short child. Pediatr Rev 2005:26|11|:410 420. Rowan Legg A. Canadian Paediatric Society. Community Paediatrics Committee. Managing functional constipation in children . Paediatr Child Health 2011:16 (10):661 665. Rowan Legg A . Canadian Paediatric Society Community Paediatrics Committee. Oral health care tor children: a call for action . Paediatr Child Health 2013:18(1):37- 43. Schneeweiss S. LalaniA. Hospital for Sick Children handbook of paediatric emergency medicine. Sudbury: Jones and Bartlett ; 2008. Scott R 6 . Recurrent abdominal pain during childhood. CanFam Physician 1994:40:539 547. Scruggs K Johnson MI. Paediatrics 5 minute reviews. Current Clinical Strategies Publishing 2001 2002. SEER Cancer Statistics Review National Cancer Institute. Bcthesda MD. Available at: http:/7seer.cancer .govJfaststats 7selections . php ?40 utput ( Accessed on April 28.2021). SegeIGB. Anemia Pediatr in Rev 1988:10:77 88. Shalini P. Management ol obstructive sleep apnea in children: UploOate. 2021 Shane AL , Mody RK Crump JA, et al . Practice guidelines loi the diagnosisand management of infectious diarrhea . Clin Infect Dis 2017:65:1963 1973. Shields M . Measured obesity: ovciwcight Canadian children and adolescents. Nutrition findings from the Canadian Community Health Survey. Statistics Canada 2005. Silbcibach M , Hannon D. Presentation of congenital heart disease in the neonate and young infant , Pediatr Rev 2007; 28|4|:123 13 t Silver sides CK Kicss M , Beauchesnc L el al. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: outflow tract obstruction , coarctation ol the aorta , tetralogy of Fallot Ebstein anomaly and Marfan's syndrome. Can J Cardiol 2010: 26( 3):c80 97. Silvcrstein J Kilgensmilh G Copeland K. et al. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association . Diabetes Care 2005:28:186 208. Singh RK Singh TP. Etiology and diagnosis of heart failure in infants and children . Rose BD (editor ). Waltham : UpToDate. 2013. Sorokan SI. Finlay JC Jefferies AL: Canadian Paediatric Society Fetus and Newborn Committee Infectious Diseases and Immunization Committee. Newborn male circumcision . Paediatr Child Health 2015;20|6|:311

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Special Writing Groupofthe Committee. Rheumatic fever, endocarditis, and Kawasaki disease ofthecouncilon cardiovascular disease in the young of the Ameiican Heart Association. Guidelines for the diagnosis of rheumatic fever Jones criteria.1992 update. JAMA 1992:268:2069. Speiser PW. Arlt W Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21- hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocr Metab 2018 :103(11) 4043 4083. Standards of medical care in diabetes 2020 ( American Diabetes Association ). Diabetes Care. 2020:43: S163 S182. Strahm B , Malkin D. Hereditary cancer predisposition in children: genetic basis and clinical implications. Int J Cancer 200G;119 (9):2001 2006. Styne DM. Glaser NS. Nelson 's essentia Is of paediatrics. 4th ed. Philadelphia: WB Saunders: 2002. Chapter 17 Endocrinology; p 711-766. Summary of recommendations from the Canadian Asthma Consensus Guidelines. 2003 and Canadian Paediatric Asthma Consensus Guidelines.2003 ( updated December 2004) CMAJ 2005:173(suppl):S1-56. TenembaumS. Disseminated encephalomyelitis in children. Clin Neurol Neurosur 2008:110 (9|:928 938. Clin Neurol Neurosur 2008;110|9|428 938. Teri LT Shea P. Infantile colic: Manage me ntand outcome: UpToDate. 2021. Tiwari T Murphy TV. Moran J , et al. Recommended antimicrobial agentsfor the treatment and postexposure prophylaxis of pertussis: 2005 C0 C guidelines. MMWR Recomm Rep 2005:54 ( RR 14|:1 16. Vaughan VC Bchrman RE. Nelson textbook of paediatrics. Vick GW. Bezold LI . Classification of alrial septal defects (ASDs), and clinical features and diagnosis of isolated ASOs in children. Rose 80 (editor ). Waltham: UpToDate. 2014. Virbalas J . Smith L . Upper airway obstruction. Pediatr Rev 2015:36) 2): 62 73. doi:10.1542 / pit.36 2 62 Vissers IE , van Ravenswaaij CM . Admiraal R et at. Mutations in a new member of the chiomodomain gene family cause CHARGE syndrome. Nat Genet 2004:36|9):95S 957. Walsh PR Johnson S Treatment and management of children with haemolytic uraemic syndiome. Arch Dis Child 2018:103:285-291. Waid MGK Ornstein A Nice A etal. The medical assessment of bruising in suspected child maltreatment cases: a clinical perspective. Paediatr Child Health 2013:18(8 ) 434 438. Whcrrctt D Hunt C Mitchell 8 et al Canadian Oiabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management ol Diabetes in Canada: type 1 diabetes in children and adolescents. Can J Diabetes 2013:37(suppl 1):SI 53 5162 . WHO Multicentie Growth Reference Study Gioup. WHO Child Growth Standards based on lengthfheight wclghtand age . Ada Paediatr 2006:Suppl 450:76 85. Wormscr GP Datlwyler RJ. Shapiro ED. et al. The clinical assessment , tiealmcnt. and prevention of Lyme disease, human granulocytic anaplasmosis. and babesiosis: clinical practice guidelines by the Infectious

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Diseases Society of America . Clm Infect Da 200643:1089. Wubbel L McCracken 0 McCracken GH Jr. Management bacterial meningitis. Pediatr Rev 1998:19|3|:78 84 . Zaripov IN Midglcy A Christmas SE etal. Juvenile idiopathic arthritis: liom aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol 2021:19.135. hltps:/ /doi .org /10.1186 /s12969 021 00 G 29 8 Zclla GC Israel EJ. Chronic diarrhea in children. Pediatr Rev 2012:33:2017-218. Zorc JJ. Kiddoo DA. Shaw KN . Diagnosis and management of paediatric urinary trad infections. Clin Microbiol Rev 2005:18( 2 )417 422.

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Web - Based Resources Paediatrics ( Internet!. New York City ( NY ): Medscape: c1994 2020 [cited 2021 Apr 28], Available from: https:// www.medscape.com / paediatries. http:77www.icondata.com/healLh / pedbase. http:// www.cda adc.ca . http:// www.aboutkidshealth.ca. http://www.healthychildren .org . http:/ / www.publichealth .gc.ca. http:/ / www.cps.ca. https:// www.amboss.com / https:// www.merckmanuals . com www.uptodate.com . Gandy A. Paediatric Database ( PEOBASE ) Homepage [ Internet'. London ( OH ): Alan Gandy;1995 Nov 15 [updated 2003 Oct 7: cited 2021 Apr 28'. Available from: htlps://web. archive.org / web / 20040203153554 i' http:// www.icondata.com /health/ pedbase /. Canadian Dental Association [Internet'. Ottawa (ON ): Canadian Dental Association: c 2020 [cited 2021 Api 28|. Available from: http://www.cda - adc.ca. AboutKidsHcallh [ Internet ]. Toronto (ON ): The Hospital for Sick Children:c 2020 " cited 2021 Apr 28|. Available from: http://www . aboutkidshealth .ca . HeatlhyChildien .org [Internet ;. Itasca ( II ): American Academy of Paediatrics: c 2020 [cited 2021 Apr 28]. Available from : http://www . heallhychildien.org. Public Health Agency ol Canada |lnlernet|. Ottawa ( ON ): Government of Canada ' Gouverncmcnt du Canada ; [ updated 2021 Apr 12: cited 2021 Apr 28[. Available from : http:/ / www. puhlicheallh .gc ca A home for paediatricians. A voice for children and youth. [ Internet ) Ottawa ( ON ): Canadian Paediatric Society : c2020 (cited 2021 Apr 28]. Available liom : https:/ / www.cps.ca / cn / Wolters Kluwer . Evidence Based Clinical Decision Support at the Point of Caic [Internet ]. Waltham ( MA ): UploOate Inc ; c 2020 [cited 2021 Apr 28|. Available from: https:/ /www uplodale .com Onlano Ministry ol Health and long - term Care [Internet ' Ontario: Ontario Ministry of Health and long Tcim Care; c 2009 2020 Ontario's routine immumzolion schedule; [cited 2021 Apr 28]. [about 15 screens). Available from : http://www . hcaHh .gov.on .ca /en / public / programs/immvnization /static / lmmunization tool .Mini Schedule of well child visits [ Internet ]. Cps.ca [cited 2022 May 16]. Available from : htlps:/ /caringforkids cps.ca / handouls / pregnancy and - babies/schedule of well child visits ]. Amhoss.com.[cited 2022 May 16]. Available from : https://wwtw.iiinboss.com / us / lcnawledge /Child development and milestones / Child developmentand milestones [ Internet Merckmanuals .com . [cited 2022 May 16 '. Available from: https : / www. merckmanuals.tom / cn ca / professlonal / pedialiies / behaviotal conceins - and problems in childien /bieath holding spells ' Merckmanuals .com . [cited 2022 May 16 . Available from: , https:/ /www. merckmanuals.com /en 'ca / professionaljpediatricsi congenital cardiovascular - anomalies/ patent - ductus- arteriosus - pda ?query'patent ' o 20duclus% 20arleriosus

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Palliative Medicine Manu Sharina and Christine VVu, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors Vijithan Sugumar, KBM editor Dr. Risa Bordman, Dr. Adam Rapoport , and Dr. Donna Spaner, staff editors Acronyms

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Palliative Approach to Care Palliative Care

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Pain and Symptom Management Assessment Tools

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Care of the Dying Patient.

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Psychosocial and Spiritual Needs.

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End of Life Decision Making Types of Discussions

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Communication Approach to Communicating Bad News

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Collaboration.

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Suffering

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Paediatric Palliative Care

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Assessment Tools Symptom Management Landmark Palliative Medicine Trial

References

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Acronyms ADLs AND

CPR

activities of daily living allow natural death

DNR

cardiopulmonary resuscitation do not resuscitate

end- of 'life substitute decision maker

EOl SDM

Palliative Approach to Care Palliative Care Definition • an approach that seeks to improve the quality of life of patients and their families facing a life threatening illness, through the prevention and relief of suffering • applicable at any time during a life limiting illness, and may be delivered in conjunction with life prolonging or curative intervention • palliative approach to care is not just for EOL

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Urd a t Pal . abve Care Trials table lor more rforaat M os the st dy by Iemel el si. 2010 which d ea Is toe oe eta o< esrly palliative tare lor patients wtt aetaststc npa irnall- cell lung cancer.

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Survivorship

Cure

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Disease Management

Palliative

Pain & Symptom Management

Care

Paliative Care Unit End of life care

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Bereavement

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Hospice

Control

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See Lerda r Pal adve Care Trials table Tor more “ j etc oo tie ENABLE II trial, which details the e fetrf a oarsog- led intervention on quality of life (Oot|.spoton intecsityr. mood , and resource ose io Detects nth advanced gastrointestinal tract, lung , geoitoo nary tract, or breast cancer.

Rehabilitation

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Figure 1. Palliative care enhanced model Cocrtesy of Dr. Philippa Hawley

See lisdaut Pel

stive Can Trials table lor more by

-fonab study Back et al., 2007 which d eta Is e eftcacy of communication skills framing ci oi

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“ To gw eg bad news aid discussing transitions to oakatveca e.

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Palliative Care Assessment • comprehensive and includes physical, psychosocial, and spiritual domains of care • complete medical history includes determining the patient’s knowledge of their illness and their

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goals of care • physical symptom assessment - patient's opinion of severity is the gold standard , and may be measured using assessment tools such as the Edmonton Symptom Assessment System ( ESAS) • functional status assessment ability to perform ADLs, measured using tools such as the Palliative

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Performance Scale ( PPS) • psychosocial symptom assessment - anxiety, depression, family/caregiver distress, and cultural/ financial status • spiritual assessment - religious beliefs, values, coping mechanisms, and distress • medication review - limit polypharmacy

Pain and Symptom Management Assessment Tools • Edmonton Symptom Assessment System ( ESAS ): a tool used to screen for common symptoms seen in palliative care. Patients/caregivers are asked to rate the intensity of symptoms front 0 to 10 on a numeric rating scale where 0 represents the absence of the symptom and 10 represents the worst severity of the symptom. Assesses: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath, and “other problems" associated with specific conditions such as pruritus in liver disease and cough in lung disease, lhe ESAS provides a measure of symptom burden and allows for tracking the efficacy' of interventions over time

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Alberta Health |Services Affix patient label witin this box

Edmonton Symptom Assessment System Revised (ESAS-r ) Please circle the nnmber that best describes how you leel NOW: 0

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Other Problemifbr example cenirpetcn) Completed by federt one) Patient Family Caregiver Health Care Professional Caregiver Caregiver-assisted

Patient s Name Date fyyyy-morr-dd)

Time Ihftmm) Body diagram on reverse

Figure 2. Edmonton Symptom Assessment System ( ESAS)

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Adapted Irom: Alberta Health Services Edmonton Zone Palliative Care Program. Edmonton Symptom Assessment System revised (ESAS r ): Administration Manual. Covenant Health Palliative Institute.

• Palliative Performance Scale ( PPS ): a tool used to assess functional status. Assesses 5 components: ambulation, activity and evidence of disease , self -care , intake , and consciousness level . Has prognostic value in patients with advanced cancer Table 1. Palliative Performance Scale

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PPS Level

Ambulation

Activity and Evidence of Disease

Self Care

Intake

Conscious Level

100%

full

Normal activity and work No evidence of disease

Full

Normal

Full

90%

Full

Normal activity and work Some evidence of disease

Full

Normal

Full

80%

Full

Normal activity with effort Some evidence of disease

Full

Normal or reduced

Full

70 %

Reduced

Unable lodo normal|ob/ work Significant disease

Full

Normal or reduced

Full

60 %

Reduced

Unable to do hobby/housework Occasional assistance necessary Significant disease

Normal or reduced

Full or confusion

90 %

Mainly siI/lie

Unable to do any work Extensive disease

Occasional assistance necessaiy

Normal or reduced

Full or contusion

40 %

Mainly In bed

Unable to do most activities Extensive disease

Mainly assisted

Normal or reduced

Full or drowsy confusion

30%

Totally bed bound

Unable to do any activities Extensive disease

Total care

Normal or reduced

Full or drowsy confusion

20%

totally bed bound

Unable lo do any activities Extensive disease

Total caie

Minimal lo sips

Full or diowsys contusion

10%

totally bed bound

Unable lodo any activities Extensive disease

total care

Mouth care only

Drowsy or coma contusion

0%

Death

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Adapted Irom: Medical care of the dying, 4th ed. Victoria: Victoria Hospice Society, 2006. Version 2

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Table 2 . Symptom Management

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Symptom

Non Phormacologic Management

Pharmacologic Management

Constipation

Rule out obstruction, impaction, anorectal disease, and spinal cord pathology Hydration, orally where possible Increase mobility

Stimulant laxatives (senna), osmotic laxatives (lactulose) Titrate to bowel movement at least q 3 d

Dyspnea

Elevate head of bed,eliminate allergens,and open windovr /use fan

Oxygen, bronchodilators, opioids (e.g. morphine,hydromorphone)

Hiccups

Swallow t tsp of dry sugar,or dry bread (nasopharyngeal stimulationj'vagus nerve stimulation) Rebreathing into paper bag (increases partial pressure of CO)

Dopamine antagonists (e.g. chlorpromazine, haloperidol. metodopramide) Smooth muscle relaxants (e.g. hyoscine butylbromide (Buscopan ! ), baclofen)

Nausea and Vomiting

Frequent and small meals, avoid offensive strong odours, and treat constipation if

Raised ICR: dexamethasone Anticipatory nausea, anxiety: loraccpam Vestibular disease, vertigo: dimenhydrinatc Orug induced, hepatic, or renal failure: prochlorperaiine haloperidol Gastroesophageal reflux disease: proton pump inhibitor (RRI), H 2 antagonist Gastric stasis: metodopramide Bowel obstruction: meloclopramide dexamethasone octreotide

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Hot and cold compresses, art /music therapy relaxation techniques, physical therapy massage therapy, acupuncture, and cognitive behavioural therapy |CBT)

Nociceptive pain: non opioids (NSAIDs acetaminophen), weak opioids (e.g. codeine,tramadol), strong opioids (e.g. morphine, hydromorphone oxycodone, fentanyl) Neuropathic pain: anticonvulsants (gabapentin pregabalin). antidepressants (tricyclic antidepressants (TCAs)). selective serotonin reuptake inhibitors (SSRIs), steroids (dexamethasone) Bony pain: NSAIDs, acetaminophen and/or opioids, depending on pain severity: bisphosphonates.radiation therapy For more information on pain management, see Anesthesia A 2S

Pruritus

Bathe with tepid water, and avoid soap and bath oils

Antihistamines, phenothiacines, topical low potency corticosteroids, calamine lotion

Fatigue

Modify environment and activities to decrease Treat underlying condition (s) if present (e.g methylphenidatc, energy expenditure dexamethasone) Optlmile fluid and electrolyte intake Educate and support patient and family

Psychiatric

CBT support groups, art/music therapy

Pain

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Exercise

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Agitation: neuroleptics Confusion/ Delirium: treat underlying etiology if possible. Otherwise manage with neuroleptics (e.g.haloperidol) Depression: standard SSRIs serotonin and norepinephrine reuptake inhibitors ISNRIs) may be too slow depending on patient prognosis, may consider psychostimulants (e.g.methylphenidate. ketamine)

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Oropharyngeal Secretions (Death Rattle)

Reassure family that patient is not in respiratory distress Oral suctioning, avoid deep suctioning Discontinue unnecessary IV solutions Re positioning (on side, elevated) Monitor (oradversc effects (ierostomia delirium, sedation)

Anticholinergic agents used to dry secretions Hyoscine hydrobromide (scopolamine) SC or transdermal. glycopyrronium (glycopyrrolate) SC

Freedom from Cancer Pain

Opioid for moderate to severe pain ± Non-opioid

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± Adjuvant

Pain persisting or increasing

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WHO 's Pain Relief Ladder

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Opioid for mild to moderate pain ± Non- opioid ± Adjuvant

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Source: J Am Oeriatr Soc 2002:00: 52 Ob 5224 arid On Continuing Practice 1093:20 20 25 olid Ain Fam Physician 2009 ; 79|12) 10 S 9 I0OS

Pain persisting or increasing

Pain Management

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• tee Anesthesia A 25

Pain Syndromes • see Neurology, N 43

Care of the Dying Patient General Predictors of Decline in the Final Months of Life • decreasing activity - functional performance status declining, limited self -care, in bed or chair 50% of day, and increasing dependence in most i\ DLs

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• co - morbidity biggest predictive indicator of mortality and morbidity • general physical decline and increasing need for support • advanced disease unstable, deteriorating complex symptom burden • decreasing response to treatments, decreasing reversibility • choice of no further active treatment • progressive weight loss ( > l ()% ) in the past six months • repeated unplanned /crisis admissions • sentinel event (e.g. serious fall , bereavement, transfer to nursing home ) • serum albumin < 25 g / L • considered eligible for terminal illness disability benefits

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Non opioidiAdjuvant

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Figure 3 WHO’s Pain Relief ladder WHO’s Pain Relief ladder, available from: https://www.who.int/cancer/ palliative/painladder/en/”

See landmark Palliative Care Inals fable for more dormation on the study hy Hay lor etal. 1999 which d etails the effectiveness of advanced practice wise centered discharge planningand home follow - up intervention for older aged individuals at risk foi hospital readmissions

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See landman Palliative Care Inals fable for moie information on study by Christakis et at 2000. whxh d eta sdoctors' prognostic accuracy in terrmrally d patients aril to evaluate the determinants of that accuracy.

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Changes in the Last Hours of Life

• decreased level of consciousness • changes in breathing pattern ( Cheyne-Stokes breathing ) • airway secretions causing noisy breathing • inability to swallow safely and increased risk of aspiration • delirium (terminal restlessness) • mottling of the hands, feet, and legs • cool extremities

5 Dimensions of a Good Death

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OuaMy Entf 01 Ule Can: Patents' fenpaclms JAMA 1999;281: MJ 168

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• Pain /symptom management • Avoiding prolongation of dying • Achieving a sense of control

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Care of the Patient in the Final Days of Life • educate the family on the physiological changes in the dying process and discuss potentially difficult decisions (e.g. hydration ) • have a plan in place for an expected death in the home ( EDITH ), who to call ( not 911), and how the

death certificate will be made available to the funeral home

Relieving burden on others

• Strengthening relationships with loved ones

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• if the patient is unable to swallow, administer essential medications by non oral routes (e.g. SC ,

gastrostomy tube, IV, nasal, oral and rectal transmucosal, transderma!), with SC being the preferred option • discontinue non -essential and potentially inappropriate medications (e.g. for primary and secondary prevention); review other measures such as 1V/SC hydration and consider stopping if no longer beneficial

Psychosocial and Spiritual Needs • palliative care assessment includes addressing psychosocial and spiritual well- being • psychosocial needs pertain to the psychological and emotional well-being of patients and their carers, including concerns such as self-esteem, adaptation to illness, communication, and social functioning • patient's psychosocial experience is further shaped by the experience of pain and other symptoms related to the condition and its treatment • spiritual needs pertain to the manner in which the patient expresses meaning, value, and purpose in life. May include, but is not limited to, religious practices or philosophical reflection Approach to Assessing Psychosocial and Spiritual Needs

• holistic psychosocial assessment can help identify supports a person might need during their illness. Psychosocial issues can manifest as physical symptoms (e.g. pain, constipation, nausea ). Iherefore, it is important to be aware of physiological symptoms that may indicate depression and anxiety • mental and emotional needs - fear, worry, insomnia, panic, anxiety, nervousness, or lack of energy • social needs - family dynamics, communication, social and cultural networks, perceived social support, finances, intimacy, living arrangements, caregiver availability, etc

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• cultural needs - beliefs and preferences, linguistic needs, health behaviours, traditions, rituals, and cultural barriers to accessing health • to further explore questions about spirituality, the FICA spiritual assessment tool may be used • FICA - the four components to cover during a spiritual care assessment are: l aith or beliefs,

Importance of those beliefs, patient’s participation in a religious or spiritual Community, and how healthcare providers should Address the patient's health care issues

Interprofessional Care Plan for Psychosocial and Spiritual Needs

• interprofessional team of care providers including physicians, nurse practitioners, nurses, social workers, psychologists, chaplains, spiritual advisors, pharmacists, and physical and occupational therapists assist in the following interventions: home care, respite care, social networks and activities, problem -solving and education, one on one therapy, and group work

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End-of-Life Decision Making Types of Discussions Advance Care Planning Discussion

• it involves a mentally capable patient: 1. identifying their SUM by preparing a Power of Attorney ( POA). If no POA is chosen , then the

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SDM hierarchy list in the Health Care Consent Act applies 2. discussing one’s values, beliefs, and wishes for future health care, should one become incapable of making health care decisions

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Goals of Care Discussion

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• exploratory discussion where the health care provider and patient discuss the patient 's current

medical issues, their understanding of their illness, and possible treatments and outcomes. May or may not include discussion about code status

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PM6 Palliative Medicine

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Code Status Discussion

• discussion with patient about level of intervention they would want in the event of cardiac or respiratory arrest • full code - patient would like to receive CPU, delibrillation , and life support Do Not Resuscitate ( DNR ) patient would not like to receive CPR or life support, only active medical management comfort measures - patient would not like to receive CPR, life support, or active medical management • Allow Natural Death ( AND) alternative term to DNR . Often a gentler term to help with the

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discussion CPR is rarely effective in the patient with advanced incurable illness DNR order is almost always consistent with palliative goals of care

When to Initiate EOL Care Discussions

• recent hospitalization for serious illness, or during a transition in care • severe progressive medical condition(s) • death expected within 6 12 mo • patient rewritten will and/or spiritual wishes

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• if the patient requests medical assistance in dying ( MAID) Power of Attorney for Personal Care

• see Ethical, Legal, and Organizational Medicine, KLOM 14

Communication • strong communication is critical in all areas of medicine. This is especially true in palliative care, where difficult decisions must be made regarding goals of care, EOL care, and disclosure of

information

• be cognizant of how a patient 's (and their family's) beliefs, values, and wishes may impact their

decision making and /or their emotional response during palliative care conversations • use both verbal and non- verbal means of communicating empathy and caring to build rapport, and help de-escalate the intense emotions that patients may experience including anger, grief, and feeling overwhelmed

Approach to Communicating Bad News SPIKES S - Setting up the interview: create privacy by bringing the patient to a quiet and comfortable environment. Ensure you have enough time to have an extended conversation with the patient. Ask them if they wish for family members or other supports to be present P assess Perception : what does the patient and /or their family understand about their illness at

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present ? Use open ended questions and fill any major gaps to ensure mutual understanding 1 - Invitation : how does the patient wish to hear the information ? How many details do they want? Do they want to first understand the process that led the care team to their diagnosis/ prognosis/ treatment decision, or do they just want to hear the news upfront? K - Knowledge sharing: provide the information based on the preferences expressed in the “invitation" section in small segments using non technical terms E - Emotions: respond to the patient 's/ family 's emotions. Allow them time to process the information . Silence is okay Offer to answer any questions they may have, but also recognize that some patients may wish to discuss further details at a later time S - Strategy and Summary: if the patient and their family are comfortable, summarize the conversation and discuss next steps

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Estimating Life Expectancy

• when asked about prognosis, be wary of being overly specific • use time frames such as hours to days, days to weeks, weeks to many weeks, or months • clinicians consistently overestimate survival when prognosticating

Collaboration v. J

Interprofessional Team

• interprofessional team may include the following members:

physicians: may be primary care providers, or have specialty training in palliative care; they provide medical management and symptom relief nurses: provide patient education in addition to clinical nursing; often with advanced practices in setting of hospice or home care social workers/case managers: facilitate advance care planning conversations and other psychosocial interventions for patients and their families pharmacists: timely provision of medications, assessment of medication plans

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occupational therapists: identify important life roles and activities to patients, and address barriers to performing these activities physiotherapists: optimize patient comfort by maintaining physical function during disease progression

• dieticians: optimize a nutritional plan focused on the patient's needs and wishes

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spiritual care workers: provide spiritual and religious care for persons with life limiting disease

• all members of the palliative care team provide assessment of palliative care needs through the use of

validated tools such as the ESAS and the PPS • palliative care team collaborates through ongoing care conversations with the patient and their family to discuss the patient's condition, course of illness, treatment options, goals, and plan of care

Suffering Definition

• a multidimensional experience of severe distress that diminishes an individual’s ability to find peace in their present situation, with contributions from physical symptoms, psychological distress, existential concerns, and social relational worries

-

Key Points

• suffering can occur at any moment within the palliative context • suffering is subjective and unique to the patient • anguish and despair arc justifiable responses to difficult human situations • patients may suffer not only from illness, but also from treatments • suffering is not confined to physical symptoms • it is impossible to anticipate the source of someone’s suffering Sources of Suffering

• physical concerns impaired activities

• loss of physical independence symptoms (e.g. pain , tiredness, poor sleep, loss of appetite) • social - relational concerns • family distress or dysfunction burden on others • psychological concerns fear or dread of the unknown loss of balance and control difficulty accepting the situation overwhelmed by life circumstances comorbid depression and anxiety • spiritual concerns unfulfilled needs of love, virtue, faith, and/or hope • questioning meaning of life or death anger towards a higher being (as defined by the individual ) viewing illness as punishment • existential concerns loss of dignity

•

desire for death loss of will to live

Options to Relieve Refractory Suffering • palliative sedation therapy: the use of pharmacological agents to reduce consciousness. Only considered in patients who have been diagnosed with advanced progressive illnesses and reserved for treatment of intolerable and refractory symptoms • medical assistance in dying (MAID): in Canada, a specific process that occurs when a mentally competent patient makes a written request to end one’s life. The patient is interviewed by 2 different clinicians, one of which is the MAID provider. A physician or nurse practitioner administers medications that cause a person’s death or the patient is prescribed medications to self-administer that will cause one’s own death there are currently 2 pathways to MAID in Canada; pathway 1 where death is foreseeable and pathway 2 where the patient has a serious and incurable illness, disease, or disability but death is not immediately foreseeable recent changes have also included a waiver of final consent in situations where the individual may lose decision-making capacity before their preferred date of receiving MAID if their natural death is reasonably foreseeable • legislation in Canada continues to be under parliamentary review as new patient groups and circumstances are added » note: currently, patients with mental illness as their main diagnosis are excluded from receiving MAID. However, this will be revisited in the spring of 2023

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Types of Grief

• anticipatory grief - feelings of grief occurring before an impending loss, including being concerned for the dying person , balancing conflicting demands, and preparing for death • acute grief - immediate reaction to the death of a loved one. In the majority of cases, support from

family and friends over time will help the bereaved accept the loss • complicated grief - unanticipated progression of grief, which severely interferes with a person’s ability to function. Characterized by prolonged duration, maladaptive thoughts, dysregulated emotions, and dysfunctional behaviours; depression and anxiety may be prevalent

Self-Care Definition

• proactive, holistic pursuit of personal well - being in tandem with professional responsibility for patient well-being Benefits

• balances compassion for oneself and compassion for others

• translates improvements in professionals' quality of life to improvements in patients’ care

positively predicts competence in coping with death and achieving compassion satisfaction negatively predicts risk of fatigue and burnout • requires and cultivates self-awareness, i.e. the culmination of knowledge of and empathy for oneself • promotes sustainable resilience through the development of coping skills, the balance between professional demands and personal needs, and the commitment to overall well-being Strategies • within the workplace: individual regulation of workload demands and establishment of boundaries, opportunity for team bonding /debriefing, promotion of resources/ supports that can attend to professionals' needs, and development of a culture supportive of and conducive to self care beyond the workplace: a range of health promoting behaviours (e g balanced diet , sleep hygiene, • exercise, meditation, interpersonal fulfillment, spiritual practice )

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Paediatric Palliative Care Unique Considerations for Paediatric Patients

• the unit of care in paediatric palliative care is always the family and the afflicted child. This includes siblings, who are often affected in various ways • ideally should be offered early after diagnosing a potential life-limiting or life-threatening disease and continued through the course of treatment, along with standard /curative care • respite services for families is a key aspect of palliative care for medically complex and technologydependent children • bereavement support to parents and siblings after the death of a child is a standard offering emotional maturity and cognitive abilities vary between children and adults, and are determined by the developmental level of the child rather than their chronological age • unique paediatric life threatening illnesses less than 30% of patients referred to paediatric palliative care teams have cancer; the majority have congenital or acquired neurologic impairment, many of whom are technology dependent unique challenge of dealing with the child , parents, and siblings decision making authority, even in matters related to HOL, depends on the young person's capacity. However, many decisions are family centered, and made with the paediatric patient and the parents together

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Predominant Pediatric Conditions Receiving Palliative Care: 1 Gcnetic/congenital disease ( 40.8%) 2. Neuromuscular disease (39.2%) 3. Cancer (19.8%) 4 Respiratory disease (12.8%) 5.Gastrointestinal disease (10.7%)

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Table 3. Categories of Paediatric Patients Who May Benefit From Palliative Care Category 1

Life-threatening conditions for which curative treatment may be feasible but can fail Palliative care is involved when treatment fails or during acute crisis Palliative care is no longer required upon achieving long-term remission or successful treatment e g.cancer,irreversible organ failure

Category 2

Conditions in which premature death is inevitable Intensive treatment over a long period of time to prolong life and allow normal activities e g cystic fibrosis Ouchenne muscular dystrophy

Category 3

Progressive conditions without curative treatment options Irealmenl is eiclusrvely palliative and can extend over many years e.g Batten disease Irreversible but non progressive conditions causing severe disability e g severe cerebral palsy, multiple disabilities alter brain or spinal cord injury

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Category 4

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Source: Aguide to children's palliative care: supporting babies, children and young people with lite lliniting and life threatening condiUons and their families. Together lor Short lives 2018

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Assessment Tools Symptom Screening in Paediatrics Tool (SSPedi )

• used in children age 8 - 18 yr to assess symptoms over time and the efficacy of interventions

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• symptoms rated on a five point descriptive Likert scale • assesses depression , anxiety, irritability, memory /cognition , changes in appearance, fatigue, mouth sores, headache, pain , tingling / numbness of extremities , N / V, appetite, changes in taste, constipation, and diarrhea Mini- SSPedi

--

• a revised SSPedi geared towards children 1 7 y/o • assesses the same 15 symptoms • uses a three - point , face - based Likert scale • keep in mind the child 's stage of development when interpreting these tools • children 4 5 y /o can describe concrete aspects of their own health introspection develops around ages 6 - 8 y /o

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Memorial Symptom Assessment Scale ( MSAS )

• used in children 7+ y/o • measures frequency, severity, and distress associated with 32 common physical and psychological symptoms • uses a five- point Likert scale • used in both clinical and research settings

Symptom Management • children are often aware of their condition, and open communication with the child in regard to diagnosis and prognosis is encouraged to reduce anxiety and fear child’s stage of development and cognitive abilities should be considered when discussing concepts of illness, treatment decisions, LOL, and dying • symptoms encountered near LOL , and their respective management are similar to that in adult care (see Table 2 , PM4 ) However, the following are unique in paediatric management: • shared decision making involving the child ( to the extent possible or desired ), the parents, and the healthcare providers typically guides treatment and LOL care • symptom management may be over the course of years and therefore may require a transition plan into adult palliative services • play therapy and unstructured play reduces anxiety, depression , and aggression • creating a sense of normality in the child 's life aids in emotional wellbeing ( e.g. seeing friends, attending school, parental discipline ) • the patient 's pain and anxiety often correlate with parental anxiety and quality of life, and therefore managing these symptoms benefits the family unit • siblings should also be offered psychological supports

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Landmark Palliative Medicine Trials Trial Name

Clinical Trial Details

Reference

PALLIATIVE APPROACH TO CARE

Temeletal., 2010

HEJM 2010: 363:733 742

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Title: Early Palliative Care lor Patients with Metastatic Non-Small Cell Lung Cancer Purpose: To examine the effect of introducing early palliative care after diagnosis of metastatic non-small- cell lung cancer on patientreported outcomesand end- of -life care Methods: Patients (n 322) were randomized to receive either an early nurse -led palliative care intervention addressing physical and psychosocial needs in addition to usual oncologic care vs. routine oncology care. Primary outcomes included OoL symptom intensity, and

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mood. Results: Of 151 randomized patients 27 passed away, and 107 ( 86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better OoL, lower depressive symptoms, and longer median survival vs. standard care (11.6 mo vs. 8.9 mo P 0.02). Conclusions:Early palliative care led to significant improvements in both OoL and mood among patients. Despite lesser aggressive EOL care, theintervention group had longer survival.

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HCT01248624

Lancet. 2014 May 17;383(9930):1721 30.

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Title:Randomized Controlled Trial of Early Palliative Care for Patients With Advanced Cancer Purpose: To assess the impacts of early palliative care on patients with advanced cancer. Methods: RCI consisting of 461 patients who had advanced cancer, and a prognosis of 6 -24 mo. Patients were randomized to receive consultation and follow- up by a palliative care team or to receive standard cancer care. The outcomes of interest were quality of life, assessed using Functional Assessment of Chronic Illness Therapy -Spiritual Well-Being (FACTT -Sp) at 3 mo and Oualily of Life at the End of Life ( OUAL- E) scale: symptom severity, assessed using Edmonton Symptom Assessment System (ESAS): and satisfaction with care, assessed using FAMCAREP16. Results: Results show that there was no significant difference in the FACIT -Sp score at the primary endpoint and there was an improvement in quality of life by «2.25 points on the OUAlE -scale within the treatment group compared to the control. There was also a significant difference in satisfaction with the quality ol care by «3.79 points on the FAMCARE -P16 scale within the treatment group compared to the control. There was no significant difference in symptom severity . Conclusions: Although there was no change in quality of life at the primary endpoint, improvements in the OUAL E and f AMC ARE P16 scores are promising and warrant further research

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Clinical Trial Details

Trial Name

Reference

COSMIC

Lancet. 2022:399|10325):656 Title: Effectiveness of a three - step support strategy for relatives of patients dying in the intensive care unit Purpose: Evaluate the effectiveness of a proactive communication and support intervention involving physiciansand nurses at reducing prolonged grief in relatives Methods: RCT consisting of 87 S relatives aged >18 yr who have made a decision lo withdraw or withhold life support Patients were randomiicd to receive standard ol caie support and communication, or a physician driven, nurse aided, three step support strategy The outcome of interest was the proportion of relatives with prolonged grief as indicated by a score > 30 on the Prolonged Oriel Scale (PG -13) 6 mo after the death. Results: A smaller proportion of relatives random iced to receive the involved communication strategy experienced prolonged grief (15%) when compared to the control group (21%). Associated PO -13 scores were also comparatively lower in the group that received the involved communication strategy. Conclusions: A physician- driven, nurse - aided, three - step support strategy is effective at reducing prolonged grief in relatives coping with the loss of a family member.

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JAMA 2009:302:741-749

ENABLE II

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Title: Effects of a Palliative Care Intervention on Clinical Outcomes in Patients with Advanced Cancer: the Project ENABLE II Randomiied Controlled Trial Purpose: To determine the effect of a nursing - led intervention on Ool symptom intensity, mood, and use of resources in patients with advanced cancer. Methods: Patients were randomiced lo receive multi- component intervention vs usual care (n'322). Intervention included telephone based care by advanced palliative care trained nurses, who provide structured educational and problem- solving sessions, to encourage patient activation, sell-management, empowerment andfollow - up at least monthly with every patient.Primary outcomes included OoL symptom intensity, and mood. Intensity of service was measured using days in the hospital and number of ED visits. Results:Longitudinal intention- to - treat analyses for the total sample revealed higher QoL. lower depressed mood, and a trend toward lower symptom intensity. Similar results were seen among patients who passed away, except there was no change in symptom intensity. No differences were noted in the number of days in the hospital. ICU or ED visits. Conclusions: A nurse - led, palliative care - focused intervention addressing physical and psychosocial care along with oncology care improved scores for Ool and mood

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J Clin Oncol 2015 May 1;33(13):1438 - 45

ENABLE III

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Title: Early vs. Delayed Initiation ol Concurrent PalliativcOncology Care Purpose: To determine the impact of early vs. delayed initiation of concurrent palliative oncology care on mood, symptom impact, quality of life, and 1- yrsurvival rale. Methods: RCT consisting of 207 patients with advanced cancer. Patients were randomized to receive in- person palliative care (PC) consultation, structured PC telehealth nurse coaching sessions, and monthly follow - ups upon admission or within 3 mo of admission. The outcomes of interest were quality of life, symptom impact, mood 1- yr survival, hospital/intensive care unit days, emergency room visits,

.

chemotherapy in the last 14 d, and death location. Results: Mood and quality of life were not significantly different between the two groups.1- yr survival rates were greater in the early intervention compared to the delayed intervention.Relative rates of hospital days, ICU days, emergency room visits, and chemotherapy in the last 14 d of life were similar between the two groups Conclusions: Although , self -reported outcomes, and resource use were not significantly different between the Iwo groups, there wasan improvement in 1- yr survival rales

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Back el al. 2007

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Associations between end of - life discussions, patient mental health,medical care near death, and

JAMA Intern. Med. 2007: 167:453 - 460

Title: Efficacy of Communication Skills Training for Giving Bad News and Discussing Transitions to Palliative Care Purpose: To evaluate the efficacy ol a residential communication skills workshop ( Oncotalk ) for medical oncology fellows in changing observable communication behaviours. Methods: A cohort of 115 medical oncology fellows took part in Oncotalk which emphasized skills practice in small groups. The primary outcomes included participant communication skills measured during standardized patientencounters before and after the workshop in giving bad news and discussing transitions to palliative care. Comparisons were made using each participant as his or her own control. Results: Post - workshop encounters showed that participants improved in bad news skills (P*0.001) and transition skills (P'0.001). Conclusions: Oncotalk was a successful teaching model for improving communication skillsfor postgraduate medical trainees.

JAMA . 2008:300( 14):1665 - 73

Title: Impacts of End of life (EOL) discussions Purpose: lodetcrminc whether end of life discussions with a physician will result in less intensive intcrvenlions. Methods: longitudinal cohort study consisting of 332 pairs consisting of a patient with advanced cancer and then caregiver. Pans were followed from admission to death. Outcomes of interest were medicalinterventions including ventilation, resuscitation and hospice in the

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final week oflife. Results: Of the 332 pairs 123 patients received an EOldiscussion. This did not result in higher rates of major depressive disorder. However EOL discussions were associated with earlier admissions to hospice (65.6 % vs. 44.5%) lower rates of ventilation (1.6% vs.11%), resuscitation (0.8% vs. 6.7%) and ICU admission (4.1% vs.12.4%). Conclusions: EOL discussions result in less aggressive medical care and earlier hospice admission.

caregiver bereavement adjustment

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PATIENT ASSESSMENT

.

Naylor el al. 1999

JAMA 1999:281:613 - 620

Title: Comprehensive Discharge Planning and HomeFollow - up of Hospitalized Elders: A Randomized Clinical Trial Purpose: To examine effectiveness of advanced practice nurse - centered discharge planning and home follow - up intervention for ciders at risk for hospital readmissions Methods: Patients aged > 64 yr were randomized to receive comprehensive discharge planning and home follow -up vs.routine discharge. Primary outcome was time to first readmission. Results: Intervention group had longer time to first readmission, fewer multiple readmissions, fewer hospital days per patient, and lower healthcare costs. Control group patients were more likely than intervention group patients to be readmitted at least once. Ho significant differences were noted in postdischarge acute care visits, functional status, depression, or patient satisfaction. Conclusions: Intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalizalion while reducing costs

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Summary Review Papei: Crit Care Nuts Clin North Am. 2015 Sep:27|3):315 -39

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Chrlslakis et al.. 2000

BMJ 2000:320:469

Title: Extent and Determinants ol Error In Doctors ' Prognoses in Terminally III Patients: Prospective Cohort Study Purpose: Todescribe doctors' prognostic accuracy in terminally ill patients and loevaluate the determinants ol that accuracy. Methods: Prospective cohort study involving 343 doctors who provided survival estimates for 468 terminally ill patients at the time of hospice referral. Main outcome measures were the estimated and actual survival of patients. Results:Median survival was 24 d. Only 20% ( 92/468) ol predictions were accurate (within 33% of actual survival); 63% (295 /468) were overly optimisticand 17% (81/468) were overly pessimistic.Overall, doctors overestimated survival by a factor of 5.3. Conclusions: Doctors are systematically optimistic in estimating prognosis for terminally ill patients. This phenomenon may adversely affect the quality of care given to patients near the EOL.

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References .

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Abdulla A Adams N Bone M, el al Guidance on the management of pain in older people. Age and Aging 2013:42:1-57. AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons J Am Geriatr Soc 2002:50(Suppl6):S 205-S224. Anderson F Downing GM, Hill J et al Palliative performance scale (PPS): a new tool J Palliat Care 1996:12|1):5-11. Arbuckle R, Abetz - Webbl "Not just little adults": gualitative methods to support the development of pediatric patient-reported outcomes. Pabent 20 t3:6 3):143-159. Association for Children's Palliative Cate ( ACT),'Royal College of Paediatrics and Child Health (RCPCH) In: a guide to the development chidren's palliative care services:report of the join working party. ACT RCPCH: Bristol UK 1997 Bacon C. The Palliative Approach: Improving Care for Canadians with Life-limiting Illnesses. The Way Forward. Government of Canada 2019. Baile WF, Buckman R Lenci R et al. SPIKES-a sin-step protocol for delivering bad news: application to the patient with cancer.Oncologist 2000:5:302. Bates AT. Addressing existential suffering. BCMJ 2016:58|5):268 - 273. BC guidelines Palliative Care for the Patient with Incurable Cancer or Advanced Disease Part 1: Approach to Care [Internet] [updated 2017:cited 2019 Aug 19], Available from https: www2.gov.bc.ca'assets gov health/practitioner -pro/bc-guideIines7palliafive1.pdf. Berry M. Brink E Harris J.et al. Supporting relatives and carers at the endof a patient's life BMJ 2017:356. Bluebond- langner M. Brook L Craft A et al. A guide to children's palliative care: supporting babies, children and young people with Irle-limitrng and life- threateningconditions and their families. Together for Short Lives 2018Boucher S Downing J Shemilt R The role of play in children's palliative care.Children 2014:1:302-317 Bruera E, Kuehn N.Miller MJ, etal. The Edmonton Symptom Assessment System (ESAS): A simple method for the assessment palliative care patients.J Palliat Care 1991:7.-6-9. Buccheri G.Ferrigno D. Tamburini M. Karnofsky and EC 0G performance status scoring in lung cancer: a prospective, longitudinal study of 536 pabents from a single institution. Eur J Cancer 1996:32(7):1135-1141. CareSearch. Dignity Conserving Care [ Internet! [updated 2019 Oct 21: cited 2019 Aug 19[.Available from:https://www.caresearch.com.au/caresearchitabidi600 DefaulLasp>. Chpca.net. Let's Talk About Hospice Palliative Care First [Internet][updated 2019 Dec:cited 2020 Jun 30] Available from: https:/,' www.chpca.ca, wp-content /upioads' 201912/euthanasia one page stats.pdf. ‘ Clary P Lawson P. Pharmacological Pearls for End - of- Life Care. Am Fam Physician 2009:79(12):1059 1065. ” “ seriously systemabereviewand analysis Downar J, Goldman R Pinto R. et al.The surprise question for predicting death in meta .CMAJ 2017:189:E484 -E493. ill patients:a Dupuis LL.Johnston DL. Baggott C, et al. Validation of the Symptom Screening in Pediatncs Tool in children receiving cancer (realmentsJ Natl Cancer Inst 2018:110|6):661-668. Feudtner C, KangTI Hexem KR et al.Pediatric palliative care patients:a prospective multicenter cohort study. Pediatrics 2011:127( 6|:1094-1101. Granek L, Buchman S. Improving physician well-being: lessons from palliative care. CMAJ 2019:191(14):E380-E381. Hanks G, Cherny HI, Christakis NA et al.Oxford Textbook of Palliative Medicine 4th. Oxford University Press:1551. Health Canada.Framework on Palliative Care in Canada. Government of Canada 2019. Kearney MK,Weininger RB, Vachon MLS, et al. Self -care of physicians caring for pabents at the end of life.JAMA 2009;301|11):11S5-1164. KittelsonSM, Elie MC Pennypacker L. Palliative Care Symptom Management.Crit Care Nurs Clin North Am. 2015 Sep;27(3):31S-39. Knowles S. Symptom management in palliative care.On Continuing Practice 1993:20:20-25. Lindsay J Dooley M. Marbn J. et al. Reducing potentially inappropriate medications in palliative cancer patients: evidence to support depresenbrng approaches.Supportive Care in Cancer 2014:22(41:11131119. MacLeod R, van den 8lock L (editors).Textbook of Palliative Care.Cham:Springer 2018.1-16. Mahoney FI Barthel DW.Functional evaluation: the Barthel Index: a simple index of independence useful in scoring improvement in the rehabilitation of the chronically ill Maryland State Med J 1965:14:61 65 Mi lls J Wand T. Fraser JA. Exploring the meaning and pracbce of self -care among palliative care nursesand doctors: a qualitative study. BMC Palliat Care 2018:17:63. Medical cate of the dying 4 th ed.Victoria: Victoria Hospice Society 2006. 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Sanchez-Reilly S, Morrison LJ, Carey E, et al. Caring for oneself to care for others: physicians and their self - care.J Support Oncol 2013:11(20):75-81. Sanso N. Galiana L Olivet A. et al. Palliative care professionals' inner life: exploring the relationships among awareness, self- care, and compassion satisfaction and fabgue. burnout, and coping with death.J Pam Symptom Manag 2015;50 [2|:200-207. Singer PA, Marlin DK,Kelner M. Ouality end-of -life care:Patients' perspectives. JAMA 1999;281(2):163-168. Slocum -Gori S Hemsworth D Chan W \V. et al.Understanding compassion satisfacbon compassion fatigue, and burnout a survey of the hospice palliative care workforce. Pal hat Med 2013:27(21:172-178. Sorensen JB, Klee M, Palshof T, etal. Performance status assessment in cancer patients.An inter-observer variability study. 8rJCancer 1993:67|4):773-775. Sourkes B Frankel L,Brown M et al.Food, toys, andlove:pediatric palliative care. Curr ProblPediatrAdolesc Health Care 2005:35(9|:350-386. 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Toronto (ON):Cancer Care Ontario; 2016. Weaver MS, Heinze KE, Kelly KP et al. Palliative care asa standard of care in pediatric oncology.Pediatr Blood Cancer 2015:62(Suppl 5):S829-S 833. World Health Organization. Cancer: WHO Definition of Palliative Care [Internet], World Health Organization: [cited 2019 Aug 20], Available from: https:/ ,’www.who.mt' cancer.’ palliabve definition al!_ World Health Organization. Cancer: WHO's cancer pain ladder for adults [Internet], World Health Organization: [cited 2020 Jun 30].Available from: http: ,vww.woo. nl cancer 'palliative pa n adder err. Yennurajalingam S,Bruera E. Oxford AmericanHandbook of Hospice and Palliative Medicine and Supportive Care.2nd ed. New York:Oxford University Press:2016.510 p.

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20 mm trunk, >6 mm face, hands, and teet) poorly defined borders, recurrent lesion,poor ditterenUation and type ol lesion (e.g. sclerosing, morphealorm)

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Table 4. Surgical Margins for Squamous Cell Carcinoma Type of Lesion

Surgical Margins

Low - Risk

4 mm

High- Risk'

6 mm

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’High risk features include: immunosuppressed patient depth >6 mm, ear /lip, non sun exposed sites, poorly defined borders, recurrent lesion, poor differentiation, and histologic features (acantholytic. spindle, desmoplastic, perineural invasion)

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PL6 Plastic Surgery Table 5. Surgical Margins for Malignant Melanoma Depth o( Lesion'

Surgical Margins

In ulu

5 mm

20 mm

'Determined via excisional biopsy "With or without ulceration

Basic Surgical Techniques Sutures and Suturing ANESTHESIA

• irrigate before injecting anesthetic, followed by debridement and more vigorous irrigation Table 6 . Toxic Limit and Ouration of Action (1 cc of 1% solution contains 10 mg lidocaine) Without Epinephrine With Epinephrine ( vasoconstrictor, limits bleeding ) lidocaine ( XylocaineT

5 mg / kg,lasts 45 60 min

7 mgfkg, lasts 2 6 h

Bupivicaino (Marcainc )

2 mg / kg. lasts 2 - 4 h

3 mg/ kg, lasts 3 -7 h

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* Lidocaine toxicity symptoms include: circumoral numbness, light headedness, and drowsiness followed by tremors and seizures. Cardiac and

respiratory signs are late findings

Traumatic tattoos are permanent discolourations resulting (tom new skin growth over foreign material or dirt left behind in the dermis. Copious Irrigation and debridement should be done A SAP in order to prevent traumatic tattoos, as they are very difficult to treat later

• e.g. when using 1% lidocaine without epinephrine in a 70 kg patient: 1% = lg/ 100 cc = 1000 mg / 100 cc = 10 mg /cc toxic limit = 5 mg / kg x 70 kg = 350 mg max bolus injection = 350 mg * 10 mg/cc = 35 cc ( may add more after 30 min ) IRRIGATION AND DEBRIDEMENT • irrigate copiously with a physiologic solution such as RL or NS to remove surface clots, foreign material , and bacteria • debride all obviously devitalized tissue; irregular or jagged wounds must be excised to produce sharp wound edges that will assist healing when approximated • there is high - risk of infection for any wound closed primarily after 8 h

Sirnplo Interrupted

SUTURES

• use of a particular suture material is dependent on surgeon preference; however , skin should be closed with a non absorbable, monofilament suture material when traumatic mechanisms are involved to prevent harboring bacteria in suture material

-

Sub - culicular

Table 7. Suture Materials: Absorbable vs. Non- absorbable and Monofilament vs. Multifilament Suture Materials

Uses

Examples

Absorbable

Deep sutures undershort - term tension Skin closure in children

Plain gut - Vicryl ' Polysorb - , Biosyn Monocryl®, Caprosyn chromic gut, fast absorbing gut

Non- Absorbable

Skin closure Sites of long-term tension

Nylon, polypropylene (Prolene ;), Lower likelihood of wound dehiscence, stainless steel, silk Ticron ®, more difficult to tie, makes track marks Ethibond -

Monofilament

Multililamonl

Everyday use and optimal for contaminated and infected wounds (lower likelihood of bacterial trapping in suture material) Used to close deep layers, such as in traumatic degloving injuries

-.

.

Notes

.

loses at least 50% of their strength in 4 wk: eventually absorbed

.

.

.

Monosofr Monocryl - Biosyn - , 1

Prolene 1

Vicryl ' and silk, Ticron , Ethibond ' -

Horizontal Mattress

Slides through tissue with less friction: more memory/stiffness: more difficult to tie; requires multiple throws (lower knot security)

less memory/ stiffness, thus easier to work with (higher knot security): greater infection risk

Verticil Miittross

BASIC SUTURING TECHNIQUES

Basic Suture Methods

c.

• simple interrupted: can be used in almost all situations • sub- cuticular: good cosmetic result but weak , used in combination with deep sutures; not used in

j

trauma Deep Dermal

+

Figure 11. Basic suture methods

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PL7 Plastic Surgery • vertical / horizontal mattress: for areas difficult to evert (e.g. volar hand ) •continuous over and over ( i .e. “ running," “ baseball stitch"): time -saving , good for hemostasis •deep/ buried dermal: simple interrupted sutures placed in dermal layer, reduces skin tension for improved healing and are the only sutures that close the wound

Toronto Notes 2023

Steps to Ensuring an Optimized Scar • Incisions should be made along

resting skin tension lines

Other Skin Closure Materials • tapes: (e.g. steri-strips ) may be indicated for superficial wounds and those with opposable edges; tape

• Attain close apposition of wound

marks and can be used as the primary closing material or as additional reinforcement after primary surface sutures have been removed •skin adhesives: ( e.g. 2-octyl cyanoacrylate , Dermabond*) works well on small areas without much tension or shearing; may cause irreversible tattooing •staples: steel-titanium alloys that incite minimal tissue reaction (healing is comparable to wounds closed by suture)

• Evert wound edges • Use a ppropriately sized suture for skin closure (5-0 on face: 3-0.4-0

Excision • plan your incision along relaxed skin tension lines to minimize appearance of scar • use elliptical incision to prevent standing cone deformity ( heaped up skin at end of incision ), so the length of the ellipse should be approximately 3x the width . if needed, undermine skin edges ( separate skin from underlying fascia to allow wound edge manipulation and decrease tension ) • use layered closure including deep dermal sutures ( decreases tension )

Skin Biopsy Types and Techniques SHAVE BIOPSY • used for superficial lesions where sampling of the full thickness of the dermis is not necessary or

edges

• Minimize tension on skin by closing in layers

elsewhere)

• Ensure equal width and depth of

tissue on both sides • Remove sutures within 5 7 d from the face, 10-14 d from scalplotsof extremities

-

Relaxed Skin Tension Lines Natural skin/wrinkle lines with minimal linear tension. Placing incisions parallel to resting skin tension lines minimizes widening/hypertrophy and helps to camouflage scars. Rrlaxed skin tension lines are usually parallel to any existing wrinkle lines and perpendicular to the orientation of underlying muscle fibres (perpendicular to lines of maximum extensibility)

practical • most suitable lesions for shave biopsies are benign lesions either elevated above the skin or have pathology confined to the epidermis (e.g. seborrheic or actinic keratoses, skin tags, and warts ) • high-risk of recurrence with shave biopsy for any lesions, including actinic or seborrheic keratoses • rapid, requires little training, and does not require sutures for closure (caution in patients on anticoagulant treatment) • heals by secondary intent ( moist dressings should be used ) • should not be used for pigmented lesions - an unsuspected melanoma cannot be properly staged if

partially removed NEEDLE BIOPSY

• 21 G for lymph node biopsy • Trucut * needle biopsy for breast masses suspected for carcinoma «

needle biopsy has fallen out of favour for lymph node biopsies; excisional biopsy is the preferred method in this circumstance

INCISIONAL BIOPSY

Figure 12. Incision of lesions along relaxed skin tension lines

• can be a punch biopsy, oran ellipse within the lesion ( normal tissue must be included in biopsy ) • gives pathologists a portion of the lesion and the border with normal skin • punch biopsies involve the removal of a full thickness core of tissue to allow sampling of the epidermis, dermis, fat, and potentially muscle depending on the area; performed with a round, disposable circular cutting surface on a plastic handle ranging in diameter from 2-10 mm • punch biopsy wounds can be closed with suture or left to heal by secondary' intention EXCISIONAL BIOPSY • performed for lesions that require complete removal for diagnostic purposes • performed for lesions that cannot be adequately punch biopsied due to depth of lesion below surface • for small pigmented lesions and atypical moles; if concerned about melanoma, can do a narrow

margin excision for diagnosis and treatment (depending on depth in the case of melanoma ) • best for small lesions that are easily removed and primarily closed

• requires the greatest amount of expertise and time • always requires sutures for closure TECHNIQUE

General

• all shave and punch biopsies performed in clinic are done using aseptic technique, but are not sterile • sterile gloves are indicated for biopsies and excisions in all patients

+

Preparing the Site • common skin antiseptics ( Betadine’, chlorhexidine) can be used to prepare the biopsy site

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PL8 Plastic Surgery

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• chlorhexidine is used in concentrations ranging from 0.5--!%. It is not typically used on the face, as it could get into the eyes or ears and may burn or cause damage. Most chlorhexidine preps also contain alcohol, which can be flammable, so allow to dry before the biopsy and certainly before using any cautery • Betadine* (7.5% povidone-iodine ) is safer for the head and neck (as to avoid the above problems with chlorhexidine) and around the eyes and ears. It is also used in "contaminated' areas such as the feet and groin • mark the intended lesion and surgical margins with a surgical marker as the first step, since they may be temporarily obliterated following injection of the anesthetic • for all biopsies, a sterile drape technique is indicated. Sterile towels are placed around the biopsy site after the area is cleansed and anesthetized Anesthesia • most commonly used local anesthetic is 1% or 2% lidocaine ( with epinephrine) • small amounts of epinephrine are added to constrict blood vessels, decrease bleeding, prolong anesthesia , and limit lidocaine toxicity. 'Ihe local with epinephrine can be injected directly into the lesion • local anesthetics with epinephrine may be used anywhere in the body, including the digits

s

Wounds • wound: disruption of the normal anatomical relationships of tissue as a result of injury

Types of Wounds laceration: sharply cut tissue • abrasion: superficial skin layer is removed, variable depth • contusion: injury caused by forceful blow to the skin and soft tissue; entire outer layer of skin intact,

yet injured

• avulsion: skin and soft tissue forcefully separated from deeper structures, potentially compromising blood supply or resulting in full detachment (amputation ) • puncture wounds: cutaneous opening relatively small as compared with depth (e.g. needle), including bite wounds • crush injuries: caused by compression • burns: thermal, chemical, electrical • ulcers: an open wound that develops on skin as a result of injury, poor circulation , or pressure

Principles of Wound Healing Table 8. Factors Influencing Wound Healing Local

General

Mechanical (local trauma, significant crush, avulsion, tension)

Age (affects healing rate)

Stood supply (ischemia/circulation )

lutrition

Technique and suture materials

Tobacco smoking

Retained foreign body

Alcohol consumption

Infection Venous HTN

Chronic loess (eg. Oil cancer, dyslipidemia renal failure, stroke)

RVD

Tissue irradiation

.

.

Immunosuppression (steroids, chemotherapy)

Senetic predisposition to abnormal healing (e.g. hypertrophic or keloid scarring, collagen vascular disease)

Skin type

STAGES OF WOUND HEALING

• growth factors released by tissues play an important role • scar is mature once it has completed the final stage, usually after 1 -2 yr

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PL9 Plastic Surgery

Toronto Notes 2023

I

PHASE

[

PROCESS

1. Inflammatory Phase (Reactive ) ( Days 1-6) • Limits damage, prevents further injury • Debris and organisms cleared via inflammatory response: •Neutrophils (24 46 h ) •Macrophages: critical to wound healing by orchestrating growth factors for collagen production ( 48 96 h ) •Lymphocytes: role poorly defined (5 7 d )

1. Hemostasis vasoconstriction + platelet plug 2. Chemotaxis migration of macrophages and PMN

2. Proliferative Phase ( Regenerative ) ( Oay 4 - Week 3 ) • Fibroblasts attracted and activated by macrophage growth factors • Reparative process: re epithetialization matrix synthesis, angiogenesis ( relieves ischemia ) • Tensile strength begins to increase at 4 5 d

1. Collagen synthesis ( mainly type III ) 2. Angiogenesis 3. Epithehaluation

-

-

-

-

-

.

-

3 Remodeling Phase ( Maturation) ( Week 3- Year 1) • Increasing collagen organization and stronger crosslinks • Type I collagen replaces Type III until normal 4:1 ratio achieved • Peak tensile strength at 60 d -80% of pre-injury strength

1. Contraction

2. Scarring 3. Remodeling of scar

Figure 13. Stages of wound healing

TYPES OF WOUND HEALING

Primary (1°) Healing (First Intention) • definition: wound closure by direct approximation of edges within hours of wound creation ( i.e. with sutures, staples, skin graft, etc.) • indication: recent (6-8 h, longer with facial wounds ) wounds • contraindications: animal / human bites, crush injuries, infection, long time lapse since injury' ( >6-8 h ), retained foreign body Secondary ( 2°) Healing/Spontaneous Healing (Second Intention) • definition: wound left open to heal spontaneously (epithelialization occurs at 1 mm/d from wound margins in concentric pattern, contraction (myofibroblasts), and granulation )- maintained in inflammatory phase until wound closed; requires dressing changes • indication: when 1° closure not possible or indicated ( see Primary Healing )

Myofibroblasts are the cells responsible for wound contraction

Tertiary (3 °) Healing /Delayed Primary Healing (Third Intention) • definition: intentionally interrupt healing process ( e.g. with packing, sharp debridement), then wound can be closed primarily at 4 -10 d post-injury after granulation tissue has formed and there is < 105 bacteria/g of tissue • indication: contaminated ( high bacterial count ), long time lapse since initial injury, severe crush component with significant tissue devitalization, closure of fasciotomv wounds

• prolongation of inflammatory phase decreases bacterial count and lessens chance of infection after closure ABNORMAL HEALING

Hypertrophic Scar definition: scar remains within boundaries of original scar red , raised, widened , frequently pruritic common sites: back, shoulder, sternum treatment: scar massage, pressure garments, silicone gel sheeting, corticosteroid injection, surgical excision if other options fail ( however, may still recur)

• • • •

Keloid Scar

• definition: scar grows outside boundaries of original scar • red , raised, widened , frequently pruritic • caused by: • genetic factors ( highest rates in Black, and Asian individuals) • excess tension on wound or delayed closure ( as in burn wounds ) • common sites: central chest, back, shoulders, deltoid, ear, angle of mandible • treatment: multimodal therapy including: pressure garments, silicone gel sheeting, corticosteroid injection, fractional carbon dioxide ablative laser, surgical excision if radiation to be performed within the next 48 hours ( however, this is typically very unsuccessful and there is often recurrence)

LJ

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PL10 Plastic Surgery

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Spread Scar

• characterized by having exactly the same order of collagen fibres as normal scars • clinically, a typical spread scar is flat , wide, and often depressed • treatment: surgical excision and closure Chronic Wound • wound fails to achieve primary wound healing within 4-6 wk • common chronic wounds include: diabetic, pressure, and venous stasis ulcers • treatment: need to address underlying cause of chronicity (i.e. infection, ischemia, metabolic conditions, immunosuppression, radiation) • Marjolin’s ulcer: squamous cell carcinoma arising in a chronic wound secondary to genetic changes caused by chronic inflammation. All chronic wounds should be biopsied to rule out Marjolin’s ulcer

Infected Wounds Definitions

• the presence of bacteria within a wound may be divided into 4 categories: contamination: the presence of non - replicating microorganisms within a wound

colonization: the presence of replicating microorganisms within a wound critical colonization: increasing bacterial burden; have delayed healing infection: the presence of >105 microorganisms in a wound without intact epithelium or small amounts of a very virulent organism (e.g. GBS); have delayed healing and exhibit classic signs of infection signs of infection: redness, swelling, pain, clinically unwell

Management of Acute Contaminated Wounds ( 8 h, severely contaminated, immunocompromised, involvement of deeper structures (e.g. joints, fractures) use systemic antibiotics if wound cultures are positive and there are signs of infection; tailor

Risk Factors for Infection

• Virulence of the infecting microorganism

• Amount of bacteria present

• Host resistance

• Immunocompromised host

Wound Exudate Characteristics

• Serous drainage (plasma): thin: dear or light yellowish

• Sanguineous drainage (fresh blood):

.

bright red Serosanguincous drainage ( mix ol blood and serous fluid): thin and watery: pale red to pink • Purulent drainage (infection ): thick and opaque; white, yellow, or pale

green

antibiotics as cultures return Management of Late Contaminated Wounds (>24 h)

• tetanus prophylaxis • irrigation and debridement • systemic antibiotics if there are clinical signs of infection

• closure: final closure via secondary intention ( most common ), delayed wound closure (3° closure), skin graft , or flap

Table 9. Risks for Tetanus Infection

-

-

Wound Characteristics

Tetanus Prone

Time Since Injury Depth of Injury

>

>1 cm

10 years of ago if using BaostrixTMwho have never received Tdap Td is preferred to tetanus toxoid (TTI for persons 7 9 years of age, or >65 years of ago if only Adacol M,is available, or those who have recurved a Tdap previously. If TT is administered, an adsorbed TT product is preferred to fluid TT fall OTaP/DTP/T dap 0T/Td products contain adsorbed tetanus loxoidl 'Give TIC 250 UIM for all ogos It can and should bo given simultaneously with the tetanus containing vaccine for infants No vaccine or TIG is recommended for infants 50 yr, peripheral vascular disease, and malnutrition Clinical Features

• pain out of proportion to clinical findings and beyond border of erythema • edema, tenderness, ± crepitus (subcutaneous gas from anaerobes), ± sepsis-type symptoms (e.g. nausea, fever, diarrhea, dizziness, malaise) • overlying skin changes including blistering and ecchymoses • patients may look deceptively well at first, but have some physiological abnormalities on initial labs and may rapidly become very sick/ toxic • late findings: skin turns dusky blue and black (secondary to thrombosis and necrosis) induration, formation of bullae cutaneous gangrene, subcutaneous emphysema Investigations

• a clinical diagnosis • CT scan only if suspect it is not necrotizing fasciitis ( looking for abscess, gas collection, myonecrosis and possible source of infection) elevated CK: usually means myonecrosis ( late sign ) severely • • bedside incision, exploration , and incisional biopsy when ruling out conditions, clinical feature is not supportive, or difficult exam • during incisional biopsy, often see "dishwater pus" (GAS ) and a hemostat easily passed along fascial plane ( fascial biopsy to rule out in equivocal situations )

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PLI 7 Plastic Surgery

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Treatment • vigorous resuscitation ( ABCs)

• urgent surgical debridement: remove all necrotic tissue, copious irrigation with plans for repeat surgery in 24 48 h • IV antibiotics: as appropriate for clinical scenario; consider penicillin 4 million 1 U IV q 4 h and clindamycin 900 mg IV q6 h until final cultures available ( the combination can be synergistic if GAS) or vancomycin and clindamycin • postoperative ICC admission and infectious disease consult after urgent surgical debridement by

-

plastic surgery

IV I®

Ulcers

,

Lower Limb Ulcers Traumatic Ulcers (Acute) • failure of wound to heal, usually due to compromised blood supply and unstable scar, secondary to pressure or bacterial colonization / infection

• usually over bony prominence ± edema ± pigmentation changes ± pain

• treatment , in consultation with vascular surgery

any debridement of ulcer and compromised tissues must be preceded by ABIs and vascular Doppler ulcers or compromised tissues left to heal by secondary intention with dressings may need reconstruction with local or distant flap in select cases; vascular status of limb must be assessed clinically and via vascular studies ( i.e. AB1, duplex Doppler ) Table 14 . Venous vs. Arterial vs . Diabetic Ulcers Characteristic

Venous (70% of vascular ulcers)

Arterial

Diabetic

Cause

Valvular incompetence Venous HTN

2* to small and /or large vessel disease ( be aware of risk factors)

Peripheral neuropathy:decreased sensation Atherosclerosis: microvascular disease

Dependent edema , trauma Rapid onset t thrombophlebitis,

Arteriosclerosis, claudication Usually > 45 yr Slow progression

History

varicosities

DM Peripheral neuropathy Irauma / prcssure

Medial malleolus (‘Gaiter' locations) Vellow exudates Granulation tissue Varicose veins Brown discolouration of surrounding skin

Distal locations (e.g. lower limb, feel )

Pressure point distribution ( more likely metatarsal heads)

Pale/white, necrotic base t dry eschar covering

Necrotic base

Wound Margins

Irregular

Even ( "punched out")

Irregular or "punched out " or deep

Deep

Superficial / deep

Common Distribution Appearance

.

In patients with DM ABI can be falsely normal due to incompressible arteries secondary to plaques/calcification

Depth

Superficial

Surrounding Skin

Venous stasis discolouration ( brown ) Thin, shiny, dry skin; hairless, cool

Pulses

Normal distal pulses

Decreased or no distal pulses

Decreased pulses likely ( lake caution in calcified vessels)

Vascular Exam

ABI '0.9 Doppler : abnormal venous system

ABI « 0.9 Pallor on elevation , rubor on dependency

ABI is inaccurately high (due to PVD ) Usually associated with arterial disease ( microvascular /

Moderately painful Increased with leg dependency, decreased with elevation No rest pain

Extremely painful Decreased with dependency, increased with leg elevation and exercise ( claudication) Rest pain

Thin, dry skin ± hyperkeratotic border Hypersensitive/ ischemic

Delayed venous filling

macrovascular disease)

Pain

Treatment

.

Rest , leg elevation Rest , no elevalion no compression Compression at 30 mmHg ( stockings Moist wound dressing • topical and /or systemic antibiotics if infected or elastic bandages) ( Ensure ABI is safe for compression ) Modify risk factors (smoking , diet, exercise etc.) Moist wound dressings

.

t

topical, systemic antibiotics if

infected wound dressings

Vascular surgical consultation ( angioplasty

or bypass) Treat underlying conditions ( DM . proximal arterial occlusion , etc.)

Painless (if neuropathy ) No claudication or rest pain Associated paresthesia anesthesia

.

Control DM Carelul wound care Fool care Orthotics, off loading Early intervention for infections ( topical and /or systemic antibiotics if infected )

r

T

LJ

Vascular surgical consultation

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PL1S Plastic Surgery

Toronto Notes 2023

Pressure Ulcers Common Sites • over bony prominences; 95% on lower body

Stages of Development

1. hyperemia: disappears 1 h after pressure removed 2. ischemia: follows 2-6 h of pressure 3. necrosis: follows >6 h of pressure 4. ulcer: necrotic area breaks down

Classification (National Pressure Ulcer Advisory Panel 2014) • Stage I : non blanchable erythema present > l h after pressure relief, skin intact • Stage II: partial - thickness skin loss • Stage 111: full - thickness skin loss into subcutaneous tissue • Stage IV: full- thickness skin loss into muscle, bone, tendon, or joint if an eschar is present, must fully debride before staging possible • Stage X: unstageable

-

Prevention • clean and dry skin, frequently reposition, special beds or pressure relief surface, proper nutrition , activity, early identification of individuals at risk ( e.g. immobility, incontinence, paraplegia ,

immunocompromised , DM , etc.), treatment of underlying medical conditions

Treatment

• treatment plan individualized to patient • 4 main principles: preventative measures ( pressure relief, assess for pressure points e.g. wheelchairs; manage continence issues, divert contaminants e.g. urine and feces, ensure appropriate nutrition ) • treatment of underlying medical issues including nutrition • moisture reduction and pressure relief

A Nutritional formal!( niiched with Arginine, tint , and Antioiidantsfor the Healing ol Pressure Ukers: ARandomired Trial Ann Intern Med 2015:162(3|:167-174 Purpose: to deter - - e whether supplementation with arginine, nut. and antioidants within a high-calorie, high-protein formula improves pressure ulcer healing. Methods: 200 adrift patients from long -term care and home care serties with stage II. Ill , aid IV pressure ulcers received either an energy -dense, protein - rich oral formula enriched with arginine, line, and antioedantsoran egualrolumeol an isocaloric isonitrogenousfocmnlaforSwk. Results: Supplementation with ' he enriched firinula resulted nr a greater reduction in pressure ulcer area . A more Ireguenl reduction in area ol < 0 % oi greater at 8 wk was also seen. Conclusion : ( mong malnourished patients with pressure ulcers.8 wk of supplementation with an oral nutritional formula ennehed with arginine, zinc, and antioxidants imprests pressure ulcer healing.

.

.

wound bed preparation and treatment • systemic antibiotics for infections

• assess for possible reconstruction

Complications

• cellulitis, osteomyelitis, sepsis, gangrene

Burns Burn Injuries Causal Conditions thermal ( flame contact, scald ) • chemical • radiation ( U V, medical / therapeutic ) • electrical •

Epidermis

Dermis:

( Nerves Vessels

Most Common Etiologies

• children: scald burns • adults: Ha me burns

Zone ol hyperemia F7T71 Zone of stasis

Table 15. Skin Function and Burn Injury Skin Function

Consequence of Burn Injury

Thermoregulation

Prone to lose body heat

Loss ot large amounts of water and protein from the skin and other body tissues Mechanical Barrier to Bacterial Invasion and High risk of infection Immunological Organ

Control of Fluid loss

-

Intervention Required

Must keep patient covered and warm Adequate fluid resuscitation is imperative

Antimicrobial dressings (systemic antibiotics if signs of specific infection present )

H Zone of coagulation

£

iI

—

"

^

Blood vessels and most nerves are found in the dermis © Figure 18. Zones of thermal injury ri

Tetanus prophylaxis if not already administered

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PL19 Plastic Surgery

Toronto Notes 2023

Pathophysiology of Burn Wounds • amount of tissue destruction is based on temperature, time of exposure, and specific heat of the causative agent

• zone of hyperemia: vasodilation from inflammation; entirely viable, cells recover within 7 d; contributes to systemic consequences seen with major burns • zone of stasis (edema ): decreased perfusion; microvascular sludging and thrombosis of vessels results in progressive tissue necrosis -> cellular death in 24- 48 h without proper treatment • factors favouring cell survival: moist, aseptic environment, rich blood supply zone where appropriate early intervention has most profound effect in minimizing injury • zone of coagulation ( ischemia ): no blood flow to tissue -» irreversible cell damage -> cellular death/ necrosis

Diagnosis and Prognosis

Prognosis best determined by bum size (TBSA), age of patient, presence/ absence of inhalation injury

• burn size % of TBSA burned: rule of 9s for 2" and 3° burns only (children < 10 yr use Lund Browder chart ) • for patchy burns, surface area covered by patient 's palm ( fingers adducted ) represents approximately 1% of TBSA • age: more complications if < 3 yr or >60 yr • depth: difficult to assess initially history of ctiologic agent and time of exposure helpful (see Table 15 , PL 18 ) • location : face and neck, hands, feet, perineum arc critical areas requiring special care of a burn unit (see Indicationsfor Transfer to Burn Centre, PL 20) • inhalation injury: can severely compromise respiratory system , affect fluid requirement estimation ( underestimate), mortality secondary to ARDS • associated injuries (e.g. fractures) • comorbid factors can exacerbate extent of injury (e.g. concurrent disability, alcoholism , seizure disorders, chronic renal failure, other trauma )

-

Circumferential burns can restrict

respiratory excursion and/or blood flow

-

Anterior

Posterior

4 .'

to octremities and require cscharotomy

TBSA does not include areas with 1" bums

'

4.

1

/ \ 18%

4m

yv

18%

-4m

-

416%

4W%

9%

Figure 19. Rule of 9s for TBSA

I

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PL20 Plastic Surgery

Toronto Notes 2023

O CSJ

5

Area Age 0 Age 1 Age 5 Age 10 Age 15 Adult A = Vi head area 9 V48 V46 V45 V4454354 B = 14 thigh area 2 543 Vi 4 Vi 454454434 C = 54 leg area 25425433354354

1

.

1e

Figure 20. Lund - Browder diagram

Table 16. Burn Depth (1st, 2 nd , 3rd degree) Nomenclature

Traditional Nomendature

Depth

Clinical Features

Erythema /Superficial

First degree

Epidermis

Painful, sensation intact, erythema blanchable

-

Second degree

Into superficial

Deep Partial Thickness

Second degree

Into deep ( reticular ) dermis

Painful sensation intact erythema, blisters with clear fluid, blanchable. hair follicles present Insensate, difficult to distinguish from full thickness, does not blanch , some hair folliclesstill attached, softer than full thickness burn

Full Thickness

Third degree

Through epidermis and dermis Injury to underiymg tissue structures |e.g. muscle, bone)

Superficial Partial Thickness

-

( papillary ) dermis

Fourth degree

,

Injury to underlying tissue structures (e.g. muscle, bone) Insensate ( nerve endings destroyed ), hard leathery eschar that is black , grey, white, or cherry red in colour ; hairs do not stay attached , may see thrombosed veins

Indications for Transfer to Burn Centre American Burn Association Criteria • patients with partial or full - thickness burns that involve the hands, feet , genitalia , face, eyes, ears, and /or major joints or perineum • electrical burns including lightning ( internal injury underestimated by TBSA ), and chemical burns • inhalation injury ( high risk of mortality and may lead to respirator) distress ) • burn injuries in patients with medical comorbidities which could complicate management and

-

recovery • any patients with simultaneous trauma and burns should he stabilized for trauma first , then triaged appropriately to burn centre • any patients with burn injury who will require special emotional, social, and rehabilitation intervention • children with burns in a hospital not equipped with paediatric care specialists

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PL21 Plastic Surgery

Toronto Notes 2023

Acute Care of Burn Patients •adhere to ATLS protocol • resuscitation using Parkland formula to treat fluid loss secondary to injury and cardiac output. Parkland formula is a starting estimate and patients may require more volume. Other formulas exist, but the Parkland formula is predominantly used in North America (see Table 17 ) required if: • extra fluid administration • burn >80% T'BSA • 4" burns • associated traumatic injury • electrical burn inhalation injury delayed start of resuscitation • paediatric burns • monitor resuscitation urine output is best measure: maintain at >0.5 cc/ kg/ h (adults) and 1.0 cc/ kg/ h in children < 12 yr maintain a clear sensorium, HR < 120/min, MAP >70 mmHg •burn -specific care • escharotomy in circumferential extremity burns, including digits prevent and /or treat burn shock: 2 large bore lVs for fluid resuscitation • insert l'oley catheter to monitor urine output threatening conditions ( e g. inhalation injury, CO poisoning ) • identify and treat immediate life • determine TBSA affected first, since depth is difficult to determine initially (easier to determine after 24 h ) • tetanus prophylaxis if needed • all patients with burns >10% TBSA, or deeper than superficial-partial thickness, need 0.5 cc

-

.

tetanus toxoid also give 250 U of tetanus lg if prior immunization is absent / unclear, or the last booster >10 yr ago •baseline laboratory studies ( Hb, U /A, BUN, CXR, electrolytes, Cr, glucose, CK, ECG, cross- match if traumatic injury, ABG , carboxyhemoglobin ) •cleanse, debride, and treat the burn injury (antimicrobial dressings ) •early excision and grafting are standard of care and important for outcome

Respiratory Problems •3 major causes • burn eschar encircling chest distress may be apparent immediately perform escharotomy to relieve constriction • CO poisoning may present immediately or later treat with 100% 02 by facemask (decreases half-life of carboxyhemoglobin from 210 to 59 min ) until carboxyhemoglobin 30% TBSA • Depth: full thickness and deep partial thickness • Patient age (higher risk with very young and very old)

• Comorbidities • Wound dryness

•

Wound temperature

•

to wound Acidosis

• Secondary impairment of blood flow

Microbial Factors Density >105 organisms per gram of tissue • Motility • Virulence and metabolic products (endotoxin, exotoxin, permeability factors, other factors) • Antimicrobial resistance

•

-

.

early excision and grafting is the mainstay of treatment for deep/ full thickness burns initial dressing should decrease bacterial proliferation

Other Considerations in Burn Management Altered Hemodynamics ( X CO, t SVR) Vascular Permeability and Edema 4

> Hypermetabolism Immunosuppression 4 Progressive Pulmonary Insufficiency

Renal Failure (2° to X Renat Blood Row) 4-

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Increased Gut Mucosal Permeability ( Gl Bleed Risk)

Figure 21. Systemic effects of severe burns

+

• nutrition

hypermetabolism: TBSA > 40% have BMR 2- 2.5x predicted consider nutritional supplementation ( e.g. calories, vitamin C, vitamin A , Ca 2+, Zn 2 + I- e 2+) '

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Toronto Notes 2023

PL23 Plastic Surgery

• immunosuppression and sepsis must keep bacterial count < 105 bacteria / g of tissue ( blood culture may not be positive) signs of sepsis: sudden onset of hyper/ hypothermia, unexpected CHF or pulmonary edema, development of ARDS, ileus >48 h post-burn, mental status changes, azotemia, thrombocytopenia, hypofibrinogenemia, hyper/ hypoglycemia (especially if burn >40% TBSA ) • GI bleed may occur with burns >40% TBSA ( usually subclinical ) treatment: tube feeding or NPO if there is a Gl bleed, antacids, H 2 blockers ( preventative) • renal failure secondary to under resuscitation, drugs, myoglobin, etc. • progressive pulmonary' insufficiency • can occur after: smoke inhalation, pneumonia, cardiac decompensation, sepsis • wound contracture and hypertrophic scarring outcomes optimized with timely wound closure, splinting, pressure garments, and physiotherapy

Special Considerations CHEMICAL • major categories: acid bums, alkaline burns, phosphorus burns, chemical injection injuries • common agents: cement, hydrofluoric acid , phenol, tar • mechanism of injury: chemical solutions coagulate tissue protein leading to necrosis acids -> coagulation necrosis • alkalines > saponification followed by liquefactive necrosis • severity related to: type of chemical (alkali worse than acid ), temperature, volume, concentration, contact time, site affected, mechanism of chemical action, degree of tissue penetration • bums are deeper than they initially appear and may progress with time Treatment (General)

• ABCs, monitoring • remove contaminated clothing and brush off any dry powders before irrigation • irrigation with water for 1 2 h under low pressure (contraindicated in elemental metal burns, such as sodium, potassium , magnesium , and lithium; in these cases, soak in mineral oil instead ) • inspect eyes; if affected , wash with saline and refer to ophthalmology • inspect nails, hair, and webspaces • correct metabolic abnormalities and provide tetanus prophylaxis if necessary • contact poison control line if necessary • local wound care 12 h after initial dilution ( debridement) • wound closure same as for thermal burn • beware of underestimated fluid resuscitation, renal, liver, and pulmonary damage

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Table 20. Special Bums and Treatments Burns

Treatment

Arid Burn

Water irrigation,followed by dilute solution of sodium bicarbonate

Hydrofluoric Acid

Water irrigation:clip fingernails to avoid acid trapping:topical calcium gel t subcutaneous injection of calcium gluconate 10 c calcium gluconate IV depending on amount of exposure and pain

Sulfuric Acid

Treat with soap lime prior to irrigation as direct water exposure produces extreme heat

Tar

Remove with repeated application of petroleum based antibiotic ointments (e.g. Polysporin ' )

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1

ELECTRICAL BURNS

• injury occurs due to flow of current through body, arc flash, or clothing catching on fire • depth of burn depends on voltage and resistance of the tissue ( injury more severe in tissues with high resistance) • often presents as small punctate burns on skin, with extensive deep tissue damage which requires

debridement • electrical burns require ongoing monitoring ( ECG and neurovascular status), as latent injuries can occur

-

• watch for system specific damages and abnormalities • abdominal: intraperitoneal damage bone: fractures and dislocations especially of the spine and shoulder cardiopulmonary: anoxia, ventricular fibrillation, arrhythmias muscle: myoglobinuria indicates significant muscle damage -> compartment sy ndrome neurological: seizures and spinal cord damage ophthalmology: cataract formation (late complication ) * renal: acute tubular necrosis resulting from toxic levels of myoglobin and hemoglobin vascular: vessel thrombosis -> tissue necrosis ( increased Cr, K+, and acidity), decrease in RBC count (beware of hemorrhages/delayed vessel rupture )

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PL24 Plastic Surgery

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Treatment

• ABCs, primary and secondary survey, treat associated injuries • beware of cardiac arrhythmias (continue cardiac monitoring) • monitor: hemochromogenuria, compartment syndrome, urine output • wound management: topical agent with good penetrating ability (silver sulfadiazine or mafenide acetate) • debride nonviable tissue early and repeat prn (every 48 h ) to prevent sepsis • amputations frequently required FROSTBITE

• see Emergency Medicine. ER46

s

Hand

30%, then percutaneous pinning ( K wires) and splint, or OKU'

-

-

Proximal and Middle Phalanx Fractures •check for: rotation , scissoring (overlap of fingers on making a fist ) , shortening of digit • non displaced or minimally displaced: closed reduction ( if extra articular ), buddy tape to neighbouring stable digit , elevate hand, careful motion of extremity with splint to prevent reinjury,

-

-

-

splinted for 2 3 wk

•displaced , non - reducible, not stable with closed reduction , or rotational or scissoring deformity:

-

percutaneous pinning ( K wircs) or OR 11', and splint

Metacarpal Fractures

•generally accept varying degrees of deviation before reduction required: up to 10“ ( D2), 20* ( D3), 30“

( D4), or 40“ ( D5) • Boxer’s fracture: acute angulation of the neck of the 5th metacarpal into palm mechanism: blow on the distal dorsal aspect of closed fist loss of prominence of metacarpal head, volar displacement of head up to 30-40“ angulation may be acceptable closed reduction should be considered to decrease the angle if stable, ulnar gutter splint for 4-6 wk • Bennett’s fracture: two-piece fracture/dislocation of the base of the thumb metacarpal, usually intra-

-

_

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articular » unstable fracture AFL pulls MC shaft proximally and radially, causing adduction of thumb treat with percutaneous pinning or OR1F, followed by thumb spica for 6 wk • Rolando fracture: T- or Y-shaped fracture of the base of the thumb metacarpal treated like a Bennett’s fracture

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PL29 Plastic Surgery

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DISLOCATIONS

• treatment: must be reduced as soon as possible • dislocation vs. subluxation

•

dislocation: severe injury where articular surfaces of a joint are no longer in contact with one another • subluxation: articular surfaces of a joint are partially out of place (i.e. “partial dislocation” - often unstable and requires reduction )

PIP and DIP Dislocations (PIP more common than DIP )

• usually dorsal dislocation (commonly from hyperextension ) • 3 views of hand needed with x- ray imaging to assess degree of dislocation ( posteroanterior, oblique,

and lateral ) • if closed dislocation: closed reduction and splinting in position of function for 1 wk or buddy taping, and early mobilization ( prolonged immobilization causes stiffness) • open injuries are treated with wound care, irrigation , and debridement, followed by closed or open

reduction and antibiotics

MCP Dislocations (relatively rare) • dorsal dislocations much more common than volar dislocations • dorsal dislocation of proximal phalanx on metacarpal head; most commonly index finger ( hyperextension ) • two types of dorsal dislocation • simple ( reducible with manipulation ): treat with closed reduction and splinting for 2 4 wk at 60

-

-

70" MCP flexion complex ( irreducible, most commonly due to volar plate blocking the reduction ): treat with open reduction

UCL Injury of the Hand

• forced abduction of thumb (e.g. ski pole injury ) • skier’s thumb: acute UCL injury; if stable (elbow valgus stress test ), treated with splint x 6 8 wk ; if

-

unstable, patient may have Stener lesion • Gamekeeper’s thumb: chronic UCL injury, often requires open repair and tendon graft for stabilization • Stener lesion: the distal portion of the UCL can detach and flip superficial to the adductor aponeurosis and will not appropriately heal; requires open repair ( requires x ray imaging to diagnose ) : radially deviate thumb MCP joint in full extension and at 30" flexion and compare with evaluation • non injured hand UCL rupture is presumed if injured side deviates more than 30" in full extension or more than 15" in flexion

-

.

-

Dupuytren’s Disease Definition

• proliferative disorder of the palmar fascia , forming nodules (usually painless), fibrous cords, and

flexion contractures at the MCP and interphalangeal joints • flexor tendons not involved • Dupuytren’s diathesis: male sex, early age of onset, strong family history (autosomal dominant inheritance ), involvement of multiple digits, bilateral involvement, and involvement of sites other than palmar aspect of hand , including the plantar fascia ( Ledderhose's) and the penis ( Peyronie’s; see Urology Table 24 , U 33)

.

Epidemiology • unusual in Asian patients or patients of African descent, high incidence in northern European patients, men > women, often presents in 5th-7th decade of life; associated with but not caused by alcohol use, smoking, and DM

Clinical Features • nodules, cords, and contractures of MCP, PIP, and DIP • order of digit involvement ( most common to least common ): ring > little > long > thumb > index • risk of recurrence

1i A

-

m

£ Cord

!

Nodule

'

\

T

'Palmar

aponeurosis

Figure 26. Dupuytren’s disease

Treatment

• palmar pit or nodule: no surgery ( steroid injections for pain )

• palpable band /cord with no limitation of extension ( i.e. no contracture) of either MCP or PIP: no surgery • MCP contracture > 30" or PIP contracture of any degree: needle aponeurotomy, collagenase

Clostridium histolyticum (Xiaflex*) injection (indicated if cord is palpable), or surgical fasciectomy • contractures impeding function and /or hygiene: needle aponeurotomy, collagenase injection, or surgical fasciectomy • MCP joints have better outcomes than PIP joints post treatment (achievement of near full extension,

lower risk of recurrence)

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PL30 Plastic Surgery

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Carpal Tunnel Syndrome Definition

• median nerve compression at the level of the flexor retinaculum / transverse carpal ligament Etiology

• median nerve entrapment at wrist • primary cause is idiopathic

• secondary causes: space occupying lesions (tumours, hypertrophic synovial tissue, fracture callus, and osteophytes); metabolic and physiological ( pregnancy, hypothyroidism, acromegaly, and RA); job/ hobby-related repetitive trauma, especially forced wrist flexion Epidemiology

• l::M »4:l , most common entrapment neuropathy Clinical Features

• classically, patient awakened at night with numb/ painful hand, relieved by shaking/dangling/ rubbing

• on exam, sensory loss in median nerve distribution (see Figure 3, PL3), but thenar eminence sensory ; tunnel ) loss is spared ( palmar cutaneous branch given off prior to carpal • decreased light touch and 2- point discrimination at DIP radial and ulnar creases; discriminative

touch often lost first

• advanced cases: thenar wasting/ weakness due to involvement of the motor branch of the median nerve ( paresthesia on percussion of nerve ) • ± Tinel 's sign • ± Durban 's sign ( paresthesia after pressure over carpal tunnel < 30 seconds) • ± Phalen’s sign (wrist flexion induces symptoms)

Investigations

• generally a clinical diagnosis • NCS and EMG studies may be used to objectively confirm the diagnosis if clinical history is atypical Treatment

• avoid repetitive wrist and hand motion , wrist splints at night and when repetitive wrist motion required • conservative: night -time splinting to keep wrist in neutral position • medical: NSAlDs, local corticosteroids injection ( relief from local corticosteroid injections is also diagnostic) • surgical decompression: transverse carpal ligament incision to decompress median nerve • indications for surgery: persistent signs and symptoms of median nerve compression not relieved by conservative management, or if motor function is compromised

Brachial Plexus Etiology

• common causes of brachial plexus injury: complication of childbirth and trauma • other causes of injury: compression from tumours, supernumerary ribs Common Palsies Table 23. Named Neonatal Palsies of the Brachial Plexus Location of Injury

Palsey

-

Mechanism of Injury

Features

-

Head /shoulder distraction (e.g. “ Waiter 's lip deformity' (shoulder internal rotation, elbow extension and pronation, wrist motorcycle) flexion )

-

Traction on abducted arm

Duchenne Erb Palsy

Upper brachial plexus (C 5 C 6)

Klumpko’s Palsy

Lower brachial plexus (C8 I1)

"Claw hand"

May include Horner 's syndrome

Differential Diagnosis of Adult- Acquired Brachial Plexus Palsies

• trauma ( blunt , penetrating)

• thoracic outlet syndrome

• associated with large cervical rib, anomalous first rib, strenuous arm work, and neck muscle

r

hypertrophy

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neurogenic: compression of brachial plexus, resulting in upper limb paresthesia, pain, and

weakness vascular: compression / thrombosis of subclavian artery/vein, resulting in pain; pallor and Raynaud 's if arterial; swelling and cyanosis if venous

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PL31 Plastic Surgery

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• tumour

schwannoma: well-defined margins enable total resection

• neurofibromas: associated with neurofibromatosis type 1 other: e.g. Pancoast syndrome (apical lung tumour )

• neuropathy ( compressive, post -irradiation, viral , diabetic, idiopathic) Investigations • EMG •MR1: gold standard for identifying soft tissue masses and nerve roots

•CT myelogram •closed injuries: if avulsion suspected, then CT myelogram or MR1 initially; otherwise, EMG / NCS 12 wk post injury to assess healing progress •open injuries: OK for exploration within a few days post injury (once patient stable)

-

-

Management

Table 24 . Management of Brachial Plexus Injuries* Closed Injuries

-

Concussive/compressive

Olten sell resolving ( unless eipanding mass, e.g. hematoma)

Traction /stretch Obstetric palsy

II no continued insult, follow lor 3 4 mo (or improvement Surgery il no significant improvement and/or residual paresis at age 6 mo

Sharp or vascular injury

Open Injuries

‘All injuries listed require splinting as well as OT and

-

Explore immediately in OK

PI consults to maintain ROM and function in the joint

Nerve Transfers

• indicated when nerve injury is close to the effector muscle or when other reconstructive options are not possible (e.g. preganglionic root avulsion, complete loss of motor, and /or sensory function ); can also serve as adjunct to nerve grafting • involves the use of an expendable nerve as a donor, such as one that supplies redundant innervation or one with less importance to daily functioning • donor nerve serves to: reconstruct the injured nerve closer to its effector muscle to better facilitate reinnervation, or directly innervate effector muscle ( neurotization ) • cortical plasticity involved in re-programming new nerve function • can also serve as adjunct to nerve grafting • both motor and sensory nerve transfers are possible, allowing motor and /or sensory restoration by neurotization • three types of donors: intraplexal (e.g. ulnar or median nerve fascicles) extraplexal (e.g. contralateral C7 nerve root, intercostal nerve) distal (e.g. radial nerve branches)

Craniofacial Injuries • low velocity vs. high velocity injuries determine degree of damage • fractures cause bruising, swelling, and tenderness > loss of function • management: most can wait ~5 d for swelling to decrease before OR1F required

Approach to Facial Injuries • AT'LS protocol •inspect , palpate, clinical assessment for injury to underlying structures (e.g. facial nerve, bony injuries, septal hematoma, ocular involvement, etc.) • tetanus prophyl:. x : • radiological evaluation: CT scan with fine cuts of 1.5 mm through the orbit

-

• wound irrigation with NS/ RL and removal of foreign materials •conservative debridement of detached or nonviable tissue • repair laceration (s) at the time of presentation with 4 0 nylon sutures when the patient 's general condition allows • consider intracranial trauma; rule out skull fracture

-

Signs of Basal Skull Fracture • Battle's sign (bruised mastoid process) • Hemotympanum Raccoon eyes (periorbital bruising) • CSF otorrhea/rhinorrhea

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Investigations •CT (gold standard )

axial and coronal (specifically request 1.5 mm cuts): for fractures of upper, middle, and lower face indicated for significant head trauma , suspected facial fractures, and preoperative assessment • panorex radiograph: shows entire upper and lower jaw; best for isolated mandible fracture, but patient must be able to sit ; however, if high clinical suspicion and negative panorex, CT should be done

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PI.32 Plastic Surgery

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Treatment Goals

-

• re establish normal occlusion if occlusion is an issue • normal eye function ( extraocular eye movements and visual acuity ) • re -establish facial height and width to re - establish appearance • consultation when indicated ( dentistry, ophthalmology, neurosurgery)

5. Lower transverse maxillary ( 4 palatel 6. Upper transverse mandibular 7. Lower transverse mandibular

8. Pterygomaxillary 9. Posterior vertical

Figure 27. Craniofacial horizontal and vertical buttresses

Mandibular Fractures • two points of injury since it is a ring structure ( includes fractures and dislocations ) •commonly at sites of weakness (condylar neck, angle of mandible)

Subcondyle

Condyle

Etiology

• anterior force: bilateral fractures

Ramus

• lateral force: ipsilateral subcondylar and contralateral angle or body fracture • note: classified as open if fracture into tooth bearing area ( alveolus)

“

Angle

Clinical Features • pain, swelling, difficulty opening mouth ( “ trismus” ) • malocclusion, asymmetry of dental arch damaged , loose, or lost teeth • palpable “step” along mandible • numbness in CN V 3 distribution • intra oral lacerations or hematoma ( sublingual )

Body

"1Symphysis

"

Parasymphysis © Susan Parle 2009

Figure 28. Mandibular fracture sites

-

•chin deviating toward side of a fractured condyle Classification Table 25 . Mandibular Fracture Classifications by Anatomic Region Areas/Boundaries

Symphysis

Mid line of the mandible: between the central Incisors from the alveolar process through the interior border ol the mandible

Body

From the symphysis to the distal alveolar border of the third molar

Angle

Ramus

Triangular region betvreen the anterior border oi the masseter and the poslerosuperior insertion of the masseter distal to the third molar Part of the mandible that extends posterosuperiorly into the condylar and coronoid processes

Condylar *

Area of condylar process of mandible

Subcondylar

Area below the condylar neck ( i.e. sigmoid notch ) ol the mandible

Coronoid Process

Area ol the coronoid process ol mandible

r

'Moxl common mandibular Iracturu type

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Treatment

• maxillary and mandibular arch bars wired together ( intermaxillary fixation ) or ORIF ( indications depend on whether fracture is unilateral / bilateral, etc. ); ideally managed within 18 h • antibiotics from initial presentation until at least 3 doses postoperativelv; if late presentation , may consider treatment with antibiotics for an extended course

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PL33 Plastic Surgery

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Maxillary Fractures Table 26. Le Fort Classification Le Fort I

Le Fort II

Alternative Name

Guerin fracture

Pyramidal fracture

Type of Fracture

Horizontal

Pyramidal

Transverse

Structures Involved

Piriform aperture

Nasal bones

Nasofrontal suture

Maxillary sinus

Medial orbital wall

2ygomaticofronlal suture

Pterygoid plates

Pterygoid plates

Pterygoid plates

Anatomical Result

Maxilla dividedInto 2 segments

Le Fort III Craniofacial disjunction

Manila

Zygomatic arch

Maxillary teeth and midscctlon ol the maxilla separated Irom upper lace

Entire midfacial skeleton detached from cranial base

Nasal Fractures

Le Fort Fractures

Le Fort II Fractures

Etiology

• lateral force -> more common • anterior force -> can produce more serious injuries • most common facial fracture Clinical Features

Le Fort III Fractures

• epistaxis / hemorrhage, deviation /flattening of nose, swelling, periorbital ecchymosis, tenderness over nasal dorsum , crepitus, septal hematoma, respiratory obstruction , subconjunctival hemorrhage

Figure 29. Le Fort fractures

Treatment

• treated for airway or cosmetic issues

• always inspect for, and drain, septal hematoma as this is a potential cause of septal necrosis and

-

perforation completed with small incision in the septal mucosa followed by packing • closed reduction with Asch or Walsham forceps under anesthesia, pack nostrils with petroleum or non -adhesive gauze packing, nasal splint for 7 d • best reduction immediately ( sudden increase in intraorbital pressure Clinical Features •restricted tOM (if muscle trapped ) • periorbital edema and bruising, subconjunctival hemorrhage • ptosis, exophthalmos, exorbitism, enophthalmos, and hypoglobus may be present • diplopia may be present • orbital rim step-offs with possible infraorbital nerve anesthesia •orbital entrapment clinical diagnosis that is a surgical emergency • diplopia with straight gaze: unable to look up past neutral ( entrapment of inferior rectus), limited

Figure 31. Blow-out fracture

hOM

severe pain or N / V with upward globe movement Investigations

•CT (diagnostic): axial, coronal, and sagittal views - with fine cuts through orbit: rounding of inferior rectus can be a sign of orbital entrapment

• diagnostic maneuver for entrapment is forced duction test ( pulling on inferior rectus muscle with forceps to ensure full ROM ) under general anesthesia in the OR

Treatment •surgical repair indicated if: entrapment, any size defect with enophthalmos (if patient is bothered by it), or persistent diplopia (>10 d) • reconstruction of orbital floor with bone graft or alloplastic material (e.g. titanium meshes, MEDPOR', MEDPOR TITAN*) •after repair, many patients can have diplopia for several weeks

Complications

• persistent diplopia • enophthalmos Superior Orbital Fissure Syndrome • fracture of SOF causing ptosis, proptosis, anesthesia in CN V1 distribution, and painful ophthalmoplegia ( paralysis of CN III, IV, VI ) • uncommon complication seen in Le Fort 11 and 111 fractures ( 1 /130) • recover)’ time reported as 4.8 23 wk following operative reduction of fractures

-

Orbital Apex Syndrome

• fracture through optic canal with involvement of CN 11 at apex of orbit

•symptoms are the same as SOF syndrome plus vision loss • treatment is steroids or urgent decompression of fracture in optic canal ( posterior craniotomy for decompression )

Traumatic Auricular Hematoma (Cauliflower Ear ) Definition • trauma to the auricle that creates a subperichondrial hematoma that, if not corrected quickly, will form a permanent disfiguring nodularity known as “cauliflower ear” Epidemiology • higher prevalence in athletes who participate in contact risk sports (e.g. mixed martial arts, boxing ); however, it is not exclusive to athletes

Clinical Features • painless or slightly tender swelling of the upper aspect of the pinna • becomes firmer and harder with time if left untreated • colour is skin coloured or slightly bluish

ry

-

Differential Diagnosis • relapsing polychondritis, auricular pseudocyst , epidermoid cyst

+

Treatment • aspiration, incision and drainage, and splinting of the auricular hematoma within 7 d ( preferably first 72 h)

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PL35 Plastic Surgery

Toronto Notes 2023

Breast Anatomy Vascular Supply Subclavian artery

Thoracoacromial artery Axillary artery

Lateral thoracic artery

Internal thoracic artery

Thoracodorsal artery Internal thoracic perforating branches

/

Medial intercostal perforators

Anterolateral intercostal perforators

CMidoii Nodigui 2016

Figure 32. Breast vasculature

Innervation

- • lateral and upper portions of the breast innervated by lower fibres of the cervical plexus (C3, C4) • innervated in a dcrmatomal pattern from branches of the thoracic intercostal nerves (T 3 6) medially innervated from anterior cutaneous branches of l VI intercostal nerves laterally innervated from lateral cutaneous nerve branches of 1I VI 1 intercostal nerves

. NACsupplied by

anterior and lateral cutaneous branches of intercostal nerve IV

additional innervation by cutaneous branches of intercostal nerves III and VI Intercostobrachial nerve, Cervical plexus

Anterolateral intercostal

_

Anteromedial

-intercosal nerves

nerves 3D Ruth Chang 2016

Figure 33. Innervation of the breast

Breast Reduction Indications

• symptomatic (general symptoms) musculoskeletal pain ( back, bra strap location, neck), chronic headache, paresthesia in upper limb, rashes/irritation under the breast , breast discomfort, and physical impairment • breast reduction methods can be classified based on pedicle ( i.e. blood supply to the NAC ) and skin resection pattern ( i.e. the resultant scar)

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A

B

Inferior pedicle

Superior pedicle technique

technique

Superomedial pedicle technique

C

Figure 34 . Inverted T (“Wise”) pattern reduction

D

E

Figure 35. Vertical pedicles for breast reduction

.

.

John R . Fowler. Nandkinnar M. Rawed Ultrasound ot the Hand and Upper Extremity 1st ed. 2017 Tieme Publishers, www.thicme.com (reprinted with permission)

Common Types of Pedicles • inferior pedicle: derived from the fourth , fifth , and sixth intercostal perforators; most commonly used with the inverted T ( “ Wise") pattern reduction; versatile in small -large breast reduction recommended pedicle width 6 - 8 cm , 8- 10 cm in large breasts •superior pedicle: derived from the internal mammary perforator of the second intercostal space • medial pedicle: blood supplied by internal mammary perforators from third intercostal space, and may have contribution from fourth intercostal space • superomedial pedicle: incorporates the descending artery from the second intercostal space as the medial pedicle base extends superolaterally to the breast meridian • bipedicle: used in McKissock 's technique ( well- vascularized dermal - parenchymal vertical bipedicle) Table 27. Type of Skin Resections /Scar Options Inverted!Pattern

Indications

Description

large breasts Breasts with poor gualilyskin that are challenging to remodel

Commonly used in association with inferior pedicle large portion ol skin removed in horizontal and vertical dnection

F

Figure 36. Skate flap incision outline A) elevation of wings B) elevation of entire flap C) caudal folding of flap D) E) skate flap with primary closure of donor site with skin graft F)

iamotoi ol nipple co

Skin integrity important to shape and hold breast parenchyma Vertical Pattern

Surgeon preference

1cm Decreased contralateral nipple sensation Necrosis ol gralt or donor nipple

Table 31. Types of Areolar Reconstruction Description

Advantages

Disadvantages

Tattoo"

Conducted 3 - 4 mo after nipple reconstruction when most of the projection has stabilized

Can provide more accurate colour matching with limited morbidity

May require touch-ups due to pigment lading overtime with skin sloughing

Skin Graft’

Full thickness skin grails, commonly from inner aspect ol thigh or opposite areola

Provides texture and pigment resembling a natuial areola

Donor site morbidity

‘ Tattoo and skin grlilting can be used In conjunction

Aesthetic Surgery Aesthetic Procedures Table 32 . Aesthetic Procedures Location

Procedure

Description

HeadfNeck

Hair transplants

Aesthetic improvement of hair growth patterns using hair follicle grafts or flaps

Skin

Other

Otoplasty

Surgical reconstruction of external ear

Foreheadfbrow lift

Surgical procedure to lift the forehead and eyebrows

Rhytidectomy

Surgical procedure lo reduce wrinkling and sagging ol the lace and neck; “face lift"

Blcpharop tasty

Surgical procedure lo shape or modify the appearance ol eyelids by removing excess eyelid skin tlal pads

Rhinoplasty

Surgical reconstruction olthe nose t nasal aiiway

Genioplasly

Chin augmentation via osleolomy oi synthetic implant to improve contour

Chemical peel

Application ol oneor more exfoliating agents to the skin resulting in destruction ol portions of the epidermis and/ or dermis with subsequent (issue regenerabon

Dermabrasion

Skin resurfacing with a rapidly rotating abrasive tool; often used lo reduce scars, irregular skin surfaces, and fine lines

Laser resurfacing

Application ol laser to the skin which ultimately results in collagen reconfiguration and subsequent skin shrinking and tightening:often used lo reduce scars and wrinkles

Injectable Idlers

An injectable substance is used lo decrease facial rhytids; can augmcnl lips to create fuller appearance; substances include: collagen, fat hyaluronic acid, and calcium hydioxyapatile ( most common substances include hyaluronic acid and fat)

.

Abdominoplasty

Removal ol excess skin and repair of rectus muscle laxity (redus diastasis); "lummy luck "

Call augmentation

Augmentation of calf muscle with implants

Liposuction

Surgical removal of adipose tissue lor body contouring (not a weight loss procedure)

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PL-11 Plastic Surgery

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Gender-Affirming Surgery (Transition-Related Surgery) • ensure appropriate use of gender pronouns • some procedures require I vr trial of hormone

therapy, preoperative letters of evaluation and documentation from mental health professionals as outlined by the World Professional Association for Transgender Health Standards of Care - Version 7 guidelines

Table 33. Surgical Options for Transgender Women Procedure

Description

Follow - Up

Breast Augmentation

Implant- based, fat- grafting, or combined surgery to increase breast sire

Surveillance for implant rupture Adhere to breast cancer screening guidelines in addition to gender- specific medical maintenance

Contouring Procedures

Altering fal distribution in distinguishing regions ol the body (abdomen, flank, hip , and bullock ) using liposuction oi fal grafting (limited by availability ol autologous fal)

Short- term restrictions on placing body weight on fat grafted areas ( * 2 wk ) 100% of injected fal volume nol maintained long- term

Facial Feminization

t Hairline suigery iForehead augmentation or osteotomy

Hair transplant may be needed in adjunct May have altered lip sensation and altered sensation of lower incisors with genioplasty

t

Rhinoplasty

± Genioplasty (implant alone is usually not sufficient )

Chondrolaryngoplasty

Cartilage removal to reduce thyroid cartilage size

Risk of long- term hoarseness based on anatomical proximity of recurrent laryngeal nerve to site of surgery

Vocal Cord Surgery

Alteration ol vocal cord length to increase vocal pitch

Nol all procedures are permanent (i.e. cricothyroid approximation) Some procedures may narrow air way (i.e. anterior glottal web formation) Nol guaranteed to achieve exact desired pitch change

Vaginoplasty

see Urology Itanution -Relati' dSurgeries , fable 26. U 47

.

Table 34 . Surgical Options for Transgender Men Follow -Up

Procedure

Description

Chest Masculinization

Most common technique is double incision free nipple Loss of nipple sensation graft technique May need liposuction for patients with excess subcutaneous tissue

Contouring Procedures

see fob /e 33 t Forehead augmentation

Facial Masculinizalion

May have altered lip sensation and altered sensation of lower incisors with genioplasty

* Maxillary augmentation i

Mandibular augmentation

t Rhinoplasty t

Thyroid Cartilage Enhancement

•

Genioplasty

Cartilage added to increase thyroid cartilage prominence

Risk of vocal cord paralysis due to surgery

VocalCord Surgery

Alteration ol vocal cord length to decrease vocal pitch Nol guaranteed lo achieve exact desired pitch change

Phalloplasty , Metoidioplasty

see Urology , hansilion Rclolcd Suigeiia table 26. U 47

.

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for further information on gender- affirming surgical techniques, see Urology, Transition Related Surgeries, U47

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PL-12 Plastic Surgery

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Paediatric Plastic Surgery Craniofacial Anomalies Table 35. Paediatric Craniofacial Anomalies Definition

Epidemiology

Clinical Features

Treatment

Cleft Lip

Failure of fusion of maxillary and medial nasal processes

1in 1000 live births (increased incidence in Asian individuals, decreased incidence in individuals of African descent )

Classified as incomplete/ complete and unilateral/ bilateral:2/3 cases: unilateral, left - sided, male

Surgery ( 3 mo): Millard, or Fisher (additional corrective surgeries usually required later on • especially lor nasal deformity

Cleft Palate

Failure of fusion of lateral palatine /median palatine processes and nasal septum

Isolated cleft palate: 0.5 in 1000 (no racial variation) F -M 4% chance ol dell II one parent or sibling have dell 17% chance of cleft if both sibling and parent have deft

Classified as incomplete/ complete and unilateral/

Special bottles for feeding SIP Surgery ( 6 - 9 mo): Von langenbeckor Follow 2 Plasty ENT consult - often recurrent otitis media, requiring myringotomy tubes

tin 2000 live newborns: M:E - 52:48 Syndromes include: Crouzon's, Apert's Saelhre- Chotzen, Carpenter's Pfeiffer’s JacksonWeiss and Boston - type syndromes

Primary (no known cause) or secondary ( associated with a known cause or syndrome)

Craniosynoslosis

.

bilateral Isolated (common In females) or in conjunction with deft lip (common in males)

.

.. .

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Multidisciplinary learn (including neurosurgery ENf genetics, dentistry,paediatrics SLP) the type,timing, and procedure are dependent on which sutures (lambdoid, sagittal, etc ) are involved Early surgery prevents secondary deformities

. .

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.

Congenital Hand Anomalies Table 36. American Society for Surgery of the Hand ( ASSH ) Classification of Congenital Hand

Anomalies Classification

Example

Features

Treatment

Failure ol Formation

Transverse absence (congenital amputation)

Atanylevel (oflenbelowelbow/ wrist)

Early prosthesis

longitudinal absence (pliocomelia)

Absent humerus lhalidomide association Radial deviation

Radial deficiency (radial club hand)

Thumb hypoplasia M »F

Physiotherapy ' splinting Soft tissue release if splinting fails Distraction osteogenesis (Ilizarov distraction) wedge osteotomy

tendon transfer Pollicitation thumb hypoplasia

Ulnar club hand

Syndromes include:Fanconi anemia Holt -Ogram. and CHARGE syndromes. Degree ranges from small thumb with alt components to complete absence

.

Rare, compared to radial club band Stable wrist

Failure of Differentiation/ Separation

.

.

.

.

.

of index finger

Splinting and soft tissue stietching therapies Soft tissue release (if above fails) Correction of angulation (Ilizarov distraction)

Autosomal dominant Olten functionally normal (depending on degree)

First web space syndactyly release Osteotomy / tendon transfer of thumb (if hypoplastic)

Syndactyly

Syndromes include: Apert, Poland, and HollOram syndromes 1in 3000 live births M:F 2:1

Surgical separation before 6-12 moot age May require a skin graft to cover the Angers Usually good result

Symbracbydactyly

Short lingers with sborl nails at Fingertips

Digital separation Webspace deepening

Camptodactyly

Congenita! flexion conlracture (usually at PIP especially 5th digit)

Early splinting Volat release Arthroplasty (rarely)

Clinodactyly

Radial or ulnar deviation Oden middle phalanx

None (usually): it severe, osteotomy with grading

.

Image reproduced with permission from Medscape Drugs £ Diseases (https://ernedicinejriedscape.com') Cleft Lip and ' Palate and Mouth and Pharynx Deformities, 2021 available at: https:// eniedkine medscape com/ altide /837347 overview

Depends on degree - may involve no treatment, webspace deepening, tendon transfer,or pollicization

Clell hand

-

Figure 38 . Veau classification of cleft lip and palate

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Table 36. American Society for Surgery of the Hand ( ASSH ) Classification of Congenital Hand Anomalies Classification

Example

Features

Treatment

Duplication

Polydactyly

Congenital duplication of digits May be radial (increased in Asian individuals and Indigenous peoples) or central or ulnar (increased in individuals ol African descent)

Amputation of least functional digit Usually >1 yr of age ( when functional status can be

assessed)

Overgrowth

Macrodactyly

Rare

None (if miId) Soft tissue / bony reduction

Undergrowth

Brachydadyly

Short phalanges

Removal of nonfunctional stumps Osteotomies/ tendon transfers Distraction osteogenesis

Symbrachydactyly

Short webbed Fingers

As above syndactyly release

Variety of presentations

Urgent release for acute, progressive edema distal to band in newborn Other reconstruction is case specific

Variety of presentations

Treatment depends on etiology

Phalangeal/free toe transfer ftrachysyndactyly i.e. amniotic (annular ) band syndrome

Constriction Band Syndrome

Generalized Skeletal Achondroplasia, Marfan Abnormality syndrome, Madelung's deformity

References American Society for Surgery of the Hand. Ihe hand: examination and diagnosis, 3rd cd. Philadelphia: Churchill Livingston, 1990. Barr JE. Principles of wound cleansing. Ostomy Wound Manage.199 S:41|Suppl 7A):1S5- 225. Betedjiklian PK, Bozenika DJ. Revievrof hand surgery. Philadelphia: WBSaunders, 2004. Bolognia JL, Jorizzo JL, Rapim RP (editors).Textbook of dermatology.2nd ed.Vol.1and 2. Toronto: Mosby, 2008. Britt LD Turnkey DO, Feliciano DV. Acute care surgery: principles and practice. New York: Springer, 2007. Brown 01, Borschcl GH. Michigan manual of plastic surgery. Philadelphia: WBSaunders 2004. Capobianco CM. Zgonis T. An overview of negative pressure wound therapy foi the lower extremity. Clin Podiatr Med Surg. 2009 Oct:26( 4):619 - 31 American Bum Associalion/ Amencan College of Surgeons Guidelines for Ihe operation ol burn centers. Resources for Optimal Care of Ihe Injuicd Patient, 200 G. Cereda E Kletsy C Serioli M et at. A nutritional formula enriched with arginine,zinc, and anboxidanls for Ihe healing of pressure ulcers: a randomized trial. Ann Intern Med 2015:162(3) 167 174. Chasmar LR. The versatile rhombic ( Limberg) flap. Can J Plast Surg 2007:16:67-71. Chuang DCI: Neurotization proceduresfor brachial plexus injuries. Hand Clin1995:11:633 -645. Daver BM, Antia NH.Furnas DW. Handbook of plastic surgery for the general surgeon, 2nd ed. New Delhi: Oxford University Press.1995. Department of Health,Western Australia. Guidelinesfor use of nanocrystalline silver dressing - Acticoal '. Perth: Health Networks Branch. Oeparlmcnl of Health, Western Australia . 2011. Dias JJ Dhukatam V Kumar P. The natural history ol unlrealed dorsal wrist ganglia and patient reported outcome 6 years after intervention. J Hand Sutg Eur Vol 2007;32(5):502 -508. Dichr S Hamp A Jamieson B. Clinical inquiries: do topical antibiotics improve wound healing? J Earn Practice 2007:56:140 144. Francis KR. Lamaute HR Davis JM etal. Implications olrisk factors in necrotizing fasciitis. Am Surg 1993;59:304 - 308. Georgiade GS,Riefkohl R.Levin IS. Georgiade plastic, maxillofacial and reconstructive surgery,3rd ed. Baltimore:Williams A Wilkins,1997. Giladi M, Malay S, Chung KC. A systematic review of the management of acute pyogenic flexor tenosynovitis.J Hand Surg-Eur Vol 2015:40(7):720 -728. Giuffre JL, Kakar S. Bishop AT, et al. Current concepts of the treatment of adult brachial plexus injuries. J Hand Surg Am 2010:35:678 - 688. Gourgtolis S VilliasC GcrmanosS, el al. Acute hmb compartment syndrome: a review. J Surg Educ 2007:64:178 -186 . Graham B. Regelir G Naglie G et al. Development and validation of diagnosbc criteria for caipal tunnel syndrome. J Hand Suig 2006:31(61:919 - 924. Greene FI Page Dl Fleming ID el al. AJCC cancer staging handbook: from the AJCC cancer staging manual 6 th ed. Chicago: Springer, 2002. Gullelh Y Goldberg N, Silverman R, et al. What is the best surgical margin for a basal cell carcinoma: a meta - analysis ol the literature. Plast Reconstr Surg 2010:126:1222-1231. GuoS. DiPietro LA FactorsAlfecting Wound Healing.J Dent Res 2010;89:219-229. Harrison V.The newborn baby. 5th ed. Juta 4 Company. 2008. Chapter:Congenital Abnormalities. Hollmann H. Eren H Sander K, et al. Orbital floor fractures - short - and intermediate - term complications depending on treatment procedures. Head Face Med 2016:12:1. Huang CC, Boyce SM. Surgical marginsol excision lor basal cell carcinoma and squamous cell carcinoma. Semin Cutan Med Surg 2004; 23:167-173. Hunt IK Doherty GM Way LW (editors) Current suigicaldiagnosis and treatment, 12th ed. Norwalk: McGraw - Hill 2006. Chapter Wound Healing Jants JE. Essentials ol plastic surgery: a U! Southwestern Medical Center handbook. St. Louis: Ouality Medical, 2007. Jarbrink K. Ni 6, Sonnergren H et al. Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review. Syst Rev 2016.5(1):152. Johnson RE. Murad MH.Gynecomastia: pathophysiology, evaluation, and management. Mayo Din Proc 2009;84:1010 -1015. Jones V, Grey JE, Harding KG. Wound dressings. 8MJ. 2006;332( 7544):777 80. Kargul G. Deutinger M. Reconstruction of breast areola complex. Comparison of different techniques. Handchir Mikrochir 2001;33:133-137. Kaufman CL. Marvin MR Chilton PM, el al Immunobiology in VCA. Transplant International. 2016:29|6|:644 654. Khalifian S Brazio PS Mohan R el al. Facial transplantation: Ihe I»st 9 yeais. lancet 2014:384:2153 - 2163. Koshy JC. Feldman EM. Duke -Obi CJ, et al. Pearls of mandibular trauma management. Semin Plast Surg 2010:24:357-374. Kraft R.Herndon ON. Al -Mousawi AM. et al. Burn size and survival probability in paediatric patents in modern burn care:a prospective observational cohort study.Lancet 2012;379:1013-1021. Kraut RY.Brown E, Korownyk.et al. The impact of breast reduction surgery on breastfeeding:systematic review of observational studies. PLoS One 2017;12:e0186591 Kuhn JE Lebus V GF. Bible JE. Thoracic outlet syndrome. J Am Acad Orthop Surg 2015:23:222 -232. lavigne E Holowaly EJ Pan SY et al. Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta - analysisof observational studies. BMJ 2013:346:12399. Liu C Bayer A , Cosgrove SE et al Infectious Diseases Society of America. Clinical practice guidelines by Ihe Infectious Diseases Society of Amcixa for Ihe treatment of melhicillin - resistant Staphylococcus aureus infections in adults and children Clin Inlecl Dis. 2011 Feb1;52( 3)»18 55. Merrell 6A Barrie KA Katz DL,el al. Results of nerve Iransfer techniques for restoration ol shoulder and elbow function in the con text of a meta - analysis of Ihe English literature. J Hand Surg Am 2001:26:303 - 314. Miller IJ. WilsonSC. MassieJP. etal. Breast augmentation in raale- to- female transgender patients: technical considerations andoutcomes.J Plast Reconstr Aes 2019;21:63-74. Morrison SD, Vyas KS. Motakef S, et al. Facial feminizati on: systematic review of the literature.Plast Reconstr Surg. 2016;137(6):1759 -1770. MuangmanP, Chuntrasakul C Silthram S, et al. Compar ison ol efficacy of silver sulfadiazine and Acti coat for treatment of paitial thickness burn wounds. J Med Assoc Thailand 2006:89:953- 958. Nahhas AF, Scarbrough CA Trotter S. Arevicw of Ihe global guidelines on surgical margins for nonmelanoma skin cancers J Clin Aesthet Dermatol. 2017 Apr;10(4):37 46. Neal SI Fields KB. Peripheral nerve entrapment and in|ury in the upper extremity, Am Fam Physician. 2010:81(21:147 155. Noble J. Textbook ol primary care medicine 3rd ed St. Louis: Mosby. 2001. Ong YS. Samuel M, Song C. Meta - analysis ol early excision of bums. Burns 2006;32:145 -150. Patel BC Skidmore K Hutchison J.etal.Cauliflower Ear. [Updated 2021 F eb 25. cited 2021 Jun 6).SlatPearls [Internet). Treasure Island (FL):SlatPearls Publishing. Available from: https:/ /wwvr.ncbi.nlm.nih.gov/ books/NBK470424i'. Patil RK. Koul AR. Early active mobilisation vs. immobilisation after extrinsic extensor tendon repair: a prospective randomised trial. IndianJ Plast Surg 2012:45(01):29 - 37. Peterson U. Peterson's principles of oral and maxillofacial surgery. Vol 1. Shelton: People's Medical Publishing House 2011. Chapter: Maxillofacial Trauma. Richards AM. Key notes in plastic surgery Great Britain: Blackwell Science 2002 Rybak MJ, Le J, Lodise IP et al. Therapeutic monitoring ol vancomycin for seiiousmelhicillin resislanl staphylococcus aureus infections: a revised consensus guidelineand review by the American Society of

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Health - System Pharmacists, the Infectious Diseases Society ol America, the Pediatric Infectious Oiseases Society, and the Society of Infectious Diseases and Pharmacists. Am J Health Syst Pharm 2020: 77:835. Salzberg CA, Ashikari AY.Koch RM, et al.An 8- year experience of direct - to-implant immediate breast reconstruction using humanacellular dermal matrix (Alio Derm).Plast Reconstr Surg 2011:127:514- 324. Schechter LS. Gender confirmation surgery. Springer Nature Switzerland AG 2020. Sermer NB. Piactical plastic surgery for nonsurgeons. Philadelphia: HanleyiBelfus, 2001. Sibbald RG, Williamson 0 Oistcd HI, et al. Preparing the wound bed - debridement, bacterial balance, and moisture balance. Ostomy Wound Manage 2000:46:44 - 35. Srmonacd F Burton N Glicco MP el al. Surgical therapy ol cutaneous squamous cell carcinoma: our experience Acta Bio Medica Alcnei Parm 2018:89( 2) 242 8 Singer AJ Hollander JE Subrainanian S etal. Pressure dynamics ol various irrigation lechnigues commonly used inthe emergency department. Ann Emerg Med 1994;24:36 - 40. Sisti A, Grimaldil, Tassinari J et al. Nipple-areola complex reconstruction techniques: a literature review. Eur J Surg Oncol 2016;42:441- 465. Shahriari H, Ferenczi K. Heald PVI . Breast implant - associated anaplastic large cell lymphoma: a review and assessment of cutaneous manifestations. Int J Womens Dermatology 2017;3:140 -144. Smith DJ, Brown AS Cruse CW et al.Plastic and reconstructive surgery Chicago:Plastic Surgery Educational Foundation 1987. Smith 7M Broyles JM Guo Y, et al Human acellular dermis increases surgical site infection and overall complication profile when compared with submuscular breast reconstruction: an updated meta - analysis incorporating new products J Plast Reconstr Acsthet Surg 2018;71:1547-1556. Spear SI Parikh PM Seisin E el al. Acellular dermis -assisted breast reconstruebon Aesthetic Plast Surg 2008:32:418- 425. Stevens DL BisnoAL Chambers HE,etal.Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2044 update by the Infectious Diseases Society of America.Clin Infect Dis 2O14:59:e10- e52. Slone C Plastic surgery: (acts. London:Greenwich Medical Media, 2001 Sun 6, Wu 7, Wang X et al: Nerve transfer helps repair brachial plexus injury by increasing cercbial cortical plasticity Neural Regen Res 2010:9:2111- 2114. fchcrnevG, Chokocva AA New safety margins for melanoma surgery: nice possibility ol drinking "|usl that cup ol codec ?" Open Access Maced J Med Sci 2016:5:352- 358 Ihotne CH Grabb i Smith's plastic surgery.6th ed.Philadelphia: Lippincott Williams S Wilkins, 2007. Townsend CM. Sabiston textbook of surgery - the biological basis of modern sugical practice 16th ed. Philadelphia: WBSaunders 2001. Chapter:plastic and reconstructive surgery. Wanq I. Regmi, S. Liu H. et al . Free lateral tarsal artery perforator flap with funeboning extensor digitorum brevis muscle lor thenar reconstruebon: a case report. Arch Orthop Itauma Surg 137.273 - 276 (2017). Wolff K, Johnson RA. Fitzpatrick's colour atlasand synopsis of clinical dermatology 6th ed. New York: McGraw -Hill 2009. Wcinzwelg J, Plastic surgery secrets Philadelphia: Hanley and Bcllus, 1999 Wilson SC Morrison SD. Anzai L, et al. Masculinizing top surgery: a systematic review of techniques and outcomes. Ann Plas Surg 2018:80(6):679 - 683. Zingg M. Laedrach K Chen J, et al. Classification and treatment of zygomatic fractures: a review of 1.025 cases. J Oral Maxillofac Surg 1992:50:778 - 790.

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Psychiatry Tania Da Silva, Kawaan Elsawi, and Rachel Goud, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors

Vijithan Sugumar, EBM editor

Dr. Saulo Castel, Dr. Tamara Milovic, and Dr. Jerome Perera, staff editors Acronyms

PS 2

Psychiatric Assessment History Mental Status Exam

PS2

Assessment and Plan

PS 4

.

Suicide

PS 5

Psychotic Disorders Differential Diagnosis of Psychosis Schizophrenia Schizophreniform Disorder Brief Psychotic Disorder Schizoaffective Disorder Delusional Disorder

PS7

Mood Disorders Mood Episodes Depressive Disorders Postpartum Mood Disorders Bipolar Disorders

PS10

Anxiety Disorders Panic Disorder Agoraphobia Generalized Anxiety Disorder Social Anxiety Phobic Disorders

PS15

.

PS 39

Personality Disorders

PS 42

Child Psychiatry Developmental Concepts Mood Disorders in Children and Adolescents Anxiety Disorders in Children and Adolescents

PS 44

Neurodevelopmental Disorders Autism Spectrum Disorder Attention Deficit Hyperactivity Disorder

PS 46

.

Disruptive, Impulse Control, and Conduct Disorder Oppositional Defiant Disorder Conduct Disorder Intermittent Explosive Disorder

PS 48

Psychotherapy

PS 49

Pharmacotherapy Antipsychotics Antidepressants Mood Stabilizers Anxiolytics

PS51

.

Obsessive- Compulsive and Related Disorders Obsessive Compulsive Disorder Related Disorders

PS19

Trauma - and Stressor -Related Disorders Post-Traumatic Stress Disorder Adjustment Disorder

PS20

Bereavement

PS22

Neurocognitive Disorders,

PS 23

-

Eating Disorders Anorexia Nervosa Bulimia Nervosa Binge-Eating Disorder Avoidant/Restrictive Food Intake Disorder

Delirium

Major Neurocognitive Disorder (Dementia) Substance-Related and Addictive Disorders

Somatic Therapies Repetitive Transcranial Magnetic Stimulation (rTMS) Magnetic Seizure Therapy (Experimental) Neurosurgical Treatments Other Therapy Modalities

PS 60

Canadian Legal Issues Common Forms Consent Community Treatment Order (CTO) Duty to Inform/Warn

PS62

Landmark Psychiatry Clinical Trials

PS64

References

PS 64

Nicotine Alcohol Opioids Cocaine Amphetamines

Cannabis Hallucinogens “Club Drugs” Somatic Symptom and Related Disorders PS33 Somatic Symptom Disorder Illness Anxiety Disorder Conversion Disorder (Functional Neurological Symptom Disorder)

Dissociative Disorders Dissociative Identity Disorder Dissociative Amnesia Depersonalization/ Derealization Disorder

PS35

Sleep Disorders

PS36

Sexuality and Gender. Gender Dysphoria Paraphilic Disorders

PS37

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LJ

Sexual Addiction Sexual Dysfunction

PS1 Psychiatry

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Acronyms 5 - HT

serotonin acetylcholine assertive community treatment attention deficit hyperactivity disorder activities of daily living anorexia nervosa autism spectrum disorder antisocial personality disorder bulimia nervosa cognitive behavioural therapy

ACh ACT ADHD

ADL AN

ASD

ASPD BN

CBT CD CRA

DBT D2 EOT EPS ERP

dialectical behavioural therapy dizygotic electroconvulsive therapy extrapyramidal symptoms exposure with response

GAD GMC IPT IADL

prevention generalized anxiety disorder general medical condition interpersonal therapy instructional activities of daily

conduct disorder

MBCT M6SR

CTO

community reinforcement approac community treatment order

DA

dopamine

MDD MDE

living mindfulness - based cognitive therapy mindfulness -based stress reduction major depressive disorder major depressive episode

MET Ml

MS t MST MZ NA NMS NOS

OCD OCP OCPD ODD PCP PD

motivational enhancement therapy motivational interviewing mental status examination magnetic stimulation therapy monozygotic Narcotics Anonymous neuroleptic malignant syndrome not otherwise specified obsessive - compulsive disorder oral contraceptive pill obsessive-compulsive personality disorder oppositional defiant disorder phencyclidine personality disorder

PDD

pervasive developmental

PTSD rTMS

disorder post - traumatic stress idisorder repetitive transcranial magnetic stimulation

SGA

second generation antipsychotics syndrome of inappropriate antidiuretic hormone secretion serotonin and norepinephrine reuptake inhibitors serotonin syndrome

S1ADH

SNRI

SS SSRI

selective serotonin rcuptake inhibitor tricyclic antidepr essant tardive dyskinesia extended-release

TCA

ro

XR

Psychiatric Assessment History Introduction • name, role, purpose, circumstances ( i.e. approximate time ) • limits of confidentiality ( i.e. safety of dependents, harm to self or others)

Identifying Data • necessary: name, age, gender ( preferred pronouns ), living situation (accommodation , independently, or with others), marital / relationship status, children , source of income/support , or occupation • adjunct: outpatient/inpatient, referral source, known/unknown to provider

Chief Complaint • in patient's own words, with duration of symptoms History of Present Illness • context: events, problems, stressors, losses, changes • symptoms: onset, duration, intensity, progression, fluctuation with day/season • impact on functioning: social, occupational, ADL/IADLs, personal care/survival • coping strategies, treatments, personal / professional supports • reason for seeking help that specific day • prior episodes/experiences , longitudinal course (duration / frequency ) • last period of wellness, changes to usual personality when unwell • opinions about cause /nature of concerns, willingness to engage, hopes/ expectations of treatment Psychiatric Functional Inquiry • mood: depression , mania • other: trauma, obsessions/compulsions, disordered eating • anxiety: worries, panic attacks, phobias, or social anxiety

• psychosis: hallucinations, delusions • safety / risk: self ( suicidal ideation / intent/plan ( see ,S'mc /< /c, PS5 ), self-harm , neglect ), others (homicide, aggression, violence), dependents ( children, elderly, disabled, pets), driving, cooking/ fires

Past Psychiatric History • previous psychiatric diagnoses and mental health contacts • hospitalizations: approximate total, date of last discharge • emergency department visits ( for mental health crisis) • suicide attempts: number, severity, medical intervention , most recent • self harming behaviour ( cutting ) • aggression / violence, legal ( charges) • treatments: pharmacological and non - pharmacological (effectiveness, side effects )

O

Screening Ouestions for Major Psychiatric Disorders • Have you been feeling down, depressed, or hopeless? • Do you feel anxious or worry about things? • Has there been a time in your life where you have felt euphoric, extremely talkative, had a lot of energy, and a decreased need for sleep? • Do you see or hear things that you think other people cannot? • Have you ever thought of harming yourself or killing yourself ?

Psychiatric Functional Inquiry MOAPS

Mood

Other (medical problems and substance use) Anxiety Psychosis Safety

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Substance Use History • type: tobacco, cannabis, alcohol, other (stimulants, hallucinogens, prescription drugs, gambling/ online) • use: first , typical, last , periods of abstinence • withdrawal symptoms ( i e. seizures , delirium tremens) • previous treatments: counselling , detox , groups • impact on symptoms, motivation to change

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PS3 Psychiatry Past Medical/Surgical History

• all medical, surgical, neurological ( i.e. head trauma, seizures) conditions/illnesses • allergies Medications

• names, doses, frequency

• adherence, effectiveness, side effects • over the counter, supplements Family Psychiatric/Medical History

• diagnoses, treatments, hospitalizations, suicide attempts, substance use, legal • perceptions regarding mental illness, engagement witn treatments • if relevant: any past medical or genetic illness

Always Remember to Ask About Abuse

See Family Medicine. FM30

Past Personal/Developmental History ( as relevant) • birthplace, immigration history ( if applicable), ethnicity/ nationality, religion /spirituality • family members: ages, occupations, personalities, quality of relationships • history of verbal, physical, or sexual abuse • prenatal and perinatal history: desired vs. unplanned pregnancy, maternal and fetal health, domestic violence, maternal substance use and exposures, complications of pregnancy/dclivery • early childhood to age 3: developmental milestones, temperament, family stability, primary

caregivers/attachment figures • middle childhood to age II : school performance, peer relationships, bullying, activity/ attention level, behavioural challenges • late childhood to adolescence: school performance, drugs/alcohol, legal problems, peer and family relationships, extra-curriculars • sexuality: puberty, gender identity, sexual orientation , sexual functioning /experiences, romantic relationships • adulthood: education, employment, relationships • hobbies, interests, sources of meaning, strengths, accomplishments, aspirations, hopes Collateral History • source, details provided

Mental Status Exam General Appearance

• age (chronological vs. apparent ), gender, ethnicity • posture, grooming, hygiene, manner of dress, body habitus, distinguishing features

• eye contact, facial expression, alertness • attitude: polite, friendly, collaborative, uncooperative, guarded /suspicious, evasive, agitated , aggressive/hostile • reliability (consistency, congruent with collateral), ease of building rapport • gait, psychomotor changes (slowing/agitation ), tics, tremors, tardive dyskinesia, dystonia , catatonia

Speech

Mental Status Exam

ASEPTIC Appearance and behaviour Speech Emotion ( mood and affect) Perception Thought content and process Insight and judgment Cognition

• rate ( i.e. pressured , slowed ), rhythm , volume, tone, quantity, spontaneity, latency, language fluency, articulation The MSE is analogous to the physical

Mood and Affect • mood : subjective emotional state ( in patient’s own words)

exam. It focuses on current signs, affect,

• mood congruence ( inferred by comparing the patient’s subjective mood with their affect ) • many clinicians use a 0- 10 scale (0: worst; 10: best ) when rating mood to get a subjective norm for each patient that can help to monitor changes over time and with treatment

Spectrum of Affect Full > Restricted > Blunted > Flat: quality (euthymic depressed, anxious, elated )

• affect: objective emotional state inferred from emotional responses to stimuli; described in terms of quality (euthymic, depressed , elevated , anxious, irritable) • range ( full, restricted , flat, blunted ) • stability ( continuum front fixed to labile)

behaviour, and cognition

.

Perception

• hallucination: sensory perception in the absence of appropriate stimuli that is similar in quality to a true perception • auditory (most common ), visual, gustatory, olfactory, tactile • illusion: misperception of a real external stimulus ( i.e. mistaking a coat on a rack as a person late at night) • depersonalization: change in self-awareness such that the person feels unreal, distant, or detached from their body, and /or unable to feel emotion • derealization: feeling that the world /outer environment is unreal

There Is poor correlation between clinical impression of suicide risk and frequency of attempts

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PS'l Psychiatry Thought Process/Form

• coherence (coherent, incoherent) • stream goal directed: clearly answers questions in a linear, organized, logical fashion circumstantial: speech that is indirect and delayed in reaching its goal; eventually comes back to the point tangential: speech is oblique or irrelevant; does not come back to the original point loosening of associations/derailment: illogical shifting between topics flight of ideas: quickly skipping from one idea to another where the ideas are marginally connected , usually associated with racing thoughts in mania • word salad: jumble of words lacking meaning or logical coherence • perseveration: repetition of the same verbal or motor response to stimuli • echolalia: repetition of phrases or words spoken by someone else • thought blocking: sudden cessation of flow of thought and speech • clang associations: speech based on sound such as rhyming or punning • neologism: use of novel words or of existing words in a novel fashion

-

Thought Content

• major themes discussed by patient • suicidal ideation / homicidal ideation: frequency and pervasiveness of thoughts, plan , intent , active vs.

passive, protective factors • preoccupations, ruminations: reflections/ thoughts at length, not fixed or false • obsession: recurrent and persistent thought , impulse, or image which is intrusive or inappropriate and

Cognitive Assessment Use MMSE to assess • Orientation (time and place) • Memory (immediate and delayed recall) • Attentlo n and concentration • Language (comprehension, reading, writing, repetition, naming) • Spatial ability (intersecting pentagons) Gross screen for cognitive dysfunction: Total score is out of 30; 75 yr sex: male race/ethnic background: White people or Indigenous peoples in Canada marital status: widowed /divorced living situation: alone; no children 6 mo 1 6 mo

Differential Diagnosis of Psychosis Approach • differentiate among psychotic disorders and distinguish them from other primary diagnoses with psychotic features • consider symptoms, persistence, and time • symptoms: the primary diagnosis needs full criteria to be met mood : depressive episodes with psychotic features, manic episodes with psychotic features psychotic: consider symptoms in Criterion A of schizophrenia (see Criteria for Schizophrenia , PS8 ) • persistence: is there a time when certain symptom clusters are present without other clusters ? i.e. if there is a period of time with mood symptoms, but not psychotic symptoms, consider mood

Figure 1. Differentiating psychotic disorders by duration

DDx for Psychosis

• Primary psychotic disorders:

•

disorder

i.e. if psychotic symptoms occur only with mood symptoms, consider mood disorder with

psychotic features • i.e. if during a 2 wk period where psychotic symptoms persist in the absence of mood symptoms,

•

-

consider schizoaffective disorder i.e. if long periods with psychotic symptoms and brief or rare mood symptoms, consider

schizophrenia • time: how long have the symptoms been present?

•

Table 1. Differentiating Psychotic Disorders Disorder

Psychotic Symptoms

Brief Psychotic Disorder

>1 positive symptoms ol Criterion

Schizophreniform Disorder

Criterion A

1 Gmo

Schizophrenia

Criterion A

>

Schizoaffective Disorder

Criterion A * major mood episode ( MDE or manic) >2 wk of psychotic symptoms without mood symptoms

>1

Delusional Disorder

>1 delusions|if hallucinations, lelatedto delusional theme)

>

A

Duration 2 mo • have never met criteria for MDE, manic, or hypomanic episodes • symptoms are not due to the direct physiological effects of a substance or GMC • symptoms cause clinically significant distress or impairment in social, occupational, or other

important areas of functioning Treatment • similar to Bipolar I: mood stabilizer ± psychotherapy

Monotherapy with antidepressants should be avoided in patients with bipolar depression as patients can switch horn depression into mania

The 4 L' s for Bipolar Depression Lithium, lamotriginc. Lurasidonc. SeroqueL

A Randoumed Controlled Trialof Cognitive Therapy for Bipolar Disorder:focus onloug -Teim Orange J Clin Psychiatry 2006:67:277 86 Purpose: lo evaluate long term change with cognitive therapy plus emotive techniques lor the treatment of bipolar disorder. Methods: 3 ded RCI including patents with DSM IV b poiar I or it disorder allocated to either a ( mo trial o!cognitive therapy (Cl) with emotive techniques or treatment as usual. Both groups received mood stobilirers. Main outcomes were relapse rates, dysfunctional attitudes, psychosocialfuncliomag, hopelessness, self control , and medication adherence. Patients were assessed by independent raters htnded to treatmentgroup. Results: At 6 no CT patients erepe rienced fewer depressive symptoms and fewer dysfunctional attitudes, ( here was a non sgr ficant ( p 0.06) trend to greater time to depressive relapse. At 12 mo follow up, CT patents had lower Toung Mania Rating scores and improved behavioural self control. At IB mo Cl patients repotted lets soveiity ol illness. Conclusions: Cl appears to piovide benefits in the 12 mo after completion ol therapy.

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Efficacy of Cognitive Behavioural Therapy in Patients with Bipolar Disorder: A Meta Analysis

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dRandomited Controlled Trials PLoS One 20 U;12|5|:e01/ 6849 Purpose: lo determine the efficacy of cognitive behavioural therapy (CBT) in the treatment of type I and II bipolar disorder. Methods: A systematic review and meta -arutyui of RCIs of Cll in the trealmeof of adults with bipolar disorder. Results: It nefeen RCIs includmg 1284 patients with type I or II BO weie included. C81 lowered the relapse rate|pooUd 0R*0.506; 95 \ 0 0.218 0.921) end improved depieisme symptoms|g 0.494; 95% CI - 0.963 to D.026), mania seventy ) 0.581:95% CM 127 to 0.035), and psychosodal functioning |g*0.45J ; 95\ 0*0.106 0.809). treater effects weie seen with CBI treatment duration > 90 mil. Relapse rates were lower in people with type I bipolar disorder. *

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Anxiety Disorders Definition

• fear is a universal human experience which can serve as an adaptive mechanism to facilitate appropriate reactions to external threat • anxiety may be seen as pathological fear when: fear is greatly out of proportion to risk /severity of threat response continues beyond existence of threat ( prolonged , excessive, etc.) or becomes generalized to other similar or dissimilar situations social or occupational functioning is impaired

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PS16 Psychiatry • manifestations of anxiety are a result of the activation of the sympathetic nervous system and can be described through: physiology: main brain structure involved is the amygdala; neurotransmitters involved include 5 HT, cholecystokinin , epinephrine, norepinephrine, and DA psychology: one’s thoughts about a given situation or stimulus contribute to the feeling of fear and

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perception of threat

• behaviour: anxiety can lead to avoidance which can perpetuate the fear /avoidance • often comorbid with substance use and depression; more than 50°u have multiple anxiety disorders

• when starting medication for anxiety: start low, go slow, aim high , and explain symptoms to expect prior to initiation of therapy to prevent non -adherence due to side effects

• psychotherapy: individual or group CBT Differential Diagnosis Table 2. Differential Diagnosis of Anxiety Disorders Post-Ml. arrhythmia, congestive heart failure pulmonary embolus,mitral valve prolapse

Cardiovascular Respiratory

,

Asthma. COPD. pneumonia

Endocrine

Hyperthyroidism, hypoglycemia, hyperadrenalism. hyperparathyroidism

Metabolic

Vitamin BUleficiency, folate deficiency, porphyria, hypoxemia.hypercalcemia

Neurologic

Neoplasm, vestibular dysfunction, encephalitis, trauma (contusion or hematoma). MS. temporal lobe epilepsy, migraine

Infectious

Cerebral (meningitis, HIV syphilis) or systemic

Gl

Gastritis, esophageal spasm

Substance-Induced

Intoxication ( caffeine, cannabis, amphetamines, cocaine, thyroid replacement, OTC for colds/ decongestants, steroids), withdrawal (benzodiazepines, alcohol)

.

Medical Workup of Anxiety Disorder • only proceed with medical workup as clinically indicated • routine screening: vitals, physical exam, CBC, electrolytes, thyroid function test, glucose, EGG • additional screening: extended electrolytes, vitamin Bi:, (5- HCG, folate, chest x- ray, any other tests as per DDx in Table 2 Risk Factors for the Development of Anxiety Disorders •

biological endocrine disorders ( i.e. hyperthyroidism ), respiratory conditions ( i.e. asthma ), CNS conditions (Le. temporal lobe epilepsy ), substances/ medications (Le. excessive stimulant use ), chronic medical illness personal or family history of anxiety or mood disorder • XX >XY chromosomes

• psychological • current stress, early childhood adversity or trauma , early parental loss, parental factors

Panic Disorder DSM- 5 DIAGNOSTIC CRITERIA FOR PANIC DISORDER

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders.Sth ed.2013. American Psychiatric Association

A. recurrent unexpected panic attacks; a panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time four ( or more) of the following symptoms occur palpitations, pounding heart, or accelerated heart rate sweating trembling or shaking sensations of shortness of breath or smothering feelings of choking • chest pain or discomfort • nausea or abdominal distress • feeling dizzy, unsteady, light - headed , or faint • chills or heat sensations paresthesias ( numbness or tingling sensations) ( feelings of unreality ) or depersonalization ( being detached from oneself ) derealization • • fear of losing control or "going crazy”

• fear of dying

B. at least one of the attacks has been followed by 1 mo (or more) of one or both of the following: persistent concern or worry about additional panic attacks or their consequences « a significant maladaptive change in behaviour related to the attacks C. the disturbance is not attributable to the physiological effects of a substance or another medical condition D. the disturbance is not better explained by another mental disorder

Situational trigger

Panic attack

Increased anxiety and generalization to other situations

Mentally associated with situation

t

]

Figure 2. Mechanism of panic attacks

Criteria for Panic Attack ( >4) STUDENTS FEAR the 3 Cs Sweating Trembling/shaking Unsteadiness, dizziness Depersonalization. Derealization Excessive heart rate, palpitations Nausea 'abdominal distress Tingling numbness Shortness of breath Fear of dying, losing control, going crazy 3 Cs: Chest pain, Chills hot flashes. Choking

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Duration typically 5-10 min

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Toronto Notes 2023

PS17 Psychiatry

Epidemiology

• lifetime prevalence: 5% (one of the top five most common reasons to see a family physician ); M:l = l :2 '

3

• onset: average early- mid 20s, familial pattern

• comorbidities: depression, agoraphobia, medical comorbidity Panic Attack vs. Panic Disorder Panic disorder requires recurrent unexpected panic attacks + fear of another panic attack . Panic attacks can occur in the context of many different disorders

Treatment • pharmacological and psychological treatment together can be very effective

.

• psychological CBT: exposure ( graduated exposure to unpleasant sensations of arousal associated with a panic attack for experiential disconfirmation of their fears), cognitive restructuring (addressing underlying beliefs regarding the panic attacks), relaxation techniques ( visualization, box breathing ), psychoeducation • pharmacological ( first line agents) • SSKIs: fluoxetine, citalopram , escitalopram, paroxetine, sertraline, fluvoxamine SNR!: venlafaxine extended release • with SSKI /SNKls, start with low doses and titrate up as tolerated • anxiety disorders often require treatment at higher doses for a longer period of time than depression (full response may take up to 12 wk ) treat for up to 1 yr after symptoms resolve to avoid relapse explain expected adverse effects prior to initiation of therapy to prevent non -adherence other antidepressants: ( mirtazapine, TCAs) benzodiazepines considered 2nd line (short-term, lowest effective dose, helpful while titrating antidepressant)

Starting Medication for Anxiety Start low. go slow, aim high , and explain symptoms to expect prior to initiation of therapy to prevent non-adherence due

Prognosis

to side effects

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• 85% can achieve good results, 10 20% continue with significant symptoms. Longer term , 65% achieve remission

• clinical course: chronic, but episodic with psychosocial stressors

Agoraphobia DSM- 5 DIAGNOSTIC CRITERIA FOR AGORAPHOBIA

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Reprinted with permission from the Diagnostic and Statistical Manual ol Mental Disorders , 5th cd 2013. American Psychiatric Association

A. marked fear or anxiety about two (or more) of the following five situations: • using public transportation being in open spaces being in enclosed places standing in line or being in a crowd

being outside of the home alone B. the individual fears or avoids these situations because of thoughts that escape might be difficult or help might not be available in the event of developing panic like symptoms or other incapacitating or embarrassing symptoms C. the agoraphobic situations almost always provoke fear or anxiety D. the agoraphobic situations are actively avoided , require the presence of a companion , or are endured with intense fear or anxiety L the fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations and to the sociocultural context !•' the fear, anxiety, or avoidance is persistent, typically lasting S6 mo G. the fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning H. if another medical condition is present, the fear, anxiety, or avoidance is clearly excessive I. the fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder and are not related exclusively to obsessions, perceived defects or flaws in physical appearance, reminders of traumatic events, or fear of separation Note: agoraphobia is diagnosed irrespective of the presence of panic disorder. If an individual's presentation meets criteria for panic disorder and agoraphobia , both diagnoses should be assigned

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Treatment

• as per specific panic disorder

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PS18 Psychiatry

Generalized Anxiety Disorder DSM- 5 DIAGNOSTIC CRITERIA FOR GENERALIZED ANXIETY DISORDER Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Sth ed . 2013. American Psychiatric Association A.excessive anxiety and worry (apprehensive expectation ), occurring more days than not for at least 6 mo, about a number of events or activities ( such as work or school performance )

B. the individual finds it difficult to control the worry C. the anxiety and worry are associated with three (or more) of the following six symptoms (svith at least some symptoms having been present for more days than not for the past 6 mo) 1. restlessness or feeling keyed up or on edge 2. being easily fatigued 3. difficulty concentrating or mind going blank 4. irritability 5. muscle tension 6. sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep) D.the anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning E. the disturbance is not attributable to the physiological effects of a substance or another medical

.

Criteria for GAD (>3) C-FIRST Concentration issues Fatigue Irritability Restlessness Sleep disturbance Tension (muscle)

condition

l: the disturbance is not better explained by another mental disorder Epidemiology

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• I yr prevalence: 1 4%, lifetime prevalence 6%; M:l = l :2 8% of all who seek primary care treatment ( WHO) • in primary care: 70% initially present with physical symptoms as main concern • bimodal age of onset: before 20 or middle adulthood

.

Source: Depression and other common mental disorders: Global health estimates. Geneva:World Health Organization 2017.

Treatment

• lifestyle: avoid caffeine and EtOH, sleep hygiene • psychological: CBT (cognitive restructuring), muscle relaxation techniques, mindfulness • biological 1st line: SSRIs (escitalopram, sertraline, paroxetine), SNRls (venlafaxine XR, duloxetine), pregabalin benzodiazepines considered 2 nd line (short -term, lowest effective dose, helpful while titrating antidepressant ) • (1- blockers not recommended Prognosis

• good with treatment • depends on pre morbid personality functioning, stability of relationships, work, and severity of

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environmental stress

Social Anxiety • definition: marked and persistent ( >6 mo) fear of social or performance situations in which one is exposed to unfamiliar people or to possible scrutiny by others. They fear that they will be negatively evaluated in a way that may be humiliating, embarrassing, or lead to rejection (e.g. public speaking, initiating or maintaining conversation, dating, eating in public) • situations are avoided or endured with intense anxiety and causes significant distress or impairment in functioning • lifetime prevalence 8-12%; M:F ratio approximately equal

Phobic Disorders Specific Phobias

• definition: marked and persistent ( >6 mo) fear that is excessive or unreasonable, cued by presence or anticipation of a specific object or situation

• lifetime prevalence 10- 13%; M:l; ratio variable • types: animal /inscct, environment (e.g. heights, storms), blood / injection / injury, situational ( e.g. airplane, closed spaces), other ( e.g. loud noise, clowns), multiple fears

Diagnostic Criteria for Phobic Disorders

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• marked fear/anxiety about a specific object/situation • exposure to stimulus almost invariably provokes an immediate fear /anxiety response; may present as a panic attack • phobic object/situation is actively avoided or endured with intense anxiety. • fear/anxiety out of proportion to actual danger/sociocultural context and persistent ( lasting 6 mo or

+

more) • person recognizes fear as excessive or unreasonable • significant impact on daily routine, occupational /social functioning, and /or marked distress

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Toronto Notes 2023

PS19 Psychiatry

Treatment • psychological: psychoeducation, CBT (focusing on both in vivo and virtual exposure therapy, gradually facing feared situations)

• biological: minimal role for medications

Obsessive-Compulsive and Related Disorders Obsessive- Compulsive Disorder DSM- 5 DIAGNOSTIC CRITERIA FOR OBSESSIVE-COMPULSIVE DISORDER

.

Reprinted with permission horn the Diagnostic and Statistical Manual of Mental Disorders 5th ed.2013.American Psychiatric Association

A. presence of obsessions, compulsions, or both * obsessions are defined by (1) and ( 2) 1. recurrent and persistent thoughts, urges, or images that are experienced, at some time during the disturbance, as intrusive and unwanted, and that in most individuals cause marked anxiety or distress 2. the individual attempts to ignore or suppress such thoughts, urges, or images, or to neutralize them with some other thought or action (Le. by performing a compulsion) compulsions are defined by (1) and (2) 1. repetitive behaviours (e.g. hand washing, ordering, checking ) or mental acts (e g. praying, counting, repeating words silently) that the individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly 2. the behaviours or mental acts are aimed at preventing or reducing anxiety or distress, or pres enting some dreaded event or situation; however, these behaviours or mental acts are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive B. the obsessions or compulsions are time -consuming (e.g. take >1 h /d ) or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning C.the obsessive-compulsive symptoms are not attributable to the physiological effects D.the disturbance is not better explained by the symptoms of another mental disorder • specifiers: with good or fair insight, with poor insight, with absent insight /delusional beliefs, ticrelated • most common obsessions: contamination fear, pathological doubts, harm (sex, aggression ), somatic dysfunctions, need for symmetry, religious • most common compulsions: checking, washing, repeating, ordering, counting, need to ask, and

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hoarding • rituals serve to counteract the anxiety induced by the obsessive thoughts Epidemiology

• lifetime prevalence 3% • mean age of onset: 20 yr, onset after 35 yr rare • rate of OCD in first degree relatives is higher than in the general population • common comorbidities: anxiety disorders ( >75%), depressive or bipolar disorder (>60%), obsessive compulsive PD, tic disorders, substance use disorder, body dysmorphic disorder, trichotillomania, and excoriation disorder

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Risk Factors • etiology unknown but linked with: neurological abnormalities: neurological dysfunction (brain injury, Sydenham’s or Huntington’s chorea ), abnormal EEG, and abnormal evoked auditory potentials family history of OCD or 'l'ourette’s disorder paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) in children following group A p-streptococcal infection; also linked to D8/ 17 antigen positivity • social isolation, physical abuse, negative emotionality Treatment

• CBT: ERP which involves exposure to feared situations using various techniques (e.g. imaginal exposure, systematic desensitization , flooding ) with the addition of preventing the compulsive behaviours; cognitive strategies include challenging underlying beliefs • pharmacotherapy: SSRls ( 12 -16 wk potential delay until response, higher therapeutic dosages than used for depression ), clomipramine; adjunctive antipsychotics ( risperidone, aripiprazole) for refractor)- OCD • neurosurgery or neurostimulation: anterior cingulotomy for severe refractory OCD, two techniques: radiofrequency thermolesion and gamma knife capsulotomy or cingulotomy (50-70% response rate ); ECT (particularly for those with comorbid severe depression )

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Prognosis • may be refractor) and chronic with waxing and waning symptoms ( 1 perceived flaws in physical appearance not observed by others repetitive behaviours (e.g. mirror checking, excessive grooming, skin picking, or reassurance seeking ) or mental acts (e g. comparing self to others) related to appearance

.

± muscle dysmorphia causes clinically significant distress or functional impairment rule out eating disorder mean age of onset: 15 y/o symptoms tend to be chronic; high rate of suicidal ideation and attempts; comorbidity with MDD, social anxiety disorder, and OCD treatment: SSRls, CBT (specific to body dysmorphic disorder) Hoarding Disorder

• persistent difficulty discarding possessions regardless of actual value • feels the need to save items, discarding creates distress • results in possessions cluttering/ compromising active living areas ( may be uncluttered with 3rd party intervention , i.e. family member, cleaners, authorities) • causes clinically significant distress or functional impairment • rule out brain injury, cerebrovascular disease, Prader-Willi syndrome, OCD, MDD ( low energy ), psychotic disorder (delusions), neurocognitive disorder, ASD (restricted interests) • tends to begin in teens and worsens over time, more common in older populations, large genetic

component • treatment: CBT ( specific to hoarding disorder) Trichotillomania (Hair-Pulling Disorder )

• recurrent pulling out own hair resulting in hair loss ( usually involves scalp, eyebrows, or eyelashes but may include other hair ) • repeated attempts to stop or decrease hair pulling • causes clinically significant distress or functional impairment • rule out dermatological condition, body dysmorphic disorder • treatment: CBT (habit reversal training), SSRls, 2 nd gen. antipsychotics, N -acetylcysteine, or lithium Excoriation (Skin-Picking) Disorder recurrent skin picking resulting in lesions

• repeated attempts to stop or decrease skin picking • causes clinically significant distress or functionalimpairment • rule out scabies, substance use (e.g. cocaine), psychotic disorder (e.g. delusions, tactile hallucinations),

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body dysmorphic disorder, stereotypic movement disorder, non suicidal self injury • treatment similar to trichotillomania (described above)

Trauma- and Stressor-Related Disorders Post-Traumatic Stress Disorder DSM- 5 DIAGNOSTIC CRITERIA FOR POST- TRAUMATIC STRESS DISORDER

.

.

Reprinted with permission Irom the Diagnostic and Statistical Manual of Mental Disorders 5th ed. 2013. American Psychiatric Association

A.exposure to actual or threatened death , serious injury, or sexual violence in one (or more) of the

following ways: 1. directly experiencing the traumatic event(s) 2. witnessing, in person, the event(s) as it occurred to others 3. learning that the traumatic event (s) occurred to a close family member or close friend; in cases of actual or threatened death of a family member or friend , the event(s) must have been violent or accidental 4. experiencing repeated or extreme exposure to aversive details of the traumatic event (s) (e g first responders collecting human remains: police officers repeatedly exposed to details of child abuse) B. presence of one (or more) of the following intrusion symptoms associated with the traumatic event(s), beginning after the traumatic event(s) occurred: 1. recurrent, involuntary, and intrusive distressing memories of the traumatic event(s) 2. recurrent distressing dreams in which the content and/or affect of the dream are related to

..

The Trauma Triangle

The perpetrator The victim The rescuer

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the traumatic event(s) 3. dissociative reactions (e.g. flashbacks) in which the individual feels or acts as if the traumatic event(s) were recurring 4. intense or prolonged psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic cvent(s) 5. marked physiological reactions to internal or external cues that symbolize or resemble an aspect of the traumatic event(s)

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PS21 Psychiatry

C. persistent avoidance of stimuli associated with the traumatic event(s), beginning after the traumatic event (s) occurred , as evidenced by one or both of the following: 1. avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s) 2. avoidance of or efforts to avoid external reminders ( people, places, conversations, activities, objects, situations) that arouse distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s) D.negative alterations in cognitions and mood associated with the traumatic event ( s), beginning or worsening after the traumatic event(s) occurred, as evidenced by two (or more) of the following: 1. inability to remember an important aspect of the traumatic event(s) 2. persistent and exaggerated negative beliefs or expectations about oneself, others, or the world 3. persistent, distorted cognitions about the cause or consequences of the traumatic event(s) that lead the individual to blame himself/herself or others 4. persistent negative emotional state (e.g. fear, horror, anger, guilt, or shame) 5. markedly diminished interest or participation in significant activities 6. feelings of detachment or estrangement from others 7. persistent inability to experience positive emotions E. marked alterations in arousal and reactivity' associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred, as evidenced by two (or more) of the following: 1. irritable behaviour and angry outbursts ( with little or no provocation ) typically expressed as verbal or physical aggression toward people or objects 2. reckless or self destructive behaviour 3. hypervigilance 4. exaggerated startle response 5. problems with concentration 6. sleep disturbance (e.g. difficulty falling or staying asleep or restless sleep) E duration of the disturbance (criteria B, C, D, and E ) is more than 1 mo G. the disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning H.the disturbance is not attributable to the physiological effects of a substance or another medical condition • specifiers: with dissociative symptoms ( not attributable to physiologic effects of a substance or a medical condition ): this could involve either depersonalization ( persistent or recurrent experiences of feeling detached from, or as if one were an outside observer of one’s mental processes or body) or derealization ( persistent or recurrent experiences of unreality of surroundings) with delayed expression: the full diagnostic criteria are not met until 6 mo after the event

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Epidemiology

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Criteria for Post Traumatic Stress Disorder TRAUMA Traumatic event Re-experience the event Avoidance of stimuli associated with the trauma Unable to function More than a Month Arousal increased negative alterations in cognition and mood

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•lifetime prevalence in Canada is 9%; onset in mid -late 20s •75% have another comorbid psychiatric disorder; increased risk of suicide 2-3x • high rates of chronic pain, sleep problems, sexual dysfunction , cognitive dysfunction • prevalence F:M=2:1 • most common forms of trauma: unexpected death of someone close, sexual assault, serious illness or injury to someone close, physical assault by partner or caregiver • risk factors: severity, duration , and proximity to trauma • differential diagnosis: bipolar disorder, borderline personality disorder, acute stress disorder ( 3 d 1 mo after trauma)

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Treatment

• trauma therapy, CBT stage 1 - safety and stabilization: emotional regulation techniques ( i.e. breathing, relaxation ) to help build coping skills, medications for FI'SD, manage substance use stage 2 - remembrance and mourning: exposure to traumatic memories and work through distorted thoughts, relational patterns, and grief stage 3 - reconnection and integration: exposure therapy, etc. create a new future, new relationships, strengthen identity •early intervention via psychological support ( not de-briefing ) •psychotherapy: CBT, DBT, supportive, eye movement desensitization and reprocessing ( EMDR) •biological • first line: fluoxetine, paroxetine, sertraline, venlafaxine XR (50-80% response with residual symptoms is common ) prazosin ( for treating disturbing dreams and nightmares) benzodiazepines ( for acute anxiety; use with extreme caution ) adjunctive atypical antipsychotics ( risperidone, olanzapine)

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Prognosis and Complications

• substance use disorder, relationship difficulties, depression , impaired social and occupational functioning disorders, personality disorders •50% of patients with FI SD have complete recovery' within 3 mo, symptoms tend to diminish with age

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Toronto Notes 2023

PS22 Psychiatry

Adjustment Disorder Definition • a diagnosis encompassing patients who have difficulty coping with a stressful life event or situation and develop acute, often transient, emotional or behavioural symptoms that resemble less severe versions of other psychiatric conditions

Acute Stress Disorder • May be a precursor to PTSO

• Similar symptoms to PISD • Symptoms persist for 3 d to1 mo after exposure to a trauma

DSM- 5 DIAGNOSTIC CRITERIA FOR ADJUSTMENT DISORDER

.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders Sth ed. 2013.American Psychiatric Association

A.the development of emotional or behavioural symptoms in response to an identifiable stressorfs) occurring within 3 mo of the onset of the stressor(s) B.these symptoms or behaviours are clinically significant as evidenced by either of the following: marked distress that is in excess of what would be expected from exposure to the stressor • significant impairment in social or occupational (academic) functioning C.the stress-related disturbance does not meet criteria for another mental disorder and is not merely' an exacerbation of a pre-existing mental disorder D.the symptoms do not represent normal bereavement h.once the stressor (or its consequences) has terminated, the symptoms do not persist for more than an additional 6 mo • specifiers: with depressed mood, with anxiety, with mixed anxiety/depression, with conduct disturbance, with mixed disturbance of conduct/ emotions, unspecified Classification • types of stressors • single (e.g. termination of romantic relationship ) multiple (e.g. marked business difficulties and marital problems) • recurrent (e.g. seasonal business crises) continuous (e.g. living in a crime ridden neighbourhood ) • developmental events (e.g. going to school, leaving parental home, getting married, becoming a parent, failing to attain occupational goals, retirement )

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Epidemiology

• FM=2:1, prevalence 2-8% of the population Treatment • brief psychotherapy: individual or group ( particularly useful for patients dealing with unique and specific medical issues; e.g. colostomy or renal dialysis groups), crisis intervention • biological: medications can be used to treat associated symptoms ( insomnia, anxiety, or depression ) benzodiazepines may be used for those with significant anxiety symptoms (short term, low dose, regular schedule)

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Bereavement Clinical Features • bereavement or grief is a reaction (involving thoughts, feelings, behaviours, and physiological responses) to significant loss, typically the death of a loved one; mourning is the process of integrating and adapting to the loss • length and characteristics of “normal" bereavement vary between individual cultures • normal response: protest 4 searching and acute anguish -» despair and detachment -> reorganization • presence of the following symptoms may indicate abnormal grief / presence of MDD: • guilt about things other than actions taken or not taken by the survivor at the time of death thoughts of death other than the survivor feeling that they would be better off dead or should have died with the deceased person; morbid preoccupation w ith worthlessness • marked psychomotor retardation; prolonged and marked functional impairment • hallucinatory experiences other than hearing the voice or transiently seeing the image of the deceased person dysphoria that is pervasive and independent of thoughts or triggers of the deceased; absence of mood reactivity • after 12 mo, if patient continues to vearn / long for the deceased , experience intense sorrow/emotional pain in response to the death , remain preoccupied with the deceased or with the circumstances of their death, then may start to consider a diagnosis of “persistent complex bereavement disorder" • if a patient meets criteria for MDD, even in the context of a loss or bereavement scenario, they are still

Risk Factors for Poor Bereavement Outcome • Poor social supports • Unanticipated death or lack of preparation for death • Highly dependent relationship with deceased • High initial distress Other concurrent stresses and losses Death of a child • Pre existing psychiatric disorders, especially depression and separation anxiety

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Bereavement is associated with a significant increase in morbidity and mortality acutely following the loss, with effects seen up to 1 yr after ri LJ

diagnosed with MDD Treatment • support and watchful W'aiting should be first line, as well as education and normalization of the grief

process • management should include assessment for secondary mental health or medical conditions, such as PTSD, depression , suicidal ideation, increaased substance use, and cardiovascular illnesses

Loneliness is the most common symptom that continues to persist in normal bereavement and may last several years

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PS23 Psychiatry

• normal grief should not be treated with antidepressant or anti-anxiety medications as it is important to allow the person to experience the whole mourning process to achieve resolution • psychosocial: grief therapy ( individual or group) is indicated for those needing additional support or experiencing complex grief / hereavement or significant MOD • pharmacotherapy: if MOD present , past history of mood disorders, or severe symptoms

s

Neurocognitive Disorders Delirium • see Neurology. N21 DSM- 5 DIAGNOSTIC CRITERIA FOR DELIRIUM Reprinted with permission Irom the Diagnostic and Statistical Manual ol Mental Disorders. Sth ed. 2013. American Psychiatric Association A a disturbance in attention ( i e reduced ability to direct, focus, sustain , and shift attention ) and awareness ( i.e. reduced orientation to the environment ) B. the disturbance develops over a short period of time ( usually hours to a few days ), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day C.an additional disturbance in cognition (e.g. memory deficit, disorientation, language, visuospatial ability, or perception )

.

..

D.the disturbances in criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal ( e.g. coma ) E. there is evidence from the history, physical exam , or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e. due to a drug of abuse or to a medication ), or exposure to a toxin, or is due to multiple etiologies

Confusion Assessment Method (CAM ) for Diagnosis of Delirium

Highly sensitive and specific method to diagnose delirium Ftort 1: an assessment instrument that screens for overall cognitive impairment Part 2: includes four features found

best able to distinguish delirium from other cognitive impairments Need (1) (2) (3 or 4) (1) Acute onset and fluctuating course ( 2) Inattention (3) Disorganized thinking (4) Altered level of consciousness hyperactive or hypoactive

Clinical Features

• common symptoms

• disturbance of attention: distractibility, disorientation ( time, place, rarely person )

• sleep/ wake disturbance (daytime sedation , nighttime agitation or wakefulness) psychotic-like symptoms such as delusions, misinterpretations, illusions, and hallucinations (visual hallucinations are organic until proven otherwise) affective symptoms (anxiety, fear, depression, irritability, anger, euphoria, apathy) • shifts in psychomotor activity ( groping / picking at clothes, attempts to get out of bed when unsafe, sudden movements, sluggishness, lethargy ) • note: fluctuation / major changes in all of the above over the course of the day are to be expected so collateral history is important • hyperactive 30% vs. hypoactive 24% vs. mixed level of activity 46%

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Risk Factors

• a wide range of medical conditions can precipitate delirium in a susceptible individual and there may be multiple underlying etiologies as a result • polypharmacy particularly involving psychoactive drugs, anticholinergics, and serotonergic

medications (e.g. Cogentin , Benadryl*, benzodiazepines, opioids, and corticosteroids) • infection, dehydration, malnutrition, immobility ( including use of restraints), and use of bladder catheters • hospitalization (incidence 10-56%); frail and surgical patients are at the greatest risk • previous delirium • nursing home residents ( incidence 60% ) • old age (especially males ) • severe illness (e.g. cancer, AIDS ) • recent anesthesia or surgery (e.g. emergency hip fracture surgery, cardiac surgery) • brain vulnerability: pre-existing neurologic or neurocognitive disorder, substance use disorder, past psychiatric illness

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Etiology of Delirium

I WATCH DEATH Infectious (encephalitis, meningitis, urinary tract infection, pneumonia) Withdrawal (alcohol, barbiturates, benzodiazepines)

Acute metabolic disorder (electrolyte imbalance, hepatic or renal failure) Trauma ( head injury, postoperative) CNS pathology (stroke, hemorrhage, tumour, seizure disorder, Parkinson's) Hypoxia (anemia , cardiac failure, pulmonary embolus) Deficiencies (vitamin Bui, folic acid, thiamine) Endocrinopathies ( thyroid , glucose, parathyroid , adrenal) Acute vascular (shock, vasculitis, hypertensive encephalopathy) Toxins: substance use, sedatives, opioids (especially morphine), anesthetics, anticholinergics, anticonvulsants, dopaminergic agents, steroids, insulin, glyburide, antibiotics (especially quinolones), NSAIDs Heavy metals (arsenic, lead, mercury)

Assessment

• observation: for disturbances in consciousness, incoherent and /or disorganized speech , inability to

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concentrate upon conversation, disruption of sleep wake cycle • history: often gathered from collateral sources as patients may be confused and/or uncooperative • clinical instruments: Confusion Assessment Method (CAM ) and formal mental status testing, such as the Mini-Mental State Examination , used as needed, are helpful for baseline and ongoing assessment of altered mental state ( i.e. score will improve as symptoms resolve) • physical examination: may be difficult to perform; focus on vital signs, hydration status, potential infectious foci , unambiguous neurologic deficits, and suggestive features of general appearance (e.g. jaundice ) • medication review: drug toxicity accounts for approximately 30% of all delirium cases (including OTC, non-prescribed medications)

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Toronto Notes 2023

PS24 Psychiatry

Investigations • standard bloodwork: CBC and differential, electrolytes ( including Ca -% Mg-’, and PO-ti ), glucose, BUN, Cr, TSH /T4, LFI's, vitamin Bi’, folate, albumin , toxicology screen; if indicated, order blood cultures and infectious serologies ( HIV VDRL, Hep B/C) • standard imaging: CXR and CT head (indicated especially if focal neurological deficit, acute change in status, anticoagulant use, acute incontinence, gait abnormality, Hx of cancer ); if indicated , abdominal x ray for constipation and MK1 head to detect or exclude subacute stroke and multifocal inflammatory lesions in patients with negative head CT • standard urinalysis: urine dip; if indicated, urine drug screen, urine C&S if indicated; lumbar puncture and EEG (typical finding in delirium is generalized slowing, can also be used to rule out underlying seizures or post-ictal states as etiology')

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Management • goal is to treat the underlying causes of delirium while minimizing the physical and psychological distress to the patient • step I: identify and manage underlying cause

identify and treat underlying cause immediately stop all non essential medications maintain nutrition , hydration, electrolyte balance, and monitor vitals work to ensure regular bowel movements and skin care practices to present pressure ulcers • step 2: optimize the environment environment: quiet, well-lit, near window for cues regarding time of day » optimize hearing and vision; protect sleep (with medications if need be) room near nursing station for closer observation; constant care if patient climbing out of bed, pulling out lines • family member present (or consider 1:1 sitter) for reassurance and re-orientation • frequent orientation: calendar, clock, reminders • avoid frequent changes of assigned nursing staff as well as room transfers implement falls prevention strategies and enable safe mobility physical restraints to maintain safety only if necessary; minimize lines and catheters calm , supportive approach; therapeutic communication • step 3: pharmacotherapy low dose, high potency antipsychotics: haloperidol has the most evidence and can be given IV or 1M; initiate Haldol* 0.5-1 mg IM/IV in elderly patients ql -2 h until agitation is under control for STAT or PRN situation; 0.5-2 mg PO q4-6 h - monitor for signs of EPS and QT prolongation alternatives include risperidone, which is less sedating (0.25-03 mg PO BID; less sedating), olanzapine ( more sedating, can be anticholinergic itself ), quetiapine (if EPS sensitive but risk of hypotension; 6.25-50 mg PO qHS), aripiprazole (does not prolong QTc) caution: all neuroleptics prolong the QT interval and decrease seizure threshold , thus increasing risk of cardiac arrhythmias and seizures, respectively; also, patients with Parkinson's disease or Lewy body dementia are particularly at high risk of EPS ECG to assess QT interval when considering treatment with an antipsychotic agent benzodiazepines only used in alcohol/substance withdrawal delirium; otherwise, can worsen delirium (antipsychotics are not useful in EtOH or benzodiazepine withdrawal delirium); however, benzodiazepines should not be stopped if they are a long-standing medication or this may precipitate the delirium try to minimize drugs with anticholinergic effects • note: antipsychotic medications are used in delirium to treat severe patient agitation, changing delirium from the hyperactive to hvpoactive state; they do not treat the underlying “acute brain state" driving the delirium

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Factors favouring psychosis over delirium t. Auditory hallucinations that are structured and consistent 2. fersonal or family history of psychosis 3. Gradual onset (unless substance induced) 4. History of a prodrome (insidious functional decline) Factors favouring delirium over psychosis 1Visual or tactile hallucinations 2. Acute onset 3. No previous history of psychosis 4. Sleep wake changes 5. More global cognitive impairment 6. Recent medical illness/medication changes

iBtenmtmas fur Preventing Delirium in Hosyitafizeit Non-ICU Patients

Cnctrane DU Syst Rev 2016:00005563 Purpose: Is assess effectiveness of interventions to pretest ffeSnam in hospitalized patients in the nos-lCll setting. Methods: Hi s study included RCTs on both phamacologital and non pharmacological mtemectrons for delirium in hospitalized patients in

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the oos-lCtl setting. lesults: iff t als involving 1(082 patients assessing 22 Afferent isterreetions were included. Strong entente was identified In support the use of nlb-coapoaent interventions for the prevention of deism.Ibltcomponeiit interventions include ay utervention that uses nun-pharmacological approaches to target multiple risk factorsfor deirn.Use of die (.spectral index to monitor acesres a reduced incidence of postoperative deirwa.hidenee tn date dues not support the use af cci esterase inhibitors, antipsychotics or metetosia to reduce incidence of delirium

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Prognosis

• up to 50% I yr mortality rate after episode of delirium

Major Neurocognitive Disorder (Dementia) • see Neurology, N 22 DSM-5 DIAGNOSTIC CRITERIA FOR MAJOR NEUROCOGNITIVE DISORDER Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Slh ed. 2013.American Psychiatric Association

A.evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition ) based on 1. concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function;

and 2. a substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment B.the cognitive deficits interfere with independence in everyday activities ( i.e. at a minimum, requiring assistance with complex IADLS such as paring bills or managing medications) Cthe cognitive deficits do not occur exclusively in the context of a delirium

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Toronto Notes 2023

PS25 Psychiatry

D.the cognitive deficits are not better explained by another mental disorder (e.g. major depressive disorder, schizophrenia) Note: if deficits do not interfere (as in B ) and cognitive impairments are mild-moderate (as in A.2), this is considered “ mild neurocognitive disorder;” see Neurology N22

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Specify whether due to:

• Alzheimer's disease • frontotemporal lobar degeneration • Lewy body disease • vascular disease

• traumatic brain injury • normal pressure hydrocephalus •substance/medication use • HIV infection • Prion disease • Parkinson’s disease • Huntington's disease • another medical condition (e.g. nutritional deficiency ) • multiple etiologies • unspecified • also specify if mild, moderate or severe; major neurocognitive disorder diagnosis requires an impairment in functioning Epidemiology • prevalence increases with age: 5% in patients >65 yr, 35-50% in patients >85 yr • probability of dementia in an older person with reported memory loss is estimated to be 60 % • prevalence is increased in people with Downs syndrome and head trauma • Alzheimer's disease comprises > 50% of cases; vascular causes comprise approximately 15% of cases ( other causes of dementia neurocognitive disorder see Neurology N 23) • disease course: insidious onset, usually leading to death within 8 10 yr of first symptoms

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Subtypes

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The 7 As of Dementia Amnesia: loss of memory Aphasia: loss of language ability Apraxia: loss of ability to carry out purposeful movement Agnosia: no longer rccogniics things through the senses Anosognosia: not knowing what one does not know Apathy: loss of Initiative Altered perception

• with or without behavioural disturbance (e.g. wandering, agitation ) •early-onset: 65 yr Assessment and Investigations (to rule out reversible causes ) • history: consider the 7 A’s of dementia, significant changes in ADls and IADLS, medication compliance and substance use, risk factors for dementia and delirium , mood / anxicty and psychotic symptoms, screen for non - Alzheimer’s dementias, assess safety and consent /capacity issues tests (e.g. MMSE, Rowland Universal Dementia Assessment Scale, frontal Assessment cognitive •

The "Mini Cog” Rapid Assessment 3 word immediate recall Clock drawn to “10 past 11“

3 word delayed recall

Battery, MoCA )

• MoCA 18-25 suggestive of mild neurocognitive disorder ( NCD ), 1 yr after cognitive decline, fluctuating degree of cognitive impairment, sleep disturbances • Vascular disease (15 30%); vascular risk factors, focal neurological signs, abrupt onset, stepwise progression, executive dysfunction > memory impairment personality and mood changes (loss of motivation) Normal pressure hydrocephalus: abnormal gait (“magnetic gait”), early incontinence, rapidly progressive; dilated ventricles on imaging

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Substance- Related and Addictive Disorders Overview • substance use disorder ( SUD): a neurobiological disorder involving compulsive drug seeking and drug taking, despite adverse consequences, with loss of control over drug use ( think issues with the “3 Cs”: compulsive, consequences, control ) • it is possible to have a substance use disorder without physiological dependence ( i.e. withdrawal syndrome or tolerance); dependence is the hallmark of substance use disorders and comes in the following forms: behavioural: substance-seeking activities and pathological use patterns physical: physiologic withdrawal effects without use or tolerance • cognitive: continuous or intermittent cravings for the substance to avoid dysphoria or to attain the desired effects of the substance • drug misuse: drug use that deviates from the approved social or medical pattern, usually causing impairment or disruption to function in self or others • these disorders are usually chronic with a relapsing and remitting course • there are 10 separate classes of substances identified in the DSM-5: alcohol; caffeine; cannabis hallucinogens ( PCP or similarly acting arylcyclohexylamines, and other hallucinogens); inhalants; opioids; sedatives, hypnotics, and anxiolytics (alcohol included ); stimulants ( amphetamine- tvpe substances, cocaine, and other stimulants); tobacco; and other (or unknown ) substances • whereas substance use disorders imply addiction to substances, addictive disorders include process ( behavioural ) addictions such as gambling Epidemiology • the lifetime prevalence of SUD in Canada is 21.6% lifetime and 10.1% for the last 12 mo; for alcohol use disorder it is 18.1% and 3.2%; for cannabis use disorder 6.8% and 1.3% and for other substances, 4.0% and 0.7%, respectively (data before the legalization of cannabis use in Canada ) • 47% of those with substance use disorder have mental health problems

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Toronto Notes 2023

PS27 Psychiatry

29% of those with a mental health disorder have a substance use disorder • 47% of those with schizophrenia and 25% of those with an anxiety disorder have a substance use

disorder Etiology

almost all drugs (and activities) related to dependence, directly or indirectly increase dopamine release from the ventral tegmental neurons synapsing onto the nucleus accumbens ( known as the brain’s ‘reward pathway’), an action that contributes to their rewarding properties; with repeated use, the)' can modulate signaling pathways w'hich further encourages their use, contributing to their addictive potential • substance use disorders arise from multifactorial interactions between genetic (neurobiology), individual ( psychological ), and environmental factors ( low socioeconomic status, peer influence, adverse childhood or traumatic experiences, social isolation, systemic racism, and chronic stress) • certain comorbid conditions may also predispose individuals to a substance use disorder (e.g. mental illness, chronic disease, acute and chronic pain ) • environmental factors play a significant role in the exposure to the substance. For instance, the over prescription of opioids for pain in North America played a major role in the development of the opioid use disorder crisis Diagnosis • each specific substance is addressed as a separate use disorder and diagnosed utilizing the same overarching criteria (e.g. a single patient may have moderate alcohol use disorder, and a mild stimulant use disorder) • testing for illicit drugs is most commonly done on urine or blood samples serum toxicology screen measures recent alcohol consumption but has no relation to the diagnosis of alcohol use disorder toxicology may be helpful in differentiating withdrawal from other mental disorders urine drug screens are useful for detecting recent drug use, but not for diagnosing substance use

disorders • substance use disorders are measured on a continuum front mild to severe based on the number of criteria met within 12 mo mild: 2-3 moderate: 4-5 severe: 6 or more • criteria for substance use disorders ( PEC WITH MCAT ) use despite Physical or psychological problem (e.g. alcoholic liver disease or cocaine related nasal problems) failure to fulfill External roles at work/school / home Craving or a strong desire to use substance

Withdrawal continued use despite Interpersonal problems Tolerance: needing to use more substance to get same effect • use in physically Hazardous situations More substance used or for longer period than intended unsuccessful attempts to Cut down Activities given up due to substance excessive Time spent on using or finding substance Table 4. Substance Symptomatology Drugs

Symptoms of Intoxication

Sym ptoms of Withdrawal

CHS Depressants

Alcohol , opioids, barbiturates, benzodiazepines, GHB

Euphoria, slurred speech , disinhibition , confusion, poor coordination , coma (severe)

Anxiety, anhedonia, tremor, seizures, insomnia , psychosis, delirium , death

Stimulants

Amphetamines, methylphenidate, Euphoria, mania, psychomotor agitation , anxiety, psychosis MDMA , cocaine (especially paranoia ), insomnia , cardiovascular complications (stroke Ml, arrhythmias), seizure

‘Crash’, craving, dysphoria, suicidality

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Hallucinogens

LSD, mescaline, psilocybin , PCP, ketamine, ibogaine salvia

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Distortion of sensory stimuli and enhancementof feelings, psychosis (+ visual hallucinations), delirium, anxiety (panic), poor coordination

Usually absent

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Questions to Characterize Substance Use and Risk Assessment (THE WATER ) • When was the last Time you used? How long can you go without using? • Have you Experienced medical or legal consequences of your use? • Any previous attempts to cut down or quit, and did you experience any Withdrawal symptoms? How has your substance use Affected your work, school, relationships?

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Are there any Triggers that you know will cause you to use? Substances can be very Expensive, how do you support your drug use? • By what Route (oral ingestion, inhalation (snorting), smoking. IV) do you usually use?

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General Approach to Assessment • a comprehensive evaluation should inquire about drug history including names of substances used , amount, frequency, duration, routes, last use, injection drug use, needle sharing, symptoms of withdrawal, consequences of use ( medical, social, or personal), previous treatment programs and medical (e.g. HIV', hepatitis B and C, chronic pain ), psychiatric (e.g. mood and anxiety disorders), and social history (e.g. family and housing arrangements, any child safety concerns) • ask about more socially accepted substances (e.g. nicotine, alcohol ) before asking about use of cannabis, misuse of prescription medicines, and about illicit drugs • obtaining collateral history is recommended as well as evaluating patient insight into the problem

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Toronto Notes 2023

PS28 Psychiatry

Lab Testing • urine, saliva, sweat, and hair can be tested for the presence of drugs • urine is most commonly used due to ease of collection and adequate sensitivity and specificity, but it does not reflect serum concentrations • proper urine drug testing involves an initial screening test ( qualitative) followed by confirmatory testing for substances with positive screening results • most confirmatory tests use gas or high - performance liquid chromatography • post ingestion window of detection with urine test: amphetamine ( 48 h ), barbiturates ( 1 21 d ), short acting benzodiazepine (72 h ), long acting benzodiazepine ( 30 d ), cocaine ( 12 72 h), morphine (48 72 h ), methadone ( 72 h ), oxycodone ( 2 4 d ), PCP (8 d ), cannabis (3 d for single use to >30 d for heavy

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users) • limitations: negative tests cannot rule out substance use, and positive results cannot determine how much or frequency of use General Approach to Treatment • approach must be appropriate to the patient’s current state of change (see Public Health and Preventive Medicine, Health Promotion Strategies, PH11) • patients will change when the pain of change appears less than the pain of staving the same • provider can help by providing psychoeducation (emphasize neurobiologic model of addiction ), motivation, and hope • principles of motivational interviewing (see Psychotherapy, PS-19 ) non- judgmental stance space for patient to talk and reflect offer accurate empathic reflections back to patient to help frame issue • encourage and offer referral to evidence based services social: 12 step programs (alcoholics anonymous, narcotics anonymous), family education, and support • psychological therapy: addiction counselling, MET, CBT, contingency management, group therapy, family' therapy, marital counselling medical management ( differs depending on substance): acute detoxification, pharmacologic agents to aid maintenance. Ontario has the RAAM- Rapid Access to Addiction Medicine clinics that offer timely, low barrier, specialized services by self-referral • harm reduction whenever possible: safe-sex practices, avoid driving while intoxicated, avoid substances with child care, safe needle practices/exchange, pill-testing kits, reducing tobacco use • comorbid psychiatric conditions: many will resolve with successful treatment of the substance use disorder but patients who meet full criteria for another disorder should be treated for that disorder

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with psychological and pharmacologic therapies • always consider duty to inform Ministry of Transportation for risk of driving or operating other

vehicles

Nicotine • see l amilv Medicine. FMI 3 Confabulations: the fabrication of imaginary experiences to compensate for memory loss

Alcohol •see f amily Medicine, FM15 and Emergency Medicine. ER 34

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History • Validated screening questionnaire for alcohol use disorders C ever felt the need to Cut down on your drinking? A ever felt Annoyed at criticism of your drinking?

G ever feel Guilty about your drinking? E ever need a drink first thing in the morning ( Eye opener )? for men, a score of > 2 is a positive screen; for women, a score of >1 is a positive screen • if positive CAGE, then assess further to distinguish between problem drinking and alcohol

use disorder

Canada's Low-Risk Alcohol Drinking Guidelines Moderate Drinking

Men:3 or less'd (slSfrark)

Make sure to ask about other alcohols: mouthwash, rubbing alcohol, methanol, ethylene glycol aftershave (may be used as a cheaper alternative)

A "Standard Drink" (SD) Spirit (40%);1.5 oz. Of 43 ml T able Wine (12%): 5 oz. or 142 ml Fortified Wine (18%): 3 oz. or 85 ml Regular Beer (5%):12 oz. or 341 mL

OR

Women: 2 or less/d (slO/wk)

Elderly:1 or less/d

Biochemical Markers of Prolonged Alcohol Use

• elevated liver function tests ( AST, ALT, GGT ), MCV, and carbohydrate-deficient transferrin (CDT ) • ASTrALT ratio >2:1 and elevated GGT are suggestive of alcohol use

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1 pint of beer 1.5 SO 1 bottle of wine * 5 SD 1"mickey" 8 SD (375 mL) 2&er "17 SD (750 mL)

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Alcohol Intoxication • throughout Canada, the legal limit for impaired driving is a BAC >0.08% ( >80 mg/dL or 17.4 mmol/ L ) which is typically reached after 4 drinks in women and 5 drinks in men in a 2 h period

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Toronto N'otcs 2023

PS29 Psychiatry

• most signs of intoxication are present at over >21.7 mmol / L ( 100 mg/dL ): altered perception, impaired

judgement, ataxia, hyper- reflexia, impaired coordination, changes in mood / personality, prolonged reaction time, and slurred speech * respiratory depression and arrest can occur with >60 mmol/ L ( non -tolerant drinkers ) and 90-120 mmol/ L (tolerant drinkers) Management of Alcohol Intoxication

Delirium Tremens

•stabilize patient if there is reduced level of consciousness or vomiting; assess airways and respiratory

( alcohol withdrawal delirium )

function

• administer IV crystalloid fluids if evidence of volume depiction or shock ; correct electrolytes and hypoglycemia • monitor for signs of alcohol withdrawal following detoxification in patients with alcohol use disorder Alcohol Withdrawal

• medical emergency: occurs within 12-48 h after prolonged heavy drinking and can be life -threatening • 50% of middle-class, functional individuals with alcohol use disorder have experienced alcohol withdrawal; 80% in hospitalized / homeless individuals alcohol withdrawal can be described as having 4 stages, however not all stages may be experienced: stage 1 (onset 4 12 h after last drink ): “ the shakes" tremor, sweating, agitation , anorexia , cramps, diarrhea , sleep disturbance, anxiety, insomnia , headache. The majority of alcohol withdrawal presentations are mild to moderate ( stage I ) stage 2 (onset 12 24 h ): alcoholic hallucinosis: visual, auditory, olfactory, or tactile hallucinations stage 3 (onset 12 -48 h ): alcohol withdrawal seizures, usually tonic-clonic, non -focal, and brief (can occur as early as 2 h after alcohol consumption ) stage 4 (onset 48-96 h ): delirium tremens, conftision/disorientation, delusions, hallucinations, agitation, tremors, autonomic hyperactivity (diaphoresis, fever, tachycardia, HTN ) •course: almost completely reversible in young; elderly often left with cognitive deficits •20% mortality rate of severe presentations (delirium tremens ) if untreated

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Autonomic hyperactivity (diaphoresis, tachycardia, increased respiration) • Hand tremor • Insomnia • Psychomotor agitation

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Anxiety • Nausea or vomiting Tonic-clonic seizures Visual/tactile/auditory hallucinations , Persecutory delusions

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Management of Alcohol Withdrawal

Assessment for Alcohol (Cl WA • monitor using the Clinical Institute Withdrawal '

• areas of assessment include (SHAN T AS TAV ):

- A ) scoring system

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physical ( 5): paroxysmal Sweats, Headache/ fullness in head Agitation, Nausea and vomiting, Tremor psychological/cognitive ( 2) : Anxiety, orientation/clouding of Sensorium perceptual (3): Tactile disturbances, Auditory disturbances, Visual disturbances all categories are scored from 0-7 (except: orientation /sensorium 0-4), maximum score of 67 mild 20 • check for signs of hepatic failure (e.g. ascites, jaundice, and coagulopathy ) Table 5. CIWA- A Scale Treatment Protocol for Alcohol Withdrawal Diazepam 20 mg PO ql 2 h PRM until CIWA - A 65 or patient has severe liver disease, Use a short acting benzodiazepine severe asthma or respiratory failure Lorazepam 1 4 mg P0/5UIM q1 2 h

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If hallucinations are present

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Haloperidol 2 5 mg IM / P0 q1 - 4 h max 5 doses/d or atypical antipsychotics (olanzapine, risperidone) Diazepam 20 mg x 3 doses as seizure prophylaxis (haloperidol lowers seizure threshold )

Admit to hospital if

Still In withdrawal alter >80 mg of diazepam Delirium tremens , recurrentarrhythmias or multiple seizures Medically ill or unsafe to discharge home

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Wernicke- Korsakoff Syndrome • alcohol-induced amnestic disorders due to thiamine deficiency (poor nutrition or malabsorption) • necrotic lesions: mammillary bodies, thalamus, brainstem • Wernicke’s encephalopathy ( acute and reversible ): triad of oculomotor dysfunction such as nystagmus (CN VI palsy (eye pointing inwards)), gait ataxia, and confusion. If untreated, may progress to Korsakoff’s syndrome • Korsakoff 's syndrome ( chronic and only 20% reversible with treatment ): anterograde amnesia and compensatory confabulation; cannot occur only during an acute delirium or dementia and must

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• management

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Wernicke’s preventative treatment (any patient in withdrawal ): thiamine 100 250 mg IM/1V x 1

dose Wernicke’s acute treatment: thiamine 500 mg IV BID/T1D x 72 h, then reassess Korsakoff’s: IV treatment as for Wernicke’s followed by thiamine 100 mg PO T1D x 3-12 mo

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Toronto Notes 2023

PS30 Psychiatry

Treatment of Alcohol Use Disorder • non - pharmacological see General Approach to Treatment, PS28

• pharmacological »

naltrexone ( Revia*): opioid antagonist, shown to be successful in reducing the “high ” associated with alcohol, moderately effective in reducing cravings, frequency or intensity of alcohol binges; can be started if still consuming alcohol or abstinent but can precipitate withdrawal in those with

physical opioid dependence acamprosate (Campral*): NMDA glutamate receptor antagonist; useful in maintaining abstinence and decreasing cravings disulfiram (Antabuse*): prevents oxidation of alcohol ( blocks acetaldehyde dehydrogenase ) and causes an adverse reaction to alcohol ( nausea /vomiting, tachycardia, shortness of breath, headache); if patient relapses, must wait 48 h before restarting Antabuse*; prescribed only when treatment goal is abstinence; RCT evidence is generally poor or negative due to poor medication adherence; contraindicated in severe renal disease, pregnancy, psychoses, and cardiac disease some evidence for the use of gabapentin, topiramate, and ondansetron as anti-craving agents, but not approved by Health Canada approved for this indication (currently under investigation )

Opioids •types of opioids: heroin , morphine, oxycodone, Tylenol #3* (codeine), hydromorphone, fentanyl, methadone, meperidine (Demerol*) •in addition to working on opiate receptors, opiates also act on the dopaminergic system, which

mediates their addictive properties • most commonly used are: Percocet* (oxycodone/acetaminophen ), Vicodin* ( hydrocodone/ acetaminophen ), and OxyContin* (oxycodone) • major risks associated with the use of contaminated needles: increased risk of hepatitis B and C, bacterial endocarditis, and H1V/A1DS • recent considerations of inadvertent overdose secondary to contamination with fentanyl in the drug supply “opioid crisis" leading to 9000 deaths in Canada between January 2016 and June 2018 Acute Intoxication

•direct effect on receptors in CNS resulting in decreased pain perception, sedation , decreased sex drive, nausea / vomiting, decreased G1 motility (constipation and anorexia), pupil constriction (e.g. pinpoint pupils; exception is meperidine), and respiratory depression (can be fatal ) • medical emergency: typical syndrome includes shallow respirations, miosis, bradycardia , hypothermia, decreased level of consciousness • management

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ABCs IV glucose

naloxone hydrochloride ( Narcan*): 0.4 mg up to 2 mg IV for diagnosis treatment: intubation and mechanical ventilation , ± naloxone drip, until patient alert without naloxone (up to > 48 h with long acting opioids ) •caution: opioids have a longer half -life than naloxone; may need to observe for toxic reaction for at least 2:24 h

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Opioid Antagonists Naltrexone vs. Naloxone Naltrexone (Revia :) • Can be used for EtOH dependence (although not routinely used) Long half- life (>1 h) Naloxone (Narcan ) Used for life-threatening CNS/ respiratory depression in opioid overdose Short half-life ( 2 distinct personality states or an experience of possession • can manifest as sudden alterations in sense of self and agency (ego-dystonic emotions, behaviours, speech) « features recurrent episodes of amnesia ( declarative or procedural) as well as episodes of depersonalization and derealization • rare (6 symptoms of hyperactivity-impulsivity • for older adolescents and adults ( > age 17), >5 symptoms required •does not occur exclusively during the course of another psychiatric disorder • DDx: learning disorders, hearing /visual defects, thyroid , atopic conditions, congenital problems ( fetal alcohol syndrome, fragile X syndrome), lead poisoning, history of head injury, traumatic life events (abuse ) •specify current severity ( mild / moderate/severe); if in partial remission ( past diagnosis, has not met full criteria >6 mo, still functional impairment present)

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Table 13. Core Symptoms of ADHD ( DSM- 5) Inattention

Hyperactivity

Impulsivity

Careless mistakes

Fidgets, squirms in seal Leaves seal when expected to remain sealed

Difficulty awaiting turn

Cannot sustain attention in tasks ot play Does not listen when spoken to directly fails to complete tasks Disorganized

Avoids and/or dislikes tasks that require sustained mental effort loses things necessaty for tasks or activities

Runs and climbs excessively Cannot play quietly

Comparative Efficacy and Tolerability of Medications for Attention Deficit Hyperactivity Disorder iaChildren , Adolescents, and Adults: A Systematic leview and Network Meta Analysis lancet 2018:5:727738 Purpose Estimate the comparative efficacy and tolerability of oral medications for ADHO in children , adolescents, and adults. Methods: Reviewof double blind RCTscocnparing amphetamines, atomoxetine. bupropion , donidne. guanfacine. methylphenidate and modafiiti] with each other or placebo. Conclusions lei mg into account both efficacy and solely, evidence from this mela analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred hrst-cheice medications for theshort term treatment of ADHD.

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Contrary to the concerns of many parents and health care providers, treatment with stimulant medications of ADHD in childhood does not increase the likelihood of substance misuse later in life

Blurts out answers before questions completed Interrupts/inlrudes on others

“On the go", driven by a motor Talks excessively

Distractible Forgetful

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Clinical Features • difficult to differentiate from highly variable normative behaviour before age 4, but often identified upon school entry • present across multiple settings (i.e. school, home, extracurricular) • rule out developmental delay, sensory impairments, genetic syndromes, encephalopathies, or toxins (alcohol, lead ) • increased risk of substance use disorder, depression, anxiety, academic failure, poor social skills, comorbid CD and /or ODD, adult ASFD • associated with family history of ADHD, difficult temperamental characteristics

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Toronto Notes 2023

PS 18 Psychiatry

Treatment • non -pharmacologicai: psychoeducation, behavioural management (e.g. parent training, classroom management, social skills training) • pharmacological: 1 st line: stimulants ( methylphenidate amphetamines); 2 nd line: atomoxetine and guanfacine XK; 3rd line: donidine, bupropion , imipramine

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• for comorbid symptoms: antidepressants, antipsychotics • psychosocial intervention is first line for children 6

Prognosis

• 70-80% continue into adolescence, but hyperactive symptoms usually abate • 65% continue into adulthood; secondary personality disorders and compensatory anxiety disorders are identifiable

Disruptive, Impulse Control, and Conduct Disorder Oppositional Defiant Disorder • prevalence: 2 -16%, M = T after puberty Diagnosis • pattern of negativistic/hostile and defiant behaviour for >6 mo, with >1 non-sibling, with >4 symptoms manifested in 3 areas of: angry/irritable mood: easily loses temper, touchy or easily an noyed, often angry and resentful argumentative/defiant: argues with adults / authority figure, defies requests/ rules, deliberately annoys, blames others for their own mistakes or misbehaviour vindictiveness: spiteful or vindictive twice in past 6 mo note: difference between normal behaviour and ODD is frequency of symptoms (most days if age 5 yr) exceeds what is normative for one’s age, gender, culture •behaviour causes significant distress or impairment in social, academic, or occupational functioning •behaviours do not occur exclusively during the course of a psychotic, substance use, or mood disorder •severity ( mild / moderate /severe) according to number of settings in which symptoms are present •diagnosis of disruptive mood dysregulation disorder supersedes ODD if criteria for both are met

Clinical Features •first symptoms usually appear during preschool and rarely later than early adolescence •associated with poor school performance, few friends, strained parent/child relationships, risk of developing mood disorders later on, often precedes CD Treatment • parent: parent management training, psychoeducation for parents and family •behavioural therapy: to teach, practice, and reinforce prosocial behaviour •social: school / day carc interventions

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• pharmacotherapy for comorbid disorders

Conduct Disorder

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-=

• prevalence: 1.5 3.4% (M:l' 4:1) Etiology

• parental / familial factors: parental psychopathology ( e.g. ASPD, substance use disorder), child - rearing practices ( e.g. child abuse, discipline), low socioeconomic status ( SKS), family violence •child factors: difficult temperament, ODD, learning problems, ADHD, neurobiology

Diagnosis • pattern of behaviour that violates rights of others and age appropriate social norms with S3 criteria noted in past 12 mo and Si in past 6 mo: aggression to people and animals: bullying, initiating physical fights, use of weapons, forced sex, cruel to people and / or animals, stealing while confronting a person ( i.e. armed robbery) destruction of property: arson , deliberately destroying others’ property deceitfulness or theft: breaking and entering, conning others, stealing nontrivial items without

confrontation violation of rules: out all night before age 13, often truant from school before age 13, runaway >2 times at least overnight or for long periods of time disturbance causes clinically significant impairment in social, academic, or occupational

functioning if 18 yr, criteria not met for ASPD

D

(

Children with ODD like MRATs and BEARS" Rule breaker Annoying Temper Blames others Easily annoyed Argues with adults Resentful Spiteful/ vindictive

A Systematic Review aid Analysis of tong -Term Outcomes in Attention Deficit Hyperactivity Diorder: Effects of Treatment and Non-Treatment

BMC Med 2012:10:95

-

Purpose: lo determine Ike long term outcomes of

-

AOHDand whether thereis an effect on long term outcomes with treatment. Methods: Systematic reriew of studies, including patients with diagnosed or symptomatic presentation of ADHD, assigned to pharmacological, non pharmacological multi modal treatments, or a no treatment control. Outcome measures included use/ addictive behaviour, academic outcomes, antisocial behaviour, social function , occupation , sell esteem , driving outcomes, services use a nd obesity . Results: Unnealed parlkpeelt with AOHO had poorer outcomes vs. non -AOKD participants in 74% (n'244|of studies, wtrde 26% (n'89) showed similar outcomes.72% (n -37) of studiesshowed a benefit from ADHD treatment vs. untreated ADHD and 28% ( n 15|showed no benefit Treatment ol ADHD was found to be beneficial in studies looking at driving P00%), obesity (100%) self -esteem|90%), social function (13%) academic outcomes|?1%|, drag usef addictive behaviour (67%).antisocial behaviour |SO%|, andoccupatron (33%). Conclusion: Overal people with ADHD have poorer long- term outcomes than controls (those without ADHD|. For those with ADHD, treatment improves long term outcomes.

-

. -

.

-

-

-

.

.

.

-

Conduct Disorder Diagnosis

TRAP Theft: breaking and entering, deceiving, non-confrontational stealing Rule breaking: running away, skipping school, out late Aggression: people, animals, weapons,

+

forced sex Property destruction

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Toronto Notes 2023

PS19 Psychiatry

•diagnostic types

• childhood -onset ( >1 criterion prior to age 10) • adolescent -onset ( no criteria until age 10)

unspecified onset (insufficient information ) mild, moderate, severe •differential: ADHD, depression, head injury, substance misuse Treatment

•early intervention necessary and more effective: long- term follow- up required • psychosocial: parent management training, anger replacement training , CBT, family therapy, education /employment programs, social .skills training • pharmacotherapy for comorbid disorders Prognosis

• poor prognostic indicators include: early-age onset, high frequency, variety of behaviours, pervasiveness (i.e. in home, school, community), comorbid ADHD, early sexual activity, substance misuse

•50% of children with CD develop ASPD as adults

Intermittent Explosive Disorder Diagnosis

• recurrent behavioural outbursts representing a failure to control aggressive impulses in children ages S6, manifested as either:

verbal or physical aggression that does not damage others or property, occurring > 2 times per wk for 3 mo 3 outbursts involving physical damage to another person, animal, or piece of property in the last 12 mo • outbursts are out of proportion to triggers and are not premeditated /for primary gain • outbursts cause clinically significant distress or impairment in occupation or interpersonal functioning, or financial / legal consequences See Paediatrics

• Child Abuse, PIS , Chronic Abdominal Pain, P48, Developmental Delay, P 2 . Intellectual Disability. P27, Learning Disabilities, P29, Sleep Disturbances, P15 See Neurology

• Tic Disorders, N 35, Tourette's Syndrome, N 35

Psychotherapy • treatment in which a person with mental or physical difficulties aims to achieve symptomatic relief through interactions with another person • psychotherapy is delivered by a trained counsellor, social worker, nurse, psychologist, general practitioner, or psychiatrist • various types of therapy exist based on diverse theories of human psychology and mental illness etiology Common Factors of Psychotherapy •good evidence that effective psychotherapy creates observable changes in brain circuitry and connectivity, but these changes are different from those observed with successful pharmacologic and other treatment modalities •studies suggest that up to 60 90% of therapy outcome is due to common factors with only 10 40% due

to specific factors

-

-

•common factors are warmth ( unconditional positive regard ), accurate empathy, genuineness, goodness of fit , relationship with provider; predict positive outcomes

n

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PS50 Psychiatry

Toronto Notes 2023

Table 14 . Summary of Psychotherapeutic Modalities

.

Approach Technique, and Theory

Ideal Candidates

Duration

Supportive Therapy

Adjustment disorders, somatic Uses empathy, validation, and reflection to facilitate adaptation and coping symptoms andrelated disorders, severe psychotic or Help patients leel sale, secuie, and encouraged personality disorders Adjunct to pharmacologic management in most disorders

Individuals in crisis or with severe symptoms in acute or chronic settings

Variable Isingle session to years, though often short - intermittent )

Interpersonal Therapy

Mood disorders

Individuals with depression or bipolar disorder with some insightand difficult social functioning Absence of severe psychotic process. personality disorder, or comorbid substance use disorder

Weekly sessions, 12-20 sessions

Type

Indications

Focuses on how interpersonal relationships impact symptoms 4 key problem areas addressed:1. grief and loss 2.

.

.

role transitions 3. conflict, 4. interpersonal deficits Break the interpersonal cycle: depression,self esteem. social withdrawal

Cognitive Behavioural Therapy

Most mental health disorders including:mood, anxiety 0 C 0. personality, eating, substance use, psychotic disorders

.

-

Individuals with motivation to change Combines theory and method from cognitive and behavioural therapies to leach the patient to change and who are able to participate in connections between thinking patterns, habitual homework behaviours, and mood/ anxiety problems Cognitive component includes using thought records to helpmonitor thoughts and identify inaccurate automatic thoughts Behavioural component includes techniques such as systematic descnsiliialion (mastering aniiety provoking situations by approaching them gradually and m a relaxed stale that limits anxiety), flooding (confronting feared stimulus foi prolonged periods until it is no longer frightening), positive reinforcement ( strengthening behaviour and causing it to occur more frequently by rewarding it), negative reinforcement (causing behaviour to occur more frequently by removing a noxious stimulus when desired behaviour occurs), extinction (causing a behaviour to diminish by not rewarding il), and punishment /aversion therapy (causing a behaviour to diminish by applying a noxious stimulus)

Typically weekly or twice weekly sessions.12 -20 sessions Maintenance therapy can be carried out over years

-

Dialectical Behavioural Borderline personality disorder Therapy that combines CBT techniques with 8 uddhist Therapy Zen mindfulness practices and dialectical philosophy Focuses on 4 types of skills: mindfulness, emotional regulation,interpersonal effectiveness, and distress

Individuals with borderline personality disorder or borderline personality trait and severe problems of emotional dysregulation, impulsivity orself harm

Typically 1 yr Weekly individual and group therapy

Individuals with problematic substance use maladaptive behaviour patterns [ therapy disengagement, medication noncompliancc poor healthhabits)

Brief interventions (efficacy with as little as 15 inm, single session ), better result with more sessions Addiction is a chronic condition, often need boosters over lime

.

tolerance Involves 4 components: individual therapy, group skillstraining, phone consultations, and a consultation team

Motivational Interviewing and Motivational Enhancement hcrapy

Substance use disorders Techniques can be applied to facilitate behavioural change in most psychological problems

Spiritol Ml (CAPE): Compassion, Acceptance,

.

Partnership Evocation Principles ol Ml (RULE ) : Resist "righting reflex " Understand client and Ihcir reasons for change, listen Empower by conveying hope and supporting autonomy Icchniqucsof Ml (OARS ): Open - ended questions Affirmations lo validate client Reflections (the skill of accurale empathy), Summaries lo help client organize self

.

.

.

Croup Psychotherapy

Family Therapy

Aims topromote self - understanding, acceptance, social skills

Most mental health disorders including mood, anxiety. OCD. personality, eating, substance use. and psychotic disorders can benefit from group therapy as part of treatment

Familysystem considered more influential than individual, especially for children Focus on here and now re - establishing parental authority, strengthening normal boundaries, and rearranging alliances

.

Emerging evidence for treating Derived from Buddhist meditative and philosophical practices; aims to help people attend lo thoughts adjustment disorder MDD (relapse prevention), anxiety behaviours, and emotions in the moment and non pain disorders, insomnia judgmentally using guided breathing exercises substance use disorder (relapse prevention)

Psychoanalytic / Psychodynamic Therapy

Anxiety, obsessional thinking, conversion disorder, depression

.

.

.

MET - 4 sessions

Adolescents, individuals not currently in crisis, absence of severe psychotic symptoms

Mindfulness -based Cognitive Therapy / Mindfulness -based Stress Reduction

.

.

.

Most mental health disorders including mood, anxiety OCD personality, eating, substance use. and psychotic disorders can benefitfrom group therapy as part of treatment

. .

-

.

theory: exploration of meaning of early experiences and how they affect emotions and patterns of behaviour Recollection (remembering), repetition (reliving with the therapist), working through (gaining insight ) Techniques: free association, dream interpretation. transference analysis

Variable Often time limited (e.g. weekly sessions for 12 wk)

-

Children and adolescents with families willing to engage in treatment

Often short - term (e.g.12 sessions)

Individuals who are motivated and

Generally weekly sessions for 8 wk

willing lo engage in therapy

ri Psychologically minded, highly motivated, wish lo understand selves and not just relieve symptoms Able to withstand difficult emotions without fleeing or self - destructive acts High level of function

Time intensive:

LJ

Psychoanalysis: 4 - 5 times /wk lor 3 - 7 yr Psychodynamically oriented therapy: 2 3 times /wk for fewer yr

-

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Toronto Notes 2023

PS51 Psychiatry

Pharmacotherapy Dopamine Pathways Affected by Antipsychotks

Antipsychotics

Pathway

Effects

Mesolimbic

Emotion

Associated

Pathology

•“antipsychotics" used to be called “ neuroleptics”

• overall mechanism of action: functionally antagonize, to varying degrees, D2 activity in target brain pathways • primarily indicated for psychotic symptoms in: schizophrenia and related disorders, manic episodes, depressive episodes, substance use, medical conditions (e.g. neoplasm )

•other uses: treatment-resistant MDD, severe GAD, complex PTSD, severe OCD, borderline PD, behavioural symptoms of dementia, delirium, 'l ourette syndrome, substance use disorder in dual diagnosis, Huntington s disease, ASD, and impulse control disorders '

adjunctive management of agitation, aggression , severe anxiety, and severe sleep difficulties when sedative hypnotics are contraindicated • onset: acute, rapid calming effect and decrease in agitation; antipsychotic effect with improvement in thought disorder, delusions, and hallucinations may take 1-4 wk • rational use • no reason to combine two or more antipsychotics, although this is quite common in clinical

-

symptoms ol

reward

schiiophrenia ( delusions, hallucinations)

Mesocortkal Cognition, executive function

LOWdopamine

causes negative

symptoms of schiiophrenia

10W dopamine causes EPS

Nigrostriatal Movement

-

Tubero infundibular

practice

all antipsychotics are equally effective, except for clozapine (considered to be most effective in treatment resistant schizophrenia ) atypical antipsychotics ( i.e. second generation ) are as effective as typical ( i.e. first generation ) antipsychotics and have different adverse effect profiles; main difference is lower risk of EPS and TD but more metabolic side effects (see sidebar ) choose a drug to which the patient has responded to in the past or that was used successfully in a family member • route: PC), short acting or long acting depot IM injections, and sublingual; more recently there is inhaled loxapine mainly used in the setting of acute agitation • if no response in 4 -6 wk, switch drugs •duration: minimum 6 mo and usually for life in most patients with primary psychotic disorders;

HIGH dopamine

causes positive

origination,

Prolactin

LOWdopamine

hormone release

causes hyper

-

prolactinemia

-

-

-

Typical (first Generation) vs. Atypical (Second Generation) Antipsychotics

Typical

Atypical

Block Mechanism Block postsynaptlc postsynaptic dopamine dopamine receptors ( D2) receptors (02) Block serotonin receptors (5 HT2) on presynaptic dopaminergic

-

variable for other indications Long- Acting Preparations

terminals, triggering DA release, and reversing 0A blockade in some pathways. Some are partial 02 agonists

• antipsychotics formulated in oil for IM injection • received on an outpatient basis • indications: initially meant for individuals with schizophrenia or other chronic psychosis who relapse

because of non -adherence, but current initial evidence suggests they are better than oral preparations overall • should have been exposed to oral form prior to first injection • dosing: start at low dosages, then titrate every 2 4 wk to maximize safety and minimize side effects • side effects: similar to side effect profile to oral preparation of the same drug

-

Canadian Guidelines for the Treatment of Acute Psychosis in the Emergency Setting • haloperidol 5 mg IM ± lorazepam 2 mg IM • loxapine PO or IM 25 mg ± lorazepam 2 mg IM • olanzapine 2.5 10 mg ( PO, IM, oral quick dissolve it’s time to peak is the same as regular PO, 4 6 hr ) • risperidone 2 mg ( M tab, liquid )

-

-

-

-

Pros

Inexpensive Plenty ol injectable

EPS less prevalent low risk ol tardive

lotms available

syndromes Mood stabilizing

-

effects

Cons

EPS more

Expensive Fewinjectable

including

lorms available Metabolic side effects

prevalent,

tardive syndromes in long term Hot mood stabilizing

-

.

( weight gain hyperglycemia

. abnormalities. metabolic

syndrome)

Exacerbation (or new onset) olobsessive behaviour

Anticholinergic Effects Red

asa

Hot

asa

hare

Dry

asa

bone

Blind Mad

asa

bat

asa

hatter

beet

+

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PS52 Psychiatry

Toronto Notes 2023

Table 15. Common Antipsychotic Agents Starting Dose

Maintenance

Maximum

Relative Potency (mg)

Typicals (in order ol potency Irom high to low ) Haloperidol (Haldol!)

2 5 mg IM q4 -8 h 0.5 - 5 mg PO B/TIO 0.2 mg / kg / d PO

Based on clinical effect

20 mgfd PO

2

Fluphenaiine enanthate ( Moditen ' Modecate (or IM formulation)

2.5 -10 mgfd PO

1- 5 mg PO OHS 25 mg IM / SC q1- 3 wk

20 mg /d PO

2

Zudopenlhixol HCI (Clopixol - )

20 - 30 mg/d PO

20 - 40 mg / d PO

100 mg/ d PO

4

Zudopenthixo! acetate (Acuphase 3)

50 -150 mg IM q48 -72 h

Zuclopenthixol decanoale (Cloxipol Depot' )

100 mg IM q1- 4 wk

150 - 300 mg IM q2 wk

600 mgIM / wk

Perplsenaiinc (Irilafon ' )

8 16 mqP0 8 / IID

4 8 mg PO T /OID

64 mg / d PO

TO

Lonapme HCI (Loxitane )

10 mg P 01ID 12.5-50 mg IM q4 - 6 h

60 -100 mg /d PO

250 mg /d PO

10

Chlorpromazlne ( Largactil : )

10 -25 mgP0 Bl / /0ID

400 mg/d PO

1000 mgfd PO

100

4 8 mg/ d P0

8 mg / d P 0

2

.

400 mg IM (q2 wk)

Atypicals (in order ol potency from high lo low)

Risperidone (Risperdal , Risperdal Consta ' lor IM long acting preparation Risperdal 1 M - Tab lor melting form - placed on tongue) 1

12 mg once daily /BID

25 mglMq2 wk

.

.

Paliperidone (Invega ' Invega Sustenna lone v) orTrima ' ( three months) forIM long acting

-

3 mgfdP0

3 12 mg/d P 0

12 mgfd P0

4

5 mg/dPO

10 -20 mg/dPO

30 mg/d P 0

5

Asenapinc (Saphris )

5 mg $1BID

5 10 mg St BID

10 mg St BID

5

Ziprasidone ( Zeldox )

20 mg P 0 BIO

40 - 80 mg PO BID

160 mg/d P0

6

10 -15 mg /dPO

’

preparalions) Olanzapine ( Zyprexa 3, Zyprexa Zydrs ' lor melting form - placed on tongue)

’ ’ Aripipraiole (Ability )

-

10 -15 mgfd P0

30 mg/d P0

Ouetiapine (Seroquel 25 mg PO BID Seroqnel XR ! for extended release 3 }

400 - 800 mg /dPO

800 mg / d P0

7.5 75

25 mg P0 BIO

300 600 mgfd P0

900 mq / d P0

100

9

.

Clozapine (Clozaril ' )

See landmark Psychiatry Trials table lor more information on Milt, which details a comparison b elween first and second-generation antipsychotics m the treatmentof sdnroplirenia.

Metabolic and Cardiovascular Adverse thesis Associated with Antipsychotic Drugs N at Rev Endocrinol 2012:8:114-126 All atypical antipsytbobts can cause cardiovascular and metabolic side effects, such as obesity, dyslipidemia. hyperglycemia, and vreightgain. Olanrapme anddoupme are most likely to cause these adverse effects. Ihe medianism that nnderkes the metabolic and cardiovascular effects is not Inly understood. However, the histamine, dopamine, serotonin, and muscarinic receptors are implicated.

OTc prolongation is an important adverse effect of all antipsycholics; although not required, consider getting ECG prior to and after initiating new medication and to monitor OTc Typicals: chlorpromazine and haloperidol warrant systematic baseline and follow up ECG Atypicals: ziprasidone has the highest risk among atypicals, clozapine also warrants systematic baseline and follow - up ECG

Features ol Neuroleptic Malignant Syndrome FARM Fever Autonomic changes ( e.g. increased HR /BP, sweating) Rigidity of muscles Mental status changes (e g confusion)

..

FARM symptoms are also seen in serotonin syndrome ( SS) SS can be distinguished from NMS by the following:

SS

NMS

.

Twilchy shivering, restless

Severe globalrigidity

Flushed, sweaty

Pallor

.

Vomiting,diarrhea abdominal pain

No Gl symptoms

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PS53 Psychiatry

Table 16. Commonly Used Atypical Antipsychotics

Advantages

Risperidone

Olanzapine

Ouetiapine

( Risperdal )/

(Zyprexa

(Seroquel )

Paliperidone (Invega )

Zydis’l

Lower incidence of EPS than typical antipsychotics at lower doses («8 mg) Associated with less weight gain compared to clozapine and

Better overall efficacy compared to

.

haloperidol Well tolerated Low incidence of EPS and ID

olanzapine

Associated with slightly less weight gain compared to clozapine and olanzapine, but more than the other atypicals Mood stabilizing

Clozapine (Clozaril )

Aripiprazole ( Ability )

Most cltective for treatment resistant

less weight gain and risk of metabolic syndrome compared toolanzapineand a lower incidence olEPS compared to haloperidol Mood stabilizing

-

schizophrenia

Docs not worsen tardive symptoms: may ( real them Approximately 50 % of patients benefit , especially paranoid patients and those with onset after 20 yr

Disadvantages Relative toOther

SGAs

Highest risk of EPS/ID among SGAs avoid il high risk for EPS or existing movement disorder or elderly Elevated prolactin sexual dysfunction ,

-

-

Weight gain and

-

metabolic effects avoid in DM Sedating avoid if high risk for fallsor fracture

-

-

Sedating /orthostatic hypotension avoid if high risk for falls or fracture DT prolongation in high doses caution

-

If cardiac risk

.

galactorrhea

gynecomastia. menstrual

disturbance infertility

.

Weight gain and

-

Insomnia , akathisia

metabolic effects avoid m DM Sedalingforthostatic hypotension avoid if high risk for fallsor fracture Potentially severe constipation - avoid if risk of fecal impaction or bowel perforation Cardiomyopathy caution if existing heart disease Reduces seizure threshold caution il seizure disorder

-

-

-

-

Agranulocytosis (1%) avoid in existing leukopenia / neutropenia , requires ongoing CBC monitoring

-

Comments

Ouick dissolve

Ouick dissolve

acting (Consta 3/ Invega Irinza )

formulation ( Eydis ) used commonly in ER setting for better compliance ( but does

IM - tabs). and long

formulations available

-

Weekly blood counts for 6 mo. Ihenq 2 wk Do not use with other drugs that may cause bone

notactlaslcr )

marrow suppression

Acute IM form available

due to risk of agranulocytosis

Note: Risk o! weight gain: Clozapine > Olanzapine * Ouetiapine > Risperidone

Table 17. Side Effects of Antipsychotics System

Side Effects

Anticholinergic

Dry mouth , urinary retention , constipation , blurred vision , confusional slates

a-adrenergic Blockade

Orthostatic hypotension , erectile dysfunction, failure toeiaculate

Dopaminergic Blockade

Extrapyramidal syndromes, galactorrhea , amenorrhea , erectile dysfunction , weight gain

-

Anti Histamine

Sedation , weight gam

Hematologic

Agranulocytosis (clozapine)

Hypersensitivity Reactions

liver dysfunction , blood dyscrasias skin rashes, neuroleptic malignant syndrome, altered temperature regulation ( hypothermia or hyperthermia )

.

Endocrine

Metabolic syndrome

Cardiac

OT prolongation

Neuroleptic Malignant Syndrome •

psychiatric emergency • hypothesis: due to strong DA blockade; increased incidence with high potency and depot

antipsychotics • risk factors

medication factors: sudden increase in dosage, starting a new drug • patient factors: medical illness , dehydration , exhaustion , poor nutrition , external heat load , male,

rn LJ

young adults

• clinical features

tetrad: mental status changes ( usually occur first ), fever, rigidity, autonomic instability over 24 - 72 h develops • • labs: increased creatine phosphokinase, leukocytosis, myoglobinuria • treatment: supportive - discontinue antipsychotic drug , hydration , cooling blankets, dantrolene ( hvdantoin derivative, used as a muscle relaxant ), bromocriptine ( DA agonist ) • mortality: 5%

+

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PS51 Psychiatry

Extrapyramidal Symptoms incidence related to increased dose and potency • acute (early - onset ; reversible ) vs. tardive ( late -onset; often irreversible )

•

Table 18. Extrapyramidal Symptoms Dystonia

Akathisia

Parkinsonism

Acute or Tardive

Both

Both

Acute

tardive

High- Risk Groups

Acute: young Asian and Black males

Older females

Older females

Older patients

Presentation

Sustained abnormal posture: torsions, twisting, contraction of muscle groups; muscle spasms (l.e. oculogyric crisis, laryngospasm. torticollis)

Motor restlessness; crawling sensation in legs relieved by walking: very distressing, increased risk of suicide and poor adherence

tremor; rigidity (cogwheeling): akinesia: postural instability (dccrcascd/absent arm swing, stooped posture. shuffling gait, difficulty pivoting)

Purposeless, involuntary, constant movements that involve facial and mouth musculature:less commonly - the limbs: rarely, the diaphragm ( "hiccups”)

Onset

Acute: within 5 d tardive: »90 d

Acute: within 10 d tardive: >90 d

Acute: within 30 d

Tardive: > 90 d. more commonly yr

Treatment

Acute : benztropine or diphenhydramine, usually IM

Acute:lorazcpam, propranolol, benztropine , or diphenhydramine: best

Acute: benztropine: reduce dosage or change antipsychotic to low potency atypical antipsychotic

tardive: no good

approach: reduce dose or

change antipsychotic to lower potency

Dyskinesia

treatment: may try clozapine: discontinue drug or reduce dosage Recently the FOA approved valbenazine and deutetrabenazinefor the treatment ol tardive dyskinesia

Anticholinergic Agents

• types • benztropine ( Cogentin*) 2 mg PO, IM , or IV once daily ( 1 6 mg ) • diphenhydramine ( Benadryl * ) 25 50 mg PO/ IM Qll) do • not routinely prescribe with antipsychotics give anticholinergic agents only if at high - risk for acute EPS or if acute EPS develops • do not give these for tardive syndromes because they worsen the condition

-

-

Antidepressants • onset of effect relief of neuro- vegetative/ phvsical symptoms: 1-3 svk relief of emotional /cognitive symptoms: 2-6 wk • tapering of most antidepressants is usually required to avoid withdrawal reactions: speed of taper is based on the medication ’s half life and the patient ’s Individual sensitivity ( i e. fluoxetine does not require a taper due to its long half - life; paroxetine and venlafaxine require a slower taper than sertraline or citalopram ) • must be vigilant over the first 2 wk of therapy: neuro- vegetative symptoms may start to resolve while emotional and cognitive symptoms may not ( patients may be at risk for suicidal behaviour during this time , particularly in children /adolescents )

-

.

• treatment of bipolar depression • patients with bipolar disorder ( bipolar depression ) should not be treated with an antidepressant as the first-line therapy patients with bipolar disorder should only be treated with an antidepressant if combined with a mood stabilizer or antipsychotic; monotherapy with antidepressants is not advisable as the depression can switch to mania maintenance of patients with bipolar disorder with antidepressants is not advisable except in specific cases

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Table 19 . Common Antidepressants Class

Drug

Daily Starting Dose

Therapeutic Dose

|mg)'

(mg)

20 50 100 10

20 80 150300 20 60 50 200

Comments

Useful lor typical and atypical depression, seasonal depression, anxiety disorders 0C 0 eating disorders All SSRIs have similar effectiveness bul consider side effect profiles and hall lives

fluoxetine ( Proaac * ) lluvoxarnine ( Luvox | paroxetine (Paxil ' ) sertraline (Zololl 3) citalopram ( Celexa - *) escitalopram (Cipralex 1)

SO 20 10

20 - 40 10 - 20

SNRI

venlafaxinc ((flexor 3) desvenfafaxine (Pristiq : ) duloxetine (Cymballa : )

37.5 - 75 SO 30

75 - 225 50 -100 30 60

Useful for depression, anxiety disorders, neuropathic pain

HDRI

bupropion (Wellbutrin -)

100

300 - 450

Useful for depression, seasonal depression: not recommended for anxiety disorder treatment because of stimulating effects Causes less sexual dysfunction (may reverse effects of SSRIsfSNR Is), weight gain, and sedation Increased risk of seizures at higher doses Conliaindicated with history ol sciiurc, stroke, brain tumour, brain injury, dosed

SSRI

.

.

Citalopram and escitalopiam have the fewest drug interactions and ate sleep v/ ake neutral Sertraline is the safest SSRI in pregnancy and breastfeeding fluoxetine is the most activating SSRI (recommend taking in the AM) Fluoxetine does not require a taper due to long half - life and is the most used in children and adolescents as it has most evidence fluvoxainlno is sedating (should be taken in PM ) and can be involved in many drug drug Interactions For OCD, aim for maximum doses, sometimes higher

head injury

.

Important to specify formulation, as available in IR SR. XI ( longest)

TCA ( 3” Amines)

amitriptyline (Elavil!) imipramine (Tofranil!) clomipramine ( Anafranil 1 )

25- 50 25- 50 25 50

150 - 300 150 -300 100 - 250

Useful for OCD Idomipramine is gold standard), melancholic depression, can also be used in other types of depression and anxiety disorders Requires ECG monitoring Check blood levels if using higher dosage Highly lethal in overdose

TCA ( 2" Amines)

nortriptyline (Aventyf ’ ) dcsipramine (Norpramin |

25 50 25 50

75-150 150 300

Preferred to tertiary amines because ol lower propensity for anticholinergic adverse effects Requires (CG monitoring Check blood levels if using higher dosage Highly lethal in overdose

MAOI

phenelzine (Nardil ) tranylcypromine (Parnate ' )

15 20

60 - 90 10 - 60

Useful for moderate/ seveie depression that does not respond to other antidepressants: atypical depression; anxiety disorders Requires strict adherence to MAOI diet, (lova tyramine)

RIMA

300

300 600

Useful for some anxiety disorders (e.g. social phobia) and depression

HaSSA

moclobeinidelManerix ' l mil tazaplne (Renteronr1)

15

15 45

Useful In depression with prominent features of insomnia,agitation, or cachexia

SPARI

vilazodone IViibryd )

10

10 40

Useful in those with constipation as diarrhea is a common side effect

Serotonin Receptor Modulator

vortioxeline (Irintellix :)

5

5 20

May improve cognitive function

-

' for depression (start with X M this dose for treatment ot anxiety disorders) MAOI = monoamine oxidase inhibitors; NaSSA = noradrenergic and specific serotonergic agent; NDRI = norepinephrine and dopamine reuptake inhibitors; RIMA = reversible inhibition ol MAO -A; SNRI = serotonin and norepinephrine reuptake inhibitors; SSRI selective serotonin reuptake inhibitors; TCA * tricyclic antidepressants; SPARI serotonin partial agonist and reuptakc inhibitor

-

-

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PS56 Psychiatry Treatment Approach for Depression Select and initiate a first-line antidepressant

Monitor i

’

Early improvement

-

Psychopharmacology of SSRIs

Post-Synaptic Serotonin Receptor Stimulated

4

NO

Optimize dose

Consider factors for switch vs. adjunct

after 2 4 wk?

4

*

5HT1A centrally

Switch to a 2nd or 3rd line antidepressant

YES

5HI2A in spinal cord

1 Add adjunctive medication

superior efficacy

paroiebne

Warn patients anxiety may worsen *! first 1 2 wk of treatment

longer evaluation period for more persistant depression

r

-

Symptom remission ?

NO

Early improvement after 2-4 wk?

for 6 El wk

4

-

SHT3A in gut

YES

Continue treatment Optimize dose

Sena: dysfunction: delayed ejaculation, anorgasflia. decreased interest' libido

5HT205HT2A in brain Activation:anxiety. insomnia Worst with fbimetne.

Monitor: consider

l

Relief of depression Anxiolytic effect

Early treatment failure T Switch to another first-line antidepressant preferably with

EffectSide Effect

Gl upset nausea. vomiting bioatng lake with food ,

NO

YES Risk factors for recurrence?

NO

>

Maintain treatment for 6 9 mo

-

YES Maintain treatment for 2 yr or longer

Figure 3. Depression treatment algorithm

.

.

.

Adapted bom: Sidney H. Kennedy, Raymond W. Lem. Roger S. McIntyre, et al The Canadian Journal of Pay criatry (61.9) p. 21 copyright : 2020. Modified by Permission of SAGE Publications. Inc.

• optimization : increase dosage to maximum tolerated or highest therapeutic dosage • augmentation : the addition of a medication that is not considered an antidepressant to an antidepressant regimen ( i.e. thyroid hormone, lithium, atypical antipsychotics (aripiprazole, quetiapine, olanzapine, risperidone)) • combination: the addition of another antidepressant to an existing treatment regimen ( i.e. the addition of bupropion or mirtazapine to an SSR1 or SNR1) •switch: change of the primary antidepressant (within or outside a class) • note: it is important to fully treat depression symptoms ( i.e. to remission ) to decrease relapse rates Serotonin Syndrome • thought to be due to over-stimulation of the serotonergic system •can result from medication combinations such as more than oneSSRI SSRl + SNR 1 SSRI or SNR! MAOl, SSRI + tryptophan, MAOI + meperidine, MAOI + tryptophan • rare but potentially life- threatening adverse reaction to SSRIs and SNRIs •symptoms include: nausea, diarrhea, palpitations, chills, diaphoresis, restlessness, confusion, and lethargy, but can progress to myoclonus, hyperthermia, rigor, and hypertonicity • treatment: discontinue medication and administer emergency medical care as needed • important to distinguish from NMS

.

.

Symptoms of Antidepressant Discontinuation ( mainly from serotonin reuptake inhibition activity)

FINISH

-

Flu like symptoms Insomnia Nausea Imbalance

-

Sensory disturbances Hyperarousal (anxiety/agitation )

Discontinuation Syndrome •caused by the abrupt cessation of some antidepressants; most commonly with paroxetine,

tluvoxamine, and venlafaxine (drugs with shortest half -lives) •symptoms usually begin within 1 3 d and can include anxiety, insomnia, irritability, mood lability, N / V, dizziness, headache, dystonia, tremor, chills, fatigue, lethargy, and myalgia ("flu - like symptoms") • treatment: symptoms may last between 1-3 wk, but can be relieved within 24 h by restarting antidepressant at the same dosage the patient was taking initially and initiating a slower taper over several weeks •consider avoiding drugs with a short half-life

-

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Table 20. Features of Commonly Used Antidepressant Classes SSRI

TCA

SNRI

MAOI

NaSSA

RIM A

NDRI

SPARI

Serotonin receptor

modulator Examples

Mode of Action

Side Effects

. .

.

.

amitriptyline

fluoxetine sertraline citalopram

xenlafaxine duloxetine

Block serotonin

Block norepinephrine and serotonin

Block norepinephrine

reuptake

(clomipramine also blocks serotonin reuptake)

reuptake only

CMS: restlessness tremor, insomnia, headache, drowsiness EPS Gl:NY diarrhea, abdominal cramps, weight gam

.

.

.

Sexual dysfunction: erectile dysfunction, anorgasmia CVS:increased HR.increased OTc.serotomn syndrome SIADH. decreased

Low dose side effects similar toSSRIs (serotonergic) Higher dose side effects: tremors tachycardia sweating insomnia orthostatic hypotension increase in BP (noradrenergic ) SIADH

.

.

phenelzine

bupropion

modobemide

mirtazapine

vilacodone

vortioxetine

Irreversible inhibition of MAO AandB increases duration that NE. dopamine,and 5HI are in the synaptic cleft by preventing their degradation

Block

Reversible inhibitor of monoamine oxidase A leads to increased duration of

Enhance central noradrenergic and serotonergic activity by inhibiting presynaptic o- 2 adrenergic receptors

5 HT1A partial agonism causes downregulation ofpresynaptic 5 HT1Areceptors todisinhibit serotonin release, and 5HT4 agonism treats

5HT1A agonism downregulates presynaptic 5HT1A receptors to disrnhibit serotonin

clomipramine

.

.

.

reuptake

Anticholinergic effects: (see Table 77.KJ3 ) Noradrenergic effects: tremors, tachycardia, sweating a - t adrenergic effects: orthostatic hypotension, falls ORS prolongation

norepinephrine and dopamine reuptake

.

norepinephrine dopamine. and SHT in the synaptic deft by preventing their degradation

constipation

.

Antihistamine effects (minimal): sedation, weight gain

CVS: orthostatic hypotension, hypertensive crises with lyramine rich foods (e g wine, cheese), or combination with serotonergic

..

.

CHS: dizziness headache, tremor, insomnia, agitation, anxiety, lower seizure threshold

CHS (usually CNS: sedation minor): dizziness, dizziness Endocrine: headache tremor, insomnia increase in CVS: cholesterol, dysrhythmia increase in hypotension triglycerides, dysrhythmia HIM Gl: dry mouth weight gain N/ V diarrhea, Gl: dry mouth Gl: constipation N/Y constipation, abdominal pain AIT elevation

.

.

.

.

release,and 5HT7 antagonism theoretically enhances cognitive function

CNS:sedation Gl: nausea, diarrhea

Gl: nausea

Relatively safe in overdose

Relatively safe in

.

.

.

.

.

dyspepsia

decreased appetite

GU: delayed

or adrenergic medications,

ejaculation

Other: diaphoresis

headache, flushes, reflex tachycardia, postural

.

hypotension,

insomnia Minimal anticholinergic

platelet aggregation increased risk of

effects

bleeding Risk in Overdose

Relatively safe in overdose

Tachycardia and H' V seen in acute overdose

Toxic in overdose Toxic in overdose, 3 times therapeutic but wider margin of dose may be lethal safety than TCA Presentation: anticholinergic effects CNS stimulation, then depression and seizures ECG: prolonged ORS and OIc (relied

Tremors and seizures seen in overdose

Risk of fatal overdose when combined with SSRIs. SNRIs or

Relatively safe in overdose

overdose

.

clomipramine

.

severity)

Treatment: activated charcoal, cathartics, supportive treatment, IV diazepam for seizure,

physosligmine salicylate for coma Do not give ipecac, as can cause rapid neurologic deterioration and seizures MAOI. SNRI Drug Interactions Some SSRIs ( fluoxetine, fluvoiamine

.

paroxetine) strongly inhibit cytochrome P450 enzymes,

therefore win affect levels of drugs metabolized by P450 system

MAOI.SSRI Low inhibition of cytochrome P450 compounds

.

MAOI SSRI ElOH

Hypertensive crises with noradrenergic medications |i£. TCA decongestants, amphetamines) Serotonin syndrome with serotonergic drugs (i.e. SSRI

.

. . . dextromethorphan

SNRI tryptophan

)

MAOI MAOI.paroxetine Drugs that reduce Opioids seizure threshold:

.

.

MAOI RIMA

MAOI

MAOI No inhibition of cytochrome P450

anbpsychotics

systemic steroids, guinolone antibiotics antimalanal drugs

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Mood Stabilizers General Prescribing Information • examples: lithium , divalproex, lamotrigine, carbamazepine • used mainly for long- term stabilization of bipolar disorder, also used as first-line monotherapy or in conjunction with atypical antipsychotics for acute episodes of bipolar disorder (i.e. depression and mania) • vary in their ability to “treat” ( i.e. reduce symptoms acutely) or “stabilize” ( i.e. prevent relapse and recurrence ) manic and depressive symptoms; multi- agent therapy can be avoided in many patients but it is common • before initiating, get baseline: CBC with differential and platelets, ECG ( if patient > 45 y/o or cardiovascular risk ), BUN , creatinine, extended electrolytes, TSH, LFTs for divalproex and

carbamazepine • screening for: pregnancy, thyroid disease, neurological, renal, liver, cardiovascular diseases

• full effects may take 2-4 wk, thus may need acute coverage with benzodiazepines or antipsychotics

Specific Prescribing Information • detailed pharmacological guidelines available online from the Canadian Network for Mood and Anxiety Treatments (CANMAT ) and International Society for Bipolar Disorders (1SBD) • for clinical information for treating bipolar disorder (see Mood Disorders, PS 10 ) • be mindful that divalproex and carbamazepine are teratogenic thus if prescribed for women at reproductive age, a reliable contraceptive strategy is required Table 21. Commonly Used Mood Stabilizers Lithium Indications

Lamotrigine (Lamictal )

Divalproex (Epival }

Carbamazepine (Tegretol )

1st line Acute mania (monotherapy or with adjunct SGA) Bipolar I depression (monotherapy or in combination with divalproei, SSRI, or bupropion) Bipolar disorder maintenance (monotherapy or with adiunct SGA)

1st line Bipolar I depression (monotherapy) Bipolar disorder maintenance (limited efficacy in preventing mania,more effective when combined with titnum)

1st line Acute mania (monotherapy or with adjunct SGA) Bipolar I depression ( combination with lithium or SSRI) Bipolar disorder maintenance (monotherapy or with ad unct SGA)

2nd line Acute mania (monotherapy) Bipolar disorder maintenance (monotherapy or in combination with lithium)

Other uses Bipolar It depression Augmentation of antidepressants in MOD

Hot recommended for acute mania

Other uses Bipolar II depression

.

Other uses Rapid cycling bipolar disorder

Other uses Bipolar II depression Rapid cycling bipolar disorder Mixed phase /dysphoric mania

and OCD Schizoaffective disorder Chronic aggression, antisocial behaviour Recurrent depression Unknown Therapeutic response within 7-14 d

May rahibrt 5 - HT3 receptors May potentiate DA activity

Depresses synaptic transmission

Raises seizure threshold

Depresses synaptic transmission Rases seizure threshold

Dosage

Adult 600-1500 mg/d Geriatric:150 - 600 mgd Usually daily dosing Blood levels monitored and dose adjusted accordingly

Hote:very slow titration required due to riskof Stevens - Johnson Syndrome Oose adjusted in patients taking other anticonvulsants such as divalproei Daily dose:100 -200 ing/d

750- 2500 mg/d Usually daily dosing with ER preparation

400 1600 mgi'd Usually BID orTID dosing

Therapeutic Level

/ (1.0-1.25 mmol/L Adult: 0.8 -1.0 mmoll for acute mania) : Geriatric: 0.6-0.8 rmtol

Therapeutic plasma level not established Dosing based on therapeutic response

17- 50 mmol/L Same therapeutic levels as used for seizure prophylaxis (no data specific for mood stabilizing effect)

350-700 pmol/L Same therapeutic levels as used for seizure prophylaxis (no data specific for mood stabilizing effect)

Monitoring

Monitor serum levels every S-7 d until therapeutic (always 12 h after dose) Then monitor monthly,then q2- 3 mo Monitor thyroid function creatinine q6 mo

Monitor for skin rash and suicidality when initiating treatment

Monitor serum levels every 5 -7 d until

Monitor serum levels every 5 -7 d until

therapeutic LFTs weekly x 1mo then monthly, then q2-3 mo due to risk of l.ver dysfunction Watch for signs of liver dysfunction: nausea, edema, malaise Check platelets and monitor levels to adjust dosage and confirm adherence

therapeutic Weekly blood counts for 1st mo due to risk of agranulocytosis Watch for signs of blood dyscrasas: fever,rash,sore throat, easy bruising

Gl: H/V, diarrhea, stomach pain GU: polyuria, polydipsia,nephrogenic diabetic insipidus, glomerulonephritis, renal failure, decreased glomerular filtration rate CHS: fine tremor, headache,fatigue, lethargy Hematologic: reversible benign leukocytosis Other: teratogenic (Ebstein's anomaly), hypothyroidism, weight gain, edema, worsening of psoriasis, bradycardia ECG changes

Skin:rash (consider discontinuing due to risk of Steven-Johnson syndrome which is an emergency), slow dose titration to reduce risk Otherwise,usually well tolerated (Gl:H/V diarrhea CHS: ataxia,dizziness, diplopia, headache, somnolence Other:anxiety )

Gl: liver dysfunction. H V. diarrhea CHS: ataxia, drowsiness, tremor,

Gl:H/V diarrhea, hepatic toxicity CHS: atana dizziness, slurred speech, drowsiness, confusion, nystagmus,

Mode of Action

.

Side Effects

.

.

sedation,cognitive blurring Other: hair loss, weight gain, thrombocytopenia,nexal tube defects when used in pregnancy,polycystic ovarian syndrome

.

Interactions

.

HSAIDs, thiazides.ACEI and metronidazole decrease clearance,risk for lithium toxicity

0CP

-

.

.

.

diplopia Hematologic:transient leukopenia (10%) ra reagranulocytosis, aplastic

.

anemia

rm

Stun:rash (5% risk; consider discontinuing drug because of risk of Stevens-Johnson syndrome) Other: neural tube defects when used in pregnancy

t J

0CP

-

+

Toronto Notes 2023

PS59 Psychiatry

Lithium Toxicity

• clinical diagnosis as toxicity can occur at therapeutic levels • common causes: overdose, sodium /fluid loss, concurrent medical illness or initiation of NSAIDs,

diuretics, or ACE1 • clinical features Gl: severe nausea / vomiting and diarrhea cerebellar: ataxia, slurred speech, lack of coordination cerebral: drowsiness, myoclonus, tremor, upper motor neuron signs, seizures, delirium, coma

Longterm lithium use can lead to a nephropathy and diabetes insipidus in

some patients

• management

discontinue lithium for several days and begin again at a lower dose when lithium level has fallen to a non toxic range monitor serum lithium levels, creatinine, BUN, electrolytes IV saline hemodialysis if lithium >2 mmol/ L, coma, shock, severe dehydration, failure to respond to treatment after 24 h, or deterioration

-

Anxiolytics •anxiolytics mask or alleviate symptoms • indications • short-term treatment of anxiety disorders, insomnia, alcohol withdrawal (especially delirium tremens), barbiturate withdrawal, akathisia due to antipsychotics, seizure disorders, musculoskeletal disorders, agitation or aggression associated with acute mania, or psychosis • relative contraindications major depression (except as an adjunct to other treatment), history' of drug /alcohol misuse, caution in pregnancy/ breastfeeding myasthenia gravis is a relative contraindication for benzodiazepines • mechanism of action benzodiazepines: potentiate binding of GABA to its receptors; results in decreased neuronal activity buspirone: partial agonist of 5-HT1A receptors Benzodiazepines •should be used for limited periods (i.e. davs-weeks ) to avoid tolerance and dependence •all benzodiazepines are sedating, decrease respirator)' drive, and increase risk for falls, confusion, and motor vehicle accidents; be wary with use in the elderly, especially in combination with other

psychotropic medications •have similar efficacy, so choice depends on half-life, metabolites, and route or schedule of administration • taper slowly over weeks- months because they can cause withdrawal reactions (see below) •beware of use with alcohol and other CNS depressants because of potentiation of CNS depression; caution with drinking and driving/machinery use • side effects CNS: drowsiness, cognitive impairment, reduced motor coordination (falls), memory impairment dependence, tolerance, withdrawal • withdrawal low dose withdrawal symptoms: tachycardia, HTN, panic, rebound insomnia, anxiety, impaired memory and concentration, perceptual disturbances • high dose or rapid withdrawal symptoms: hyperpyrexia, seizures, death onset: 1-2 d (short-acting), 2 -4 d (long-acting) duration: days-weeks • complication with above 50 mg diazepam / d or abrupt withdrawal: autonomic hyperactivity, seizures, delirium, arrhythmias management: taper slowly; may need to switch to a long-acting benzodiazepine similar to but less severe than alcohol withdrawal; can be fatal • overdose overdose is common but rarely fatal unless combined with other substances more dangerous or potentially fatal when combined with alcohol, other CNS depressants, opioids, orTCAs

-

Benzodiazepine Antagonist Flumazenil (Anexate : ) Use for suspected benzodiazepine overdose Specific antagonist at the benzodiazepine receptor site

Benzodiazepines That are Safe for Patients with Impaired Liver Function

LOT Lorazepam

Oxazepam Temazepam

Buspirone (Buspar - ) • primary use: GAL) • may be preferred over benzodiazepines because it is non -sedating, has no interaction with alcohol, does not alter seizure threshold, not prone to abuse •onset of action: 2 wk •side effects: dizziness, drowsiness, nausea, headache, nervousness, EPS Z - drugs for Sleep

-

-

• non benzodiazepine sedatives indicated for short term management of insomnia •examples include zopiclone ( Imovane*), eszopidone ( Lunesta*), and zolpidem (Sublinox’) • anecdotally provide a more restful sleep than benzodiazepines •similar side effect profile and warnings to benzodiazepines •should not be used long term due to side effects and likelihood of dependency

-

+

Toronto Notes 2023

PS60 Psychiatry

Table 22. Dosing and Indications for Common Anxiolytics Class

Drug

Dose Range (mg/d)

ti/ 2|h)

tmax (h)

Appropriate Use

Clonazepam|Rivotril!)

0.25 - 4

18 - 50

1- 4

Seizure prevention , akathisia. generalized anxiety disorder, panic disorder

Benzodiazepines

Long -acting

-

Short - acting

-

Diazepam (Valium 1 )

2 40

30 -100

12

Seizure prevention , muscle relaxant , alcohol withdrawal , generalized anxiety

Chlordiazepoxrde ( Librium ; ) Flurazepam|Dalmane: )

5- 300

30-100

1- 4

Alcohol withdrawal

15 - 30

50 - 160

0.5 -1

Alprazolam (Xanax 1 )

0.25- 4.0

6- 20

1-2

Should be avoided Should be avoided due to high dependency rate

Lorazepam ( Ativan )

0.5- 6.0

10 - 20

1- 4

Alcohol withdrawal ( no first pass liver metabolism ), akathisia. short term sedation (or anxiety during procedures (e.g. Cl or MRI). generalized anxiety; sublingual or IM for rapid action

Oxazepam (Serax )

10 -120

8-12

2- 3

Alcohol withdrawal ( no first pass liver metabolism ), generalized anxiety disorder

temazepam ( Restoril 1 )

7.5 -30

triazolam IHs!cion )

0.125 - 0.5

8 20 1.5 -5

12

Shortest tV2, rapid sleep without daytime sedation (e g. overnight plane travel ), but risk of rebound insomnia

Buspirone ( Buspar - )

15 - 30

2- 3

1-1.5

Generalized anxiety disorder

-

'

’

-

2-5

-

-

-

-

Should be avoided

Azapirones

Somatic Therapies Electroconvulsive Therapy • the fastest and most effective acute treatment of depression • ECT is a safe and controlled way of producing seizures to treat mental illness • various methodological improvements have been made since the first treatment in 1938 to reduce

adverse effects • modern ECT: induction of a generalized seizure using an electrical pulse through scalp electrodes while the patient is under general anesthesia with a muscle relaxant • considerations: unilateral vs. bilateral electrode placement, pulse rate, energy, number, and spacing of treatments • usual course is 6-12 treatments, 2 -3 treatments per wk • indications treatment - resistant depression ( unipolar, bipolar I , bipolar II ): psychotic features, catatonic features, when medications may be unsafe or rapid response is needed (e.g. cachexia, severe dehydration , frail elderly, high suicide risk , pregnancy) • catatonia: refractory, severe, or life-threatening schizophrenia: treatment - resistant, acute symptoms, catatonia, history of NMS mania: refractory, severe or life- threatening situation • personal or family history of good response to ECT

inconclusive evidence for OCD • adverse effects: risk of anesthesia ( equal to risk of ECT ), memory loss ( may he retrograde and /or anterograde, tends to resolve by 6-9 mo, permanent impairment controversial ), transient headaches, transient myalgias • unilateral ECT causes less memory loss than bilateral but may not be as effective • contraindications: no absolute contraindications; relative contraindications: increased intracranial pressure, recent ( 30 d over >2 hospitalizations in the past 3 yr ), or the person has been subject to a previous CTO in the past 3 yr a community treatment plan for the person has been made examination by a physician within the previous 72 h before entering into the CTO plan • ability of the person subject to the CTO to comply with it consultation with a rights advisor and consent of the person or the person’s substitute decision maker • CTOs are valid for 6 mo unless they are renewed or terminated at an earlier date such as when the person or his/ her substitute decision-maker withdraws consent to the community treatment plan • CTO process is consent-based and all statutory protections governing informed consent apply • the rights of a person subject to a CTO include the right to a review by the Consent and Capacity Board with appeal to the courts each time a CI'O is issued or renewed a mandatory' review by the Consent and Capacity Board every second time a CTO is renewed the right to request a re-examination by the issuing physician to determine if the CTO is still necessary for the person to live in the community the right to review findings of incapacity' to consent to treatment provisions for rights advice

Duty to Inform/Warn • see Ethical, Legal , and Organizational Medicine, ELOM10

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PS6! Psychiatr\

T

Landmark Psychiatry Clinical Trials Trial

Reference

Results

Schizophrenia

-

Psychiatr Serv 2008;59( 5):500 506

CATIE

Title: What CATIE Found: Results From the Schizophrenia Trial Purpose: Compare the effectiveness of a proxy first - generation antipsychotic (perphenazine) to several second-generation

antipsych olics. Methods:1460 patients with chronic schizophrenia were randomly assigned in a double -blind study to receive one of perphenazine, olanzapine,quetiapine risperidone, or ziprasidone for up to 18 mo. Results: Perphenazine did not differ significantly in overal effectiveness or benehts compared to the second-generation antipsych olics. Perphenazine was the most cost - effective drug. Individual clinical circumstances impacted drug effectiveness. Patients who have a poor response to an initial medication may tolerate and see greater effectiveness with a different medication. Conclusions: First and second- generation antipsychotics did not differ in overall effectiveness. Patient factors must be considered when prescribing antipsychotic medications.

.

Major Depressive Oisorder

Am J Psychiatry 2019,176|6):428- 438

TRANSFORMS

Title: Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined with a Newly Initiated Oral Antidepressant in Treatment -Resistant Depression: A Randomized Double -Blind Active- Controlled Study Purpose: Evaluate the efficacy and safety of flexibly dosed esketamine nasal spray for patients with treatment - resistant depression. Methods: Patients with treatment-resistant depression vrere randomly assigned treatment of esketamine nasal spray with a newly initiated antidepressant or a placebo nasal spray with a newly initiated antidepressant. Results: 197 participants completed the study. Patients receiving the esketamine nasal spray plus antidepressant treatment demonstrated a change in Montgomery - Asberg Depression Rating Scale score that was signifrcantly greater than placebo nasal spray plus antidepressant atd 28. Clinically meaningful improvements were found in the esketamine group earlier in the study timeline. Conclusions : Esketamine nasal spray was a safe, rapid-acting, and efficacious therapy for treatment- resistant depression.

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Toronto Notes 2023

PS65 Psvchiatn

Lineham 104.Combs KA.Murray AM.etal. Two - year randomized controlled trial andfoliow-up of dralecbcalbehaviour therapy vs. therapy by experts for suicidal behavnurs and boderline personality disorder. Arch Gen Psychiat 2006:63:757-766. Locher C.Koechhn H.ion SR. etal. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin- norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents:a systematic review and meta-analysis. JAMA Psychiatry 2017:74(101:1011-1020. Lopez M.IorpacM6. The Texas children's medication algorithm project report of the leias consensus conference panel on medication treatment of childhood attenton- defidt’hyperactivity disorder. Part I. Am Acad Child Adolescent Psychiat 2000:39:908 -919. MacO.een GM Frey 6 M.Ismail 2 et al. Canadian Network for Mood and Anxiety treatments (CANMAT) 2016 dimcal guidelines for the management of adits with major depressive disorder: Section 6. Special populations: Youth, women, and the elderly. Can J Psychiatry 2016:61:588 - 603. March J Silva S Petrytki S. et al. Fluoxetine, cognitive - behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TAOS) randomized controlled trial. JAMA 2004:292:807 820. McClellan J Kowatch R Findlmg Rl et al. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Cfnfd Adolesc Psychiatry 2007:46:107-125. Mildowitz DJ Chung 8. Family- focused therapy for bipolar disorder: reflections on 30 years of research Fam Process 2016:55:483 499 Moore TH Zammil S Iingfotd Hughes A et al Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review, lancet 2007:370:319 -328. Morishita T Fayed SM Higuchi MA et al. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics 2014:11(3):475-484. MTACooperetnie Group.A 14-month randomized clinical trial of treatment strategies for attention deficit 'hyperactivity disorder Arch Gen Psychiat 199956:1073-1036. Nakamura M.Ogasa M Guarino J et al. lurasidone in the treatment of acute schizophrenias double-blind,placebo- controlled trial J Qin Psychiatry 2009:70(6) 829-836. National Corabo abngCenbe for Women 'sand Children's Health ( UK). Autism:recogn t on.referral and diagnosis of children and young people on the aubsmspectrum.London: RC 0G Press: 2011 Sep. National Institute on Drug Abuse. Research report series: methamphetamme abuse and addrcbon.Reprinted 2002 Jan. NIH Publication No.: 02- 4210. NobleJ.Teitbook of primary care medicine 3rd ed. Mosby, 2000.466- 470. Pagmn D.de Oueiroz V.PiniS.etal. Efficacy of ECT in depression: a meta -analybc review.J ECT 2004:20:13-20. Pari G Huf W PjreJcE.etal- Bnght -lighttherapy in the treatment of mood disorders.Neuropsychobiology 2011:64(3):152-162. Patten SB.Wang JL WiliamsJV. et al.Descriptive epidemiology of major depression in Canada.Can J Psychiatry 2006;51:84-90. Patterson CJ.Gauthier S.Bergman H, et al. Canadian consensus conference on dementia:a physician's guide to using the recommendations. CMAJ 1999:160:1738-1742. Pentbla H.JaasJrelainen E. Hirvonen N et al. Duration of untreated psychosis as predictor of longterm outcomein schizophrenia: systemabc review and meta-analysis.Br J Psychiatry 2014:205(2):88 - 94. Perou R. Bitsko RH.BtumbergSJ.et al.Mental health surveillance among children - Un.ted States 2005 -2011.MMWR Suppl 2013;62(2):1-35. Pinkofsky HB.Mnemonics for DSM-IV personality disorders. Psychiatr Serv 1997;48(9):T197H98. Pliszka SR Greenhil LL Crismon ML et al. Textbook of psych airy. London:Oxford University Press 1997.109. RavindranAY.Baineaves LG Faulkner 6 etal. CANMAT 2016 clinical guidelines for the management of adults with major depressive disorder:section 5. complementary and alternativemedicine treatment. CanJ Psychiat 2016:61(9|:576 -587. Rayner L Price A Evans A etal. Antidepressants for depression in physically ill people.Cochrane DB Syst Rev 2010;CD007503. Remares M Rosa AR. franco C et al. A systematic review on the role of anticonvulsants m the treatment of acute bipolar depression Inti J Neuropsychopharm 2012:10:1-12. Rosenbaum S Sherrington C Iiedemann A et al. Exercise augmentation compared with usual care for post - traumatic stress disorder : a randomized controlled trial. Acta Psychiatr Scand 2015;131|5):350 - 359. Rush A Triveri M.Wisniewski S etal Acute and longer- term outcomes in depressed outpabenls requiring one or several treatment steps: a STAR'D report Am J Psychiat 2006:163|11):190S -1917. Russo EB. Cannabirroids ra the management of difficult to treat pain. Ther Clin Risk Manag 2003:4(11:245 259 , Sadock BJ SadockVA Ruiz P et al. Kaplan & Sadock 's synopsis of psychiatry:behavioral scenees clii cal psychiatry 11th ed Wollers Kluwer. 2014. Schneider LS. Da get men KS Insel P. et al. Risk ol death with atypical antipsychotic drug treatment for dementia: mela -ana lysis of randomized placebo-controlled trials. JAMA 2005:294:1934 -1943. Schuch FB. Vasconcelos-roreno MP. Borovrsky C. et al. Exercise and severe major depression :effect on symptom severity and quality of life at discharge in an inpetent cohort J Psychiat Res 2015:61:25-32. Senger HL lorierfne mnemonic. Am J Psychiat 1997;154(9):1321. Srddiqi N. Harrison JK.Clegg A. et al.Interventions for preventing delirium rn hospitalized non-tCU patients. Cochrane Database Syst Rev 2016X 0005563. Srnyor M.Schaffer A.Levitt A.The sequenced treatment alternatives to relieve depression (STAR'D) trial: a review. Can J Psychiatry 2010;55( 3):126-135. Srriwardena AN.Oureshi M2.Dyas JV. et at. Magic bullets for insomnia? Patients’ use and experiences of newer ( 2 drugs) vs. older (benzodiazepine) hypnobes for sleep problems in primary care. Br J Gen Pract 2008:58:417-442. Stahl SM.Psychopharmacology of antipsychotics. London: Martin Dunitz.1999. Stoner SC.Pace HA. Asenapine:a clinical review of a second-generation anbpsychobc- Ctiitica! Therapeutics 2012:34:1023-1040. Shoebe M Sctrut H.Sboehe W. et al.Health outcomes of bereavement lancet 2007:370(9603).1960-1973. Szewayk M. Women's health:depression and related disorders.Primary Care 19972483-101. TroidenR.Iheformaton of homosexual identities. J Homosexuality 1989:17:43-73. Wanreke L Breaking Lheurges of obsessive- compulsive disorder. Can J Diag 1996;13:107-120. Weller EB. Weller RA, Fristad MA et al. Bipolar disorder in children: misdiagnosis,underd:ag osi5. and future directions. J Am Acad Child Adolescent Psychiat 1995:34:709-714. World Health Organization. Depression and other common mental disorders:Global health estimates.Geneva 2017. Whittington CJ Kendall T Fonagy P et al. Selective serotonin reuptake inhibitors in childhood depression:systematic review of published vs. unpublished data.Lancet 2004:363:1341-1345. Yatham IN Kennedy SH Parikh SV et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders DSBQl cotlaoocabve update of CANMAT guidelines for the management ol patients with bipolar disorder: update 2013. Bipolar Disorders 2013:15:1-44. Timmerman M. Interview guide for evaluating DSM - V psychiatric disorders and the mental status examination. Psych Products Press 2013

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Public Health and Preventive Medicine Jenny Cho and Muhammad Maaz, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors Vijithan Sugumar, KBM editor Dr. Andrew Pinto and Dr. Jason Pennington, staff editors Acronyms

PH2

Public Health Context Public Health in Canada Legislation and Public Health in Canada

PH2

Determinants of Health PH3 Concepts of Health Groups Facing Systemic Barriers Discrimination, and Structural Violence Indigenous Health in Canada Disease Prevention

.

Measurements of Health and Disease in a Population

PH12

.

Epidemiology Interpreting Test Results

PH13

Effectiveness of Interventions

Types of Study Design Qualitative vs. Quantitative Observational Study Designs Experimental Study Designs Summary Study Designs

PH16

Methods of Analysis Distributions Data Analysis Common Statistical Tests

PH19

Causation Assessing Evidence Health System Planning and Quality Continuous Quality Improvement

.

Economic Evaluation

PH 22

.PH23

Managing Disease Outbreaks Definitions Steps to Control an Outbreak Infection Control Targets

PH24

Environmental Health Environmental Risk Assessment Air Water Soil

PH 26

Food Environmental Racism Occupational Health Taking an Occupational Health History

PH 29

Occupational Hazards. Workplace Legislation Workplace Health Promotion Workplace Primary Prevention Workplace Secondary Prevention Workplace Tertiary Prevention

PH30

Appendix - Mandatory Reporting. Reportable Diseases Other Reportable Conditions

PH31

...

Landmark Public Health and Preventive Medicine Trials PH32 References

, PH33

rT L

+ PHI Public Health and Preventive Medicine

Toronto Notes 2023

Toronto Notes 2023

PH 2 Public Health and Preventive Medicine

Acronyms ADLs At CAS

activities of daily living attributable risk Children’s Aid Society LbA cost benefit analysis CEA cost effectiveness analysis CFR case fatality rate CTFPHC Canadian Task Force on Preventive Health Care disability adjusted life year DALY dichlorodiphenyltrichloroethane DDT evidence- based medicine EBM

FP FN

FOOT IMR ITT IICO MERS MHO

MOH MMR NNH

false positives false negatives fecal occult blood test infant mortality ratio intention to treat analysis low income cut off Middle East respiratory syndrome Medical Health Officer Medical Officer of Health maternal mortality ratio number needed to harm

- -

-

N NT NPV

OR PFT PH AC PP PPV PSA PYU OALY 01 RR

number needed to beat negative predictive value odds ratio pulmonary function test Public Health Agency of Canada per protocol analysis positive predictive value prostate screening antigen potential years of life lost quality adjusted life year quality improvement relative risk

Public Health Context .

•see Ethical Lenal, and Organizational Medicine. Overview of Canadian Healthcare System. ELOM2 for the organization of health care in Canada including the legal foundation and historical context

Definitions • population health refers to the health of defined groups of people, their health determinants, trends in health, and health inequalities influenced by: physical, biological, social, environmental, and economic factors; personal health behaviours; access to and quality of healthcare services broader scope compared to public health; accounts for socioeconomic, policy, and historical issues

•public health an organized effort by society to promote, protect, improve, and when necessary, restore the health of individuals, specified groups, or the entire population a combination of sciences, skills, and values that function through collective societal activities and involve programs, services, and institutions aimed at protecting and improving the health of the population as a whole public health services in many provinces (e.g. Ontario) are administered, funded, and delivered entirely separately from healthcare services •epidemiology’ “study of the distribution |...] of determinants of disease, health- related states, and events in populations” • Public Health and Preventive Medicine (formerly called Community Medicine) the medical specialty that focuses on population rather than individuals’ health works with diverse populations to improve population health, address social determinants of health, and promote health equity 5 yr Royal College training in medical skills and knowledge, epidemiology, statistics, social sciences, public administration, policy development, program management, and leadership Sources: Shah , CP. Chapter 2 Measurementand Investigation. Public Health and Preventive Medicine in Canada] 5e. Toronto: Elsevier. 2003 "

Shah, CP. Chapler 15 Community Health Services. Public Health and Preventive Medicine in Canada. Se. Toronto: Elsevier, 2003

Public Health in Canada The public health service in Canada is composed of various agencies at the federal ( Public Health Agency of Canada ), provincial ( Public Health Ontario), and municipal /local levels (local public health units). The organization of the public health system in each province varies widely and is usually separate from the healthcare system. Mission of the Public Health Agency of Canada (federal only): to promote and protect the health of Canadians through leadership, partnership, innovation, preparedness, and action in public health •local public health units and services within regional health authorities ( in most provinces except Ontario, where local public health units are either autonomous or within local government ) provide programs and activities for health protection, promotion, and disease prevention at local and regional levels • catchment-area populations range widely ( hundreds to millions), covering areas of 15-1.5 million km • the “core functions" of public health include six essential activities The Association of Faculties of Medicine of Canada Public Health Educators ' Network. AFMC Primer on Population Health[Internet). The organization of health services in Canada; [cited 2006 Mar 25[. Available from https://phpriiner.afnic.ca/enl

1. health protection: measures taken to address potential health risks at the population level through regulation and advising government (e.g. safe water and food supply ) 2. health surveillance: monitoring and predicting health outcomes and determinants with systematic, longitudinal data collection 3 disease and injury prevention: addressing infectious disease through preventive (e.g. vaccination, droplet protection ) and control (e.g. quarantine) measures; reduce morbidity through lifestyle improvement

.

severe acute respiratory syndrome safety data sheets SOS SMR standardized mortality ratio TP true positives true negatives TN WHMIS Workplace Hazardous Materials SARS

WHO WSIB

Information System World Health Organization Workplace Safety and Insurance 2: "

=

m

Preparing for the LMCC The AFMC Primer on Population Health is the core text for the LMCC and is available as an online resource on the AFMC website (http:// phprimer.afmc.ca)

For the LMCC exam it is recommended that you also read Chapter 15 in Shah CP. Public health and preventive medicine in Canada. 5th ed. Toronto: Elsevier. 2003 ,

G

Historical Perspective Over the last century, the focus of pubic health has evolved: Infectious diseases: a prominent issue in low and middle-income countries and higher income countries aike:includes emergent dseases caused by unfamiliar or new pathogens, inefficient or inappropriate antibiotic use. travel global wanning (e g. HV drug resistant TB. C0V1D-19). and the manufactured conditions of crisis and/or routine conditions of poverty imposed on Indigenous. Black, and other communities of colour • Chronic disea ses: have increased morbidity and mortality (e g. heart disease and cancer due to risk factors and 'or exposures) and disproportionatety affect Indigenous populations throughout the world • Social determinants of health: driven by a growing body of evidence since the 1980s that universal access to health care services did not ameliorate health inequalities, and that significant improvements in health could only be achieved by going 'upstream ' with action on policies

.

-

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Example of a Municipal Health Unit The Middlesex London Health Unit • Serves 450000 people living, working, visiting, and studying in the city of London and Middesex county • 275 fulFtime staff indudingMOHs (physicians), public health nurses, epidemiologists, health promotion educators, dental hygiene managers.

-

etc • Services indude infectious disease control, ensuring environmental health standards, health promotion, and providing family health programs

+

PH3 Public Health and Preventive Medicine

Toronto Notes 2023

4. population health assessment: studying and engaging with a community to understand their needs and improve policies and services 5. health promotion: advocating for improved health through broad community and government measures (e.g. policy, interventions, community organizations) 6. emergency preparedness and response: developing protocols and infrastructure for natural (e.g. hurricane) and man- made (e.g. opioid crisis ) disasters. In many types of health - related disasters, public health leads the disaster response

.

.

Sources:Shah CP. Chapter 15 Community Health Services. Public Health and Preventive Medicine in Canada 5e. Toronto:Elsevier, 2003 the Association of Faculties olMedicine of Canada Public Health Educators ' Network. AFMC Primer on Population Health [Internet] The organization of healthservices in Canada:[cited 2006 Mar 25]. Available from https://phprimer.afmc.ca/en/ ,

Legislation and Public Health in Canada Table 1. Legislation and Public Health in Canada Federal

Provincial

Municipal (Ontario)

Health Canada • Provides health services to the Canadian military and velerans • Provides non-insured health benefits |NIH8) to status First Nations peoples and Inuit and is responsible for the funding of healthcare services on reserve • Approves new drugs and medical devices • Food Guide Public Health Agency of Canada |main Government of Canada agency responsible for public heallh) • An independent body created post -SARS to strengthen public health capacity and response • Focuses on preventing chronic diseases, preventing injuries, and responding to public health emergencies and infectious disease outbreaks • Activities include CIFPHC guideline secretarial, knowledge brokers • Oversees immigration screening, protects Canadian borders (e.g. airporl heallh inspection) • Liaises with the WHO on global health issues Canadian Food Inspection Agency • Regulates food labeling • Deals wilh animal -related infections Canadian Institutes of HeallhResearch ( CIHR) • Formed in 2000 to support research to improve heallh and the health care system

Each province has its own Public Health Act or equivalent (e.g. the Heallh Protection and PromotionPel in Ontario) and agencies (e.g. Public Health Ontario) • Designates the creation of geographic areas for the provision of public health services • Gives powers to the Chief Medical Officer ol Health to control public health hazards • Specifies diseases to he reported to public health units by physicians, laboratories, and hospitals (seeytppem/M PH31) • Mandates programs that address public health issues, environmental health, and chronic disease prevention

Local public health units (e.g. Middlesex London Health Unit) deliver programs mandated by provincial, municipal, or regional legislation and are responsible for the delivery of most public health services, such as: • Infectious disease control, including the follow - up of reported diseases and management of local outbreaks • Inspection of food premises, including those in hospitals,nursing homes, and

.

.

restaurants

Chief Public Health Officer (CPHO) of Canada • Responsible for the Public Health Agency of Canada (PHAQ and reports to the Minister of Health • As the federal government’s lead public health professional, provides advice to the Minister of Health and Government of Canada and collaborates with other governments, jurisdictions, agencies, organizations, and countries on health matters • Communicates public health information to health professionals, stakeholders, and the public • In an emergency, such as an outbreak or natural disaster, directs PHAC staff, including medical professionals, scientists, and epidemiologists, to coordinate emergency response Sauce: Government ol Canada: the role ol the chief public health ollicer [Internet!- Government ol Canada: [updated 2016 Feb 8; cited 2022 July[:[about too screere[.Avaiable Irom: htlps:' wvbw .cdradd.ca en'public-health 'corporatefccganuatioral-structure canada -chiel-pubic-heaHh-ollicerirole-chel-Fwbfichealth-olfker.html

.

.'

• Family health services, including pre -

conception, preschool, school - aged, and adult health programs

• Tobaccocontrol legislation enforcement • Assessment and management ollocal environmental health risks

• Collection and dissemination of local health status reports

• Oral health • By -laws may be approved by municipal governments to facilitate public health issues

Medical Officer of Health (MOH) (Ontario) May be called “Medical Health Officer" (MHO) in other provinces Appointed to each public health unit by the board of health Position held by a Public Health and Preventive Medicine specialist physician Responsibilities include oversight of a multidisciplinary team who: • Collect and analyze epidemiological data

• Provide occupational and environmental health surveillance

• Implement health programs, including tobacco use prevention inspections (restaurants, physician's offices, tattoo parlors) and prenatal courses

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.

The MOH by tew ten require en irdrndujlpremne egency to take « refraui hem any action due to a public health hazard (Section 13 and 22 ot the Health Protection and Promotion Act)

Determinants of Health Concepts of Health

-

• wellness: “ state of dynamic physical, mental , social, and spiritual well being that enables a person to achieve full potential and have an enjoyable life” • disease: “ abnormal, medically-defined changes in the structure or function of the human body" • illness: “an individual 's experience or subjective perception of a lack of physical or mental well -being and consequent inability to function normally in social roles" • illness behaviour: an individual’s actions resulting from and responding to their illness, including their interactions with , or avoidance of, the healthcare system • sickness: views the individual and their society hold towards a health condition, affecting their thoughts and actions • impairment: “any loss or abnormality of psychological , physiological , or anatomical structure or

function" disability : “any restriction or lack of ability to perform an activity within the range considered • normal for a human being ” • handicap: a disadvantage for an individual arising from impairment or disability “ limits or prevents the fulfillment of an individual 's normal role as determined by society and depends on age, sex , social, and cultural factors"

Determinants of Health Income and social status Employment and working conditions Education and literacy Childhood oeperiences Physical environments Social supports and coping skills Healthy behaviours Access to health services Biology and genetic endowment

Gender Culture Exposure to colonization and racialized

prejudice Racism Soiree Social iMermirunli cl hcuKh and health int’qujAlici ,Inter nd,. Govumnwnt ol Canada:[mcdlud

2022 June 14; cited June 2022]. Available hem hltpv «Yvw .canjda.u' vn/publK -hejnh,Servlcevhealth-

piomotlcn'populjUcn-heallh' whal.dvleriTurei-heanh. I- If

+

PH I Public Health and Preventive Medicine

Toronto Notes 2023

• health equity: when all people have “ the opportunity to attain their full health potential" and no one is “ disadvantaged from achieving this potential because of their social position or other socially determined circumstance." Health inequities are systematic differences in the health of individuals/

groups which are considered unjust • health equality: defined as where populations have equal or similar health status. Health inequalities are ssystematic differences in the health of groups that do not necessarily carry a moral judgement Source: ACC Institute ol Human Services. Special Needs Education. Impanmrnl. Disability, and Handicap: what's the dillerence llnlcrnetf Instituted

’

Human Services: 2018 Nov 9 Idled 2020 Apr 281 Available lioni: hHps://acc.cdu.sipen/linpalinicnl dlsablllly aiid handicap whats the difference/ ^

^

Determinants of Health • I 974: the Honourable Marc Lalonde, federal Minister of Health , publishes A New Perspective on the Health of Canadians which outlines four factors that determine health : “ human biology, environment , lifestyle, and health care organizations." The idea of determinants of health has since been expanded and refined to include many additional factors Sources: Shah.CP. Concepts. Determinants, and Promotion ol Health. Public Health and Preventive Medicine in Canada. Se. Toronto: Elsevier. 2003 The Association of Faculties of Medicine of Canada Public Health Educators’ Network. AFMC primer on population health [Internet ]. Chapter 1. Concepts of

health andillness [cited Jul 2022); [ about 7 p.|. Available from https://phprimer.afmc.ca /en/part-i/chapter-1/

Water and General socioeconomic, cultural, and environmental/ conditions / /

^

Unemployment

sanitation

Health care

Definitions ol Health • Multidimensional definition ol health, as defined by the WHO in 1948: "state ol complete physical, menial and social well being and not merely the absence ol disease or infirmity " • WHO updated the definition (socio ecological definition) of health In 1986: "The ability to Identify and to realize aspirations, to satisfy needs, and to change or cope with the environment Health is therefore a resource for everyday life, not the objective of living. Health is a positive concept emphasizing social and personal resources, as well as physical capacities" (Ottawa Charter for Health Promotion) • Other definitions of health have since been proposed that incorporate other dimensions of health • "Health is a social, economic,

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.

and political issue and above all a fundamental human right” The

services

-

Housing Living and working conditions

Work environment

Education

Agriculture and food production

People's Charter for Health

• "Health is the continuous and

Social and community networks

harmonious interaction and balance between the physical, emotional, spiritual, and mental /intellectual realms" The National Aboriginal Health Organization

Individual lifestylu factors /

. .

Age sex and hereditary factors

Cassandra Cetlm 2015

j

Figure 1. Population health model Adapted from Dalilgrecn G, Whitehead M. European strategies lor tackling social inequities in health: Leveling up Purl 2. World Health Organization. 2006

• cultural humility: an approach to health care based on humble acknowledgement of oneself as a learner when it comes to understanding a person's experience , This is a life - long process of learning

-

and being self reflexive • cultural safety: developed by Ur. lrihapeti Ramsden , a Maori nurse scientist, in the 1980s and is “concerned with the power relationships between nurses and those in their care. The recipients of nursing care are empowered to decide what is culturally safe rather than complying passively with the authority of nurses or other health professionals" - Cancer Australia “an approach that considers how social and historical contexts, as well as structural and interpersonal power imbalances, shape health and health care experiences. Practitioners are selfreflective/self-aware with regards to their position of power and the impact of this role in relation to patients” - HeretoHelp British Columbia • cultural awareness: an attitude that includes awareness about differences between cultures

• cultural sensitivity: an attitude that recognizes the differences between cultures and that these differences are important to acknowledge in health care • cultural competency: an approach that focuses on practitioners’ attaining skills, knowledge, and attitudes to work in more effective and respectful ways with Indigenous patients and people of

different cultures

Groups Facing Systemic Barriers, Discrimination, and Structural Violence • certain groups are at greater risk for poorer health outcomes not due to their identity, but rather due to systemic barriers , discrimination , and structural violence (e .g. harmful policies, historic, and contemporary factors). The readers are strongly cautioned against pathologizing entire groups and are encouraged to further read into the historical factors that have contributed to creating systemic barriers which perpetuate inequities • see Colonization ami Healthcare, PH7 ; l.lhical. Lenal , and Organizational Medicine , Indigenous Disproportionate Over - Representation of Biological , Psychological and Social Co - Morbidities , BLOM 27; Indigenous Health , BLOM24

Stale ol the Art Bcview : Poverty and the Developing ( rain Pediatrics 2016:13( 4): c 201S 30) S Socioeconomic stalus ISIS) plays an important role inportable bum development, lower SES is associated with developmental delay, lower academic achievement, and morebelravioural andemotional problems. SES has been found lo influence brain regions that support memury.emotion regulation, r ighei ordei cognitive functioning, and regions that support language and literacy.Some passible mechanisms underlying these changes include ep genetics, material deprivation (e.g.cognitive stimulation, nutrient deficiencies!, stress (e.g. - egathre parenting behaviours), and environmental toxins. There is a needlor primary care providers to build capacity to address poverty in their practice and facilitate referral to evidence based community intervention programs.

.

Ottawa Charier for Health Promotion (1986) • Health promotion: the process of enabling people to increase control over, and improve their health • Some health promotion can be achieved through clinical interactions with patients, but most health promotion is done at the population level by public health professionals and agencies through engaging

stakeholders, formulating policy, and influencing upstream factors • The Ottawa Charter is a framework for thinking about health promotion • The Ottawa Charter states that governments and health care providers should be involved in a health promotion process that includes: 1. Building healthy public policy 2. Creating supportive environments 3. Strengthening community action 4. Developing personal skills 5. Re-orienting health services

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Table 2. Equity- Seeking Groups Facing Systemic Barriers

Indigenous Peoples

Physical

Environmental

Personal Risk Factors

three distinct groups: First Nations ( status and non- status Indians as per (lie Indian Acl|, Metis, andlnuit the original inhabitants ol the land now tailed Canada All Indigenous communities and individuals experience the eflccts ol (oloniralion but sometimes in very dilfcicnt ways

A history ol surviving coloniralion and genocide Systemic racism lower income Higher risk ol experiencing violence and unemployment Homelessness

limited overcrowded housing in disrepair in community Homelessness oil-reserve exposures to environmental toxins (poor drinking water ) duelo land dispossession and loss ol environmental stewardship

Movements towards decolonization and addressing unemployment, and lack of the tecommendalions ol facilities the truth and Reconciliation Obesity (higher SMI) secondary Commission lo poorer access to high quality Menial health awaicness and increasing health literacy nutrition flood insecurity) Higher rales of smoking Indigenous - specific chronic substance misuse, and suicide disease management, secondary to mtergeneiational including DM Culturally appiopriate and trauma interdisciplinary harm reduction, substance use treatment, and smoking cessation piograms Cultural continuity (language and cultural programs ate protective against depression and suicide) Incorporation ol Traditional Medicine into the care plan (wellness journey) for Indigenous patients v/ ho want Uns lobe part of their care Health practitioner training in cultural humility and safety

Sub -Saharan African Ancestry, diverse cultures and histories (people may self -id entity by geographic or ancestral regions (e.g.Caribbean. Ghanaian Somali, African American.Black Canadian, etc.) but socially classified by society based on hair /skin

Variable,depending on socioeconomic status and immigrant statusi'history in Canada The Nova Scotian Black population has been in Canada for centuries; historically displaced into rural settings Newer immigrants tend to live in urban centres

Anti-Black systemic racism in Canada (officially acknowledged by the United Nations, the Canadian Public Health Association, and several provincial and local governments) has led ID physical and mental health inequities High BMI Higher risk DM and HTN (poor data quality for identifying disparities in Canada due to lack of collection of race -based data)

Eldei abuse lack ol emotional support Isolation

Low hazard tolerance Higher rates of Institutionalization Mobility issues

Inactivity Polypharmacy Medical comorbiditics

Aging in place of choice Falls and injury prevention Menial health promotion Preventing abuse and neglect

Housing availability Unsafe housing Lack of recreational space

Poor supervision Food insecurity High - risk behaviours

Improvements in ( amity income most significant Access locally childhood

.

Black Individuals and Communities

.

phenotype as 'Black ') 3rd largest “visible minority" group in Canada 43 o Canadian- born

Isolated Seniors

Individuals »65 yr

Individuals/Children in Poverty

Based onllCOs

People with Disabilities

low income Family dysfunction IICO is an income threshold Lackol educational below which a family will likely opportunities devote a larger share ol its income on the necessities ol food, shelter, and clothing than the aveiagc lamily

.

Includes impaiiments activity limitations, and participation

low income low education status

lesliklions

Discrimination

Person born outside of Canada who has been granted the light to live in Canada permanently by immigration authorities

lifestyle adaptation, loss

ol traditional livelihood,

.

Higher risk DM and HTN Ipoor data quality for

identifying disparities in Canada due to lack of collection of race- based data)

Substance misuse Poor nutrition Inactivity Dependency lorADls

Institutionalization Barriers to access Transportation challenges

Access to community services Cultural perspectives (including reliance on alternative health practices)

Exposure lo diseases and conditions in country ol origin, in current country of residence, or during immigration process Unstable or precarious housing (e.g. smoke Irom wood fires incidence of TB)

.

Barriers finding employment that matches skills and qualifications Exposure to cultural discrimination and isolation which can impact health English language learner Healthy immigrant effect (health worsens over time to match that of the general population) Cultural or religious expectations

Nate: this chart delineates the major challenges laced by each group, but the issues listed are not unique tD each papulation. Sources: Shah CP. The Health of Vulnerable Groups. Public Health and Preventive Medicine in Canada 5e. Toronto: Elsevier 2003.

.

Cullurally -specific and safe practices Anti - racist approaches to care, policy, and programming Movements to reallocate police funding to more appropriate social services to curb police violence through transparency and public oversight

education Access lo sale housing

Stigma

New Immigrants

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Population Specific Interventions

Definition

.

.

Transportation support

Multidisciplinary care Unique suppoit lor individuals with specific disabilities (c.g. trisomy 21) Women'shealth Mental health Comprehensive medical exam Dental and vision screening Vaccinations Cancer screening Receive language and employment training Support integrating into local community Benefit from culturally appropriate and culturally safe interventions,ideally developed in collaboration with the specific target communities

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Toronto Notes 2023

PH6 Public Health and Preventive Medicine

Table 2. Equity- Seeking Groups Facing Systemic Barriers

Persons Experiencing Homelessness

Definition

Physical

Environmental

Personal Risk Factors

Population- Specific Interventions

An individual who lacks permanent housing or

low income Food insecurity Mental illness

A history of colonial subjugation and land

Higher rates of adverse childhood events and subsequent substance use Greater risk of experiencing violence due to lack of housing and protection

Housing First policies

Employment English language learner Longstanding prior lack of access to health care (chronically neglected problems) Cultural or religious

Vaccinations Women's health Mental health Comprehensive medical eiam Dental and vision screening Political advocacy Language training Support for transitioning into the workplace Support integrating into local community

adequate housing

Forced to flee country of origin because of a well- founded fear of persecution and given protection by the Government of Canada Refugee claimant: arrive in Canada and ask to be considered refugee

Refugees

Religious Minorities

LGBTI02S Individuals

Religious minorities are those who do not practice the statistically dominant faith It varies by country, but in Canada, religious minorities are currently those who are not affiliated with one of the major Christian denominations Not all members of a minority faith practice and degree of identification varies by individual

Those who identify aslesbian (a homosexual woman), gay (a homosexual person iirespective of gender), bisexual (a person who is attracted to both genders), trans (a person whose core gender identity andfor gender expression does not align with the sex -assigned gender at birth; the sexuality of trans persons is independent of their gender diversity), intersex (an umbrella term to describe bodies that fall outside the strict maleifemale binary), questioning (regarding one's sexual or gender identity), queer (a historically reclaimed pejorative that is an umbrella term to encompass allsexual and gender diversities), two-spirited (a pan-indigenous term acknowledging gender diversity in uniquely traditional rotes as distinct from western gender diverse identities), and asexual (a person who does not experience sexual attraction to others as distinct from celibacy:asexual individuals may still have sex

expropriation Eiposure to temperature extremes Eiposure to communicable diseases in shelters

Post- traumatic stress disorders Depression Adjustment problems Partial health coverage via Interim Federal Health

Diseases and condrbons in

.

Direct and indirect effects of war

Program

expectations

Reduced employment options in Ouebec due to laws banning

government workers such as teachers, police officers, publicly employed lawyers and court workers from wearing religious symbols like hijabs turbans, and kippahs

.

Poorer mental health At risk of experiencing hate Suboptimal health and care crimes, especially those who wear visible re :g ous symbols, seeking behaviours such as Muslim women Sikh men and Jewish men

If possible and when requested, offer patients a healthcare provider of the same gender Provide accessible multi- faith spaces and chaplain services in the hospital Instill a culture of inclusion beyond tolerance and provide religious accommodation where possible Proactively consult healthcare workers if they require alternative scheduling for religious holidaysor fasting Collaborate with religious leaders and chaplains in supporting the health of their respective communities

Over-representation in youth homeless population Violence,harassment, and discrimination when seeking stable housing, employment, health,or social services

Apply an intersectional lens to understand LGBTI02S populations (racialued gender - diverse, traditional' cultural roles as in 2S) Gender - neutral language and the avoidance of

.

.

.

family violence Lower income Identity documents lacking correct name or sex designations Victims of hate crimes motivated by sexual orientation and/ or gender identity: higher prevalence of hale crimes against racialued communities with greater fatality

Higher ratesof depression, anxiety, obsessive - compulsive andphobicdisorders, suicidality, and self harm Increased risk of alcohol, tobacco, and other substance misuse Double the risk for post traumatic stress disorder than heterosexual people Greater participation in high risk sexual practices related to HIV infection Deterioration of mental health due to multiple factors (internalized queerphobia limited sociomedical infrastructure perpetuating! instigating underlying comorbidities)

-

.

Note: this chart delineates the major challenges faced by each group, but the issues listed are not unique to each population. Sources: Shah CP. The Health of Wlnerable Groups. Public Health and Preventive Medicine in Canada 5e. Toronto: Elsevier 2003.

.

.

country of origin (e.g.malaria IB onchocerciasis, etc.)

Sale housing Addictions support Mental health

.

.

.

heteronormativeassumptions

to invite patients to self identity as gender or seiual minorities Increased awareness of the broader social, legal,and medical context in which LGBTI 02S individuals live

Improve recognition that individuals who belong tomultiplemarginalded communities may face additional barriers to maintaining good health

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PH7 Public Health and Preventive Medicine

Toronto Notes 2023

Screening for Poverty • poverty is not always apparent despite being widespread ( 20% of families in Ontario live in poverty) • poverty is a risk factor for many chronic diseases, cancer, and mental illness • women, Indigenous peoples, new immigrants, and LGBTQ + are some of the groups at highest risk of living in poverty • primary healthcare providers should intervene, such as by asking the following two questions: step 1: “ Do you ever have difficulty making ends meet at the end of the month ?” for living below the poverty line, sensitivity 98% and specificity 40% step 2: “ Have you filled out and sent in your tax forms ?" tax returns are required for accessing many income security benefits like GST/HST credit, working income tax benefits, property tax credits, child benefits, etc. connect your patients to a free community tax clinic to assist them

Indigenous Health in Canada Definitions

• Indigenous peoples represent approximately 4.9% of the total population of Canada in 2016 and speak over 70 Indigenous languages • 3 distinct groups of Indigenous peoples in Canada ( per sec. 35 of the Constitution Act 1982): first

-

Nations (status and non status), Metis, and lnuit • f irst Nations: includes over 600 diverse communities in Canada; status vs non status refers to the registration of first Nations peoples under the Indian Act ( 1876), which , in addition to the establishment of the Department of Indian Affairs, was originally established by the government to administcr / manage Treaty commitments, and to remove self governing and traditional practice rights. ’Ihe Indian Act impacts the lives of countless Indigenous peoples, families and communities from birth to death • Metis: descendants of the first Nations and European settlers; nearly 2 /3 residing in cities, greatest percentage in Ontario • lnuit: roughly 75% of this population of 70000 resides in the 4 Canadian Regions known as lnuit Nunangat , the lnuit Homeland These include: Nunavut, Nunavik ( N Quebec), Nunatsiavut ( Labrador ), and Inuvialuit ( Northwest Territories). 'Ihe majority of lnuit live in Nunavut ( 30135 ), followed by Nunavik ( 11800), Inuvialuit (3110 ), and Nunatsiavut ( 2285) Another 17690 lnuit live outside of lnuit Nunangat, many in urban centres in southern Canada , including Ottawa , Edmonton , and Montreal

. -

-

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.

New Immigrants to Canada • Mandatory medical exams on entry to Canada by a designated medical practitioner • Complete medical examination for persons of all ages Chest x-ray and report for persons >11 yr t Urinalysis for persons 25 yr • Syphilis serology for persons 215 yr • HIV testing for applicants 215 yr as well as for those children who have received blood or blood products, have a known HIV- positive mother, or have an identified risk. An ELISA HIV screening test should be done for HIV land HIV 2 • Serum creatinine for persons 215 yr and children with a history of HIN (resting BP >150/90 mmHg). DM. kidney disease, or signs of impaired renal function • Provide compassionate psychosocial assessment, be aware of increased prevalence of mental health issues (c.g. PTSD depression, intimate

.

.

.

.

.

partner violence)

Assess Immunization documents and develop catch- up schedule

.-. . ' . .

Sou»:CltUamMp anil Iraniyalkn Canada Handbook |M«l» l|. townm nl cl Canada [rmHM 2022 Sapl 20;. Avodcbt lien Mtpu ’wwwxiiudt M WV Inwiigiallafl i lnynwi lMiiNp/rorpo otntNbfcoticiti itwnuab.rilml

-

.

Young and Growing Populations

• between 2006 -2016 the Indigenous populations have increased by 42.5%, 4 times that of non Indigenous Canadian population growth • 32.1 is the average age of the Indigenous population , about 8 yr younger than the non - lndigenous Canadian population

• the aging Indigenous population is also growing, with anticipated doubling of >65 age group by 2036 Colonization and Healthcare Colonizers have perpetrated specific acts throughout Canadian history that have greatly impacted the physical, mental, emotional, and spiritual health of Indigenous peoples. Physicians should therefore be aware of the historical (and current ) underpinnings of Indigenous health disparities, and the way in which health care professionals, including physicians, have acted as agents of the colonial agenda historically, which are discussed here, and their responsibility to redress previously damaged healthcare relationships ( seeEthical, Legal, and Organizational Medicine, Resources in Indigenous Health, ELOM 29). Despite institutionalized abuse and assimilation , Indigenous people have survived remarkable injustice and have built resilience through traditional knowledge and practices. Residential Schools (1870 s-1996 ) The residential school era is well-known for its lasting and damaging effects on many generations of Indigenous people. Many Indigenous students suffered from poor nutrition, hygiene, and living conditions, as well as physical, sexual, and psychological abuse from teachers and others in power. The intent of residential schools to assimilate Indigenous people also led to spiritual harms through significant loss of traditional language and culture. Residential school survivors report poorer general and self-rated health as well as increased rates of chronic and infectious diseases, mental distress, depression, substance use, and suicide. Importantly, many of these outcomes extend to subsequent generations (i.e. intergenerational trauma).

The term “residential school syndrome” has been proposed to better characterize the traditional DSM-V definition of post-traumatic stress disorder with additional criteria speci fic to residential school survivors, such as tendency to misuse alcohol and drugs (often at a young age), loss of cultural knowledge, violent or angry outbursts, and difficulty parenting. Treatment approaches must take into account a holistic view of all these criteria, rather than simply focusing on one aspect, like substance use, which often perpetuates negative stereotypes. The Truth and Reconciliation Commission (TRC) (2015) is a document jointly created by the Canadian government and residential school survivors that preserves in writing the truth of residential schools

Traditional and Complementary Medicine Use Among Indigenous Cancer Patients in Australia Canada , New Zealand , and the United Stales: A Systematic Review Integr Carreer Iher 2018:17(3): 568 581 Purpose: lo systematically review the use of traditional Indigenous and complementary medicines among Indigenous cancer patients in Australia Canada Newlealand. and the United States. Methods: St odes on the use of traditional Indigenous and complementary medicines among Indigenous cancer patients in Australia Canada. New Zealand, and the United States published between January 2000 and October 2017 were eligible for inclusion. Results: 21 articles based on 1S studies were included. Traditional Indigenousand com pfcmeotary medicines were used by between 191 to 57.7% of Indigenous patients. Ibese modalities were most often used in combination with conventional cancer treatmentsto meet spiritual, emotional, and cultural needs. These treatments bad multiple perceived spiritual, emotional, and cultiral benefits. Traditional Indigenousand comptementaiy medicine use was influenced by a patient’s perceptions of their healthcare practitioner's attitudes towardsthese modalities.

.

.

.

.

In Canada, many Indigenous healing practices include drumming, singing, smudging, herbal teas, sweat lodges, and other ceremonies. Healthcare providers are encouraged to research and explore these options as an additional therapeutic tool for Indigenous patients requesting them. Not all Indigenous patients will request such treatments and so perhaps first ask patients. “What do I need to know about you as a person to give you the best care possible?”

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PH8 Public Health and Preventive Medicine

Toronto Notes 2023

.

and delineates recommendations for reconciliation Many TRC recommendations pertain directly to health and healthcare providers. Unfortunately, seven years later they remain recommendations and have not become Calls to Action . Nutrition Trials Prom 1942 to 1952 , nutritional scientists in conjunction with the Canadian government performed unethical research on Indigenous people with tne aim of “ studying the state of nutrition of the Indian ” The lames Bay Survey is perhaps the most well known of these studies conducted on the Attawapiskat and Rupert's House Cree First Nations, though many were conducted on residential school children as well One of the lead physician scientists was Dr. Frederick iisdall ( inventor of Pablum ), former president of the Canadian Paediatric Society and paediatrician at the Hospital for Sick Children in Toronto, Ontario. Some unethical and arguably criminal acts committed by researchers were: • lack of informed consent from parents or children • Indigenous children were kept malnourished over a two year period to establish a baseline •one group of children received a flour mix not yet approved for sale that caused them to develop anemia, contributing to greater morbidity and mortality in this group with no therapeutic intervention •in an effort to control as many factors as possible, dental care was denied to observe the progression of dental cavities and gingivitis in the setting of malnutrition

.

-

.

-

-

Impact of Sustained Caloric Restriction on Residential School Survivors and Other Generations •sustained caloric restriction can cause height stunting, induce physiological changes to prioritize fat

over lean mass, and higher risk of developing type 2 diabetes •stunting negatively impacts neurological, psychological, and immune systems • due to sustained starvation, “ the child ’s physiology is essentially ‘programmed’ by hunger to continue the cycle of worsening effects, with their bodies displaying a rapid tendency for fat mass accumulation when nutritional resources become available” • other generations are at risk of having a higher BM 1 and developing obesity

-

Tuberculosis, Tuberculosis Sanatoriums, and “Indian Hospitals” kuropean colonizers brought tuberculosis ( TB ) to Indigenous populations as early as the 1700s hullgenous communities, particularly the Inuit, already had risk factors predisposing the spread of TB For example, there was malnutrition from food scarcity and overcrowding on federally mandated reserves after forced relocation from traditional territories From 1930 1940, death rates from TB in Inuit populations were roughly 700 per 100000, among the highest ever recorded in a human population. For comparison , TB was the tenth leading cause of death globally in 2016 at a crude death rate of 17 per 100000, while ischemic heart disease was the first at 126 per 100000. This led the Canadian government to forcibly relocate many Indigenous people to TB sanatoriums and “Indian hospitals," often hundreds of kilometres away. The average length of stay at these institutions was 2.5 yr and many patients never returned home.

.

.

.

-

The TB health crisis persists today; in 2016, the average annual incidence rate of T' B among the Inuit in Canada was roughly 296 times higher than Canadian-born non - lndigenous people. In March 2018, the national representational organization for Inuit people in Canada, called Inuit Tapiriit Kanatami (1TK), and the Government of Canada committed to reduce TB rates across Inuit communities by 50% by 2025 and to eliminate TB by 2030 in a project called the Inuit Tuberculosis klimination Framework. It is worth noting that “ Indian hospitals” were initially welcomed by many First Nations who were under the impression that reasonable healthcare was part of treaty terms. In reality, “Indian hospitals" were crowded, underfunded, and poorly staffed, serving to segregate sick Indigenous people from the rest of the population. They were also the site of the cycle of apprehension, coercive sterilization, chemical and physical restraints, and scientific experimentation, all of which inflicted significant morbidity and mortality When the Canadian government began closing these hospitals in the 1960s, Indigenous people continued to fight for their right to healthcare, which was finally recognized in the Indian Health

.

.

Policy of 1979

Coerced Sterilizations Throughout the twentieth century, eugenics programs existed across the country In the 1920s 1930s, both Alberta and British Columbia legalized eugenic policies in the Sexual Sterilization Acts which were not repealed until the 1970s To limit reproduction of ” unfit’’ people in the eyes of the government, Indigenous women were disproportionately targeted. This is referred to as forced or coerced sterilization and , according to various accounts by Indigenous women across the country, involved any number of the fallowing: • tubal ligations being performed without consent • being falsely told that a procedure is reversible • being pressured into signing consent forms while actively in labour or on operating tables • being given an ultimatum to undergo a tubal ligation or risk child apprehension It is important to note that many sterilizations also occurred outside legislation, in federally run “ Indian hospitals," and some have been documented as recently as 2018. At least 100 Indigenous women have come forward with accounts of coerced sterilization by physicians and nurses, spanning from the 1970s until 2018.

.

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PH9 Public Health and Preventive Medicine

Toronto Notes 2023

Sixties Scoop and Indigenous Child Welfare

-

The “Sixties Scoop” ( Johnson, 1983) ( 1951 1980s) refers to the government- mandated practice of removing Indigenous children from their families without consent for placement in foster care or adoption. As residential schools started to close, many children were transitioned to child welfare facilities as the state deemed Indigenous parents unfit to care for their children - a legacy that persists today. Similar to the Indian Residential School system, the goal was to assimilate Indigenous children into a non - lndigenous family, rather than to directly provide child welfare to Indigenous communities. Though Indigenous bands have increasingly been allowed to provide their own child welfare Indigenous children are still overrepresented in foster care. In 2016, Indigenous youth ages 0 to 4 made up about half of all foster children in private households, despite being only 8% of total youth in this age group in Canada. Youth with a history in government care may be at greater risk for substance misuse, street

.

involvement, and incarceration.

To this day, Indigenous children are disproportionately represented in the child welfare system and are often apprehended for reasons directly related to the routine conditions of poverty. The apprehensions that continue today echo the practices of the Sixties Scoop and residential school eras; the displacement of Indigenous children separates them from their language and culture and hinders the ability of Indigenous families to build resilience. Importantly, many Indigenous mothers and families avoid accessing healthcare services for fear of their children being apprehended. Indigenous Approaches to Health and Wellness

• it is important to recognize the significant diversity amongst Indigenous nations in the land now known as Canada. Even within the same nation or language group, there will be variability in practices. Despite this diversity, there are some ideas that recur across many nations

• restoring balance in the four realms of spiritual, emotional, mental, and physical health of a person acting as an individual, as well as a member of a family, community, and nation ideas represented by the medicine wheel of First Nations peoples, the Learning Blanket of Inuit peoples, and the Metis tree model all share a worldview based on holistic lifelong learning and wellness Indigenous medicines may take many forms (song, dance, smudge, ceremonies, plant medicines, etc.) practiced by experts who have decades of apprenticeship while allopathic medicine often focuses on treating illness (like HTN or DM ), Indigenous medicine may understand the cause of a condition and the approach to healing in a different way than a biomedical guideline Indigenous medicine may focus on quality' of life and not just cure • cultural humility cultural humility is a respectful, person -centered way of bringing curiosity and compassion when a patient is willing to come for support it takes courage to be humble enough to admit that we do not know what we do not know Indigenous medicine is thousands of years old and eludes randomized controlled trials Traditional Medicine is unlikely to interfere with Western Therapies Latin root of “curiosity" is “cura,” which means “ to care.” Caring about someone’s healing and their beliefs about what may help them heal is a powerful act of witnessing and honouring. Beginning with the belief that a person has wisdom about themselves that no one else does and that we can be supporters of their healing, if they consent, can be a way to honour the inherent wholeness of a person seeking care. This is especially true of Indigenous patients for whom regaining self-determination is tantamount to regaining their wellness. before assuming that an Indigenous person is interested in using traditional medicine, it is important to begin with questions and curiosity'. Dr. Chantal Perrot speaks about the Patient Dignity Questionnaire which advises healthcare workers to first ask patients, “What do I need to know about you as a person to give you the best care possible?” National Indigenous Health Organization ( N1HO) offers 8 guidelines on practicing culturally safe health care for Indigenous patients including the need to allow Indigenous patients to access ceremony, song, and prayer; the need for information and for family support; guidelines for the appropriate disposal of body parts and for handling death

Disease Prevention Natural History of Disease

• course of a disease from onset to resolution 1. pathological onset 2. presymptomatic stage: from onset to first appearance of symptoms/signs 3. clinical manifestation of disease: may regress spontaneously, be subject to remissions and relapses, or progress to death Surveillance

-

• the continuous, systematic collection, analysis, and interpretation of health related data needed for the planning, implementation, and evaluation of public health practice Sources: Public health surveillance (Internet]. World Health Organization.AvailableIrom httpsi'wwn.who.int'topics/public health survedlance/ea’

+

Toronto Notes 2023

PHll) Public Health and Preventive Medicine

• types of surveillance • passive surveillance: reporting of disease data by all institutions that see patients, relying solely on the cooperation of healthcare providers ( laboratories, hospitals, health facilities, and private practitioners ) most common, least expensive, but difficult to ensure completeness and timeliness of data active surveillance: regular visits to health facilities for reviewing medical records to identify suspected cases of disease under surveillance, or active testing of a population for the presence of a disease resource-intensive, used when a disease is targeted for eradication where every possible case must be investigated, or for outbreak investigations sentinel surveillance: selective reporting of disease data from a limited network of carefully selected reporting sites with a high probability of seeing cases in question well -designed system can be used to signal trends, identify outbreaks, and monitor the burden of disease in a community in a timely and cost effective manner compared to other

-

kinds of surveillance may not be as effective in identifying rare diseases, or diseases that occur outside the catchment area of sentinel sites

.

Sources: World HealthOiganuation . Public Health Surveillance. Accessed horn: hllps:/ /www.who. lnl /immunli lpacty K-«tttx>flat- fVKdutiOM acute 600 mL/24 h or bleeding rate of >100 mL/h

Most Common Causes of Chronic Cough in the Non smoking Patient (Cough >3 mo with Normal CXR ) GERD

. • .•

-

Asthma Postnasal drip ACEI

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LJ

..

’" Big

Three* causes of chronic cough

common cause of hemoptysis

.

.

.

Adapted from : Weinberger SE . Principles of pulmonary medicine Oth ed 2008 With permission from Elsevier

+

Toronto Notes 2023

RI Rcspirologv

Pulmonary Function Tests • useful in differentiating the pattern of lung disease (obstructive vs. restrictive ) • assess lung volumes, flow rates, and diffusion capacity • note: normal values for FEVt are approximately ±20% of the predicted values (for age, sex, and height ); “ Race” differences in predicted values are recognized but are not fully understood and likely represent genetic ancestry and the effects of the social determinants of health Table 5. Comparison of Lung Flow and Volume Parameters in Lung Disease Obstructive

Restrictive

Decreased flow rales (most marked during expiration)

Decreased lung compliance

Air trapping (increased RV/HC)

Decreased lung volumes

Figure 4A . Lung volumes and capacities m

Hyperinflation (increased IlC)

.

.

Asthma, CORD, bronchiolitis bronchiectasis/Cf •

DDx

IlD pleural disease, neuromuscular disease, chest wall disease

FEWFVC

Reduced

Elevated or normal

ILC

Elevated or normal

Reduced

RV

Elevated or normal

Reduced, normal or elevated

RV / HC

Elevated or normal

Normal or elevated ( neuromuscular disease may have elevated RV/TU ratio)

Normal or reduced depending on disease state

DLCO

It

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i

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Reduced or normal depending on whether parenchymal or extraparenchymal restriction is present

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Figure 4B . Expiratory flow volume curves Adapted with permission from Elsevier. Weinberger SE. Principles of pulmonary medicine 5th ed. 2008

.

'Bronchiectasis can be obstructive or mixed

Table 6. Common Respirology Procedures Technique

Purpose

Description

Plethysmography (" body box ")

Measure ERC

After a normal expiration, the patient inhales against a closed mouthpiece Resultant changes in the volume and pressure of the plethysmograph are used to calculate the volume of gas in the thorax Useful lor patients with air trapping

He Dilution

Measure ERC

A patient breathes from a closed circuit containing a known concentration and volume ol helium Since the amount olhelium remains constant ERC is determined based on the final concentration ol the helium in the closed system Only includes airspaces that communicate with the bronchial tree and is dependent on airflow - may underestimate volumes in patients with gas trapping

.

Bronchoscopy

A flexible or rigid bronchoscope is used for visualization of a patient's airways allows lor: Bronchial and broncho alveolar lavage ( washings) loi culture, cell count analysis, and cytology Endobronchial ortransbronchial tissue biopsies Removal of secretions/foreign bodies/blood Laser resections Airway stenting Mediastinal lymph nodes can also be sampled using a special bronchoscope equipped with an U/ S probe (EBUS)

Diagnosis and therapy

-

Lung Volumes Expiratory Reserve Volume ERV Forced Expiratory Flow Rate FEF Forced Expiratory Volume FEVr (in one second) Functional Residual Capacity FRC Inspiratory Capacity 1C Residual Volume RV TLC Total Lung Capacity Forced Vital Capacity FVC Tidal Volume VT

-

--

PvImMMv Fanctlon Tests IPFTs )

i

i

FEV,;FVC >LLN

FEV yEVC 3 d / wk Activities ( physical ) reduced Night - time Sx >1 night/wk GP visits ( unscheduled visits for exacerbations, requiring steroids) ER visits or hospitalizations for exacerbations Rescue puffer (SABA) use >3 times/ wk School or work absences

-

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R8 Rcspirology

Toronto Notes 2023

-

• long term maintenance: any patient with poor control ( Table 11 , 1( 7 ) and / or at risk of

exacerbations should be on an inhaled corticosteroid -containing regimen ( see l igure 9 ) risk of exacerbation defined as any of: 1) history of a previous requiring any of: systemic steroids, ED visit or hospitalization , 2) poorly -controlled asthma, 3) overuse of SABA (defined as use of more than 2 inhalers of SABA in I year ), or 4) current smoker 1. start with daily inhaled corticosteroids (or long acting p 2 agonist with inhaled corticosteroid (formoterol / budesonide ) as needed in patients 12 y/o especially in patients expected to have low adherence to a daily inhaled corticosteroid ) 2. add long-acting p 2 -agonists to low dose inhaled corticosteroids in adults ( use a combination inhaler; avoid separate ICS and LABA inhalers) 3. escalate inhaled corticosteroid dose 4. consider L I RA, long-acting anticholinergics, oral corticosteroids, and biologies ( e.g. anti IgE agents, including omalizumab, anti-lL5/ lL5R agents, such as mepolizumab, and antiIL - 4 /13 drugs, including dupilumab )

-

-

-

Emergency Management of Asthma •see Emergency Medicine, ER 29 1. inhaled (52 -agonist first line (MD1 route and spacer device recommended ) 2. systemic steroids ( PO or IV if severe) 3. if severe, add anticholinergic therapy ± magnesium sulfate 4. SC / I V adrenaline if caused by anaphylaxis or if unresponsive to inhaled (52 agonist 5. rapid sequence intubation in life - threatening cases ( plus 100% 02, monitors, IV access) 6. inhaled corticosteroid maintenance therapy at discharge

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-

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-

Guidelines for Asthma Management

60 mmol/ Lon two occasions supports the diagnosis) • single mutation carriers have normal sweat tests (and no disease ) PI is early: airflow limitation in small airways late: severe airflow obstruction , hyperinflation, gas trapping ABGs • hypoxemia , hypercapnia later in disease with eventual respiratory failure, and cor pulmonale • CXR hyperinflation, increased pulmonary markings (especially upper lobes )

—

.

.

Treatment

• chest physiotherapy • pancreatic enzyme replacements, high fat, high calorie diet • bronchodilators (salbutamol ± ipratropium bromide ) • inhaled mucolytic ( reduces mucus viscosity ): hypertonic saline, DNase • inhaled antibiotics ( tobramycin, colistin , aztreonam , levofloxacin , vancomycin ) • anti inflammatory medications (e.g . azithromycin , ICS if concurrent asthma ) • antibiotics oral and IV ( targeted to sputum growth if available, e.g. ciprofloxacin for Pseudomonas, if sensitive) 1 • CETR potentiators and modulators (e.g. lvacaftor, Orkambi , Svmdeko*)

-

• lung transplant

D isease Cochrane OB Syst dev 201S: CD 006897 Study: Cochrane systematic rev .ew. 8 studies. Population: SS2 patients, with severe or very severe COPO. Intervention Corticosleioids gwtn at equivalent daily dotes for 3 2 d (short duration ) vs. 10 15 d ( longer -duration ). Outcome: Treatment failure, risk of relapse, time to neit COPO exacerbation , likelihood of adverse event, length of hospital stay, and lung function at end of treatment. Results: In four studies there was no differenre m risk of treatment failuie between short-duration and longer-duration systemic corticosteroid treatment ( n*457; odds retro ( OR ) 0.72, 95% confidence interval ( Cl ) 0.36-1.4S). No d < Nerente m risk of relapse|e new event ) was observed between short duration and longer - duration systemic corticosteroid treatment ( n 457; OR 1.04. 95% Cl 0.70 -1.56). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non inferiority and comparedS d vs. 14 d pi systemc corbcosteroid treatment [ i 311; hazard ratio 0.95. 95% Cl 0.66 1.37). In five studies no difference m the likelihood of an adverse event was found between short duration and longer-duration systemic corbcosteroid treatment ( n 503; OR 0.89, 95% Cl 0.46 -1.69. length of hospital stay (u*421; mean difference (MD) 0.61 d 95 % Cl 1.51- 0.281 and lung function at the end of treatment [i*l8S; MD FEV1 -0.041: 95% Cl - 0.19 -0.10) did not differ between short-duration and longerduration treatment . Conclusions 5 d of oral corkost« o ; ds is likely to he sufheientfor treatment of adults with acute exacerbations of COPO and this renew suggests that the likelihood is low that shorter coursesoi systemic corticosteroids ( of around file days) lead to worse outcomes than are seen with longer (10 to 14 d ) courses.

-

-

-

-

*

-

*

.

-

-

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R13 Respirology

Toronto Notes 2023

Prognosis • worse prognosis associated with: frequent pulmonary exacerbations, rapid rate of decline of 1 liV 1, supplemental oxygen requirement with exercise or sleep, worsening malnutrition, infection with difficult to manage organism, Cl- - related DM, pneumothorax, massive hemoptysis • female gender and low socioeconomic class have greater risk of early death

-

'

Interstitial Lung Disease Definition

• a group of disorders which cause diffuse parenchymal lung disease, with progressive scarring of lung tissue and impairment in lung function and gas exchange Pathophysiology

• inflammatory and /or fibrosing process in the alveolar walls > distortion and destruction of normal alveoli and microvasculature • typically associated with: lung restriction (decrease in TLC and VC) decreased lung compliance (increased or normal TEVt / FVC) • impaired diffusion (decreased DLCO) • hypoxemia due to V /Q mismatch ( usually without hypercapnia until end stage) • pulmonary HT'N and cor pulmonale occur with advanced disease secondary to hypoxemia and blood vessel destruction Etiology

-

• IPI is the most common cause; however, there are numerous other causes including medication and radiation related disease • a careful review of risk factors (e.g. organic / inorganic exposures, connective tissue disease symptoms, *

occupational history, medications) is needed during patient evaluation

Known Etiology

Idiopathic

ILD Associated

Interstitial Pneumonias

with Connective Tissue Disorders

ILD Associated with Drugs or Treatments

Inherited Disorders

IFF (idiopathic pulmonary fibiosis)

Scleroderma

Antibiotics

Familial IPF

MSIP (non-specific Interstitial pneumonia )

Rheumatoid arthritis

Anti- Inflammatory Telomerase mutations Saicoidosis agents (methotreiate)

H 8 IIO (respiraloiy bronchiolitis eclated ILD)

Systemic lupus erythematosus ( Sit )

Caidiovasculat drugs (amiodarone)

Neurofibromatosis

DIP (desquamative

Polymyositis / deimatomyosilis

Antineoplastic agents (chemotherapy agents )

Tuberous sclerosis

Interstitial

(nitrofurantoin )

pneumonia )

COP ( cryptogenic oiganicing

Anti- synthetase syndiomes

Recreational drugs (e.g. crack lung, talc granulomatosis)

AIP (acute interstitial pneumonia )

Mized connective tissue disease

Radiation

UP ( lymphocytic

ANCA associated

organizing

vasculitis

pneumonia )

pneumonia )

IPPFE (idiopathic pleuroparenchymal fibroelastosis)

ATOP (acute hbiinous and organizing pneumonia )

Siogren ’ssyndrome

Correctors ( Spedfic Therapies For Class IICFTR Mutations ) for Cystic Fibrosis Cochrane Data base Syst. Iter 201S;8:C0010966 Purpose: loera'catethe effects of cyst fibrosis transmembra ie receptor |CFTR) correctors on clinically impodantoutcomes, both benefits and harms, in chi then and adults with CF and class II CFTR mutations (most commonly F 508de:). Methods: RCTscomparing CF1R correctors to placebo m people withCF class II mulalions weresearched in the Cochrane Cystic fibrosis and Genet c Disorders Cystic Fibrus s Register. Two authors independently eitracted data and assessed risk of biasand quality of evidence usi g GRADE criteria. Results: Iheq e ' ity ol ife stores (respiratory domain) favoured combination therapy (both luin acallor -lvacaftor and teiacaltor ivacaltoi| compared to p aceboat all time points.Ihe mean ’ increase in cystc Mrosis questionnaire (CFO) scores with tw ice-daily teracaflor |100 mg) and nracaftoc (ISO mg) was appioiimately 5 points|95% CI 3.20 to 2.00: S04 participants: moderate qua sty evidence!. KVft predicted improved with both combination therapies compaied to placebo at ( mo by 5.21% with lumacaftor-rracaftor 0D (95% CI 3.61it to 6.00%; 504 participations:high quality evidence),and try 2.40% nith jrracaftor ivacaftor BID (06 % Cl 0.40% to 4.40%: 204 paitcipants; low - quality evidence! Uoie participants receiving the lumacaftoi- ivacattor combination reported early breathlessness (OR 2.05: 99 % Cl 1.10 to 1.83:239 participants: high qoaiity evidence). These adverse effects were not reported in the teiacaftor - nracaftor studies Conclusions Overall, the deployment oleomb nation CF1R torrecloctherapies improve quahty -oMlleand lung (unction in patents with class II CF compaied to placebo controls. Adverse drug effects ten be mitigated with the use of tezacaftor-ivacaftoi. when clinically ind rated.

-

-

.

*

.-

.

.

Table 17. Interstitial Lung Diseases Unknown Etiology

Usually presents in childhood as recurrent lung infections that become persistent and chronic

Granulomatous

Other

Disease

HP (usually oiganic antigen)

.

langcihans- cell histiocytosis

LAM [lymphangioleio myomatosis)

Cianulomalous

Chronic eosinophilic

lymphocytic ILD

pneumonia

Pneumoconioses ( inorganic dust ):

Silicosis Asbestosis.

Gaucher 's disease

.

In ILD think FASSTEN and BAD RASH

Coal workers pneumoconiosis,

Upper Lung Disease (FASSTEN) Farmer 's lung (HP) Ankylosing spondylitis

Chronic beryllium

Sarcoidosis

disease

Silicosis TB Eosinophilic granuloma (Langerhans cell histiocytosis)

Neurofibromatosis Lower Lung Disease (BADRASH) Bronchiolitis obliterans with organizing pneumonia (BOOP) fCryptogenlc Organizing Pneumonia (COP) Asbestosis Drugs (nitrofurantoin, hydralazine. INH, amiodarone. manychemo drugs) Rhcumatologic disease Aspiration Scleroderma Hamman Rich (acute interstitial pneumonia) and IPF

+

Toronto Notes 2023

R14 Respirologv Signs and Symptoms

• dyspnea, especially on exertion

• nonproductive cough

• crackles (dry, fine, end - inspiratory) • clubbing (especially in IFF and asbestosis ) • features of cor pulmonale • note that signs and symptoms vary with underlying disease process e.g. sarcoidosis is seldom associated with crackles and clubbing Investigations Medical Imaging. MM )

• CXR ( see

•

usually decreased lung volumes

• reticular, nodular, or reticulonodular pattern ( nodular 95 percent •lo te op sis •to estrogen use •tojrotDflorPE •Race ateral teg swelling •to sa geqr o Uauma requ ring huspital nation mttc ttre past 4 «k krte PE can probably be entluded without further da gnostic testing d the patient meets ail PERC crpe ittD there is a on clmical suspicion for PE accordmgtietteflbe Wells’ criteria or a Ion gestalt arcpep.ity deter— -ej bythe clinician prior to

= -

Suspect massive PE

Results: Normal: excludes the diagnosis of PE

High probability: most likely means PE present unless pre - test probability is low 60% of V/ O scans are nondiagnostic Echocardiogram

’

•IgeesstbaSOyr

Contraindication loCE ( contrast allergy, renal dysfunction. pregnancy!

Useful to assess massive or chronic PE

^

-

-

.

-

dagrsstrctestingforPE.

Dependent on clinical status ABC

No diagnostic use in PE (insensitive and nonspecific)

May shovr respiratory alkalosis (due to hypenrent alien )

Treatment

-

•admit for observation and stratify risk in low -risk PE setting with no other indication for hospitalization and low- risk of early adverse outcomes, patients may be sent home with

anticoagulation

•oxygen: supplemental oxygen should be administered to target an oxygen saturation S9() percent • pain relief: analgesics if chest pain - narcotics or acetaminophen •acute anticoagulation: therapeutic-dose SC LMVV H or fondaparinux or unfractionated heparin or oral factor Xa inhibitors ( rivaroxaban, apixaban, edoxaban ) or direct thrombin inhibitors (dabigatran ) start ASAP

anticoagulation stops clot propagation, prevents new dots, and allows endogenous fibrinolytic system to dissolve existing thromboemboli over months; get baseline CBC, 1 NR, aPTT ± renal function ± liver function for SC LMWH: dalteparin 200 U / kg once daily, enoxaparin 1 mg /kg BID, or fondaparinux 5-10 mg once daily - no lab monitoring - avoid or reduce dose in renal dysfunction for IV heparin: bolus of 75 U / kg ( usually 5000 U) followed by infusion starting at 20 U / kg / h - aim for aPTT 2-3x control • long- term anticoagulation • for most nonpregnant patients who do not have renal insufficiency or active cancer, first -line is direct oral anticoagulants ( rivaroxaban , apixaban, edoxaban , or dabigatran ) rather than warfarin • if using warfarin instead ofDOAC: start the same day as LMWH / heparin - overlap warfarin with LMWH / heparin for at least 5 d and until INR in target range of 2 3 for at least 2 d ( use for patients with severe renal insufficiency ) LMWH instead of warfarin for pregnancy, active cancer, or high bleeding risk patients • IV thrombolytic therapy if patient has massive PE ( hypotension or clinical right heart failure) and no contraindications hastens resolution of PE but may not improve survival or long-term outcome and doubles risk of major bleeding • interventional thrombolytic therapy massive PE may be treated with catheter-directed thrombolysis by an interventional radiologist catheter-directed thrombolysis is not recommended over systemic thrombolysis •1VC filter: routine use is not indicated; use if recent proximal DVT and absolute contraindication to anticoagulation •duration of long-term anticoagulation: individualized, however generally • if reversible cause for PE (e.g. surgery, injury, pregnancy, etc.): 3-6 mo • if PE unprovoked: 6 mo to indefinite • if ongoing major risk factor (active cancer, antiphospholipid antibody, etc.): indefinite

-

Thromboprophylaxis • mandatory for most hospital patients: reduces DVT, PE all - cause mortality, cost effective •start ASAP •continue at least until discharge or recommend extending for 35 d postoperatively, if major

.

orthopaedic surgery

-

Evaluation of a Suspected Pulmonary Embolism Urndmcal probability ol embolism D-dimer (-ve) -» CT scan (+ve) ruled in (-ve) -* ruled out Intermediate or high probability CT pulmonary angiography scan (-ve) •ruled out (*ve) » ruled in Notes: • Use O-dimers only if low clinical probability, otherwise, go straight toCT • If using V/O seans (CT contrast allergy or renal failure): • Negative V/O scan rules out the diagnosis • High probability V /O scan only rules in the diagnosis if high clinical suspicion • Inconclusive V/O scan requires leg U/S to look for DVT or CT

Workup for Idiopathic Venous

Thromboembolism Thrombophilia workup : recurrent or idiopathic DVT /PE. age 200 m L of pleural fluid for visualization on PA film

• PA: blunting of lateral costophrenic angle • lateral: > 50 mL leads to blunting of posterior costophrenic angle • dense opacification of lower lung fields with concave meniscus as fluid accumulates

• decubitus: fluid will layer out unless it is loculated • supine: fluid will appear as general haziness over lung field

• CT: helpful in differentiating parenchymal from pleural abnormalities; identifying loculation. measuring density of fluid ( higher density may indicate a hemothorax ); contrast can detect pleural enhancement indicative of empyema and may identify underlying lung pathology causing effusion • VIS: detects small effusions and can guide thoracentesis • thoracentesis: indicated if pleural effusion is a new and concerning finding, if patient is unstable, and / or if patient has pneumonia and there is a concern about infected parapneumonic effusion; order blood work (serum LDH, glucose, protein, albumin ) at the same time for comparison risk of re-expansion pulmonary edema if >1.5 L of fluid is removed in one shot through a closed tap • inspect for colour, character, presence of pus, and odour of fluid send fluid for analysis (see T able 26 ) • pleural biopsy: indicated if suspect IB, mesothelioma , or other malignancy ( and if cytology non -

diagnostic)

Role of CT in Pleural Effusion • To assess for fluid loculation. pleural enhancement, thickening and nodules, parenchymal abnormalities, and adenopathy • Can provide clues to help distinguish benign from malignant effusion • May not distinguish empyema from parapneumonic effusion

Features of Mesothelioma • Multiple pleural nodules • Circumferential pleural thickening >1 cm • Mediastinal pleural involvement Imaging Features of Empyema

• Parietal pleural thickening • Pleural enhancement • Concurrent thickening and enhancement of both the visceral and parietal pleural (split pleural sign)

+

R25 Rcspirology

Toronto Notes 2023

Table 26. Analysis of Pleural Effusion Measure

Purpose

Always order: Protein, LDH

Transudate vs.eudate

LDH especially high (>1000 IU/L) in empyema,rheumatoid, malignancy

.

Complicated Parapneumonic Effusion (needs drainage if any of these are present): • Loculation • >1/ 2 hemithorax of fluid pH leaky capillaries -> interstitial and alveolar pulmonary

.

edema -> reduced compliance V /Q mismatch , shunt , hypoxemia , pulmonary HTN

Clinical Course A Exudative Phase • first 7 d of illness after exposure to ARDS precipitant • alveolar capillary endothelial cells and type 1 pneumocy tes are injured , resulting in loss of normally tight alveolar barrier • patients develop dyspnea, tachypnea , increased work of breathing these result in respiratory fatigue and eventually respiratory failure (see Hypoxemic Respiratory Failure , R 26 ) B. Fibroproliferative Phase • after day 7 • may still experience dyspnea, tachypnea, fatigue, and hypoxemia • most patients clinically improve and are able to wean off mechanical ventilation • some patients develop fibrotic lung changes that may require long-term support on supplemental oxygen or even mechanical ventilation • if fibrosis present, associated with increased mortality

.r . -

AIDS Severity PaO. F O , H l«n»| Mild 200300 Moderate 100 200
CD8+ T cells) leading to perifascicular atrophy of muscle fibres

Clinical Presentation • progressive symmetrical proximal muscle weakness (shoulder and hip) developing over wk to mo; difficulty lifting head off pillow, arising from chair, climbing stairs

• dermatological DMM has characteristic dermatological features (1'> M, children and adults) Gottron’s papules - pink-violaceous, flat-topped papules overlying the dorsal surface of the MCP and IP Gottron’s sign - erythematous, smooth or scaly patches over the extensor surface of elbows, knees, or medial malleoli heliotrope rash: violaceous rash over the eyelids; usually with edema shawl sign : poikilodermatous, erythematous rash over neck, upper chest , and shoulders mechanic's hands: dry, crackled lesions on palmar and lateral surfaces of digits, especially over the pulp space, also seen in a subtype of myositis called anti synthetase syndrome periungual erythema • cardiac • arrhythmias, congestive heart failure, conduction defect, ventricular hypertrophy, pericarditis

Malignancies Associated with DMM

..

Breast Lung Colon

• Ovarian

-

• gastrointestinal

• oropharyngeal and lower esophageal dysphagia, reflux

• pulmonary

• weakness of respiratory muscles, ILD, aspiration pneumonia

Investigations

• general lab tests: CK, CBC, ESR and /or CRP, TSH • serologic tests: ANA , anti ) o- l ( DMM ), anti-Mi 2, anti-SRP ( usually not available at commercial labs) • imaging: MR 1 may be used to localize biopsy site • EMG: characteristic findings of muscle inflammation and damage • muscle biopsy can aid in diagnosis, however not needed in those with classic skin findings and muscle weakness

-

-

-

r >

LJ

+

RH17 Rheumatology

Toronto Notes 2023

Treatment

• non -pharmacological treatment P I and OT, speech-language therapy for esophageal dysfunction • pharmacological treatment high - dose glucocorticoid (e.g. prednisone 1 mg/ kg/d ) usually not exceeding 80 mg daily and slow taper after patient improvement ( 6 wk ) • add immunosuppressive agents (azathioprine, MIX ) • 1V1G if severe or refractory

-

hydroxychloroquine for DMM rash • malignancy surveillance

• detailed history and physical ( breast, pelvic, and rectal exams ) • CXR, abdominal and pelvic VIS , fecal occult blood, Fap test , mammogram ± CT scan ( thoracic, abdominal , pelvic)

Sjogren’s Syndrome Definition • autoimmune condition characterized by dry eyes ( keratoconjunctivitis sicca/xerophthalmia ) and dry mouth ( xerostomia ), caused by lymphocytic infiltration of salivary and lacrimal glands • exists on a spectrum and may evolve into a systemic disorder ( 20% ) with diminished exocrine gland activity and extraglandular features • primary and secondary forms (associated with RA , SLH . DMM, and HIV ) • prevalence 0.5%, F»M at 10:1, 40-60 yr • increased risk of non-Hodgkin’s lymphoma (lifetime incidence 6-7%) Table 20. The American College of Rheumatology ( ACR )ZEuropean League Against Rheumatism (EULAR ) Classification Criteria for Primary Sjogren’s Syndrome (at least 1 inclusion criteria, no condition in exclusion criteria , score >4) Criteria Score Labial salivairy gland biopsy with focal lymphocytic 3 sialadenitis with focusscorea1foois '4mmi

.

-

Anti SSA - or Ro- positive

Comments

Focus scores are histopathologic grading systems Strongly associated with phenotypic ocularand serological components of Sjogren 's

3

Ocular staining score > 5 (or van Gi jsterfeld score >4 1 on at least one eye)

Schirmer 's test solid tumours)

•

Etiology and Pathophysiology • cutaneous vasculitis following: • drug exposure (allopurinol, gold , sulfonamides, penicillin , phenytoin )

• viral or bacterial infection • idiopathic causes

• small vessels involved ( post -capillary venules most frequently ) • usually causes a leukocytoclastic vasculitis: debris from neutrophils around vessels • sometimes due to cryoglobulins which precipitate in cold temperatures ri

Clinical Presentation •

-

L I

palpable purpura (usually on lower extremities) ± vesicles and ulceration, urticaria, macules, papules, bullae, subcutaneous nodules renal or joint involvement may occur, especially in children

+

Investigations

• vascular involvement ( both arteriole and venule ) established by skin biopsy

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RH 20 Rheumatology

Toronto Xotes 2023

Treatment • stop possible offending drug; treat underlying primary disease

• NSAIDs, low- dose corticosteroids

• immunosuppressive agents in resistant cases • usually self limiting

-

Small Vessel ANCA- Associated Vasculitis GRANULOMATOSIS WITH POLYANGIITIS (GPA , formerly known as Wegener’s Granulomatosis)

Definition

granulomatous inflammation of vessels that may affect the upper airways (rhinitis, sinusitis ), lungs ( pulmonary nodules, infiltrates caused by pulmonary hemorrhage), and kidneys (glomerulonephritis, renal failure) • highly associated with c-ANCA by indirect immunofluorescence ( 11 F ) and PR3-AXCA by HL1SA; however, changes in A NLA levels do not predict remission or relapse • incidence: 2-3 in 100000; more common in Northern latitudes •

Classic Features of GPA • Necrotizing granulomatous vasculitis of lower and upper respiratory tract • Focal segmental glomerulonephritis

Table 22. Classification Criteria for GPA* Score

Clinical Criteria

Criteria

Description

Nasal involvement

Crusting, ulcers, epistaxis congestion, blockage,or septal defect'

*3

Cartilaginous mvohrtment

Ear /nose cartilage inflammation, hoarseness or stridor, endobronchial involvement, or saddle nose deformity

*2

Nearing loss

Conductive or sensorineural

*

perforation

.

r

.

Laboratory Imaging, and Biopsy Criteria

c- ANCA or anti-FR3-positive

5

2

Pulmonary nodules,mass, or cavitation on chest imaging


4 kg

3. livedo reticularis 4. Neuropathy

Mottled, reticular pattern over skin Mononeuropalhy mononeuropathy multiplex , or polyneuropathy

5. Testicular pain or tenderness 6. dBP >90 mmHg

Not due to infection, trauma, or other causes

7. Elevated Cr or BUN 8. Hepatitis B positive

Cr >130 pmot / L (1.5 mg/dL), DUN >14.3 mmol/ L (40 mg/dL) Presence of hepatitis B surface antigen or Ab

9. Arteriographic abnormality 10. Biopsy of artery

Commonly aneurysms Presence of granulocytes and /or mononuclear leukocytes in the artery wall

.

not due to dieting or other factors Oilfuse myalgias or muscle weakness

.

Development of BIN with dBP »90 mmHg

'Diagnosed if 3 or more of the above to criteria present American College of Rheumatology, 1990

Etiology and Pathophysiology

• focal pan - mural necrotizing vasculitis in small and medium -sized arteries

• thrombosis, aneurysm, or dilatation at lesion site may occur • healed lesions show proliferation of fibrous tissue and endothelial cells that may lead to luminal occlusion Clinical Presentation

• systemic: fatigue, weight loss, weakness, fever, arthralgias • dermatologic: livedo reticularis, nodules, purpura , eruptions • renal: renal insufficiency leading to HTN

• neurologic: mononeuropathy multiplex in both motor and sensory nerves • abdominal: abdominal pain , mesenteric arteritis n

Investigations • blood work: CBC, CRP, Cr, BUN, urinalysis, liver enzymes, p-ANCA , hepatitis B and C serology • imaging: CT or MR1 angiography shows beading appearance of blood vessels seen • biopsy of affected organ (e.g. skin, nerve); biopsy of highly vascular tissues (e.g. liver) not recommended due to risk of aneurysm rupture

LJ

+

Treatment

• PAN with no major organ manifestations glucocorticoids ± azathioprine

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^

RH22 Rheumatology

Toronto Notes 2023

• PAN with major organ manifestations (CNS, cardiac, GI, renal ) induction therapy with high -dose glucocorticoids + cyclophosphamide for 3-6 mo followed by maintenance therapy with low dose prednisone and either azathioprinc, M I X , or leflunomide treatment should be a minimum of 18 mo

-

• hepatitis B virus -associated vasculitis

prednisone 1 mg/ kg /d PO x 7 d ( then taper and withdraw by 14 d ) ± methylprednisolone 15 mg/ kg/d IV xl -3 d after corticosteroid therapy, treat with plasma exchange + antiviral therapy

s

Large Vessel Vasculitis GIANT CELL ARTERITIS/TEMPORAL ARTERITIS Table 24. Classification Criteria for GCA * Criteria

GCA Criteria Presence of 3 or more criteria yields sensitivity of 94%, specificity of 9t%

Description

1. A9eatonsel >50

2.New H/A

Oflen temporal

3. Temporal artery abnormality 4.Elevated ESN

ESR >50 mm/ h

5. Abnormal arlery biopsy

Mononuclear cell infiltration or granulomatous inflammation,usually with mullinudeated giant cells

Temporal artery lender ness or decreased pulsations, not due lo arteriosclerosis

'Diagnosed if 3 or more of the above S criteria present

.

American College ol Rheumatology 1990

Epidemiology

• most common vasculitis in North America

-

• patients > 50 yr; peak incidence 70 80 yr • F:M=2:1

• north -south gradient ( predominance in Northern Europe and US) • affects extracranial arteries

Clinical Presentation

• new onset temporal H /A ± scalp tenderness overlying temporal artery • sudden, painless loss of vision and/or diplopia due to narrowing of the ophthalmic or posterior ciliary arteries ( PCA more common ); can affect both eyes • tongue and jaw claudication ( pain in muscles of mastication on prolonged chewing ) • PMR ( proximal pain and stiffness, constitutional symptoms, elevated HSR ) occurs in 30% of patients • aortic arch syndrome ( involvement of subclavian and brachial branches of aorta resulting in pulseless disease), aortic aneurysm ± rupture are late complications constitutional symptoms (e.g. fever of unknown origin in patients £ 65 yr) and shoulder/ pelvic girdle •

30 min ( 50% ) • ophthalmic conjunctivitis, iritis ( anterior uveitis) • cardiac and respiratory ( late findings) aortic insufficiency • apical lung fibrosis • neurologic • cauda equina syndrome • radiologic floating syndesmophytes pencil-in - cup appearance at IPs osteolysis, periostitis

• •

•

•

-

r ->

LJ

Treatment

• treat skin lesions (e.g. steroid cream , salicylic and /or retinoic acid, tar, UV light ) • NSAIDs and /or 1A steroids (as an adjuvant), benefit should be seen within a few wk, should not be the sole therapy >3 mo • DMARDs to minimize erosive disease (use earlv in peripheral joint involvement) non -biologic DMARDs ( MTX, SSZ, or leflunomide ) biologic therapies include anti-TNl' agents, anti-lL-17 (secukinumab), and anti- lL-12/23 ( ustekinumab)

+

-

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Toronto Notes 202.

RH 26 Rheumatology

'

Table 29. CASPAR Criteria for PsA* Criterion

Description

.

Current, past, or lamily history

1 Evidence of psoriasis

.

Onycholysis, pitting, hypetheralosis

2 Psoriatic nail dystrophy 3. Negative results for RE

Preferably by ELISA, ncphclometry

.

4 Dactylitis

Current or past history

5. Radiological evidence

Juxta -articular bone formation on hand or foot x -rays

the CASPAR (ClASsrfication criteria for Psoriatic ARthritis) criteria, a patient must have inflammatory articular disease (joint, spine, or en theseal) with > 3 poi nts from the above 5 categorries. Arthritis Rheum 2006 Aug54(8): 2665 2673. Classification criterialor PsA development " To meet

-

Reactive Arthritis Definition • one of the seronegative spondyloarthropathies in which patients have a peripheral arthritis ( >1 mo duration ) accompanied by one or more extra -articular manifestations that appears shortly after certain infections of the Cil or (ill tract • this term should not be confused with rheumatic fever or viral arthritidcs

Clinical Triad of Reactive Arthritis • Arthritis • Conjunctivitis/uveitis

• Urethritis/cervicitis

Etiology

• onset following an infectious episode either involving the G1 or CiU tract • Gl: Shigella, Salmonella , Campylobacter, Yersinia, C . difficile species GU: Chlamydia ( isolated in 16-44% of ReA cases), Mycoplasma species • acute clinical course • onset 1-4 wk post - infection • lasts wk to mo

• often recurring

• spinal involvement persists

“Can't See, Can’t Pee, Can't Climb a Tree” T riad of conjunctivitis, urethritis, and arthritis is 99% specific (but 51% sensitive) for ReA

Epidemiology • in HLA-B27 patients, axial > peripheral involvement • M >1

-

Clinical Presentation •

musculoskeletal • asymmetric peripheral arthritis, spondylitis/ sacroiliitis, enthesitis ( Achilles tendinitis , plantar fasciitis), dactylitis

• ophthalmic iritis (anterior uveitis), conjunctivitis

dermatologic keratoderma blennorrhagicum ( hvperkeratotic skin lesions on palms and soles) and balanitis drdnata (small , shallow, painless ulcers of glans penis and urethral meatus) are diagnostic • gastrointestinal • oral ulcers, diarrhea • genitourinary • urethritis, prostatitis, cervicitis, cystitis, sterile pyuria; presence not related to site of initiating infection

•

Investigations • diagnosis is clinical plus laboratory • evidence of antecedent or concomitant infection ( stool culture, urine , and genital swab testing ) • blood work : norntocytic , normochromic anemia , and leukocytosis

• sterile cultures • serology: HLA - B 27 positive , elevated ESR /CRP Treatment • antibiotics for non -articular infections • NSAIDs ( naproxen 500 mg BID/ TID, diclofenac 50 mg HD, indomethadn 50 mgTTD/ QlD), PT,

exercise • local therapy IA steroid injection ( triamcinolone acetonide)

r

t LJ

• topical steroid for ocular involvement • systemic therapy

corticosteroids (starting dose 20 mg /d ) DMARDs (for refractory reactive arthritis with peripheral joint involvement only ) (SSZ , MT' X ) TNP - ct inhibitors for spinal inflammation ( for disease refractory to NSAIDs, DMARDs )

+

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Toronto Notes 2023

RH 27 Rheumatology

Prognosis

-

-

• self limited, typically 3 5 mo, varies based on pathogen and patient's genetic background • chronic in 15 20% of cases

-

Crystal-Induced Arthropathies Table 30. Gout vs. Pseudogout Parameter

Gout

Gender

M »F

M- f

Age

Middle - aged males Post menopausal females

Usually elderly

Onset of Disease

Acute Acule Can become chronic if high uric acid untreated, Chondrocalcinosis is asymptomatic but the people with renal failure, kidney transplant clinical feature is generally acute

Pseudogout

First MIP classically:also midfoot, ankle,

CPPD Positive birefringence (bluewhen parallel), rhomboid - shaped Knee, wrist: monoarticular, or polyarticular

Monosodium urate Negative birefringence (yellow when parallel to compensator filter ), needle - shaped

Crystal Type

Distribution

knee, or polyarticular

il chronic

Radiology ( notefindings are nonspecific)

Erosions

Chondrocalcinosis OA (knee, wrist,2nd and 3rd MCP)

Treatment

Acute: NSAIOs.corticosteroids, colchicine Chronic: tallopurinol febuxostat

.

NSAIDs, corticosteroids

S

2 %

1 • 1st MTP - podagra

S 3

• Ankle

-

• Knee

Figure 13. Common sites of involvement of gout (asymmetric joint involvement)

Gout Definition • derangement in purine metabolism resulting in hyperuricemia; monosodium urate crystal deposits in tissues (tophi ) and synovium ( microtophi )

Etiology and Pathophysiology • uric acid can be obtained from the diet or made endogenously by xanthine oxidase, which converts xanthine to uric acid • an excess of uric acid results in hyperuricemia • uric acid can deposit in the skin /subcutaneous tissues ( tophi ), synovium ( microtophi), and kidney, where it can crystalize to form monosodium urate crystals that lead to gout • non - modifiable risk factors include: genetic mutations, male gender, and advanced age • modifiable risk factors include: diet (alcohol, purine rich foods such as meats and seafoods, fructose/ sugar sweetened foods; see list of precipitants below ) • other risk factors: renal failure, metabolic syndrome, dehydration (e.g. diuretics) Clinical Presentation

• single episode progressing to recurrent episodes of acute inflammatory arthritis • acute gouty arthritis severe pain , erythema , joint swelling, usually involving lower extremities • joint mobility may he limited • attack will subside spontaneously within d to wk ( 5 10 d ); may recur • tophi • urate deposits on cartilage, tendons, bursae, soft tissues, and synovial membranes • common sites: first MTP, ear helix, olecranon bursae, tendon insertions (common in Achilles tendon ) • kidney • gouty nephropathy » uric acid nephrolithiasis

-

Investigations • joint aspirate: >90% of joint aspirates show crystals of monosodium urate ( negatively birefringent, needle-shaped ) if done early in course of presentation • x- rays may show tophi as soft tissue swelling, bone/ joints - punched -out lesions, erosion with “over -

hanging" edge

-

• U /S shows double contour sign • correlated with hyperuricemia in the blood Treatment

• acute gout

• NSAIDs: high - dose, then taper as symptoms improve • corticosteroids: 1 A, oral, or IM ( if renal, cardiovascular, or (il disease and /or if NSAIDs

contraindicated or failed ). IV for patients with multiple joints flaring, unable to take oral medication, and already have IV line colchicine 1.2 mg at the first signs of an attack followed by 0.6 mg 1 h later and 0.6 mg BID on subsequent days until the attack has resolved

An acute gout attack may mimic cellulitis; however, joint mobility is usually preserved in cellulitis unless it overlaps a joint

Precipitants of Gout

Drugs are FACT Furosemide Aspirin 1 (low-dose)/Alcohol Cyclosporine Thiazide diuretics Foods are SALT Seafood Alcohol ( beer and spirits) Liver and kidney Turkey ( meat )

2020 American College ol Rheumatology Guideline for the Managementol Goul Arthritis Rheumatol 2020:72:879-95 • Inflate urate awering therapy (IW) lor patents viitli : • >1SC tophi • Radiographic damage attributable to gout • Freguentgoutflares (»2/yr) • Allopurino! is preferred over at other ULTsas a first line agent for all patients Rnctjdi -g CKO stage » 3| • Initiate concomitant anti-indamnratory prophylaxis (e.g.colchicine NSAIDs predn sore prednisolone) lor 3 - 6 mo • Conl .nue 01! to target and maintain strum urate 0 mgfdl • In patients with frequent gout Daiesor nomesolvingSC tophi who have failed loach eve serum urate < 0 mgfdl on uticosutlcs ualhine oxidase inhibitors, and other interventions, peglotitase should be initiated and the current ULI should be discontinued • tout flares should he managedwith NSAIOs. low - dose colchicine, nr glucocorticoids as trst -lloe agents

.

.

-

j

.

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RH 28 Rheumatology

Toronto Notes 2023

• chronic gout

• conservative

avoid foods with high purine content (e.g. visceral meats, sardines, shellfish , beans, peas) avoid drugs with hyperuricemic effects (e.g. pyrazinamide, ethambutol, thiazide, alcohol ) additional management of lifestyle factors: limiting alcohol intake, limiting high -fructose corn syrup, for overweight/obese patients weight loss is recommended ( regardless of activity level) medical antihyperuricemic drugs (first line: allopurinol (not nephrotoxic) second line: febuxostat ): decrease uric acid production by inhibiting xanthine oxidase. Start low and titrate up. Do not use febuxostat if history of cardiovascular disease uricosuric drugs ( probenecid, sulfinpyrazone ): very rarely used in combination with allopurinol or febuxostat in patients in whom hyperuricemia is not controlled with the latter • prophylaxis with low dose NSAlD/colchicine should be started with urate lowering therapy • in renal disease secondary to hyperuricemia , use low dose allopurinol nnd monitor Cr • indications for treatment with antihyperuricemic medications include • attacks (>2/yr), tophi, bone erosions/arthritis

-

-

-

Pseudogout (Calcium Pyrophosphate Dihydrate Disease) Definition

• joint inflammation caused by calcium pyrophosphate (CCP) crystal deposition in connective tissue Etiology and Pathophysiology

• acute inflammatory arthritis due to phagocytosis of IgG -coated CPPD crystals by neutrophils and subsequent release of inflammatory mediators within joint space • usually monoarticular but can be polyarticular • slower onset in comparison to gout, lasts up to 2 3 wk but is self limited

-

-

Risk Factors

• old age, advanced OA , neuropathic joints • other associated conditions: hyperparathyroidism , hypothyroidism , hypomagnesemia , hypophosphatasia ( low ALP), DM , hemochromatosis

Clinical Presentation • affects knees, wrists, MCPs, hips, shoulders; less likely elbows, ankles, big toe, spine • asymptomatic crystal deposition (seen on radiograph only ) • acute crystal arthritis (self-limited flares of acute inflammatory arthritis resembling gout ) • pseudo- OA ( progressive joint degeneration, sometimes with episodes of acute inflammatory arthritis) • pseudo-RA ( symmetrical polyarticular pattern with morning stiffness and constitutional symptoms) • frequently triggered by dehydration, acute illness, surgery, trauma Investigations

• must aspirate joint to rule out septic arthritis and gout • CPPD crystals: present in 60% of patients, often only a few crystals, positive birefringence ( blue ) and rhomboid shaped • x rays show chondrocaldnosis in 75%: radiodensities in fibrocartilaginous structures (e.g. knee menisci ) or linear radiodensities in hyaline articular cartilage

-

Treatment • acute CPP: joint aspiration, steroid injection, cool packs, temporary rest, and protection • chronic CPP: NSAlDs with gastroprotection and /or low-dose prophylactic colchicine 0.6 -1.2 mg /d PO (controversial )

Non-Articular Rheumatism Definition

• disorders that primarily affect soft tissues or periarticular structures • includes bursitis, tendinitis, tenosynovitis, fibromyalgia, and PMR

Polymyalgia Rheumatica Definition

• characterized by pain and stiffness of the proximal extremities (girdle area) • closely related to GCA (15% of patients with PMR develop GCA ) • no muscle weakness

-

• Polyarticular wrist • Hand (MCPI

r;

I

• Foot (1st MTPI • Hip

Figure 14. Common sites of involvement of CPPD

EULAR Rccornmendations for the Management of CPPD Ann RheumOis 2011;10:511 5 1. Pharmacological and non pharmacologicai treatment mould troth be used to manage CPP0. 2 treating acute CPP crystal arthritis with ice or cool packs, rest , jointaspmation and Uiojecbon of long acting glucocoitrcoids ( CC$) may be sufficient for many patients. 3 Acute CPP crystal arthritis can be treated

-

.

.

-

.

systemically with HSAIDs and low-dose oral colchicine , although their use may be Imited in older patients by tonicity and comorbidity. 4.A brief tapering course of oral or parenteral CCS or MTU may be effective for acute CPP crystal arthritis that is not amenable to IA 6CS injection. 5. Low -dose oral colchicine ixNSAIO can be used as prophylaxis against frequent recurrent acute CPP crystal arthritis. 6. For patients with OA and CPPD management goals and options are the same as those for 0A alone. 7. Ibe order of pharmacological preference (or chronic CPP ciyslal inflammatory art hubs is USAID andlor colchicine, low dose corticosteroid MIX and hydroxychloroquine I. Associated conditions should be treated d

.

-

.

.

detected. 9. Ihere are no disease- modrfyieg treatments lor CTP crystal arthritisand no treatment is MruMfor asymptomatic cboodrocaldnosis.

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Table 31. PMR Classification Criteria Scoring Algorithm *

.

Required criteria: age > 50 yr bilateral shoulder aching, and abnormal ESR.CHP

Points without U/ S (0 - 6)

Points with Abnorma I U/S" ( 0- 8)

Morning stillness duration '45 min

2

2

Hip pain or limited ROM

1

1

Absence of RForACPA

2

2

Absence ol other joint involvement

1

1

At least one shoulder with subdeltoid and/ or biceps tenosynovitis and / or glenohumeral synovitis (either posterior or axillary) and at least one hip with synovitis and/or trochanteric bursitis on U/S

N:A

1

Both shoulders with subdeltoid bursitis,biceps tenosynovitis, or glenohumeral synovitison U/S

M/ A

1

'A score oi 4 or more is categorized as PMR in the algorithm without U/ S and a score ot 5 or more is categorized as PMR in the algorithm with U/S "Optional U/S criteria

-

Ann Rlieum Ols 2012:71:484 492

Epidemiology

• incidence: 50 in 100000 per yr in those > 50 yr • age of onset typically > 50 yr , T: M = 2: I Clinical Presentation

• constitutional symptoms prominent ( fever, weight loss, malaise) • pain and stilTness of symmetrical proximal muscles ( neck, shoulder and hip girdles, thighs ) • gel phenomenon (stiffness after prolonged inactivity) • physical exam reveals tender muscles, but no true weakness or atrophy Investigations • blood work: often shows anemia of chronic disease, elevated platelets, elevated HSR and CRP, and normal CK; up to 5% of PMR reported with normal inflammatory markers

Treatment • goal of therapy: symptom relief • start with prednisone 12.5- 25 mg PO once daily, reconsider diagnosis if no response within several

days • taper slowly with improvement over 1 yr period with close monitoring, if in remission taper until discontinued • relapses should be diagnosed and treated on clinical basis; do not treat a rise in HSR as a relapse • treat relapses aggressively ( 50% relapse rate ) • monitor for steroid side effects, glucocorticoid- induced osteoporosis prevention, and follow for symptoms of GC /\

Fibromyalgia Definition

• chronic (>3 mo ), widespread (axial , left - and right -sided , upper and lower segment ), non -articular pain with characteristic tender points

Diagnosis Table 32. 2010 ACR Preliminary Diagnostic Criteria for Fibromyalgia Criteria

Comments

Y/idespread Pam Index - number ol areas in which the palienl had pain

A paticnl satisfies diagnostic critena lor fibromyalgia II the following 3 over the last wk (max score 19): conditions are met: L and R: shoulder girdle, upper arm lower arm hip upper leg lower 1. Widespread Pain Index (WPI) >7 and SS score >5 or WPI 3 6 and leg jaw SS score >9 One Area: chest, abdomen, upper back , lower back, neck 2 Symptoms have been present at a similar level lor at least 3 mo 3. Ihe patient does not have a disorder that would otherwise explain Symptom Severity (SS) Score * sum of: the pain a) severity of fatigue

.

.

. .

.

.

b) waking unrefreshed c) cognitive symptoms over the past wk d) extent ol somatic symptoms (IBS, N/ A abdominal pain/cramps, dry mouth, fever,hives, ringing in ears, vomiting,heartburn, dry eyes SOB loss of appetite, rash, hair loss, easy bruising, etc ) All (a d) rated on 0 3 scale: 0 * no problem 1 * mild 2 •moderate 3 > severe

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Arthrit Care amt Res 2010:62(5):600 610

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.Epidemiology I-:M=3: 1 '

• primarily ages 25-45, some adolescents • prevalence of 2-5% in general population • overlaps with chronic fatigue syndrome and myofascial pain syndrome • strong association with psychiatric illness Clinical Presentation • widespread aching, stiffness

• easy fatigability

• sleep disturbance: non - restorative sleep, difficulty falling asleep, and frequent wakening • symptoms aggravated by physical activity, poor sleep, emotional stress • patient feels that joints are diffusely swollen although joint examination is normal

• neurologic symptoms of hyperalgesia, paresthesias, allodynia • associated with irritable bowel or bladder syndrome, migraines, tension H /As, restless leg syndrome, obesity, depression, and anxiety

• physical exam should reveal only tenderness with palpation of soft tissues, with no specificity for trigger / tender points

Investigations

• blood work: includes TSH; all typically normal unless unrelated , underlying illness present • serology: do not order ANA or Rl unless there is clinical suspicion for a CTD or inflammatory arthritis • laboratory sleep assessment

-

Treatment

• non - pharmacological therapy graded exercise programs including aerobic ( >2() min /d, 2 -3 d / wk ) and resistance training ( >8 repetitions per exercise, 2-3 d/ wk )

other therapies with some evidence: acupuncture, CBT, hydrotherapy, meditative movement

(yoga, Tai chi ) there is no evidence for biofeedback , chiropractics, hypnotherapy, meditation • pharmacological therapy ( to help with symptoms, not curative) low dose tricyclic antidepressant (e.g. amitriptyline ) for sleep restoration select those with lower anticholinergic side effects SNR1: duloxetine, milnacipran anticonvulsant: pregabalin gabapentin analgesics may he beneficial for pain that interferes with sleep ( NSAIDs, not narcotics )

-

.

Prognosis

• variable; usually chronic, waxes and wanes, svith some pain and fatigue that usually persists Table 33. Clinical Features of Inflammatory Myopathy vs. Polymyalgia Rheumatica vs. Fibromyalgia Polymyositis F> M. 40 50 yr

PMR F> M >50 yr

Fibromyalgia F»M , 25 45 yr

Weakness

Proximal muscle Yes

Proximal muscle No

Diffuse No

Pain Stiffness

Painless Present

Painful Significant morning and gelling stiffness (shoulders, neck , hips)

Painful May have morning stiffness

Investigations

Muscle biopsy CK , EMC ruleout

ISR /CRP rule out CCA

Sleep assessment ISH

Normal

Epidemiology

Muscle Involvement

.

-

malignancy

.

.

.

ESRCRP

Usually normal

Markedly elevated

Treatment

High dose steroids,

immunosuppressants

Low dose steroids

-

-

.

Exercise, sleep restoration

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Common Medications Table 34 . Common Medications for Osteoarthritis Class

Generic Drug

Trade Name

Dosing ( PO )

Indications

Contraindications

Adverse

Tylenol:

1000 mg 110 q4 h (3 g daily mail

1st line

Severe liver disease /

Hepatoloiicity overdose

Name

Analgesics

Effects

acetaminophen

impairment

.

.

potentiates

warfarin NSAIDs

naproien

Naprosyn 1 Aleve:

meloucam

Mobicoi

200 - 600 mg TID 25 SOmg TID 50 - 75/ 200 mg TI0 125- 500 mg BID 7.5-15 mg once daily

celecoiib

Celebrex :

200 mg once daily

Advil Voltaren Arlhrotec :

ibuprofen

-

diclofenac diclofenac / misoprostol

COX -2 Inhibitors

-

Gl bleed, renal impairment, allergy to ASA NSAIDs pregnancy ( T3) anticoagulants

2nd line

Dyspepsia /GERD

.

.

.

Nausea, tinnitus, vertigo, rash, dyspepsia. Gl bleed. PUD. hepatitis, renal failure HIN nephrotic syndrome

.

Renal impairment, cardiovascular disease Gl Bleed

.

.

SameasNSAIOs above

Other Treatments

Comments

Combination analgesics (acetaminophen codeine, acetaminophen NSAIDs)

Enhanced short term effect compared to acetaminophen alone More adverse effects: sedation constipation, nausea Gl upset Short - term ( wk -mo). joint specific treatment Decrease in pain and improvement in function Used for managcmenl of an IA inflammatory process when infection has been ruled out

-

IA corticosteroid injection

.

.

IA hyaluronic acid q6 mo

Used for mild-moderate OAof the knees; however, little supporting evidence and not considered to be effective Precaution with chicken/egg allergy

Topical NSAIDs

Topical diclofenac (Pennsaid ' Voltaren Emulgcl ' ) May use for patients who fail acetaminophen treatment and who wish to avoid systemic therapy, better on small joints

Capsaicin cream

Mild decrease in pain

Glucosamine sulfate * chondroitin

Limited evidence of benefitin 0A knee. No regulation by Health Canada

.

Table 35. DMARDs Trade Name

Dosing

Plaqueml '

400 mg P0 once daily Retinal disease GGPD initially deficiency 200 - 400 mg POonce daily maintenance (5 mg/ kg ideal body weight per day to a maximum of 400 mg/d)

Gl symptoms, skin rash, macular

Salaaopyrim Arullidme ' ( US)

1000 mg P 0 BID - TID

Sulfa /ASA allergy, kidney disease GGP0 deficiency

Gl symptoms, rash, H /A leukopenia

methotrexate

Rheumatrex :

S

Folexj Mexate 3

7.5- 25 mg PO /SC weekly

Oral ulcers Gl symptoms, cirrhosis, Bone marrow suppression, liver disease, myelosuppression pneumonitis, tubular necrosis significant lung disease immunodeficiency, pregnancy EtOHuse

leflunomide

Arava ’

Generic Drug Name

Contraindications

COMMONLY USED

hydroxychloroquine

$

sulfasalazine

S

'

Adverse Effects

.

damage, neuromyopathy Requires annual ophthalmological screening to monitor for retinopathy

.

.

.

.

.

.

ss

10 - 20 mg P 0 once daily

.

Liver disease, lung disease pregnancy

.

Alopecia Gl symptoms, liver dysfunction, interstitial pulmonary fibrosis HIN

.

NOT COMMONLY USED

Neoral '

2.5 -3 mg /kg /d divided Kidney/liver disease, and given in 2 doses P 0 infection HIN

Solganal 3 Myochrysine ®

50 mg IM weekly after gradual introduction

IBD.kidney/ liver disease

s aialhiopiine

Imuran '

2 mg /kg /d P0 once

Kidney/liver disease

cyclosporine

Si gold (injectable)

S

cyclophosphamide

s

.

daily

Cytoxan '

'

1q /m /mo IV as per protocol

HTN. decreased renal function, hair growth, tremors, bleeding Rash, mouth soreness /ulcets, proteinuria, marrow suppress! on

Rash, pancytopenia ( especially thiopurine WBC t AS! ALT ), biliary stasis, S - methyItransferase ( TPMI) vomiting diarrhea deficiency

Kidney/liver disease, neutropenia

.

.

.

* r

Cardioloxicity, Gl symptoms, hemorrhagic cystitis, nephrotoxicity, bone marrow suppression,sterility, bladder cancer

AL GRAWANY

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Table 35 . DMARDs Trade Name

Dosing

Controindicotions

etanercept

Enbrel:

25 mg biweekly or 50 mg weekly SC

Fusion protein of INF receptor and Fc portion of IgG

infliximab

Remicade

3 5 mg /kg IV q8 wk

Chimeric mouse/human monoclonal anti INF

Humira '

40 mg SCq2 wk

Monoclonal anti -INF

Simponi'

50 mg SC q1mo or 2 mg/kg q8 wk

Monoclonal anti-INF

Cimna

400 mg SC q2 wk «3 then 200 mg SC q 4 wk

PEGylated monoclonal anti INF

Oterla

Day 1:10 mg (AM ) P0, titrate up to 30 mg BID by day 6

PDE4 inhibitor which reduces production of INFo

Orencia '

500 -1000 mg IV infusion ql mo or 125

Coslimulalion modulator of Icell activation

Rituxan '

1g x 2 IV infusions, 2 wk Causes 8 cell depletion, binds to CD 20 apart q 6 mo

Actemra;

4 -8 mg /kg IV q4 wk or 162 mg SCq1- 2 wk

Xcl|anr '

5 mg 8ID

Generic Drug Name

Adverse Effects

NEWER DMARDs (Biologies)

sss

SSS adalimumab

-

SSS golimumab

SSS certolizumab

'

SSS apremilast

SSS abataccpt

SSS

-

mgSCqlwk

rituximab

SSS tocilizumab

SSS tofacitmib

IL- 6 receptor antagonist

Selective JAK 1/ 3 inhibitor and thus interferes with JAK - SIAT

S$

signaling pathway

upadacitinib

Rinvoq:

15 mg once daily

Selective JAK1 inhibitor and thus interferes with JAK -STAT signaling pathway

secukmumab

Coscnlyx

150 mg monthly

Blocks IL-17 A

ss

SSS

Landmark Rheumatology Trials Trial Name

Reference

Clinical Trial Details

Lancet 2008:372:375 82

Title: Comparison of Methotrexate Monotherapy with a Combination of Methotrexate and Etanercept in Active. Early. Moderate to Severe Rheumatoid Arthritis (COME!): A Randomised, Double Blind, Parallel Treatment Trial Purpose: To compare the efficacy ol MIX monotherapy or MIX plus etaneiccpt for remission and radiographic non - progression in RA

RHEUMATOID ARTHRITIS

COMET

patients. Methods: 542 RA MTX-naive outpatients with moderale - to - severe disease for 3 - 24 mo were randomly assigned to MIX alone (titrated from 7.5- 20 mgfwk) or MIX (same titration) plus etanercept 50 mg /wk. Results : Clinical remission was achieved in 50 % ol patients on combined treatment vs 28% taking MIX alone (difference 22.05%: P'0.0001). 80% and 59%, respectively, achieved radiographic non- progression (difference 20.98%: P'0.0001). Both groups experienced similar adverse events. Discussiond yr of Ireatment with etanercept plus MIX can achieve clinical remission and radiographic non- progression in early severe

.

.

.

RA , ERA

NEJM 2000:343:1586 - 93

Title: A Comparison of Etanercept and Methotiexate in Patients with Early Rheumatoid Arthritis Purpose: To investigate the efficacy of etanercept in reducing disease activity and joint damage in patients with early and active RA. Methods: 632 patients received either SC etanercept (10 or 25 mg /wk) twice weekly or oral MIX (19 mg/wk) for 12 mo. Clinical response was defined by criteria of the American College ol Rheumatology Results: Patients on 25 mg etanercept improved quicker than those on MIX, with significantly mote improvements in disease activity within 6 mo (P'0.05). During the first 6 and 12 mo, there vrere significantly greater increases in mean erosion scores in the MIX group (P‘0.007). Fewer adverse events (P‘0.02) and infections ( P‘0.006) vrere seen in 25 mg etanercept. Conclusion: In patients with early active RA etanercept more rapidly reduced symptoms and slowed joint damage as compared to MIX.

.

.

BeSt

Arthritis Rheum 2005:52:3381- 90

Title: Clinical and Radiographic Outcomes ol Four Different Treatment Strategies in Patients with Early Rheumatoid Arthritis (the 8 eSl Study): A Randomized Controlled Trial Purpose: To identify the optimal therapeutic strategy for preventing long term joint damage and functional decline in RA. Methods: 508 patients were randomly assigned to 1 of 4 therapeutic strategies: (1) sequential disease - modifying antirheumatic diug monotherapy ( 2) step up combination therapy (3) initial combination therapy with tapered high dose prednisone, or ( 4) initial combination therapy with infliximab Results: At 3 mo. groups 3 and 4 showed significantly greater functional improvement (as defined by the Dutch version of the Health Assessment Questionnaire (D - HA 0)) with mean scores of 0.6 as compared lo mean scores of 1.0 in groups 1 and 2 (P'0.001). At 1 yr mean D - HA0 scores in groups 3 and 4 were 0.5, as compared to 0.7 in groups 1and 2 (P‘0.009). Conclusion: As compared to sequential monotherapy or step-up combination therapy, initial combination therapy with piednisone or infliximab led lo earlier functional improvements and less radiographic damage in patients with early RA.

.

.

.

.

-

.

Infliximab and MIX

NEJM 2000:343:1594 - 602

.

Title: Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis. Anti- Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group Purpose: lo assess infliximab for potential sustained benefits and effects on|Oint damage in RA. Methods: 428 patients who had active RA despite MIX therapy were treated with IV infliximab (3 or 10 mg /kg every 4 or 8 wk plus oral MIX for 54 wk) or placebo. Results: As compared lo MIX alone, infliximab plus MIX significantly reduced signs and symptoms of RA (clinical response 51.8 % vs. 17.0%: P'0.001) Ihere was grealer evidence of joint damage on MIX alone but not on infliximab plus MIX (mean change in radiographic score, 7.0 vs. 0.6. P'0.001). Conclusion: Repeated doses of infliximab plus MTX in persistently active RA was clinically effective and slowed the progression of joint damage

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Reference

Irealment o> Active Rheumatoid Arch Intern Med 1999:159:2542 50 Arthritis with leflunomide Compared with Placebo and Melhotr exale. Leflunomide Rheumatoid Arthritis Investigators Group. Strand et

al. 1999

PREMIER

Arthritis Rheum 2006:54:26 37

Clinical Trial Details

Title : Treatment of Active Rheumatoid Arlhrilis with lellunomidc Compared with Placebo and Metholrcialc . leflunomide Rheumatoid Arthritis Investigators Group Purpose: lo compare the safely and efficacy of leflunomide vs. MIX in patients with active RA . Methods: 482 patients with active RA were randomly assigned to receive leflunomide (20 mg/d ). MIX ( 7.5 -15 mgi'wk ). or placebo. Results: Clinical response and success rales on leflunomide |S 2% and 41% ) and MIX ( 46 % and 35 %) were significantly greater than those on placebo (26% and 19 %) (P' 0.001). On leflunomide. common adverse events included gastrointestinal complaints, shin rash, and reversible alopecia. Conclusion: In patients with active RA. leflunomide was associated with better clinical responses than placebo and had similar efficacies as MIX.

.

.

Title : Ihc PRiMIER Study: a Multic enter Randomiied Double Blind Clinical Trial of Combination Therapy with Adalimumab plus Melhotreiale versus Methotrexate Alone or Adalimumab Alone in Patients with Early. Aggiessive Rheumatoid Arthritis Who Had Not Had Previous Methotrexate Treatment Purpose: To compare the efficacy and safety of adalimumab plus MIX versus MIX alone or adalimumab alone in patients with early, aggressive RA who were MTX- naive. Methods: 799 patients with active disease 3 yr were randomly assigned lo adalimumab 40 mg SC every other wk plus oral MIX adalimumab 40 mg SC every other wk, or oral MTXweekly. Results: American College of Rheumatology 50 % improvement was achieved in significantly more patients on combination therapy (62%) than MIX or adalimumab ( 46 % and 41%, respectively; both P'0.001). Patients on combination therapy had significantly less radiographic progression (P'0.002 ) than those on cither monotherapy. 49 % of patients on combination therapy achieved remission at 2 yr. Conclusion: Adalimumab plus MIX was significantly superior to either MlX or adalimumab alone in early , aggressive RA .

-

.

OSTEOARTHRITIS Hyaluronan

Ann Rheum Dis 2010:69:1097-1102

Title : Intra Articular Hyaluronan is without Clinical Ellecl in Knee Osteoarthritis: a Multicenlre , Randomised. Placebo Controlled. Double Blind Study of 337 Patients Followed for 1 Year Purpose: To assess the long- term safety and efficacy of 5 hyaluronan 1A injections in knee osteoarthritis. Methods: 337 patients with knee osteoarthritis and a lequesne algofunctional index score (LFI) »10 received IA hyaluronan product ( sodium hyaluronate; Hyalgan * ) or saline weekly for 5 wk . Results: Treatment had no significant effed on time lo recurrence or baseline change in LFI or walking pain . There were also no significant differences in paracetamol consumption, patients' global assessment, responder rales, or adverse events. Conclusion: Hyaluronan injections were not clinically effective in patients with osteoarthritis of the knee with moderate- severe disease (LFI >10).

SYSTEMIC LUPUS ERYTHEMATOSUS 8 e !imumab

Lancet 2011:377:721 31

Title: Efficacy and Safely of 8elimumab in Patients with Active Systemic Lupus Erythematosus:a Randomised . Placebo - Conlroiled. Phase 3 Trial Purpose: To assess the efficacy and safely of belimumab in patients with active SLE . Methods: 867 patients (aged >18 yr ) who were seropositive with scores of > 6 on SELENA SIEDAI were randomly assigned lo belimumab 1 mg / kg or 10 mglkg. or placebo plus standard of care ( based on disease manifestation and local guidelines ). Results: Significantly higher SRI (SLE Responder Index ) rates occurred with belimumab 1 mg/kg (51%. OR 1.55; P'0.0129) and 10 mg/ kg ( 58% , 1.83; P 0.0006) than placebo ( 44%). There was a greater frequency of SELEHA - SLEDAI reduction by >4 points with belimumab 1 mg/kg [ 53%, 1.51; P‘0.0189 ) and 10 mg / kg ( 58 % 1.71: P‘0.0024 ) than placebo (46%). Conclusion: Belimumab may be the lirst targeted biologic that is specifically approved for SLE. ‘

.

Mycophenolate Mofetil or Intravenous Cyclophosphamide for lupus Nephritis. Gimlet et

NEJM 2005:353:2219 - 28

.

at 2005

Title: Mycophenolate Mofetrl or IntravenousCydophosphamide for Lupus Nephritis Purpose: To investigate if mycophenolate mofelil is effective for treating lupus nephritis. Methods: 140 patients with active lupus nephritis were randomly assigned to oral mycophenolate moletil (1000 mgld increased to 3000 mgfd) or monthly IV cyclophosphamide ( 0.5 g /m 2 increased to 1.0 g/m ), Results: 22.5% of patients on mycophenolate mofelil and 5.8% of those on cyclophosphamide experienced complete remission (absolute difference. 16.7%:95% Cl. 5.6 - 27.9%:P'0.005) , thus demonstrating that mycophenolate mofetil is more efficacious than

'

cyclophosphamide. Conclusion: In active lupus nephritis, mycophenolate mofetil wasmorc effective than IVcyclophosphamide in inducing remission and had a belter safely profile. CONNECTIVE TISSUE DISORDERS Aialhioprine or Methotrexate Maintenance for ANCA -

NEJM 2008:359:2790 - 803

Title: Arathioprine or Methotrexate Mainlenancefor ANCA - Associated Vasculitis Purpose: To compare malhioprine ( A 2 A ) and MIX lor safely and efficacy in Wegener 's granulomatosis and microscopic polyangiitis. Methods: 159 patients who achieved remission with IV cydophosphamtde and corticosteroids were randomly assigned to receive oral AZA orMIXfor 12 mo. Results: The rates of adverse events (requiring discontinuation of the study drug or causing death) were not significantly different between groups. Event - free survival was also not significantly different between groups. Conclusion: In patients wilh Wegener ' s granulomatosis and microscopic polyangiitis. AZA and MIX are similar alternatives lor maintenance therapy after initial remission.

Ann Intern Med 2009:150:670 80

Title: Pulse versus Daily Oral Cydophosphamidefor Induction of Remission in Antineutrophil Cytoplasmic Antibody- Associated Vasculitis: a Randomiied Trial Purpose: Tocompare Ihc efficacy of pulse cyclophosphamide vs . daily oral cyclophosphamide for inducing remission in ANCA associated vasculitis. Methods: 149 patients with newly diagnosed generalized ANCA- assodated vasculitis with renal involvement received cyclophosphamide 15 mg/kg every 2- 3 wk (pulse), or daily cyclophosphamide 2 mg/kg orally , plus prednisolone. Results: Ihere was no significant difference in lime lo remission |P‘0.59 ) or percentage of patients who went into remission at 9 mo ( 88.1% in pulse vs. 87.7% in oral ) The oral group had higher cumulative cyclophosphamide doses |P' 0.001). Lower rates ol leukopenia were seen in the pulse group (hazard ratio. 0.41; 95% Cl. 0.23 to 0.71). Conclusion: In ANCA- associated vasculitis, pulse cyclophosphamide induced remission as effectively as the daily oral regimen, required less cumulative cyclophosphamide, and caused lewer cases of leukopenia.

Associated Vasculitis. Pagnoux et al. 2008

CYCLOPS

.

Cyclophosphamide vs. Placebo in Scleroderma Lung Disease. Tashkin et al. 2006

NEJM 2006:354:2655 66

Title : Cyclophosphamide versus Placeboin Scleroderma lung Disease Purpose: Todetermine the efficacy of oral cyclophosphamide in patients with active alveolitis and scleroderma - related ILD. Methods:158 patients with scleroderma , restrictive lung physiology, dyspnea, and evidence of inflammatory ILD received oral cyclophosphamide|s 2 mg/kg/d ) or placebo for 1 yr. Results: Ihe mean absolute difference in 12 mo adjusted FVC between cyclophosphamide and placebo was 2.53 % (95 % Cl. 0.28 lo 4.79%), indicating great efficacy ol cyclophosphamide (P'0.03). The dillerence in FVC belwcen groups was sustained at 24 mo.

r -> LJ

+

Conclusion: In patients with symptomatic scleroderma -related ILD. oral cyclophosphamide had significant clinical benefit.

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RH31 Rheumatology

Trial Name

WGEI

Reference

Clinical Trial Details

HEJM 2005;352:351- 361

Title: Etanercept plus Standard Therapy lor Wegener 's Granulomatosis Purpose: to investigate the solely and etficocy of etanercept for remission maintenance In GPA Methods: 180 patients with GPA were randomly assigned to receive either etanercept or placebo, in addition to standaid treatment (glucocorticoids plus cyclophosphamide or MIX ). Results: Ho significant differences were observed between the etanercept and control groups in the rates of stable periods of low -level disease activity|86.5% vs. 90.6”», p-0.32). sustained remission (69.7% vs. 75.3% P‘0.39) or the time necessary to reach those outcomes. Oisease flares and adverse events were common in both groups but not significantly different. Conclusion: Etanercept is not effective for remission maintenance in GPA.

.

IMPROVE

JAMA 2010;304:2381- 88

.

Title: Mycophenolate Mofetil versus Acathiopnne for Remission Maintenance in Anti neutrophil Cytoplasmic Antibody -Associated Vasculitis (AAV): a Randomized Controlled Trial Purpose: To compare the efficacy of mycophenolate mofetil vs. arathioprine ( A 2 A ) preventing relapses in patients with AAV. Methods: following remission induction with cyclophosphamide and prednisotone 156 patients with newly diagnosed AAV were randomly assigned to A 2 A (initiated at 2 mg kg / d ) or mycophenolate mofetil (initialed at 2000 mg/d| Results: The mycophenolate mofetil group experienced significantly more relapses ( 55%) as compared to A 2 A (37.5%) (hazard ratio for mycophenolate mofetil 1.69. 95% Cl 1.06-2.70; P 0.03). There was no significant difference in the rates of severe adverse events between groups. Conclusion: Mycophenolate moletil was less effective than A 2 A lor maintaining disease remission in AAV.

.

.

'

.

RAVE

MEJM 2010:363:221- 32

.

-

Title: Rituximab versus Cyclophosphamide for ANCA -Associated Vasculitis Purpose: To investigate if rituximab is more effective and/or safer than a cyclophosphamide for treating AAV. Methods: 197 ANCA -positive patients randomly assigned to receive rituximab (375 mg /m1 for 4 wk) or cyclophosphamide (2 mg/kg /d) . Results: 64% of Ihe rituximab group reached the primary endpoint (remission of disease without the use ol prednisone at 6 mo), as compared with 53% of controls (nonInferiority P< 0.001) Rituximab was more effective than cyclophosphamide for inducing remission of relapsing disease; 67% vs. 42% reached the primary endpoint (P-0.01). Conclusion: In severe AAV rituximab was noninferior to cyclophosphamide for remission induction and may be superior in relapsing

.

.

disease.

MAINRITSAN3

.

Title: long - term Rituximab Use to Maintain Remission ol Antmcutrophil Cytoplasmic Antibody Associated Vasculitis: A Randomized Inal Purpose: To assess Ihe efficacy ol prolonged rituximab therapy in reducing AAV relapses in patients in complete remission following an initial phase of maintenance therapy. Methods: 68 patients were randomized to receive an infusion of rituximab or placebo every 6 mo for 18 mo. Results: At 28 mo estimates of relapse free survival were 96% and 74% in the rituximab and placebo groups, respectively, representing an absolute difference of 22% (Cl 9 - 36%) and a hazard ratio of 7.5 (Cl 1.67- 33.7) |P'0.003 ) Conclusion: Prolonged rituximab therapy resulted in lower rates of AAV relapse than standard maintenance therapy

Ann Intern Med 2020:173:179 187

-

.

-

.

.

.

.

GOUT

Febuxostat Compared with Altopurinol in Patients with Hyperuricemia and Gout . Becker etal. 2005

-

HEJM 2005;353:2450 61

Title: Febuxostat Compared with Altopurinol in Patients with Hyperuricemia and Gout Purpose: lo investigate the use of febuxostat as a potential alternative to altopurinol foi patients wilh hyperuricemia and gout. Methods: 762 patients with gout and with serum urate :8.0 mg/dl were randomly assigned to receive either daily febuxostat (80 or 120 mg) or daily altopurinol ( 300 mg) for 52 wk. Results: Primary endpoint (serum urate

External

A

Pampiniform plexus

spermatic fascia

Cremaster muscle

,

Internal

j

] spermatic fascia [t— Tunica vaginalis

I

Oartos fascia

-

i

t

Testis

x &

Skin

V2

v

V

Figure 1. Midline cross- section of abdominal wall

Figure 2. Anatomy of scrotum -Renal cortex

Minor calyx Major calyx

Renal vein Renal artery

J-

—V

.Renal medu !a

T3

Renal sious —y Renal pe'vts

—*

Abdominal aorta Inferior vena cava Ureter Gonadal artery and vem

(Leal pap . a anal column

Anal pyramid

rfienol capsule

IGerota's fascial

Internal iliac artery and vein

External iliac artery and vem Internal pudcnal artery

Common penile artery

i s. ~ cn

2

©

Detrusor Trigone Base detrusor Urethral muscular s ( internal sphincter, smooth muscle) Periurethral striated muscle Rhabdosphincter l«MHnal sphincter, striated musclel

icular junction

Membrane wurethra

Bulbar urethra L

Spongy (penile) urethra

_ Corpus cavemosum

-Posterior urethra

r

nterior urethra

ri L j

i -

L Corpus spongiosum t

—

k

A

=

cn

©

Meatus

+

Figure 3. Essential male genitourinary tract anatomy

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Toronto Note 2023

U3 Urology

*

Transverse Sections of Penis

Superficial dorsal vein Deep dorsal vein Dorsal artery

Skin Loose areolar tissue Deep fascia Tunica albuginea

Dorsal nerve Corpus cavernosum Deep artery

Urethra Superficial

Corpus spongiosum

' dorsal vein

I

.Deep

Skin

dorsal vein

/

Gians penis Dorsal vein Dorsal artery Dorsal nerve

- Dorsal artery

Corpus cavernosum Corpus spongiosum

Urethra Distal ( foreskin retractedl

c

:

2

Figure 4. Cross section of the penis Ductus deferens

! Seminal vesicle

Pubic symphsis Prostate Urethra

/

Ampulla of ductus deferens

Rectum Bulbourethral gland

Ductus i t :f

-

i

£ 2

—S

Figure 5. Median sagittal section of the male pelvis and perineum Sympathetic IT10-L2) ON

Parasympathetic ( S2-S4) OFF

>

Pelvic nerve

Sympathetic ( T10- L2)

•Hypogastric nerve •NE

adrenergic receptors internal urethral sphincter contraction • 3 receptor detrusor relaxation

• I roceptor




Somatic ( S2- S4 )

Hypogastric nerve

Internal urethral sphincter

Somatic IS2-S4) ON

I

Pudendal nerve

External urethral sphincter

•Pudendal nerve •ACh nicotinic receptors

external

Parasympathetic ( S2- S4 ) Off

s

urethral sphincter contraction 2

I a -

u M

Figure 6. Bladder innervation during storage phase

r -\ LJ

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Toronto Notes 2023

Ul Urology

-

-

Sympathetic (T10 L2) OFF

Parasympathetic {S2 S4) ON

ltrCACh > 33

Pelvic nerve

j>

Sympathetic ( T10- L2) Olf

•Internal urethral sphincter relaxation Somatic ( S2- S4 ) Off •External urethral sphincter relaxation

< >| NE

Parasympathetic ( S2- S4 )

•Pelvic nerve •ACh -> muscarinic receptors detrusor contraction Hypogastric nerve

—

Internal urethral sphincter

cx

Somatic (S2-S4) OFF

I

£

Pudendal nerve

s

External urethral sphincter

a Figure 7. Bladder innervation during voiding phase

Urologic History • follow OPQRST' U approach • note that pain may not be limited to the genital region ( e.g. lower abdomen, CVA ) habits urinary • • LUT S ( see Lower Urinary Tract Symptoms, U 7 ) • storage symptoms: frequency, urgency ( rush to toilet ), nocturia (1;UN ) • voiding symptoms: stream changes /straining, hesitancy, incomplete emptying, post-void

dribbling (SHED )

• dvsuria: burning, pain on voiding • hematuria: blood clots, red / pink tinged urine ( see Hematuria )

• incontinence: stress, urgency, mixed, overflow ( see Urinary Incontinence, U 6 ) • sexual function scrotal mass ( see Scrotal Masses, U 32) » ED ( see Erectile Dysfunction , U 33 ) • female sexual dysfunction (dvspareunia , low desire, arousal disorder, orgasmic dysfunction ) • infertility ( see Infertility, U 37 ) • associated symptoms • N/ V • bowel dysfunction

Always ask about sexual function on history. Change in erectile function can be one of the first symptoms that there is concomitant vascular disease. If there is new onset ED consider screening for DM and CAD risk factors

.

• constitutional symptoms • fever, chills, unintentional weight loss, night sweats, fatigue, malaise, bone pain • risk factors: past urologic disease ( e.g. UTI, stones, ST1, cancers, anatomic abnormalities ), EMHx, medications, lifestyle factors (e.g. smoking, alcohol , inactivity), trauma , previous surgical procedures

Hematuria Macroscopic (Gross) Hematuria Definition

Gross, painless hematuria in adults is bladder cancer until proven otherwise

• blood in the urine that can he seen with the naked eye Classification • see

Nephrology

Etiology

Table 1. Etiology by Age Group Age ( yr )

Etiology

0 20 20 - 40

UII . glomerulonephritis , congenital abnormalities UII. stones, bladder tumour, exercise

40 60

Male: bladder tumour, stones. UII . prostate cancer Male: 8 PH . bladder tumour , UII , RCC , prostate cancer

»

60

+

female: UII . stones , bladder tumour female: bladder tumour , UII . RCC

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U5 Urology

Table 2. Etiology by Type Pseudohematuria

Infectious / Inflammatory

Malignancy

Benign

Structural

Hematologic

Vaginal bleeding Dyes (beets, rhodamine B in candy and juices) Hemoglobin (hemolytic anemia) Myoglobin (rhabdomyolysis) Drugs (rifampin, phenazopyridine, phenytoin) Porphyria Laxatives (phenolphlhalcin)

Pyelonephritis Cystitis

RCC (mainly adults) Urothelial cancer Wilms' tumour (mainly

BPH Polyps Exercise- induced

Stones Trauma Foreign body Urethral stricture Polycystic kidneys Arteriovenous malformation Infarct Hydronephrosis Fistula

Anticoagulants Coagulation defects Sickle cell disease Thromboembolism

Urethritis Glomerulonephritis Interstitial nephritis Tuberculosis

paediatric)

Prostate cancer Leukemia

History • timing of hematuria in urinary stream beginning of micturition: anterior urethra end of micturition: bladder neck, prostatic urethra • entire duration of micturition: bladder and above • presence of blood clots • LUTS and associated symptoms • pyuria, dvsuria, urgency: UTT flank pain, radiation: ureteral obstruction • last menstrual period, history of kidney stones, UTT, or previous urologic surgery recent UTT, post-infectious glomerulonephritis, IgA nephropathy • medications ( anticoagulants, rifampin , phenazopyridine, phenytoin ) • risk factors for malignancy ( smoking , chemical exposures, Hx of cyclophosphamide therapy, pelvic

Common Uiologic Causes of Hematuria can be Classified as: TICS Trauma / Tumour/Toxins Infection /Inflammatory Calculi/Cysts Surgery/Sickle cell and other hematological causes

radiation ) Investigations • U /A , urine C&S, urine cytology • imaging lower tract: cystoscopy upper tract: CT Urogram (gold standard ), U/S • CBC ( rule out anemia, leukocytosis), electrolytes, creatinine (Cr), blood urea nitrogen ( BUN ), 1NR, partial thromboplastin time ( PI T ), PSA (in men ) Acute Management of Severe Bladder Hemorrhage • manual irrigation via catheter with normal saline to remove clots • CB1 using large ( 20 2 1 l r) 3 way Toley to help prevent clot formation

-- - '

should be done after manual irrigation of all clots • cystoscopy identify tumours or other source( s ) • coagulate obvious sites of bleeding or transurethral resection of tumours ( under general or regional anesthesia )

Upper Tract Imaging Options • CT Urography (CTU):Test of choice to evaluate the renal parenchyma and collecting system. Involves exposure to radiation and IV contrast (assess renal function and allergies) • U/S: Superior to IVP for evaluation of renal parenchyma and renal cysts: limited sensitivity for Urothelial carcinoma and small renal masses: U/S alone may be insufficient for upper tract imaging • Magnetic Resonance (MR ) Urography:Evaluation of renal parenchyma , collecting system and congenital anomalies: beneficial in paediatric or pregnant patients or when ionizing radiation has to be avoided, (assess renal function and allergies)

Microscopic Hematuria Definition • blood in the urine that is not visible to the naked eye • >2 RBCs / HPT on urinalysis of at least two separate samples

f 2 RBCs/HPfJ i

Retost after undorlying couso resolved

^

*

YES

Identify bonign rovorsiblo cousos ( o . g. infection, urethral trauma, hoavy exercise, monsos, medication, etc ) NO

YES

Referral to nephrology

(t

Evidenco of glomerular disease Cr proteinuria, dysmorphic RBC, RBC casts)?

.

NO

Negative results AND LOW RISK patient

Urinalysis, urine cytology,

.

1) Renal U/S 2) Urine cytology

*

I f

f

Positive result

HIGH RISK patient: Ago >40 yr old

iJ

Smoking history Occupational chomical oxposuro Gross homaturia Hx of storngo or voiding symptoms Hx of recurrent UTIs, urological disorders Polvic radiation exposure

+

and BP at 6.12 24, and 36 months Urological roforral

for cystoscopy

rn

Figure 8. Workup of asymptomatic microscopic hematuria

Based on CUA Guidelines. Alternatively. Uie AUA recommends cystoscopy and CT urogram lor all patients with confirmed microscopic hematuria; follow -up for negative workup is urinalysis yearly for two yr with repeat anatomic evaluation if microscopic hematuria persists

.

Activate Windows 6oAo SettrngsAcrartivate Wrncfowsr

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-

U6 Urology

Toronto Notes 2023

Lower Urinary Tract Dysfunction • two phases of lower urinary tract function 1. storage phase (bladder tilling and urine storage ) requires:

Transient Causes of Reversible Urinary Incontinence in the Elderly

• accommodation and compliance • no involuntary contraction( s) 2 . voiding phase ( bladder emptying ) requires: • coordinated detrusor contraction synchronous relaxation of outlet sphincters • no anatomic obstruction • lower urinary tract dysfunction can therefore be classified as: • failure to store: due to bladder or outlet • failure to void: due to bladder or outlet • three types of symptoms • storage ( formerly known as irritative) voiding ( formerly known as obstructive) post - voiding

DIAPERS Delirium Inflammation /Infection Aroplik vaginitis/urclhritis Plratmacculicals/Psychological Excess U/O Restricted mobility/Rctcntion Stool impaction

Urinary Incontinence Definition •

involuntary leakage of urine

Epidemiology variable prevalence in women: 25- 45% F:M=2:1 • more frequent in the elderly, affecting 5 - 15% of those living in the community and 50% of nursing home residents •

.

Urgency is the complaint of a sudden compelling desire to void that is difficult to defer it is not necessarily associated with incontinence

Table 3. Urinary Incontinence: Types and Treatments Mixed

Type

Stress

Urgency

Definition

Leakage v/ilh sudden increases in inlra abdominal pressure (cough, sneeze, exertion)

Leakage preceded by Leakage with urgency and strong, sudden urgeto void increased intra- abdominal pressure

Etiology

Sphincter incompetence Detrusor overactivity Bladder hypersensitivity Urethral hypermobility Common in middle aged and older women, and men following prostate cancer treatment, or rarely surgical treatment ol BPH

Investigations

Hi: when leakage occurs, number ol pads, LUIS, history of neurologic disease, pelvic suigeryJradiothcrapy obstetrical history, bowel and sexual function, medications, impact on quality of tile P/ E: geneial (edema, neurologic abnormalities, mobility, cognition, dexterity), abdomen (distended bladder ) CU (prolapse in women, DRE in men) , cough lest U /A, urine CtS voiding diary (type of incontinence, how often , volume ol leakage) Urodynamics

.

.

Management

Same as stress and urgency incontinence

Risk reduction: weight loss, smoking cessation Kegel exercises pelvic lloor muscle therapy (Pf Ml) Surgciy: urethral slings, or artificial sphinctei in men

Overflow

Leakage associated with urinary retention

BPH with overflow incontinence From weak bladder that does not empty ( e.g. diabetic cystopathy )

.

See Urinary Uelenlion U 1

.

Conservative: fluid management , bladder training Kegel exercises Medication: anticholinergics, p- 3

.

Combination of management of stress and urgency incontinence

Cathcterication Treat underlying cause

agonist Botulinum toxin A bladder injection Hcuromodulation

r

-

i

LJ

+

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Toronto Notes 2023

U 7 Urology

Lower Urinary Tract Symptoms Urinary Retention • storage symptoms: frequency, urgency ( strong need to void ), nocturia ( TUN ) • voiding symptoms: stream changes/straining, hesitancy, incomplete emptying, post -void dribbling (SHHD) Table 4. Etiology of Urinary Retention Outflow Obstruction

Bladder Innervation

Bladder neck or urethra: calculus , clot , foreign body , neoplasm ,

Intracranial: CVA, tumour Parkinson's, cerebral palsy Spinalcord: injury, disc herniation MS

neurological ( DSD) Prostate: 8PH prostate cancer Urethra: stricture, phimosis, traumatic disruption Miscellaneous:constipation , pelvic mass, severe prolapse in

.

.

.

DM Post abdominal or pelvic surgery

-

vromen

Pharmacologic

Infection

Anticholinergics Narcoltcs Antihypertcnsives (ganglionic blockers, melhyl dopa) OTC cold medicationscontaining

GU : Dll prostatitis, abscess ,

.

genital herpes

Inlccted foreign body Varicella toslet

ephedrine or pseudoephedrine Antihistamines Psychosomatic substances (e.g. MDMA (ecstasy))

If a trauma patient is unable to void , has blood at urethral meatus, a scrotal hematoma , or a high riding prostate , there is urethral injury until proven otherwise so catheterization is CONTRAINDICATED unless performed by urology staff or resident

Clinical Features

• suprapubic pain ( with acute retention ), incomplete emptying, weak stream • palpable and /or percussible bladder ( suprapubic ) • possible purulent / bloody meatal discharge ( with UTI ) • increased size of prostate or reduced anal sphincter tone ( with neurological disease ) on 1)R1: • neurological: presence of abnormal or absent deep tendon reflexes, reduced “anal wink," saddle anesthesia Investigations

Acute vs. Chronic Retention Acute retention is a medical emergency characterized by suprapubic pain and inability to void Oironic retention can be painless with greatly increased bladder volume and detrusor hypertrophy followed by atony (late)

• CBC, electrolytes, Cr, BUN , U /A and urine C&S, U /S, cystoscopy, urodynamic studies, PVR Treatment

• treat underlying cause • catheterization

•

acute retention

Patients with ascites may have a falsely elevated PVR measured by bladder scan

immediate catheterization to relieve retention; leave Tolev in to drain bladder; follow- up to determine cause; closely monitor fluid status and electrolytes ( risk of POD) chronic retention intermittent catheterization by patient may be used; definitive treatment depends on etiology • suprapubic catheter if obstruction precludes urethral catheter • for postoperative patients with retention :

• encourage ambulation • a blockers to relax bladder neck /outlet ( men only)

-

may need catheterization definitive treatment will depend on etiology

•

minimize narcotic use

Benign Prostatic Hyperplasia

r

Anterior libromuscular area

Transition

zone

Definition

• proliferation of epithelial tissue, connective tissue, and smooth muscle in the prostatic transition zone Etiology • unknown «

DHT required (converted from testosterone by 5-a reductase ) possible role of impaired apoptosis, estrogens, other growth factors

Epidemiology

• age - related , extremely common ( 50% of 50 y /o, 80% of 80 y /o) • 25% of men will require treatment

Urethra

Urethral

zone

Central zone Peripheral zone Ejaculatory zone

Maaghan Briailoy

Figure 9. Cross- section of prostate

Clinical Features • result from outlet obstruction and compensatory and/or age- related changes in detrusor function • voiding and storage symptoms DRfi • prostate is smooth , rubbery, and may be symmetrically enlarged

.

j

rn

LJ

Prostate size does not correlate well with symptoms in BPH

+

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Toronto Notes 2023

U8 Urology •

complications retention

overflow incontinence

Approximate Prostate Sizes 20 cc - chestnut 25 cc plum

hydronephrosis • renal insufficiency • infection • gross hematuria • bladder stones

-

50 cc lemon 75 cc - orange 300 cc - grapefruit

Investigations • mandatory: Hx including LUTS, surgery, trauma, medications (OTC and phytotherapeutic agents), impact of QOL , P/ E including DRE, VIA to exclude UTT • recommended: symptom inventory ( IPSS or AUA-Symptom Index ( SI )), PSA if > 10 yr life expectancy

or if it changes management of LUTS • optional: Ur , urine cytology, uroflowmetry, PV R, voiding diary, sexual function questionnaire • renal U / S to assess for hydronephrosis • consider cystoscopy or bladder ultrasound prior to potential surgical management to evaluate outlet and prostate volume • biopsy if suspicious for malignancy, i.e. elevated PSA or abnormal DRE Treatment

AUA BPH Symptom Score

FUNWISE Frequency Urgency Nocturia Weak stream Intermittency Straining Emptying, incomplete feeling of Each symptom graded out of 5 0 7: Mildly symptomatic 8 -19: Moderately symptomatic 20- 35: Severely symptomatic Note: dysuria not included in score but Is commonly associated with BPH

-

Table 5. Treatment of BPH ( see Table 28 , U47, Figure 6, U3 , and Figure 7, U 4 ) Conservative

Medical

Surgical

Minimally Invasive Surgical Therapies

When to use

Asymptomatic or mildly symptomatic, minimal bother

Moderately to severely symptomatic,bothersome

Absolute or relative indications, significant bother

Patients who wish to avoid or maynot tolerate surgery

Options

Watchful waiting: 50“ of patients improve

o- adrenergic antagonists: reduce smooth muscle tone (neck of bladder, prostate, urethra) 5- a reductase inhibitor: block conversion ol testosterone to DM; ad to reduce proslate sice Combination of u- adrenergic antagonists and 5-a reductase inhibitor is synergistic Antimuscarinics or p - 3 agonist ( for storage IUIS without elevated PVR) P 0E 5 inhibitors|E 0 and for storage and voiding IUIS) Desmopressin (IUIS with nocturia); risk of hyponatremia in » 65 yr

TURP (see U45) BPK VP (< 60 cc) laser prostatectomy IUIP (40 mL and basehne PSA VS ng /mLhad greater ^ reductions in relative risk (RR) of BPH - related surgery and RR of clinical progression on combmed therapy oi dutasteride monotherapy thanon tamsulosin monotherapy.

Definition • dysfunction of the urinary bladder due to deficiency in some aspect of its innervation, often presents with overflow incontinence and urgency incontinence

Neurophysiology • see Figure 6 , U3 and Figure 7, U 4 • stretch receptors in the bladder wall relay information to PMC and activate micturition reflex ( normally inhibited by cortical input ) • micturition ( voiding ) • stimulation of parasympathetic neurons ( bladder contraction) inhibition of sympathetic and somatic neurons ( internal and external sphincter relaxation , respectively) voluntary relaxation of the pelvic floor and striated urethral sphincter • urine storage • opposite of micturition • voluntary action of external sphincter ( pudendal nerve roots S2 S4 ) can inhibit urge to urinate • cerebellum, basal ganglia , thalamus, and hypothalamus all have input at PMC in the brainstem to

-

inhibit the detrusor reflex

Examples of Neurogenic Lower Urinary Tract Dysfunction • neurogenic detrusor overactivity ( NDO; formerly termed detrusor hyperreflexia ) » lesion above PMC (e.g. stroke, tumour, MS, Parkinson’s disease)

• loss of voluntary inhibition of voiding • intact pathway inferior to PMC maintains coordination of bladder and sphincter

. DSDsuprasacral lesion of spinal cord e.g. trauma, MS (

•

Finasteride forBenign Prostatic Hyperplasia Cochrane DB Syst Rev 20IO;10:CD006015 Rirpose: to eienn ne the effectmenessard safety of finasteride vs. placebo ot other active controls for Ibe treatment oi unitary tract symptoms. Summery of findings: t Finasteride improved unoaiy symptoms more than placebo nr trials >1 yr duration and significantly lowered the risk of BFH progress on. 2. Compared with o- bfockers. finasteride was less effective than either doisiosin or terazosin, but equally as effective as tamsulosin. 3.5ymptom improvement with finasteride dotamsm is equal todoraiosin alone. 4. Furasleride treatment resulted in an increased risk ol ejaculation disorder , impotence , and lowered libido compared with placebo. 5.Compared with doraiosm and teraiosin, finasteride had a lower rsk of asthenia, doziness, and postural

.

hypotension.

m

Nerve roots in micturition: "S 2 - 3- 4 keeps the urine off the floor "

, arteriovenous malformation , transverse

myelitis) loss of coordination between detrusor and sphincter (detrusor contracts on closed sphincter and vice versa ) component of detrusor overactivity as well • detrusor atony/arellexia • lesion of sacral cord or peripheral nerves (e.g. trauma, DM , disc herniation , MS, congenital spinal cord abnormality, post abdominoperineal resection ) flaccid bladder which fails to contract » may progress to poorly compliant bladder with high pressures • peripheral autonomic neuropathy deficient bladder sensation -> increasing residual urine -> decompensation (e.g. DM, neurosyphilis, herpes zoster) • muscular lesion

r -i LJ

+

• can Involve detrusor, smooth /striated sphincter

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Toronto Notes 2023

U10 Urology Neuro-Urologic Evaluation • Hx and P/ E ( urologic and general neurologic) • voiding diary, assess for incontinence, urinary symptoms, and UT1 risk ( hydration status, catheterization, voiding frequency) • catheterization volumes in patients with CIC • all patients: U /A , PVR, renal profile moderate/ high - risk (spinal cord injury, spina bifida, MS): urodynamics, renal U /S, renal profile • imaging • U/S to rule out hydronephrosis and stones; occasionally Cl' scanning with or without contrast • cystoscopy ( if suspicion of bladder tumour, hematuria )

“Spinal shock” initially manifests as atonic bladder

• urodynantic studies

• uroflowmetry to assess flow rate, pattern • filling CMG to assess capacity, compliance, detrusor overactivity • voiding CMG ( pressure-flow study) to assess bladder contractility and extent of bladder outflow »

obstruction video study to visualize bladder/bladder neck /urethra during CMG using x-ray contrast EMG and video ascertains presence of coordinated or uncoordinated voiding, allows accurate diagnosis of DSD

Treatment

• goals of treatment • prevent renal deterioration • prevent infections ( UTI ) achieve social continence

• CIC (if there is associated inability to void ) • treatment options depend on status of bladder and urethra bladder hyperactivity -> antimuscarinic medications to relax bladder (see Urinary Incontinence, U6 ) if refractory botulinum toxin injections into bladder wall (detrusor muscle) occasionally augmentation cystoplasty (enlarging bladder volume and improving compliance by grafting section of detubularized bowel onto the bladder ) occasionally urinary diversion ( ileal conduit or continent diversion ) in severe cases if

-

- bladder management unsuccessful

flaccid bladder > CIC

Dysuria Definition • painful urination

Etiology

Table 6. Differential Diagnosis of Dysuria

.

infectious

Cystitis, urelhrilis prostatitis, epididymilis/orchitis (if associated with lower trad inflammation), cervicitis, vulvovaginitis, perineal Inflammalion/infeclion tuberculosis, vestibulitis

Hcoplasm

Kidney,bladder,prostate, penis, vagina / vutva BPH

. .

Calculi

Bladder stone, urethral stone, ureteral stone

Inflammatory

Seronegative arthropathies (reactive arthritis:arthritis,uveitis, urethritis),drug side effects, autoimmune disorders, chronic pelvic pain syndrome (CPPS),interstitial cystitis

Hormonal

Endometriosis, hypoestrogenism

Trauma

Catheter insertion, post coital cystitis (honeymoon cystitis)

Psychogenic

Somatiiation disorder, depression, stress/amiely disorder Contact sensitivity,foreign body,radialion/chcmical cystitis, diverticulum

Other

-

Investigations

• focused Hx and P/ E to determine cause ( fever, d /c, conjunctivitis, CVA tenderness, back / joint pain )

• any d/c (urethral, vaginal, cervical ) should be sent for gonococcus/chlamydia testing; wet mount if vaginal d /c U /A and urine C&S if suspect infection, may start empiric ABx treatment (see Table 9, U 16 ) ± imaging of urinary tract (tumour, stones)

n LJ

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Ull Urology

Toronto Notes 2023

Hydronephrosis Definition

• the upper urinary tract consists of the kidneys and ureters • dilation of the renal pelvis, calyces, and ureters, generally caused hy obstruction of antegrade urine flow (i e. pelvicaliectasis)

.

Etiology

• mechanical « congenital: see Congenital Abnormalities, U 39 acquired intrinsic: trauma , inflammation and bleeding, calculi , urologic neoplasms, BPH , urethral stricture, phimosis, previous urological surgery extrinsic: trauma, neoplasms ( uterine fibroid; colorectal, uterine, and cervical malignancies; lymphoma), aortic aneurysm, pregnancy (gravid uterus) • functional neuropathic: neurogenic bladder, diabetic neuropathy, spinal cord disease hormonal: pregnancy ( progesterone decreases ureteral tone ) Investigations

• focused Hx, inquiring about pain (flank, lower abdomen , testes, labia ), U/O, medication use, pregnancy, trauma , fever, Hx ofUTls, calculi, FID, and urological surgery CBC, electrolytes, Cr, BUN , VIA , urine C &S • imaging studies ( U /S is >90% sensitive and specific) CT: helps delineate anatomy and potential causes (e.g. obstructing stone), but does not provide

.

much functional information

mercaptoacetyltriglycine ( M A(i 3) diuretic renogram : provides little anatomic structural information but evaluates differential renal function and demonstrates if functional obstruction exists

retrograde pvelogram: helps to delineate anatomy and can allow for stent insertion to decompress if obstruction is present Treatment

• hydronephrosis can be physiologic (e.g. pregnancy ) • treatment should be guided at improving symptoms, treating infections, or improving renal function • urgent treatment may require percutaneous nephrostomy tube or ureteral stenting to relieve pressure • treatment can include pyeloplasty to repair an obstructed UP ) in congenital or acquired UP)

obstruction

Post- Obstructive Diuresis Definition

• polyuria resulting from relief of obstructive uropathy ( i.e. elevated creatinine)

• >3 L / 24 h or >200 cc/ h for two consecutive hours Pathophysiology

• physiologic POD secondary to excretion of retained urea , Na and H 2O ( high osmotic load ) after relief of obstruction self limiting; usually resolves in 48 h with PO fluids but may persist to pathologic POD • pathologic POD is a Nan - wasting nephropathy secondary to impaired concentrating ability of the renal tubules due to: decreased reabsorption of NaCl in the thick ascending limb and urea in the collecting tubule increased medullary blood flow (solute washout ) increased flow and solute concentration in the distal nephrons

-

Management • admit patient and closely monitor hemodynamic status and electrolytes ( Na ' and K + q6- l 2 h and replace pm; follow Cr and BUN to baseline) • monitor U /O q2 h and ensure total fluid intake < U /0 by replacing every I ml. U /O with 0.5 mL 1 / 2 normal saline ( NS) IV ( PO fluids if physiologic POD) • avoid glucose-containing fluid replacement ( iatrogenic diuresis )

n LJ

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U12 Urology

Overactive Bladder Definition

• a symptom complex that includes urinary urgency with or without incontinence, urinary frequency (voiding >8 times in a 24 h period ), and nocturia (awakening ONE or more times at night to void ) Etiology

• multiple etiologies proposed ( neurogenic, myogenic, idiopathic )

• symptoms thought to be from involuntary contractions of the detrusor muscle

• may be associated with other conditions such as SU 1 in women and BPH in men (see Table 5, U 8) Epidemiology

• l :M = l: l • prevalence increases with age. 42% in males £ 75 y/o; 31% in females £ 75 y/o '

• women experience incontinence more commonly than men Diagnosis

• the diagnostic process should document symptoms that define overactive bladder and exclude other disorders that could cause the patient 's symptoms • minimal requirements for the process consist of: • focused history including past genitourinary disorders and conditions outlined in Table 7, questionnaires of LUTS and diaries of urination frequency, volume and pattern (3 d micturition diary) P/ E including genitourinary, pelvic, and rectal examination U /A to rule out hematuria and infection • in some patients, the following investigations could be considered post void residual cystoscopy to rule out recurrent infections, carcinoma in situ and other intravesical abnormalities • urodynamics to rule out obstruction in older men

-

Treatment

-

• non pharmacological: behaviour therapies such as bladder training, bladder control strategies, pelvic floor muscle training, fluid management , weight reduction ( if overweight ), and avoidance of caffeine and alcohol • pharmacological (see Table 29, U 48 ) antimuscarinics: oxybutynin hydrochloride, tolterodine, solifenacin, fesoterodine, darifenadn,

propiverine, or trospium (53 adrenoceptor agonist: mirabegron • refractory patients may be treated with: neuromuscular junction inhibition: botulinum toxin bladder injection • others percutaneous tibial nerve stimulation ( not used commonly in Canada ) sacral neuromodulation

-

-

Table 7. Conditions that Could Contribute to Symptoms of Overactive Bladder Lower Urinary Tract Conditions UII. obstruction , impaired bladder contractility Neurological Conditions

Stroke, MS , dementia , diabetic neuropathy

Systemic Diseases Functional and Behavioural

CNF, sleep disorders [primarily nocturia ) Excessive caffeine andaicohol , constipation, impaired mobility

Medication

diuretics, anticholinergic agents , narcotics, calcium - channel blocker, cholinesterase inhibitors

n LJ

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U 13 Urology

Toronto Notes 2023

Infectious and Inflammatory Diseases Table 8. Antibiotic Treatment of Urological Infections Condition

Drug

Ouration

Urethritis

Non Gonococcal aiithromycin (1 g PO )

ild

J!!

doxycydine (100 mg PO BID) Gonococcal ceftriaxone ( 250 mg IM) AND treat for Chlamydia liachamolis

7d

Simple, Uncomplicated UTI

TMP/SMX (160 mg/800 mg P 0 BID) :J H nilrofuranloin (100 mg PO BIO)

3d

Complicated UTI

ciprofloxacin (1 g PO once daily OR 400 mg IV q12 h ) OR ampicillin (1 g IV q6 h) * gentamicin (1mg/kg IV q8 h ) (used for relatively short courses because of loxicily) OR ceftriaxone (1- 2 g IV q24 h)

Recurrent/Chronic Cystitis

xl

Antibiotic therapy should always be based on local resistance patterns and adjusted according to culture and sensitivity results

Sd

Prophylactic Treatment Continuous: IMP SMX (40 mg/200 mg POOHSOR 3 x / wk )

up to 2- 3 wk up lo 2- 3 wk up to 2- 3 wk

6 -12 mo

: n:

Acute Prostatitis

nitrofurantoin (50 -100 mg PO OHS) Post- Coital: TMP-SMX (40 mg /200 mg - 80 mg!400 mg) OR nitrofurantoin ( 50- 100 mg P 0 once daily)

6 -12 mo within 2 h of coitus

ciprofloxacin (500 - 750 mg P0 BID ) OR TMP-SMX (160 mg/ 800 mg PO BID) OR IV therapy with gentamicin and ampicillin penicillin with (Maclaniase inhibitor, 3rd gen cephalosporin OR a fluoroquinolone

2 4 wk

ciprofloxacin (S00 mg PO BID)

4 - 6 wk

.

Chronic Prostatitis

within 2 h ol coitus

.

.anti- inflammatories

-

-

4 wk

4 wk |IV and oral step - down)

in blockers

Epididymitis /Orchitis

< 35 yr

(presumed S1I) celtiiaxone ( 200 mg IM )

xl

AND doxycydine (100 mg P 0 BID)

10 d

> 35 yr (presumed urinary source)

Acute Uncomplicated Pyelonephritis

ofloxacin ( 300 mg P 0 BID)

10 d

ciprofloxacin (500 mg PO BID) ± ceftriaxone (1g IV) OR ciprofloxacin ( 400 mg IV) OR IV therapy with a fluoroquinolone, gentamicin and ampicillin, extended spectrum cephalosporin, extended spectrum penicillin OR a carbapenem

7d x1

.

14 d total IV and oral slop - down

Acute uncomplicated pyelonephritis: suspected or confirmed Enterococcus infection requires treatment with ampicillin

Urinary Tract Infection • for UTls during pregnancy, see

Obstetrics, OB 31

Definition • symptoms suggestive of UTI + evidence of pyuria and bacteriuria on U /A or urine C&S if asymptomatic + 100000 Cl'- U / mL = asymptomatic bacteriuria; only requires treatment in certain patients ( e. g . pregnancy, immunosuppressed , prior to urologic surgery ) Classification

UTI in a setting of functionally and structurally normal urinary tract • complicated : structural and /or functional abnormality, male patients , immunocompromised , • uncomplicated : lower

diabetic, iatrogenic complication , pregnancy , pyelonephritis , catheter - associated • recurrent: see Recurrent/Clironic Cystitis, U14 Risk Factors • stasis and obstruction • residual urine due to impaired urine flow (e.g. PUVs, reflux, medication, BPH , urethral stricture, cystocele , neurogenic bladder) • foreign body • introduce pathogen or act as nidus of infection (e.g . catheter, instrumentation ) • decreased resistance to organisms DM , malignancy, immunosuppression , spermicide use , estrogen depletion , antimicrobial use • other factors • trauma , anatomic abnormalities , female, sexual activity, menopause, fecal incontinence

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UM Urology Clinical Features

• storage symptoms: frequency, urgency • voiding symptoms: hesitancy, post-void dribbling, dvsuria • other: suprapubic pain, hematuria, foul-smelling urine • pyelonephritis - if present: typically presents with more severe symptoms (e.g. fever/chills, CVA tenderness, flank pain) Indications for Investigations

• pyelonephritis • persistence of pyuria /symptoms following adequate antibiotic therapy • severe infection with an increase in Cr • recurrent /persistent infections • atypical pathogens (urea splitting organisms) • Hx of structural abnormalities/decreased flow

Investigations

• U /A, urine C&S (only if symptomatic) U /A: leukocytes ± nitrites ± hematuria C&S: midstream , catheterized, or suprapubic aspirate • if hematuria present, retest post treatment , if persistent need hematuria workup ( see Microscopic Hematuria, US ) • U /S, CT scan if recurrent or treatment resistant UTIs, suspected anatomic abnormalities, history indicates complicated cystitis • pelvic examination for women if recurrent UTI

-

-

Prevention of UTIs • Maintain good hydration (try cranberry preparations or D-mannose) • Avoid feminine hygiene sprays and scenlcd douches • Empty bladder immediately before and aflcr intercourse • Vaginal estrogen therapy for peri and post menopausal women with recurrent UTIs

-

Treatment

• see Table 8, Antibiotic Treatment of Urological Infections, U 13 • asymptomatic bacteriuria should not be treated (exceptions: pregnancy, before urological procedure) • if febrile, consider admission with IV therapy and rule out obstruction Prevention of UTIs

• maintain good hydration (emerging evidence re: cranberry preparations and D- mannose) • void regularly ( do not hold urine for prolonged periods of time ) • avoid feminine hygiene sprays and scented douches • empty bladder immediately before and after intercourse Organisms • typical organisms: SEEK PP (£. coli 75-95%) • atypical organisms tuberculosis ( TB)

Chlamydia trachomatis Mycoplasma ( Ureaplasma urealyticum ) fungi (Candida )

Recurrent /Chronic Cystitis Definition • >3 UTls/yr Etiology *

bacterial reinfection (80%) vs. bacterial persistence ( relapse) • bacterial reinfection recurrence of infection with either 1) a different organism , 2) the same organism if cultured >2 wk following therapy, or 3) with any organism with an intermittent sterile culture • bacterial persistence same organism cultured within 2 wk of sensitivity based therapy

-

Investigations

• assess predisposing factors

• investigations may include cystoscopy, U/S, CT Treatment • lifestyle changes (limit caffeine intake, increase fluid / H ’0 intake) • ABx (various strategies): continuous low -dose daily suppression vs. post- coital only vs. self-start

n LJ

therapy

• post - menopausal women: consider topical estrogen therapy • no treatment for asymptomatic bacteriuria except in pregnant women or patients undergoing urinary

+

tract instrumentation

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U15 Urology

Interstitial Cystitis (Painful Bladder or Bladder Pain Syndrome) Definition

• bladder pain, chronic urgency, and frequency without other identifiable causation Classification • non - ulcerative (more common ) and ulcerative ( Hunner’s lesions ) Etiology

• unknown Epidemiology

• prevalence: 20 in 100000 • 90% of cases are in females, 94 % are white • median age is 40 yr ( non ulcerative seen in younger to middle aged , while ulcerative seen in middle aged to older)

-

Clinical Features

-

-

-

• pelvic pain (typically supra pubic tenderness )

• storage symptoms ( frequency > urgency > nocturia ) • negative U /A , urine C&S, urine cytology • cystoscopy: glomerulations ( submucosal petechiae), Hunner’s lesions

Cystoscopic evaluation is not necessary to make a diagnosis

Differential Diagnosis

• urology: non-infectious cystitis ( radiation, chemical, eosinophilic, TB), OAB, bladder calculi, prostaterelated pain • gynaecology : endometriosis, vulvar disorders • neurology: pudendal nerve entrapment • MSK: pelvic floor disorders • drugs: ketamine, tiaprofenic acid Investigations • Hx, P/ E, frequency volume chart • symptom scores to establish baseline and response to treatment • U /A, urine C&S, urine cytology • cystoscopy Treatment

• first line: patient education, dietary modifications, bladder retraining, stress management

• pelvic floor physiotherapy can be added for patients with pelvic floor dysfunction or pelvic pain • second line: guided by symptom phenotype

oral: amitriptyline, cimetidine, hydroxyzine, pentosan polysulfate ( PPS), gabapentin , quercetin intravesical: dimethylsulfoxide, heparin, lidocaine, PPS, oxybutynin toxin A, sacral neuromodulation • third line: hydrodistension, botulinum endoscopic treatment if Hunner's lesions (cauterization, resection, triamcinolone injection ) • fourth line: radical surgery (substitution cystoplasty or urinary diversion ± cystectomy) »

Acute Pyelonephritis Definition

• infection of the renal parenchyma with local and systemic manifestations • clinical diagnosis of flank pain , fever, and elevated WBC Etiology

• ascending from lower UT1 (usually Gram - negative bacilli ) or hematogenous route (usually Gram positive cocci)

• causative microorganisms

Gram positives: Enterococcus faecalis, S. aureus, S. saphrophyticus Gram negatives: E. coli, Klebsiella , Proteus, Pseudomonas, Enterobacter

• common underlying causes of pyelonephritis • stones, strictures, prostatic obstruction , vesicoureteric reflux, neurogenic bladder, catheters,

r1

Clinical Features • rapid onset (< 24 h ) • LUTS including frequency, urgency, hematuria; NOT dysuria unless concurrent cystitis • fever, chills, nausea , vomiting , myalgia, malaise • CVA tenderness and / or exquisite flank pain

+

L

DM, sickle -cell disease, PCKD, immunosuppression, post- renal transplant, instrumentation, pregnancy

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U16 Urology

Toronto Notes 2023

Investigations • U /A , urine C&S • CBC and differential: leukocytosis, left shift

-

• imaging if complicated pyelonephritis or symptoms do not improve with 48 72 h of treatment

abdominal / pelvic U /S

• CT • nuclear medicine: DMSA scan can be used to help secure the diagnosis • a photopenic defect indicates active infection or scar; if normal alternative diagnoses should be considered Treatment • hemodynamically stable

.

outpatient oral ABx treatment ± single initial IV dose ( see Tabic 8 U I 3 ) severe or non - resolving admit , hydrate, and treat with IV ABx (see Table 8, UB ) • emphysematous pyelonephritis • most patients receive nephrectomy after IV ABx started and patient stabilized consider temporization with nephrostomy tubes • renal obstruction • admit for emergent stenting or percutaneous nephrostomy tube •

Prostatitis/Prostatodynia Epidemiology

• prevalence: 9 % of rnen / yr, 6% with bothersome symptoms • most common urologic diagnosis in men 50 y/o Classification

Table 9. Comparison of the Four Types of Prostatitis Chronic Pelvic Pain Syndrome (Category III)

Asymptomatic Prostatitis (Category IV )

Chronic inlection t prostatitis symptoms

Symptoms without evidence ol inlection IIIA: inflammatory DIB: noninflammatory

Incidental inflammation

LUTS, pelvic pain No systemic signs Recurrent UIIs Leukocytosis in prostatic fluid Posilivc bacterial cultures

LUIS, pelvic pain IIIA: leukocytosis in prostatic fluid 1116: no leukocytosis in

No symptoms leukocytosis in prostatic

Acute Bacterial Prostatitis (Category I)

Chronic Bacterial Prostatitis ( Category

Etiology

Acute infection SEEK PP|80% f co/r)

Clinical Features

LUTS, pelvic pain Systemic signs: fever,

.

chills, malaise leukocytosis in prostatic

Hud Positive bacterial cultures Investigations

.

Hx P / E (abdominal, external genitalia , perineum , prostale) U /A urine CSS

.

1RUS if suspect abscess

Treatment

ABx (see Table 3. U13) Catheterization if severe obstructive Drainage if abscess is present

ID

.

Hx P/E ( same as Category I pelvic floor ) 4 glass test for culture: V61 ( urethra ) V 82 ( bladder ) EPS ( post massage) V83 ( post massage ) A8 x (see Table 8.1113) - blocker if obstruction

--

fluid

prostatic fluid

No investigations unless Hx , P/E (same as Category II) considering ABx for Symptom score ( NIH -CPSI’) elevated PSA or infertility 4 glass lest Consider psychological

-

assessment Supportive measures ABx if ABx naive Multimodal therapy ( UP0 IN1) including:

.

ABx if elevated PSA. infertility, or planned prostate biopsy

o- btockers

-

Anti inflammatories Phytotherapy ( quercetin, cernilton )

' NIH

-CPSI: National Institute of Health Chronic Prostatitis Symptom Index

r *s LJ

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U17 Urology

Toronto Notes 2023

Epididymitis and Orchitis Etiology • common infectious causes sterile epididymitis • immunocompromised

It unsure between diagnoses of epididymitis and torsion , always go to OR Remember: torsion >6 h has poor prognosis

Clinical Features • sudden onset scrotal pain and swelling ± radiation along cord to flank • scrotal erythema and tenderness • Prehn’s Sign ( relief of pain with lifting of testicle )

• fever • storage symptoms, purulent d /c • reactive hydrocele Investigations

• U /A, urine C&S • ± urethral d /c: Gram stain /culture • if diagnosis uncertain , MUST rule out testicular torsion ( U /S Doppler ) • U /S can confirm diagnosis with increased vascularity Treatment

• rule out torsion (see Table 23, Investigations , U 32 ) • see Table H , UI 3 for Mix therapy • scrotal support , bed rest , ice, analgesia Complications

• if severe -> testicular atrophy • 30% have persistent infertility problems • inadequately treated acute epididymitis may lead to chronic epididymitis or epididymo orchitis

-

Urethritis Etiology

• infectious or inflammatory (e.g. reactive arthritis ) Table 10. Infectious Urethritis: Gonococcal vs. Non - Gonococcal

-

Gonococcal

Non Gonococcal

Causative Organism

Heissetio gonorrhoeae

Usually Chlamydia twcliomatis

Diagnosis

Hx ol sexual contact , thick , profuse, yellow grey purulent d/c. LUTS Gram stain |GN diplococci), urine PCR and/ or culture from urethral specimen

Hr of seiual contact, mucoid whitish purulent die,'Storage LUTS Gram stain demonstrates >4 PMN/ oil immersion field, no evidence of H. gonorrhoeae, urine PCR and/or culture Irom urethral specimen See Table 8. U13

Trcalmenl

See Table 8. U 13

Reactive Arthritis (formerly known as Reiter 's syndrome) Urethritis, uveitis (or conjunctivitis), and arthritis (can’t pee, can’t see, can’t climb a tree)

If culture negative or unresponsive to treatment consider: Ureaptasma urealyticum, Mycoplasma genitalium. Trichimonas vaginalis HSV, or adenovirus

.

-

r i c.J

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U18 Urology

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Stone Disease Epidemiology

• prevalence: ~8% and increasing • M:l;*2: l • peak incidence 30-50 yr of age

• recurrence rate: 10% at 1 yr, 50% at 5 yr, 60-80% lifetime • calcium oxalate most common stone type; others include uric acid, struvite, calcium phosphate, cystine, etc. Risk Factors

• hereditary: RTA, glucose- 6-phosphate dehydrogenase deficiency, cystinuria (defect in the proximal renal tubular reabsorption of cystine), COLA syndrome (defect in resorption of cystine, ornithine, lysine and arginine), xanthinuria, hyperoxaluria, etc. • lifestyle: minimal fluid intake ( most common risk factor ); excess vitamin C, oxalate, purines, calcium ; living or working in extreme heat • medications: loop diuretics (furosemide, bumetanide), acetazolamide, topiramate, zonisamide, indinavir, acyclovir, sulfadiazine, triamterene • medical conditions: UTT (with urea-splitting organisms: Proteus, Pseudomonas, Providencia, Klebsiella , Mycoplasma, Serratia , S. aureus), myeloproliferative disorders, inflammatory bowel disease, gout, DM, hypercalcemia disorders ( hyperparathyroidism , tumour lysis syndrome, sarcoidosis, histoplasmosis), obesity ( BM1 >30) bladder stones: bladder outlet obstruction, catheters, neurologic disease, DM ( requires different • management)

Key Points in Stone Hx Diet (especially FLUID INTAKE) • Predisposing medical conditions • Predisposing medications • Previous episodes/investigations/

-

treatments • FMHx (1st degree relative)

The Four Narrowest Passage Points for Upper Tract Stones • UPJ

Clinical Features

.

flank pain from renal capsular distention ( non-colicky) severe waxing and waning pain that can radiate from flank to groin, testis, or tip of penis from distended collecting system or ureter (ureteral colic) • writhing, persistent discomfort, nausea, vomiting, hematuria (90% microscopic), diaphoresis,

• Under vas deferens/broad ligament UVJ

• urinary obstruction -> upstream distention -> pain «

Pelvic brim

.

tachycardia, tachypnea

• occasionally symptoms of trigonal irritation (frequency, urgency), if the stone is in the lower ureter • bladder stones result in: storage and voiding LUTS, terminal hematuria, suprapubic pain • if fever, rule out concurrent pyelonephritis and /or obstruction • can also present incidentally, without any pain or symptoms Table 11. Differential Diagnosis of Renal Colic GU

Abdominal

Neurological

Pyelonephritis Ureteral obstruction from other cause: UPJ obstruction , dot colic secondary to gross hematuria , sloughed papillae Gynaecological: ectopic pregnancy, torsion/ rupture of marian cyst , PID

Abdominal aortic aneurysm (AAA )

Radiculitis ( 11): herpes zoster, nerve root compression Neuromuscular ( MSK ) back pain

Bowel ischemia Pancreatitis Other acute abdominal crisis (appendicitis, cholecystitis, diverticulitis)

Radiopaque

Location of Stones

• calyx; may cause flank discomfort , persistent infection , persistent hematuria , but if non - obstructive,

likely remains asymptomatic pelvis: tend to cause obstruction at UPJ, may cause persistent infection • ureter: 2 cm • Staghorn • UPJ obstruction with correction of obstruction • Calyceal diverticulum • Large cystine stones (poorly fragmented with SWL) • Anatomical abnormalities preventing

Investigations

• Failure of less invasive modalities

I [ Dissolution therapy ]

SWL Ureteroscopy

PCNL Stent/Nephrostomy

retrograde access

Table 12. Investigations for Renal Stones

. .

CBC U/ A Urine CAS

-

KUB x ray

-

CT Scan (non contrast)

Abdominal Ultrasound

Uric Acid

Cystoscopy

PTH, 24 h urine x 2 for volume, Cr Ca 2\ Na •, PO 1-, Mg 2’, oxalate, citrate, ± cystine

*

Who gets it ?

Most

fveryone

Why is it done ?

May show signs ol infection,! sensitivities

Presence of leukocytes NOT always indicative of infection

Cautions

90 % ol stones arc radiopaque Good for follow - up Helps rule out uric acid stones (not visible on x -ray)

.

First episode renal colic

Able losce adjaccnl organs exact location of stone(s) plan for surgery, etc.

.

.

Can assess density olstone Gold standard diagnostic lest

Paediatric cases

i Those concerning

pregnant patients, recurrent stone formers, unsure of Dx

lor bladder stone

Identify and follow up stone without radiation exposure Visualize hydronephrosis

Visualize bladder Suspected uric acid Can provide access stone (urine PH to ureter for stent placement if

Stone not seen on KUB

.

Recurrent Capstone formers paediatric cases

Need lo rule out metabolic cause lor stones

2 L/d For calcium stones: Increase citrate in diet, reduce salt, moderate oxalate- rich foods, weight loss Calcium oxalate: thiazides potassium citrate,t allopurinol M ixed calcium and struvite: ASx (stone must be removed to treat infection)

.

Increased fluid intake Alkalinization ol mine to pH 6.5 to 1 (potassium citrate, sodium bicarbonate) t allopurinol

Be carelul not be make urine too alkaline (pH >7). can result in calcium phosphate stones

Complete stone clearance ABxlor 6 wk Regular follow - up urine cultures

Aggressive stone disease seen in children and young adults Recurrent stone formation,

FMHx

Often staghorn calculi Faintly radiopaque on KUB x ray

-

Positive urine sodium nitroprusside lest, urine chromatography lor cystine

Increased fluid intake (3 - 4 L of urire/ d ) Alkalinizc urine (bicarbonate, potassium citrate),penicillamine/ o mercaptopropionylglycine or Captopril (form complex with cystine) SWL not efleclive

-

+

Can observe selected, asymptomatic renal stones

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U 21 Urology

Toronto Notes 2023

Urological Neoplasms Approach to Renal Mass [ Ultrasound ] (

T Cystic

I

]

Solid

there is controversy over optimal management of small renal masses

)

r Hypoechoic

No calcification Thin wall

( exclude

Septated

angiomyolipomal

1f

[

Stop

I

T

1f

]

Percutaneous needle biopsies of cystic renal masses may lead to peritoneal seeding

CT

Dense Calcified

Small mass (4 cm)

CT with contrast’ Possible aspiration or biopsy

Tuberous Sclerosis

• Syndrome characterized by mental

I •

T

Surgery

(

)

|

Surveillance

Surgery

J

Possible surveillance

retardation, epilepsy, and adenoma sebaceum 45-80% of patients aIso present with angiomyolipomas which are often multiple and bilateral

.

Figure 13. Workup of a renal mass 'Imaging modality may be different in cases of contrast allergy or elevated creatinine

APPROACH TO SMALL SOLID RENAL MASSES • Initial workup: kidney function (creatinine, eGl;R), chest x- ray, contrast CT or MR1, ± renal biopsy • Limited life expectancy: watchful waiting • < 2 cm: active surveillance with imaging q 3-6 months, proceed to intervention if growth >2 cm, or growth >0.5 cm / vear, or patient preference • 2-4 cm: active surveillance or definitive therapy (biopsy + thermal ablation or partial nephrectomy, if

feasible)

Benign Renal Neoplasms CYSTIC KIDNEY DISEASE

• simple cysts: usually solitary or unilateral • very com mon: up to 50 % at age 50 • usually incidental finding on abdominal imaging • Bosniak Classification is used to stratify for risk of malignancy based on cyst features from contrast CT • polycystic kidney disease renal failure in infants • autosomal recessive: multiple bilateral cysts , often leading to early • autosomal dominant: progressive bilateral disease leading to H 'I' N and renal failure, adult onset • medullary sponge kidney: cystic dilatation of the collecting ducts usually benign course, but patients are predisposed to stone disease

-

• von Hippel - Lindau syndrome: multiple bilateral cysts and /or renal cell carcinomas ( 50% incidence of RCC ) renal cysts, cerebellar, spinal and retinal hemangioblastomas, pancreatic and epididymal cysts, pheoch romocy tomas Table 14. Bosniak Classification of Renal Cysts Class

Features

Risk of Malignancy

Management Plan

I (simple cyst)

Round, no septa /calcificationsf

Near zero

No follow - up

enhancement, homogeneous, 20 H U

5-20%

Follow -up,imaging qG -12 mo surgical resection if lesion evolves

III (complex cyst)

Irregular,thickened, calcified septa with enhancement

IV (likely malignant)

.

.

.

Irregular, thickened, calcified septa with enhancement, enhancing soft tissue components

rT

.

> 50%

Surgical resection

' growing literature suggesting

might be lower

" growing literature suggesting surveillance might be safe

> 90%

Surgical resection

LJ

+

-

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U22 Urology

Toronto Notes 2023

Gerota's fascia

Table 15. Benign Renal Masses Renal Oncocytoma

Angiomyolipoma ( Renal Hamartoma ) Epidemiology

H 20 = associated with tuberous sclerosis (especially if multiple, recurrent)

T4

Clonal neoplasm consisting of blood vessels (angio ) smooth Spherical, capsulated with possible central scar Histologically organized aggregates of eosinophilic cells muscle ( myo- ) and fat ( lipoma) Hay extend into regional lymphatics and other organs and originating from intercalated cells ol collecting duct

Diagnosis

Incidental finding on CT Negative attenuation ( - 20 HU) on CT is pathognomonic Rare presentation of hematuria, flank pain, and palpable mass (same as RCC)

Adrenal

1 gland '

.

Characteristics

.

-r

3-7% of renal tumours H>F Oncocytomas also found in adrenal, thyroid, and parathyroid glands

£

Vein

become symptomatic

Management

Incidental finding on CT Difficult to distinguish from RCC on imaging - treated as RCC until proven otherwise Biopsy may be performed to rule out malignancy

Hay considersurgical excision or emboliration if Sunrei lance for most symptomatic (pain,bleeding) or higher risk of bleeding (e.g. Partial radical nephrectomy for large masses pregnancy) Potential role for mechanistic target of rapamycin (mTOR) inhibitors in unresectable/metastatic disease Follow with serial U/S

Artery >1

r CT

Ireter

Renal capsule

Renal cortex / Renal medulla

SCarfy Vanderlee

^

Figure 14. RCC staging

Malignant Renal Neoplasms RENAL CELL CARCINOMA

Etiology • cause unknown • originates from proximal convoluted tubule epithelial cells in clear cell subtype ( most common ) • hereditary forms seen with von Hippel - Lindau syndrome and hereditary papillary renal carcinoma Epidemiology • 85% of primary malignant tumours in kidney, ~3% of all malignancies M:l =1.5:l • peak incidence at ages 50 - 60 Pathology

histological subtypes: clear cell (75-85%), papillary ( 10-15%), chromophobe (5-10%), collecting duct (40 y/o must

progression : however, it is also associated with a hgh rate of adverse events. More research is needed to define optimal doselregimen. Methods: BeviewofOvid Med me. Cochrane Central

Deep Muscle

Register of Controlled Trials. Cochrane Database

.

of SB Health Technology Assessment. National Health Sciences Economic Evaluation, databaseof Jtbstractof Review of Effects for studies on HMIBC interventions , including intravesical therapy. Results: 3CG is superior in prevention of bladder cancer recurrence compared to no intravesical therapy. BCG is supenor to doxorubicin, eprubieix and mitomycinin prevention of bladder cancer recurrence.

Perivesical Fat

.

Pelvic Wall or Abdominal Wall

>

5

Submucosa

1

.

Mucosa

Prostate

1 5

See landmark Urology Inals table for more information on 10- yr outcomes for patients with localized prostate cancer after monitoring, surgery, or radiotherapy.

r -i LJ

Figure 16. UC of bladder

+

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Toronto Notes 2023

U26 Urology Treatment

Non- muscle invasive Low risk (Ta low - giade )

TURBT + intravesical chenio Follow up with cystoscopy and cytology

Muscle invasive

.

T2 T3 Radical cystectomy + PLND T urinary diversion (see Figure 15)

Advanced/Metastatic

.

T4, N+ M+

Chemo » radiation • cystectomy

- Radical cystectomy (male): Removal ot bladder and prostate en bloc

Intermediate risk ( Multifocal, recurrent Ta )

TURBT intravesical chento BCG (lyr ) High risk (T1, Tis, Ta high-grade )

TURBTiintravesical chento

-

Repeat TURBT (2 6 wk )


iliac nodes) » hematogenous Treatment

• wide surgical excision with tumour-free margins ( dependent on extent and area of penile involvement ) ± lymphadenectomy • consider less aggressive treatment modalities in CIS (cryotherapy, laser therapy, etc.), if available

rn LJ

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Scrotal Masses Varicocele Grading Grade 1: palpable only with V alsalva

Table 22. Differentiating between Scrotal Masses

manoeuvre

Palpation

Additional Findings

Torsion

Diffuse tenderness Horizontal lie of testicle

Absent cremaster reflex, negative Prehn's sign

Epididymitis

Epididymal tenderness

Present cremaster reflex , positive Prehn's sign

Orchitis

Diffuse tenderness

Present cremaster reflex, positive Prehn’s sign

Pain

Condition

Hematocele

Diffuse tenderness

Nolransillumination

Hydrocele

testis not separable from hydrocele, cord palpable

transillumination. Hx of trauma

Spermatocele

testis separable from spermatocele cord palpable

Transillumination

Varicocele

Bag of worms

Ho liansilluminalion increases in sice with valsalva decrease in size if supine

Testis separable from hernia, cord not palpable, cough impulse may transmit, may be reducible

No transillumination

.

Indirect Inguinal

-(

Tumour

- ( if hemorrhagic)

if strangulated)

Grade 2: palpable without Valsalva Grade 3: visible through scrotal skin

Suspect a Retroperitoneal Mass/ Process in a Patient with a Varicocele

if; Acute onset Right sided (isolated) Palpable abdominal mass Does not reduce while supine

. .

Hard lump /nodule Diffuse swelling

Generalized/Dependenl Edema

Often postoperative or immobilized, checkfor liver dysfunction

Idiopathic

Table 23. Benign Scrotal Masses Type

Varicocele

Spermatocele

Definition

Dilatation and tortuosity of

A benign, sperm filled epididymal retention cyst

pampiniform plexus

Etiology

Hx/P / E

15% of men Due to incompetent valves in the testicular veins 90% left -sided

"Bag of worms"

Often painless Pulsates with Valsalva

-

Multiple theories,

including: Distal obstruction Aneurysmal dilations of the epididymis Agglutinated germ cells

Hydrocele

Testicular Torsion

Inguinal Hernia

Collection of serous fluid that results from a defect or irritation in the tunica vaginalis Usually idiopathic Found in 5 -10% testicular tumours

Twisting ol the testicle causing venous occlusion and engorgement as well as arterial ischemia and infarction

Protrusion of abdominal contents through the inguinal canal into the

Trauma Cryptorchidism "Bell clapper deformity '' Many occur in sleep |50%) Necrosis of glands in 5 - 6 h

Indirect ( through internal ting, often intoscrotum): congenital Direct (through external ting rarely into scrotum): abdominal muscle

Associated with trauma/ infection Communicating: patent processus vaginalis, changes size during day { paediatric) Non - communicallng: non-patent processus vaginalis (adult)

scrotum

.

weakness

.

Non - tender, cystic mass Transilluminates

Non- tender,intrascrotal mass Cystic Transilluminates

Acute onsetsevere scrotal pain swelling Asmall bulge in the groin thatmay Glupsets cases increase in size with Valsalva and disappear when lying down Retracted and transverse testicle Canpiesentasaswollenor (horizontal lie) enlarged scrotum Negative Phren's sign Discomfort or sharp pain Absent cremasteric reHex especially when straining, lifting, or exercising

P/E U/S to rule out tumour

U/ S to rule oul tumour

U / S Doppler with probe over testicular artery Decrease uptake on 99mlcpertechnetate scintillation scan [ doughnut sign)

Hx and P / E Invagination of the scrotum Valsalva

Conservative

Emergency surgical exploration and bilateral orchiopexy Definitive diagnosis NOT necessary to

Surgical repair

Investigations

P/ E Valsava

Treatment

Conservative Conservative Surgical ligation of testicular veins Excise if symptomatic Percutaneous vein occlusion ( coils) Repair mayimprove sperm count/ motility

Needle drainage (high rate of surgical recurrence)

Surgical

take to OR Orchiectomy if absent restoration of flow to testicle

rn

TORSION OF TESTICULAR APPENDIX •

Signs and Symptoms • •

LJ

twisting of testicular/epididymal vestigial appendix

clinically similar to testicular torsion , but vertical lie and cremaster rellex preserved “

blue dot sign" blue infarcted appendage seen through scrotal skin in children (can usually be palpated as small, tender lump)

Indications for Treatment of Varicocele • Impaired sperm quality or quantity • Pain or dull ache affecting OOL Affected testis fails to grow in adolescents • Cosmetic indications ( especially in adolescents)

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Treatment

analgesia - most will subside over 5-7 d • surgical exploration and excision if refractory pain

«

Acute scrotal swelling/pain in young boys is torsion until proven otherwise

HEMATOCELE • trauma

with bleed into tunica vaginalis

• U /S helpful to exclude fracture of testis which requires surgical repair

Transilluminatlon refers to light being transmitted through tissue (l.e. due to

Treatment • ice packs, analgesics , surgical drainage, and hydrocele repair

access fluid)

Penile Complaints Table 24 . Penile Complaints Peyronie's Disease Type Definition

Etiology

Prolonged erection lasting > 4 h in the fibrous thickening of tunica absence of sexual excitement/ desire albuginea

Acquired curvature of penile shaft secondary to

Paraphimosis

Phimosis

Premature Ejaculation

Retracted foreskin (behind glans penis) that cannot be reduced

Inability to retract foreskin over glans penis

Ejaculation prior to when one or both partners desire it either before or soon after intimacy

.

Etiology unknown Irauma /repealed inflammation Familial predisposition Associated with DM. vascular disease, autoimmunity Dupuytrcn's conliacturc erectile dysfunction, urethral instrumentation

50% idiopathic Ischemic (common): Thromboembolic (sickle cell) Non lschemic: Trauma Medicalions Neurogenic

Iatrogenic (post cleaning/ instrumentation) Irauma Infectious (balanitis balanoposthitis) sexual activity

Congenital ( 90% natural separation by age 3) Balanitis Poor hygiene

Psychological factors Primary : no period of acceptable control Secondary: symptoms after a period of control, not associated with general medical condition

Penile curvature / shortening Pain with erection Poor erection distal to

Painful erections signs olnecrosis Note: non ischemic {high flow ) priapism may present without

Painful, swollen glans penis, foreskin Constricting band proximal to corona Dysuria, decreased urinary stream in children

limitation and pain when attempting to retract foreskin

Ejaculatory latency el min Inability to control or delay ejaculation Psychological distress

..

Hx/ P/E

Priapism

Differential of a Benign Scrotal Mass

plaque

-

pain

Investigations

Hx and P / E

Treatment

Supportive measures: PDE5 inhibitor for ED NSAID for pain Medical management:

Traction device Intralesional verapamil Intralesional collagenase Surgical management: Incision /excision ofplaque Plication surgery Penile prosthesis

.

.

Balanoposthitis (infection of prepuce)

Hx and P/ E Cavernosal blood gas analysis Doppler U/ S of the penis

Hx and P/E

Hx and P/E

Hx and P /E Testosteronelevels if in conjunction with impotence

Treat reversible

Manual pressure ( with analgesia) Dorsal slit Circumcision (urgent or elective to prevent recurrence)

Proper hygiene Topical corticosteroids Dorsal slit

Rule out medical condition Address psychiatric concerns,counselling

Circumcision

Medication: SSRI or clomipramine Topical lidocaine -

causes High-flow:

-

Self limited Consider arterial embolication Low - flow: Needle aspirated decompression

prilocaine

Phenylephrine Inlracorporcal injection q3 -5 min Surgical shunt no response within 1 h

Erectile Dysfunction Definition • consistent ( >3 mo duration ) or recurrent inability to obtain or maintain an adequate erection for

satisfactory sexual performance

HIS BITS Hydrocele Infection ( epididymitis/orchitis) Sperm (spermatocele) Blood (hematocele) Intestines (hernia)

Torsion Some veins (varicocele)

mm &

wS '

1. Fibrous plaque 2. Tunica albuginea 3. Corpus cavernosum 4. Buck's fascia 5. Corpus spongiosum

6. Urethra

dbjuno Li

Figure 20. Peyronie’s disease

rn LJ

Physiology • erection involves the coordination of psychologic , neurologic , hemodynamic , mechanical, and endocrine components • nerves: sympathetic (TU -L2), parasympathetic (S2- 4 ), somatic (dorsal penile / pudendal nerves (S2-4 ))

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U34 Urology

.

erection (“ POINT")

.

1. arteriolar dilatation 2. sinusoidal smooth muscle relaxation -> increased arterial inflow and compression of penile venous drainage (decreased venous outflow ) emission ("SHOOT")

parasympathetics > NO release > increased cGMP within corpora cavernosa leading to:

• sensory afferents from glans

secretions from prostate, seminal vesicles, and ejaculatory ducts enter prostatic urethra (sympathetics) • ejaculation (“SHOOT ”) bladder neck closure (sympathetic ) spasmodic contraction of bulbocavernosus and pelvic floor musculature (somatic)

• detumescence sympathetic nerves, norepinephrine, endothelin - 1 -> arteriolar and sinusoidal constriction -> penile flaccidity

Erections POINT AND SHOOT parasympathetics ~ point sympathctics/somatics - shoot

#

Etiology ("IMPOTENCE’’) Iatrogenic: pelvic surgery, pelvic

radiation Mechanical: Peyronie's, post - priapism Psychological: depression, stress, anxiety, PTSD. widower syndrome Occlusive: arterial HTN, DM, smoking, hyperlipidemia . PVD, impaired venooedusion Trauma: pcnile/pclvic bicycling Extra factors: renal failure, cirrhosis COPD. sleep apnea, malnutrition Neurogenic CNS ( e.g. Parkinson's. MS, spinal cord injury, Guillain- Barre, spina bifida , stroke) , PNS (e .g. DM. peripheral neuropathy) Chemical: antihypertensives, sedatives, antidepressants, antipsychotics. anxiolytics, anticholinergics, antihistamines, antiandrogens (including 5- a reductase inhibitors ), statins GnRH agonists, illicit drugs Endocrine: DM. hypogonadism, hyperprolactinemia, hypo/hyperthyroid

.

Classification Table 25. Classification of Erectile Dysfunction Psychogenic

-

less common Sudden

Prevalence Onset

Organic

-

More common Gradual

Frequency

Sporadic

All circumstances

Variation

With partner and circumstance

No

Older

Younger

Age

.

Organic Risk Fadors (HTN, DM dyslipidemia)

No organic risk factors

Nocturnal Morning Erection

Present

Risk factors present

.

.

Absent

-

'Combination can co cxist

Diagnosis • complete Hx ( include sexual , medical, and psychosocial aspects) • self-administered questionnaires (e.g. International Index of Erectile function, Sexual Health Inventory for Men Questionnaire, ED Intensity Scale, ED Impact Scale ) • focused P/ E , including vascular and neurologic examinations, secondary sexual characteristics

• lab investigations, dependent on clinical picture • risk factor evaluation: fasting blood glucose or HbAlc, cholesterol profile optional: T'SH, CBC, VIA, testosterone ( free and total ), prolactin, LH specialized testing including nocturnal penile tumescence monitoring usually unnecessary • • evaluation of penile vasculature only relevant with past history of trauma ( e.g. pelvic fracture ) Treatment

be managed by family physician, see sidebar for when to refer • consider early sexual counselling referral • must fully inform patient / partner of options, benefits and complications • non - invasive • lifestyle changes (alcohol, smoking, physical activity), psychological ( sexual counselling and education) change precipitating medications treat underlying causes ( DM , CVD, HTN , endocrinopathies) • can often

• minimally invasive • oral medication (see Common Medications, V 47 ) sildenafil, tadalafil, vardenafil, avanafil (not available in Canada ): inhibits PDE5 to increase intracavernosal cGMP levels all four have similar effectiveness, difference in onset of action is not clinically significant tadalafil has longer half life, no cyanopsia , and can be taken on empty or full stomach tadalafil should be taken when needed instead of a set daily dose • vacuum devices: draw blood into penis via negative pressure, then put ring at base of penis MUSE: male urethral suppository for erection - vasoactive substance ( PGE 1) capsule inserted into urethra insufficient evidence supporting low intensity shockwave therapy • in patients with hypogonal testosterone, treat with dual testosterone and PDE5 inhibitor

-

Testosterone deficiency is an uncommon cause of ED

PDE5 inhibitors are contraindicated in patients on nitrates/nitroglyccrin due to severe hypotension

Initial trial of MUSE : or intracavernosal injection should be done under medical supervision

-

-

-

• invasive intracavernous vasodilator injection /self-injection triple therapy ( papaverine, phentolamine, PGEI ), bimix ( papaverine and phentolamine ) or PGE1

Penile vascular abnormalities may be a marker of risk for CV disease. Young men with vascular ED have 50x higher risk of having a C V event

alone complications: priapism ( overdose ), fibrosis of tunica albuginea at site of repeated injections ( Peyronie’s plaque ), and injection site injuries ( pain, hematoma , etc.) • surgical penile implant ( last resort ): malleable or inflatable

uJ

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Trauma • see Emergency Medicine. Elt 7

Renal Trauma Classification According to Severity • minor • contusions and superficial lacerations/ hematomas: 90% of all blunt traumas, surgical exploration

seldom necessary

• major

•

laceration that extends into medulla and collecting system, major renal vascular injury, shattered kidney

Etiology

• 80% blunt ( MVC, assaults, falls) vs. 20% penetrating (stab wounds and gunshots) Clinical Features

• mechanism of injury raises suspicion • can be hemodynamically unstable secondary to renal vascular injury and /or other sustained injuries: ABC • upper abdominal tenderness, flank tenderness, flank contusions, lower rib/ vertebral transverse process fracture

*

Investigations

. VIA

hematuria: requires workup but degree does not correlate with the severity of injury • imaging • CT ( contrast , triphasic) if patient stable: look for renal laceration , extravasation of contrast, retroperitoneal hematoma, and associated intra-abdominal organ injury Staging (does not necessarily correlate well with clinical status)

• 1: contusion / hematoma • 11: < 1 cm laceration without urinary extravasation • III : > 1 cm laceration without urinary extravasation • IV: laceration causing urinary extravasation and /or main arterial or vein injury with contained hematoma • V: shattered kidney or avulsion of pedicle Treatment

-

• microscopic hematuria + isolated well-staged minor injuries > no hospitalization • gross hematuria + contusion / minor lacerations -> hospitalize, bedrest , repeat CT if bleeding persists • surgical intervention / minimally Invasive angiography and embolization ( majority now managed

conservatively, nonoperatively ) absolute indications hemorrhage and hemodynamic instability relative indications non -viable tissue and major laceration urinary extravasation vascular injury

» expanding or pulsating perirenal mass

» laparotomy for associated injury • follow- up with U /S or CT before discharge, and at 6 wk

Complications

• HTN in 5% of renal trauma

Bladder Trauma Classification n

• contusions: no urinary extravasation, damage to mucosa or muscularis

LJ

• intraperitoneal ruptures: often involve the bladder dome • extraperitoneal ruptures: involve anterior or lateral bladder wall in full bladder Etiology

+

• blunt ( MVC, falls, and crush injury) vs. penetrating trauma to lower abdomen , pelvis, or perineum • blunt trauma is associated with pelvic fracture in 97% of cases

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Clinical Features

• abdominal tenderness, distention, peritonitis, and inability to void

• can be hemodynamically unstable secondary to pelvic fracture, other sustained injuries: ABCs • suprapubic pain Investigations

• U /A: gross hematuria in 90% of cases • imaging (including CT cystogram and post -drainage films for extravasation) Treatment

• penetrating trauma -> surgical exploration • contusion > urethral catheter until hematuria completely resolves • extraperitoneal bladder perforations -> typically non -operative with foley insertion, and follow with cystograms surgery if: infected urine, rectal / vaginal perforation, bony spike into bladder, laparotomy for concurrent injury, bladder neck involvement , persistent urine leak , and failed conservative management • intraperitoneal rupture usually requires surgical repair and suprapubic catheterization Complications • complications of bladder injury itself are rare • mortality is around 20%, and is usually due to associated injuries rather than bladder rupture

Urethral Injuries Etiology • posterior urethra common site of injury is junction of membranous and prostatic urethra due to blunt trauma,

MVCs, pelvic fracture shearing force on fixed membranous and mobile prostatic urethra

• anterior urethra

straddle injury can crush bulbar urethra against pubic rami

• other causes iatrogenic ( instrumentation, prosthesis insertion ), penile fracture, masturbation with urethral

manipulation

• always look for associated bladder rupture Clinical Features

• blood at urethral meatus • high riding prostate on DRE • swelling and butterfly perineal hematoma • penile and/or scrotal hematoma • sensation of voiding without U /O • distended bladder

-

Investigations

• generally will perform RUG or cystoscopy prior to attempt at catheterization

All patients with suspected urethral injury should undergo RUG

Treatment

• simple contusions no treatment

• partial urethral disruption very gentle attempt at catheterization by urologist with no resistance to catheterization > l oley x 2 3 wk with resistance to catheterization -> suprapubic cystostomy or urethral catheter alignment • periodic flow rates/urethrograms to evaluate for stricture formation

-

• complete disruption

immediate repair if patient stable, delayed repair if unstable (suprapubic tube in interim )

Complications

• stricture rT LJ

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Infertility and Andrology Definition • failure to conceive after 1 yr of unprotected and properly timed intercourse • incidence 15% of all couples (35 40% female, 20% male, 25 30% combined )

-

-

Female Factors Majority of antenatal hydronephroses resolve during pregnancy or within the first year of life

• see Gynaecology. GY 23

Male Factors

ft

Reproduction .Male HPTA

•

pulsatile GnRH from hypothalamus acts on anterior pituitary' stimulating release of LH and FSH LH acts on Leydig (interstitial ) cells -> testosterone synthesis and secretion I SH acts on Sertoli cells -> structural and metabolic support to developing spermatogenic cells FSH and testosterone support germ cells (responsible for spermatogenesis) sperm route: epididymis -> vas deferens -> ejaculatory ducts -> prostatic urethra

Etiology • idiopathic (40 -50% infertile males) • testicular varicocele (35 40% infertile males) tumour

-

congenital ( Klinefelter’s triad: small, firm testes, gynecomastia, and azoospermia ) post- infectious (epididymo-orchitis, STls, mumps)

uncorrected torsion cryptorchidism (< 5% of cases) • obstructive iatrogenic (surgery:see below) infectious ( gonorrhea, chlamydia ) trauma

congenital ( absence of vas deferens, CF) bilateral ejaculatory duct obstruction, epididymal obstructions Kartagener’s syndrome ( autosomal recessive disorder causing defect in action of cilia ) • endocrine (see Endocrinology. E 51) • HPTA (2-3%) e.g. Kallmann's syndrome (congenital hypothalamic hypogonadism ), excess prolactin, excess androgens, excess estrogens • other • retrograde ejaculation secondary to surgery medications prior exposure to chemotherapy or pelvic radiation • drugs: cannabis, cocaine, tobacco, alcohol • increased testicular temperature (sauna, hot baths, tight pants, or underwear ) chronic disease: e.g. liver, renal History

• age of both partners

• medical: past illness, DM, trauma, CF, genetic syndromes, STls, cryptorchidism • surgical: vasectomy, herniorrhaphy, orchidopexy, prostate surgery • fertility: pubertal onset, previous pregnancies, duration of infertility, treatments • sexual: libido, erection /ejaculation , timing, frequency FMHx • medications: cytotoxic agents, GnRH agonists, anabolic steroids, nitrofurantoin, cimetidine, sulfasalazine, spironolactone, a blockers Hx: alcohol , tobacco, cocaine, cannabis , school performance/ learning disabilities ( suggestive of social • Klinefelter syndrome) • occupational exposures: radiation, heavy metals

.

-

Physical Exam

• general appearance: sexual development, gynecomastia, obesity, pubic hair

Common Terminology on SA Teratospermia: Abnormal morphology

Asthenospcrmia: Abnormal motility Oligospermia: Decreased sperm count Azoospermia: Absent sperm in semen Mixed types: e.g. oligoasthenospermia

Mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with congenital bilateral absence of vas deferens and epididymal cysts, even if patient manifests no symptoms of CF

WHO Guidelines Male Infertility Factors

SPERM COUNT Systemic factor/Smoking Psychological illness Endocrinopathy Retrograde ejaculation Medications Chronic disease Obstructive Unexplained

Narcotics Testicular

o

Normal Semen Values • Volume:1.5-7.6 mL • Concentration: >15 million sperm/mL • Morphology: 30% normal forms • Motility: >40% adequate forward progression • Liquefaction: complete in 20 min pH: 7.2-78 WBC: 50% epispadias (least severe) urethra opens on dorsal aspect of the penis, often associated with penile curvature Etiology • represents failure of closure of the cloacal membrane, resulting in the bladder and urethra opening directly through the abdominal wall Epidemiology • rare: incidence 1 in 30000, M:F=3:1 predominance • high morbidity -> multiple reconstructive surgeries, incontinence, infertility, reflux Treatment n

•surgical correction at birth

u I

•later corrections for incontinence, VUR, and low bladder capacity may be needed

+

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Wilms’ Tumour (Nephroblastoma) Etiology

• arises from abnormal proliferation of metanephric blastema Epidemiology

• 5-10: 5% of all childhood cancers, 5% bilateral, 10% associated with congenital malformation syndromes • most common primary malignant renal tumour of childhood • average age of incidence is 3 yr Clinical Features • abdominal mass: large, firm, unilateral (80%) • HTN (25%) • flank tenderness (30-40%) • microscopic hematuria (12-25%) • nausea /vomiting Treatment • always investigate contralateral kidney and renal vein ( for tumour thrombus) unilateral disease: radical nephrectomy or nephron -sparing surgery ± radiation ± chemotherapy • bilateral disease: nephron-sparing surgery following neoadjuvant chemotherapy

Associated Syndromes of Wilms’ Tumour • Wilms' aniridia genital anomaly retardation • Beckwith Wiedemann syndrome • Dcnys Drash syndrome

-

-

Prognosis

• Syr survival 80%

Cryptorchidism/Ectopic Testes Definition

• abnormal location of testes somewhere along the normal path of descent (external inguinal ring > inguinal canal > abdominal ) • Denis Browne pouch ( between external oblique fascia and Scarpa’s fascia ) most common • differential diagnosis: retractile testes atrophic testes disorders of sexual differentiation ( bilateral impalpable gonads) Epidemiology

• 1.0- 4.6% of full term newborns, increased risk in preterms 0.7 1.0% at I yr

.

-

Treatment

• orchiopexy • hormonal therapy not proven to be of benefit over standard surgical treatment

Normal Testicular Development and Descent in Utero • 2 nd mo: Testide begins to form • 4th mo: Begins to take on its normal appearance and migrates from its origin at the kidney to the internal inguinal ring 7th mo: The testis, surrounded In peritoneal covering, begins to descend through the internal ring, inguinal canal, and external ring to terminate in the scrotum

.

Prognosis

• reduction in fertility

-

untreated bilateral cryptorchidism: 100% infertility, due to Leydig and germ cell loss

• paternity rates: 33-65%, 90% , and 93% in formerly bilateral cryptorchid , formerly unilateral

cryptorchid, and normal men, respectively • increased malignancy risk intra-abdominal > inguinal surgical correction facilitates testicular monitoring and may reduce malignancy risk • increased risk of testicular torsion ( reduced by surgical correction )

Disorders of Sexual Differentiation Definition formerly known as intersex disorders: considered social emergency

• abnormal genitalia for chromosomal sex due to the undermasculinization of males or the virilization

of females

Classification 1.46 XY DSD • defect in testicular synthesis of androgens androgen resistance in target tissues • palpable gonad 2.46 XX DSD • most due to GVH ( 21 hydroxylase deficiency most common enzymatic defect ) -> shunt in steroid biosynthetic pathway leading to excess androgens

-

A phenotypic male newborn with bilateral non- palpable testicles should be considered 46 XX with salt wasting CAH and must undergo proper evaluation prior lo discharge

-

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U43 Urology

-

undiagnosed and untreated CAH can be associated with life threatening electrolyte abnormalities in the newborn (salt wasting CAH ) 3. ovotesticular DSD 4. mixed gonadal dysgenesis (46 XY /45 XO most common karyotype) » presence of Y chromosome -> partial testis determination to varying degrees

-

Diagnosis

• thorough T'MHx noting any consanguinity • maternal Hx, especially medication /drug use during pregnancy ( maternal hyperandrogenemia ) • P/ E: palpable gonad ( = chromosomal male), hyperpigmentation , evidence of dehydration , HTN,

stretched phallus length, position of urethral meatus tests laboratory • • plasma 17-OH - progesterone ( after 36 h oflife ) -> increased in CAH • plasma 11-deoxycortisol > increased in 1 1- (1- hydroxylase deficiency basal adrenal steroid levels serum testosterone and DHT pre- and post- hCG stimulation (2000 lU /d for 4 d ) • serum electrolytes chromosomal evaluation including sex karyotype • U /S of adrenals, gonads, uterus, and fallopian tubes •endoscopy and genitography of urogenital sinus Treatment

•steroid supplementation as indicated (e.g. CAH ) •sex assignment after extensive family consultation must consider capacity for sexually functioning genitalia in adulthood, fertility potential, and psychological impact • reconstruction of external genitalia between 6 and 12 mo • long-term psychological guidance and support for both patient and family

Enuresis

. see Paediatrics. PI

1

Bladder and Bowel Dysfunction Definition

• bladder and bowel dysfunction describes voiding and defecation symptoms without a neurogenic or anatomic cause

Clinical Features

• storage symptoms ( urgency, frequency, urge incontinence ) • voiding symptoms ( hesitancy, slow (low, intermiltency ) • gastrointestinal symptoms (constipation and encopresis) Treatment

• stool softeners ( i.e. polyethylene glycol 3350) • urotherapy and bladder retraining • pelvic floor physiotherapy

• anticholinergics (solifcnacin , propiverine, tolterodine) • neuromodulation via transcutaneous electrical nerve stimulation

Selected Urological Procedures Bladder Catheterization •catheter size measured by the Trench (T’r) scale - circumference in mm (30 T'r = 1 cm diameter ) •each 1 mm increase in diameter = approximately 3 Tr increase (standard size 14-18 T'r) •should be removed as soon as possible to reduce the risk of UT1 n

Continuous Catheterization

LJ

•indications

accurate monitoring of U /O relief of urinary' retention due to medication, neurogenic bladder, or intravesical obstruction temporary therapy for urinary incontinence

+

perineal wounds clot prevention ( 22 24 Tr) for CB1 intra- and postoperative comfort for end oflife care

-

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Alternatives to Continuous Catheterization • intermittent catheterization PVR measurement to obtain sterile diagnostic specimens for V I A , urine C&S management of neurogenic bladder or chronic urinary retention • condom catheter • suprapubic catheter

Robinson tip

Coude tip

Causes of Difficult Catheterizations and Treatment

• patient discomfort > use sufficient lubrication ( ± xylocaine ) • collapsing catheter > lubrication as above ± firmer or larger catheter ( silastic catheter ) • meatal / urethral stricture > dilate with progressively larger catheters/ balloon catheter • traumatic injury: repeated prior attempts at catheterization have created traumatic false passage • BPH > use Coude catheter as angled tip can help navigate around enlarged prostate (always angle up/

Inflation port

i («

Two- way Foloy

anteriorly)

Inflation port

• urethral disruption /obstruction > filiform and followers or suprapubic catheterization • anxious patient -> anxiolytic medication

(• Complications of Catheterization • infection: UT1, bladder fistula, bladder perforation ( rare) • meatal / urethral trauma

Contraindications • trauma: hlood at the urinary meatus, scrotal hematoma , pelvic fracture, and /or high riding prostate

Circumcision Definition • removal of some or all of the foreskin from the penis

Epidemiology • 30% worldwide • frequency varies with geography, religious affiliation, socioeconomic status

Medical Indications • pathological phimosis and recurrent paraphimosis • recurrent UT Is ( particularly in infants and in association with other urinary abnormalities ) • balanitis xerotica obliterans or other chronic inflammatory conditions

Contraindications • unstable or sick infant

congenital genital abnormalities ( hypospadias, epispadias, penoscrotal webbing, concealed penis, ventral curvature ); may need foreskin to aid in reconstruction • FMHx of bleeding disorders warrants investigation prior to circumcision •

Complications • early : bleeding, infection , glans injury, amputation , slippage of circumcision device, rarely death • late: redundant foreskin , cosmetic issues , inclusion cysts, adhesions / skin bridges , suture sinus tracts, ventral curvature, secondary buried penis, phimosis, fistula , meatal stenosis • 0.6 2% complication rate

-

Vasectomy Objective • permanent form of contraception with high probability of reversibility • no-scalpel vasectomy has lower risks of early postoperative complications than conventional

vasectomy • fascial interposition and cautery of the vas deferens reduce risk of contraceptive failure • post- vasectomy semen analyses at approximately 3 and 4 mo • other contraceptive methods should be used post -vasectomv until one azoospermic ejaculate or two consecutive ejaculates with 75%) ED (5-10% risk increases with increasing use of cautery) incontinence ( fragmentation, allowing stone fragments to pass spontaneously and less painfully

-

Indications • potential first- line therapy for renal < 1.5 cm and ureteral calculi • individuals with calculi in solitary kidney (consider stenting kidney to prevent obstruction ) • patient preference and wait - times play a large role in stone management performed under fluoroscopic guidance, so stone needs to be radio opaque (i.e. NOT for uric acid stones)

-

-

Contraindications

• acute UT1 or urosepsis • bleeding disorder or coagulopathy • pregnancy • uncontrolled HTN

n

-

t J

• obstruction distal to stone ( SU L can be used after stent or nephrostomy inserted ) not a contraindication but SWL less successful for very dense stones and in obese patients

+

Complications

• bacteriuria • bacteremia • post-procedure hematuria (common to have mild gross hematuria )

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U 17 Urology

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• ureteric obstruction ( by stone fragments) • peri - nephric hematoma

Transition- Related Surgeries • ensure appropriate use of gender pronouns • some procedures require I yr trial of hormone therapy, preoperative letters of evaluation and documentation from mental health professionals as outlined by the World Professional Association for Transgender Health Standards of Care Version 7 guidelines

-

Table 26. Surgical Options for Gender Transition ( Also known as Gender Affirmation Surgery)

-

Procedure

Description

Follow Up

Ordiioctomy

Scrotal incision and removal ol bilateral testicles Scioteelomy in some patients Formation ol vaginal cavily and vulva (clitoris , urethra , mens, labia ) using penile and scrotal skin

Eliminates need lor testosterone blockers Allows lor luck with great case

Penile Inversion Vaginoplasty

lubrication required lor penelration Prostate crams conducted vaginally Regular dilation ol vaginal cavity lo avoid stenosis Complications: granulation tissue, urinary symptoms, listula formation hair growth in neovagina

.

.

High complication rates related to urethral connection ( urethral listula stricture, post void dribblingTstream spraying, urinary retention ), skin complications and implant issues

Radial Forearm Phalloplasty Most common technique lor phallic reconstruction

loimation ol penis using radial loreaim gralt ol skin , blood vessels and

Anterolateral Thigh ( All ) Phalloplasty

High complication rate as above Pedicle flap failure very rare Urethral extension Phallus maybe very thick due to subcutaneous lal ol thigh luturepenile and testicular implants Sensory recovery may be pooler than radial arm llap Formation of a penis through release ol hormonally - enlarged clitoris from tower complication rates when compared to phalloplasty suirounding ligaments Hot capable of penetrative intercourse Major complications mayrequire Girth added fiom neighbouring tissue revision surgery: urethral strictures, urethral fistulas urethroplasty t vaginectomy and scrotoplasty

nerves Urethral extension lulure penile and testicular implants

loimation ol penis using skin , blood vessels, ncives and muscular tissue Itom thigh

Metoidioplasty

-

Common Medications Table 27. Erectile Dysfunction Medications Drug

Class

Mechanism

Adverse Effects

sildenafil tadalafil vardenafil [PDESsfor use when some

Phosphodiesterase 5 inhibitor

Selective inhibition of P 0 E5 (enzymewhich degradescGMP) leads to sinusoidal smooth muscle relaxation, increased blood (low and erection

Severe hypotensbn (very rare)

Prostaglandin El

Activation of cAMP, relaxing sinusoidal smooth muscle focal release (urethral suppository )

Penile pain Presyncope

See above

See above

thickening ol tunica albuginea at site ol repeated injections ( Peyronie's plague) Painful erection

erection present)

-

-

alprostadil ( MUSE = ). PGfc phentolamine papaverine mixture

.

alprostadil papaverine ( intracavernosal injection )

Flushing, headaches, dyspepsia Contraindicated it Hi ol priapism , or in conditions predisposing lo priapism ( leukemia, myelofibrosis, polycythemia , sickle cell disease) Contraindicated with nitrates

triple therapy also used: papaverine, phentolamine

Hematoma Contraindicated if Hi ol priapism , or in high risk ol

PGEt

priapism

.

-

Table 28. Benign Prostatic Hyperplasia Medications Drug

Class

Mechanism

terazosin doxazosin

al blockers

a adrenergic antagonists reduce stromal smooth muscle Prcsyncopc

lamsulosin allutosin sllodosin

ou selective

finasteride

S o reductase inhibitor

dulasteridc

Adverse Effects

leg edema Reduce dynamic component of bladder outlet obstruction Retrograde ejaculalion Headache Asthenia Nasal congestion

lone

Blochs conversion ol testosterone lo DHI Reduces static component ol bladder outlet obstruction Reduces prostatic volume

Sexual dysfunction PSA decreases

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U 18 Urology

Toronto Xotcs 2023

Table 29. Prostatic Carcinoma Medications ( N> 0, M >0 ) Class

Mechanism

leuprolide goserelin “ androgen deprivation therapy"

GnRH agonist

Initially stimulates LH increasing testosterone and causing “flare * (initially increases bone pain) Later causes low testosterone

Hot flashes Headache

degarelii

GnRH antagonist

Competitively binds to the pituitary gland GnRH receptors, thereby reducing the release of LH FSH and consequently testosterone by testes

Back pain Breast enlargement Decreased libido Hot flashes Headache Slow or fast heartbeat

'cyproteroneacetate

Steroidal antiandrogen

Competes with DH1 for intracellular receptors: Prevent flare produced by GnRH agonist Use forcompleteandrogen blockade May preserve potency

flutamide, bicalutamide

Non-steroidal antiandrogen

As above

Hepatotoxic: AST /ALI monitoring

abiraterone

Non -steroidal antiandrogen

Irreversible cytochrome P 450 ( CYP) 17 inhibition, blocking synthesis of androgens in tumour, testis, and adrenal glands

Adrenal insufficiency (concurrent treatment with steroids often required) Hypertriglyceridemia Peripheral edema

enralutamide

Non-steroidal antiandrogen

Androgen receptor signaling inhibitor (full antagonist)

Peripheral edema Fatigue and weakness Hot flashes

Drug

.

Adverse Effects

.

.

Decreased libido

’Very rarely used

Table 30. Continence Agents and Overactive Bladder Medications Drug

Class

Mechanism

Indication

Adverse Effects

oxybutynin

Antispasmodic

Inhibits action olacetylcholine on smooth

Overactive bladder Urge incontinence -^ urgency » frequency

Dry mouth Blurred vision Constipation Supraventricular tachycardia

Overactive bladder Urge incontinence * urgency » frequency

As above

muscle Decreases frequency of uninhibited detrusor contraction Diminishes initial urge to void

oxybutynin lolterodine Irospium solifenacin darifenacin fesoterodine

-sympathetic receptor blocker in the ^bladder : relaxes bladder during storage

Anticholinergic

phase

propiverine

mirabegron

j) lagonist

Sympathomimetic effects: Urinary sphincter contraction Anticholinergic effects: Detrusor relaxation

Overactive bladder Urge incontinence ^ urgency » frequency

Blood pressure should be monitored

imipramine

Tricyclic antidepressant

Prevents the release of neurolransmitlcrs

Stress and urge incontinence

As above Weight gain Orthostatic hypotension Prolonged PR interval

Botulinum toxin A bladder injections

Neurotoxin

Prevents the release of neurotransmillcrs

Refractory OAB incontinence both neurogenic andnon- neurogcnic

Urinary retention UII

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Note: All anticholinergics aie equally effective and long acting formulations are better tolerated Newer muscarinic M3 receptor specific agents (solifenacin, darllenacin) are equally efficacious as older drugs, however, RCTs based on head- to head compalison to long acting formulations ale lacking

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Landmark Urology Trials Trial Name

Reference

Clinical Trial Details

N Engl J Mud 2003:349:215 - 224

Title: The Influence of Finasteride on the Development of Prostate Cancer Purpose: lo determine whether the drug Finasteride |5- alpha reductase inhibitor) could prevent prostale cancer in men ages 55 and older. Methods: 18882 men 55 yr or older with a normal digital rectal examination and a ( PSA) level equal lo or less than 3.0 ng per milliliter were randomly to receive finasteride ( 5 mg per day ) or placebo for 7 yr. Results: There was a 24.8% reduction in prostate cancer prevalence over the 7 - yr period among the Finasteride arm compared lo the placebo arm ( 95 % confidence interval, 18.6 lo 30.6 percent; P'0,001).However there was a significant increase in high grade disease among men in the finasteride group compared to the placebo (6.4 % vs. 5.1% P'0.005). Conclusion: the PCPf trial in 2003 was the first study to show that a medication (Finasteride) reduces the likelihood ol developing prostale cancer. Upon long term follow - up in 2013, this reduction in risk has been attributed to less likelihood ol low - grade cancers in men taking finasteride. Although participants who developed prostate cancer while taking finasteride were mote likely to have high- grade cancers, this increase was attributed to better detection of disease rather than medication use

BENIGN PROSTATIC HYPERPLASIA PCP1

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Trial Name

Reference

Clinical Trial Details

MTOPS

HJLM 2003:349:2387-2398

Title: The Long-Term Effect ol Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostalic Hyperplasia Purpose: To determine whether therapy with doxacosin (a blocker) or finasteride (So-reductase inhibitor), alone or in combination, would delay or prevent clinical progression of benign prostatic hyperplasia (BPH). Methods: Participants were followed - up for a mean lime of 4.5 yr to compare the effects of the interventions. The primary outcome was overall clinical progression of BPH ( >4 points Irom baseline in ADA symptoms score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent UTI). Results: The risk ol overall clinical progression was significantly reduced by doxazosin ( 39% lisk reduction P - 0.001) and linastcride ( 34% risk reduction P‘0.002), as compared with placebo, and the risk was reduced even more with combination therapy (66% lor the comparison with placebo P 0.001) compared with doxazosin (P'0.001) or finasteride (P‘0.001) alone ‘ Conclusions: Long - term combination therapy with doxazosin and finasteride reduced the clinical progression of BPH sigmlicantly more than each therapy alone, as well as reduce the need for invasive therapy in the long term.

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BLADOER CARCINOMA

NEJM 2003:349:859 866

Heoadjuvanl Chemotherapy plus Cystectomy Compared with Cystectomy Alone for locally Advanced Bladder Cancer

Title: Heoadjuvanl Chemotherapy plus Cystectomy Compared with Cystectomy Alone for locally Advanced Bladder Cancer Purpose: To evaluate whether the addition of neoadjuvant chemotherapy to radical cystectomy improves oulcomcsin patients with locally advanced bladder cancer. Methods: 317 patients with transitional - cell carcinoma of Ihe bladder ( T 2 N0 M0 to IdaNOMO ) were randomized to undergo radical cystectomy or to receive three cycles of combined chemotherapy followed by radical cystedomy. Results: At 5 yr after treatment initiation, 57% of the combination therapy group vs. 43% of Ihe cystectomy group were alive ( P‘0.06) In the combinalion - lhcrapy group 38% of Ihe patients were pathologically lice of cancer at the timeof cystectomy vs 15% of the cystectomy - only group at Ihe lime of surgery (P‘0.001). Conclusions : For locally advanced bladder carcinoma, ncoadjuvantchcmotherapy significantly reduces tumour volume which is associated with improved survival

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PROSTATE CANCER

.

10 YrOutcomesAfter Monitoring Surgery, or Radiotherapy for Localized Prostate Cancer

HEJM 2016;375|15|:1415 -1424

ERSPC

HJEM 2009:360:1320-1328

Title: 10 Yr Outcomes After Monitoring, Surgery, or Radiotherapy for localized Prostate Cancer Purpose: To evaluate the effectiveness of active monitoring, radical prostatectomy, and radiotherapy in relabon to mortality and the incidence of metastases and disease progression Methods: 1643 men randomized into active monitoring, surgery, and radiotherapy. The primary outcome was prostatecancer mortality at median 10 yr of follow -up and the secondary outcomes were rale of disease progression, metastases, and all- cause deaths. Results: Ho significant difference among groups in prostate-cancer-specific deaths and in thenumbers ol deaths from any cause. Metastases developed more in the active monitoring group ( 33 men) vs. surgery group (13 men) or radiotherapy group (16 men) ( P - 0.004). Higher rates of disease progression in active -monitoring group (112 events) vs. surgery group (46 events) or radiotherapy group ( 46 events) |P 0.001). ‘ Conclusions: At 10 yr, prostate - cancer - specific mortality was low regardless of the treatment, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastasis compared to active monitoring.

.

Title:Screening and Prostate - Cancer Mortality in a Randomized European Study Purpose: To determine the reduction of prostate- cancer mortality by PSA - based screening. Methods: Participants were randomized to a group that received PSA screening an average of once every 4 yr or to a control group that did not receive such screening.The primary outcome v/ as the rate of death from prostate cancer. Results: The incidence of prostate cancer was higher in the screening group than in the control group (8.2% vs. 4.2%). The absolute risk difference was 0.71 deaths /1000 men meaning that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. Conclusions: PSA - based screening reduced the rate of mortality from prostate cancer by 20% but was associated with a high

.

risk of overdiagnosis.

-

NJEM 2015:373( 8):737 46

CHAARTED

Title: Chemohormonal Therapy in Metastatic Hormone -Sensitive Prostate Cancer Purpose: To assess whether concomitant treatment with Androgen - deprivation therapy (ADT) plus docetaxel would result in longer overall survival than that with ADT alone. Methods: Patients with metastatic, hormone- sensitive prostate cancer were randomized to receive either ADT plus docetaxel or ADT alone. The primary objective was overall survival. Results: After a median follow - up of 28.9 months, the median overall survival was 13.6 months longer in the combination therapy group than within the ADT -alone group |P 0.001). The median time to progression was 20.2 months in the ‘ combination group and 11.7 months in the ADT - alone group ( P‘0.001). Conclusions: Combination ol docetaxel and ADT lor hormone-sensitive metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.

References General Information American Joint Commitlee on Cancer. AJCC Cancer Stalmg Manual Eighth Edition. Available from: http://cancerslaging.org/. American Urological Association. Available Irom:http://www.auanet.org/guidclincv/. Canadian Urological Association. Available from: http:/ / www.cua.org/cn/ 9uidclincs /. Ferri F. Practical guide to the careol Ihe medical patient, 6lh ed. St . Louis: Mosby, 2006. Goldman L Ausiello 0. Cecil textbook of medicine 23id ed. Philadelphia: WB Saunders 2007. Macfarlane MT. House officer scries: urology 3rd ed. Philadelphia: lippincoll. 2001 Montague OK Jarow J Broderick GA. etal. Guidclmeon the management ol priapism. American Urological Association Education and Research Inc. 2003 Available from: http://www.auancl.oig/ cducation/ guidelines/priaplsm cfm. Tanagho EA, McAninch JW. Smith's generalurology 17th ed. New York: McGraw Hill 2007. Wcin AJ Kavoussi Ut Hovick AC ct al. Campbell's urology 10 th ed. Philadelphia: W8 Saunders. 2011. Wieder JA . Pocket guide to urology 4th ed. Oakland: Wicder 2010.

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Common Presenting Problems Abrams P Artibani W, Cardozo L etal Reviewing the ICS 2002 terminology report: The ongoing debate H cutout ol Urodynam 2002:21:167 178. Alshar K Dos Santos J Blais AS ft at Canadian Urological Association guideline for the manage menl olbladder and bowel dysfunction in children. CUAJ. 2021:15(2). Anger J lee U Ackerman AL etal Recurrent Uncomplicated Urinary Trad Infcctionsin Women: AUAiCUA /SUFU Guideline J Urol 2019:202|6):1273 1274 Assimos D Krambeck A,Miller HI etal. Surgical managementol stones: AUAEndourology society guidelines J Urol 2016:196(4):1153 60. Bettez M Tu LM Carlson K et al 2012 Update: Guidelines for Adult Urinary Incontinence Collaborative Consensus Document for Ihe Canadian Urological Association. CUAJ 2012:6:354 363. Bowman C Goldberg JM Care of the patient undergoing sex reassignment surgery International Journal ol Iransgenderism Ini J Transgend Health 2006:9( 3 4|:135 -16S. Bremnor JO, Sadovsky R Evaluation of dysuria in adults. Am Earn Phys 2002:65:1589 -1597

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Bryson C Honiq SC. Genitourinary Complications of Gender Affirming Surgery. Curr . Urol. Rep 2019; 6:20 - 31 Capohcchio JP Braga IH Stymanski KM. Canadian UrologicalAssocialioni'Pcdiatric Urologists of Canada guideline on the investigation and managcmcntol antcnalally detected hydronephrosis. Can. Urol. Assoc. J 2018 Apr;12(4) 85. Cohen RA Brown RS. Microscopic hematuria . NEJM 2003;348:2330 - 2338 Cooper TG Noonan E Von Echardstem S, etal. World Health Organization reference values for human semen characteristics.Hum Reprod Update 2010;16|3):231- 245. Cox A, Golda N. Nadeau G etal. CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. CUAJ 2016;10:E136 - E155. Dason S, Dason JT. Kapoor A. Guidelines for thediagnosis and management of recurrent urinary tract infection inwomen. CUAJ. 2011;5|5):316-322. Djordjevic ML Stojanovic B Bizic M. Metoidioplasty: techniques and outcomes. Transl. Androl.Urol. 2019;8(3):248. Evans SM Bandarage VP, Kronborg C cl al. Gleason group concordancebetween biopsy and radical prostatectomy specimens: Acohort study from Prostate Cancer Outcome Registry - Victoria.Prostate Int 2016:4( 41:145 151. Gofiit ON Kate R Shapiro A cl al, Gross Hematuria in Patients with Proslate Cancer: Etiology and Management. ISRN Surgery. 2013. Kavanagh A, Baverstock R,Campeaul etal. CUAguidelinc: Diagnosis, management, and surveillance of neurogenic lower urinary tract dysfunction. CMAJ 2019;13|6):1S6 165. Kassouf W, TraboulsaSL Kulkarni GS et al.CUA guidelines on the management of non-muscle invasive bladder cancer. CUAJ 2015:9:E690- E 704. Kulkarni GS, Black PC Sridhar SS, et al. Canadian Urological Association guideline: Muscle-invasive bladder cancer.CUAJ 2019;13|8):230. Mahmood J, Shamah AA, Creed TM, etal. Radiation- induced erectile dysfunction: Recent advances and future directions. Adv. Radial. Oncol. 2016;1(3):161-169. Minami, H „ Furukawa S. Sakai, et al. Physical activity and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus:The DogoStudy. J. Diabetes Investig 2018; 9|1( 193 -198. Morrison SD, Shakir A Vyas KS cl al. Phalloplasty: a review of techniques and outcomes. Plast. Reconstr. Surg 2016;138|3):S94 - 615. Mtiilon AR Iliescu EA Wilson JWL Nephrology: investigation andtreatment of recurrent kidney stones CMAJ 2002:166: 213 - 218 Nguyen HI Benson C8, Bromley B, el al Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UI0 classification system) J Pedialr Urol 2014:10( 61:982 98. Nickel JC.Prostabls. CUAJ 2011;5:306 - 315. Pearle MS. Goldfarb DS Assimos DG etal. Medical management of kidney stones: AUA guideline.J Urol 2014;192|2):316- 324. Rashid M Tamimy MS. Phalloplasty:the dream and the reality.Indian journal of plastic surgery:official publication of the Association of Plastic Sugeonsof India. 2013 May:46|2):283. Rendon RA Mason RJ. Marzouk K et al.Canadian Urological Association recommendations on prostate cancer screening and early diagnosis. CUAJ 2017;11:298 -309. Rourke KF Welk B, Kodama R et al. Canadian Urological Association guideline on male urethral stricture. Can. Urol. Assoc. J. 2020:14(10). Saad f , Apnkian A Finelli A et al. 2021 Canadian Urological Association (CUA) Canadian Uro Oncology Group (CUOG) guideline: Managements castration-resistant prostate cancel (CRPC). Can. Urol. Assoc. J 2021:15!2):E81. Santucci RA Urethral compticalionsalter transgender phalloplasty: strategies to treat them and minimue their occurrence.Clin Anal 2018:31( 2) 187 190 So A Chi K Danielson 8 et al Canadian Urological Association- Canadian Urologic Oncology Group guideline on metastatic castration- naive and castration-sensitive prostate cancer CUAJ 2020:14(2) TeichmanJMH. Acute renal colic from ureteral calculus. NEJM 2004:350:684- 693. Verta W Oosterlinck W Spinoit AF etal.A Comprehensive Review Emphasizing Anatomy, Etiology Diagnosis, and Treatment of Male Urethral Stricture Disease. Biomed Res Int 2019; 2019. Zini A, Grantmyre J Chan P. CUA guideline:Vasectomy. CUAJ 2016 Jultl 0(7- 8):E2 74.

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Overactivc Bladder Ouslander JG Management of overactivc bladder NEJM 2004:250:786 799 Yazdany 1, Jakus - Waldman S, Jeppson PC el al American Urogynecologic Society Systematic Review: The Impact of Weight loss Intervention on lower Urinary Tract Symptoms and Urinary Incontinence in Overweight and Obese Women. Female Pelvic Med Reconstr Surg 2020:26|1):16 29.

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Benign Renal Neoplasm Israel GM, Bosniak MA. An update of Bosniak renal cyst classification system Urology 2005;66:484 - 488. Richard P0 Violette PD Jewett MAS, etal. CUA guideline on the management of cystic renal lesions. CUAJ 2017:11:E66 - E 73. Jewett MAS. Rendon R lacombc l et al. Canadian guidelines lor the management of small renal masses. CUAJ 2015:9 (5 6);160 - 3. Urological Emergencies Galcjs LE Diagnosis and treatment of the acute scrotum Ain Fam Phys 1999:5:817- 824.

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Infertility and Andrology Grober ED Krakovrsky Y. Khera M. etal. Canadian Urological Association guideline on testosterone deficiency in men:Evidence-based OSA. Can.Urol.Assoc. J 2021:15|5):E 234.

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Medications Bill- Axelson A, Holmbcrgl, Ruutu M, etal. SPCG 4 Investigators. Radical prostatectomy vs. watchful waiting In early prostate cancer. NEJM 2011:3 64:1708 1717. Compendium of Pharmaceuticals and Specialties. Available from: http:/ /www ethcrapcutic5.ca Micromedex health care series Available from:http:i7www.rnicromedex.com. Rini B. Halabi S Rosenberg J, et. al. Bevacizumab plus interferon alia compared with interferon alia monotherapy in patients with metastatic renal cell carcinoma: CAIGB 90206 trial. J Clin Oncol 2008:26:54225428.

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Bill - Axelson A. Holmberg L, Ruutu M et al. Radical prostatectomy vs. watchful waiting in early prostate cancer. HEJM 2011:364:1708 -1717. Campschroer T 2hu X, Vemooij RW, el al. Alpha -blockers as medical expulsive therapy lor ureteral stones. Cochrane 0B Syst Rev 2018;4:C0008509. Carter HB Albertscn PC Barry MJ el al: Early detection ol prostate cancer : AUA guideline. J Urol 2013; 190: 419 Coelho RF. Rocco 8. Patel MB. etal. Retropubic, laparoscopic, and robot assisted radical prostatectomy: a critical review ol outcomes reported by high-volume centers. J Endourol 2010:24:2003 2015. Escudier B, EisenI Stadler WM, et al. Sorafemb in advanced dear - cell renal- cell carcinoma. NEJM 2007;356:125 -134. Grossman H8. Natale RB Tangen CM.et al. Neoadjuvantchemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. NEJM 2003;349:859 - 866. Hoffman RM. Monga M.Elliott SP, et al. Microwave thermotherapy for benign prostatic hyperplasia. Cochrane D 8 Syst Rev 2012;9:CD004135. Ilic D Evans SM,Allan CA, et al. laparoscopic and robolic - assisted vs. open radical prostatectomy for the treatmentof localised prostate cancer. Cochrane DB Syst Rev 2017:9:CD009625. James ND Hussain SA. Hall E, et al. Radiotherapy wilh or with out chemotherapy in muscle- invasive bladder cancer. NEJM 2012;366:1477 -1488. Kim SC Sco KK. Efficacy and safety ol fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a double - blind, placebo controlled study. J Urol 1998:159:425 - 427 McDonnell JD, Rochrborn CG Bautista 0M. ct al. The long term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostalic hyperplasia. NEJM 2003:349:2387- 2398. Motzer RJ, Escudier B. Tomczak P, et al. Axitimb vs. soraiemb as second - line treatment for advancedrenal cell carcinoma: overall survival analysis and updated results from a randomized phase 3 trial, lancet Oncol 2013:14:552- 562. Parsons JK,Hergan LA.Sakamoto K. etal. Efficacy of alpha - biockersfor the treatment of ureteral stones. J Urol 2007:177:983 -987. Schroder FH Hugosson J, Roobol MJ etal. Screening and prostate - cancer mortality in a randomized European study. NEJM 2009:360:1320 -1328. Wiysonge CS Kongnyuy EJ.Shey M, et al. Malecircumcision for prevention of heterosexual acquisition of HIV in men. Cochrane DB Syst Rev 2011:6:00007496. lacklind J Fink HA Macdonald R , et al Finasteride for benign prostatic hyperplasia. Cochrane 0B Syst Rev 2010:10:00006015. Wiesenthal JD. Ghiculcte 0. D 'A Honey R J cl al. A comparison of treatment modalities for renal calculi between 100 and 300 mm2: are shockwave lithotripsy, urcleroscopy and percutaneous nephrolithotomy equivalent ? J Endourol 2011:25:481 485. Will 1J. Brawer MK,Jones KM, etal. Radical prostatectomy vs. observation for localized prostate cancer. NEJM 2012:367:203-213.

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Vascular Surgery Kauniil V. Patel and George Hlzawy, chapter editors Chunyi Christie Tan and Vrati Mehra , associate editors Arjan S. Dhoot , EBM editor Dr. Elisa Greco and Dr. George Orcopoulos, staff editors Acronyms

VS2

Arterial Disease Acute Limb Ischemia Peripheral Arterial Disease

VS 2

Aortic Disease Aortic Dissection Aortic Aneurysm

VS6

Carotid Stenosis Venous Disease Venous Thromboembolism Chronic Venous Insufficiency

VS9

VS10

Lymphedema

VS11

Landmark Vascular Surgery Trials.

VS12

References

.VS13

ri LJ

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VS2 Vascular Surgery

Acronyms AAA ABI ACEI AKI All ARB BMT CAS

CCB CEA

abdominal aortic aneurysm ankle brachial index angiotensin converting enzyme inhibitor acute kidney injury

CEAP

clinical, etiological ,

CLTI

acute limb ischemia angiotensin II receptor blocker

CTA

anatomical, pathophysiological Echo (classification of venous disease) EVAR chronic limb threatening ischemia HITT computed tomography

best medical therapy carotid artery angioplasty + stenting calcium channel blocker carotid endarterectomy

CVA CVD

-

DUS

CVI DIC DVT

INR

LDL- C

disseminated intravascular

LV

coagulation deep vein thrombosis

MRA

MSK

echocardiogram endovascular aortic aneurysm repair heparin induced thrombocytopenia with thrombosis international normalized ratio low-density lipoprotein cholesterol left ventricular magnetic resonance angiography

PAD PFO PI PIT

-

angiography cerebrovascular accident cerebrovascular disease chronic venous insufficiency

duplex U/ S

musculoskeletal peripheral arterial disease patent foramen ovale prothrombin time partial thromboplastin time ( i.e.

aPIT ) TAA TBI

TEE

TEVAR TIA

thoracic aortic aneurysm

toe- brachial index

transesophageal echocardiography thoracic endovascular aortic repair transient ischemic attack

Arterial Disease Posterior

Anterior Abdominal aorta & IVC Common iliac a. & v. Internal iliac a. & v.

\

V

—— •

External iliac a . & v

1\

/:

i

-

Inguinal ligament

Common femoral a. & v.

I

Superficial fomoral a. & v. — Great saphenous v. — — Adductor hiatus Popliteal a. & v — Tibioperoneal trunk — — Deep femoral a. & v.