Target JIPMER Dec 2018 9811156083, 9788184452662

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TARGET JIPMER

(Model Questions with Solved Explanatory Answers) “Get the inside edge! Authored by Jipmerites”

DECEMBER 2018 (Supplement) DR. T. ARUN BABU

MD Pediatrics (JIPMER), DAA (CMC Vellore), MBA (HM) Fellow in Neonatal Perinatal Medicine (Canada) Associate Professor, Department of Pediatrics Indira Gandhi Medical College and Research Institute (IGMC&RI) A Government of Puducherry Institution Puducherry – 605009 Website: www.drarunbabu.in

Peepee Publishers and Distributors (P) Ltd.®

TARGET JIPMER DECEMBER 2018 (Supplement) Published by Pawaninder P. Vij and Anupam Vij Peepee Publishers and Distributors (P) Ltd. Head Office: 160, Shakti Vihar, Pitam Pura, Delhi-110 034 (India) Correspondence Address: 7/31, First Floor, Ansari Road, Daryaganj New Delhi-110 002 (India) Ph: 41512412, 23246245, 9811156083 e-mail: [email protected] e-mail: [email protected] www.peepeepub.com join us on

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© 2019 Peepee Publishers and Distributors (P) Ltd. All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic, mechanical, photocopy, recording, translated, or any information storage and retrieval system, without permission in writing from the editor and the publisher. This book has been published in good faith that the material provided by authors/ contributors is original. Every effort is made to ensure accuracy of material, but publisher and printer will not be held responsible for any inadvertent errors. In case of any dispute, all legal matters to be settled under Delhi jurisdiction only.

First Edition: 2019

ISBN: 978-81-8445-266-2

Dedication To my Parents, Teachers, my wife Dr. Sharmila, my kids Akshaya and Akash

Disclaimer: This book fully complies with the non-disclosure agreement (NDA) levied by JIPMER. This book contains Model questions with solved explanatory answers. No questions included in this book have been obtained from any candidates registered for JIPMER exam. Any resemblance to the original JIPMER questions, if present, is purely coincidental. The author, contributors, publisher or sellers cannot be held responsible for any damage or loss caused to anyone, directly or indirectly.

PREFACE We are very happy in bringing out yet another supplement of TARGET JIPMER Book. Big thanks for making TARGET JIPMER series the best book for JIPMER PGMEE preparation. This book series was started with the sole purpose of making model JIPMER questions accessible to PG aspirants. The questions have been solved by a team of subject experts from reputed academic backgrounds. This book is tailor made for JIPMER PG entrance exam preparation. Most of our contributors are JIPMER alumni and have personally written JIPMER PG exams in the last few years and are well experienced and aware of the examination pattern. JIPMER questions are mostly taken from standard textbooks and articles. Though the pattern of JIPMER questions have changed in the last few years, the high yield area remains the same. You will understand this after going through all the volumes of 4th edition of TARGET JIPMER. We have incorporated a systematic approach in solving each and every question which can be appreciated while reading this book. The schematic diagrams, tables, illustrations, bulleted key points and references are the highlights of this book and will make reading and understanding of the material easier and effective. Every solved question will have a valid reference citing a standard textbook or article in order to increase the credibility of the answers. The focused explanations should help you solve questions from same topics in the future easily. I would like to thank all the contributors for their commitment and hard work that has led to the tremendous success of this book series. I wish to thank our publishers, Mr. Pawaninder Pal Vij and Mr. Anupam Vij, the Directors of Peepee Publishers and Distributors (P) Ltd, who have always been a pillar of support to our team. I would also like to thank our publishing team for their relentless efforts in releasing this book in a short notice. I am deeply indebted to students for their overwhelming support, feedback and critical appraisal. We are looking forward to hear your feedback and are fully committed in bringing out better editions in the future. For JIPMER students, a JIPMERITE tag is a matter of pride which they carry as a badge of honour throughout their professional life. For most others it is a dream. I believe and hope that this book will make your dream come true. All the best!



T. Arun Babu



Website: www.drarunbabu.in Email: [email protected]

“Books are infinite in number and time is short. The secret of knowledge is to take what is essential.”

–Swami Vivekananda

CONTRIBUTORS Dr. Arun Babu T, MD Pediatrics (JIPMER), DAA (CMC), Fellow NPM (Canada) Associate Professor, Department of Pediatrics Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605009 (Chief Editor) Dr. Abhishek Bhaumik, MS (General Surgery) Senior Resident, Department of Surgery West Bengal HS (Surgery) Dr. Arul Varman, MD Psychiatry (JIPMER) Assistant Professor, Department of Psychiatry Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605009 (Psychiatry) Dr. Bharath Kumar V D, MD Pharmacology Assistant Professor, Department of Pharmacology BGS Global Institute of Medical Sciences, Bangalore, Karnataka Dr. Bharath’s Pharmacology MCQs and Discussion for PG Aspirants (Pharmacology) Dr. Dinesh Kumar, MD Pediatrics Assistant Professor, Department of Pediatrics Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605009 (Pediatrics) Dr. Jean Fredrick, MD Physiology Assistant Professor, Department of Physiology Mahatma Gandhi Medical College and Research Institute (MGMC&RI), Pillaiyarkuppam, Puducherry (Physiology) Dr. Kantamani Bala Teja, MS ENT Assistant Professor, Gayathri Vidya Parishad Visakhapatnam, Andhra Pradesh (Surgery) Dr. Mugunthan N, MS Anatomy, DNB, PhD, MBA Professor of Anatomy Sree Mookambika Institute of Medical Sciences Kulasekaram, Kanyakumari District,Tamil Nadu–629161 (Anatomy) Dr. Mukul Mohindra, MS (Ortho), DNB, MNAMS, Dip.SICOT (Belgium) Fellow National Board (Arthroscopy and Sports Medicine) Sports Injury Center, Safdarjung Hospital and VMM College New Delhi (Orthopaedics) Dr. Nishanth Sampath, MD Physiology Clinical Neurophysiologist, Institute of Neurosciences SRM Institute of Medical Sciences (SIMS) Chennai, Tamil Nadu (Physiology) Dr. Prasanna S, MD Microbiology (AFMC, Pune) Assistant Professor, Department of Microbiology Shri Sathya Sai Medical College and Research Institute Kancheepuram, Tamil Nadu – 603108 (Microbiology)

Dr. Ranjith AR, MD Pathology (JIPMER) Molecular Pathologist, Bangalore (Pathology) Dr. Sangeeta Dhanger, DA, DNB, MNAMS Assistant Professor, Department of Anesthesiology Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605009 (Anesthesiology) Dr. Satvinder Singh Bakshi, MS ENT (JIPMER), DNB Associate Professor, Department of Otorhinolaryngology All India Institute of Medical Sciences (AIIMS) Mangalagiri, Andhra Pradesh (ENT) Dr. Sharmila Arun Babu, MS OBG (JIPMER) Assistant Professor, Department of OBG Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605009 (OBG) Dr. Sindhujha Sekar G, (JIPMER), DGO, DNB OG Assistant Professor, Department of OBG Sri Venkateswara Medical College Hospital and Research Centre, Puducherry (OBG) Dr. Suthanthira Kannan, MD Community Medicine Senior Resident, Department of Community Medicine Government Medical College, Manjeri, Kerala (Community Medicine/PSM) Dr. Udayashankar C, MD Dermatology (JIPMER), MBA (HM) Professor and Head, Department of Dermatology Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605 009 (Dermatology) Dr. Usha S Adiga, MBBS MD PhD Professor, Department of Biochemistry KS Hegde Medical Academy, Mangalore, Karnataka (Biochemistry) Dr. Venipriya, MS Ophthalmology Senior Resident, Department of Ophthalmology Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605 009 (Ophthalmology) Dr. Vinoth Kumar S, MD General Medicine Assistant Professor, Department of General Medicine Indira Gandhi Medical College and Research Institute (IGMC&RI), Puducherry – 605 009 (General Medicine) Dr. Yatiraj Singi, MD Forensic Medicine Professor, Department of Forensic Medicine Sree Mookambika Institute of Medical Sciences Kulasekharam, District Kanya Kumari, TN (Forensic Medicine)

Editorial Team • Dr. Padmapriya, MBBS, IGMC&RI, Puducherry • Gaurang Narayan, MBBS Student, IGMC&RI, Puducherry

ACKNOWLEDGEMENTS Target JIPMER – Previous Edition Contributors Dr. Rajamahendran, MS, MCH, Assistant Professor, Department of Surg Gastro, Villupuram Medical College, Tami Nadu Dr. Pratheep, MS General Surgery MCH Oncosurgery Resident Dr. Balamurugan N, DCH, DNB, MRCPCH, Assistant Professor, Department of Pediatrics, SLIMS, Puducherry Dr. Tejswita Rajpal Hande, MBBS, DGO, MUHS, Nashik Dr. Saranya K, MD Physio (JIPMER), Assistant Professor of Physiology, JIPMER, Puducherry Dr. Abarna Devi S, DDVL (JIPMER), MD Medicine, Assistant Professor of Medicine, ESIMC, Chennai Dr. Anshu Bahl, MD Anatomy, AIIMS, New Delhi Dr. Ankit Agarwal, MD RT (JIPMER), Senior Resident, GMCH, Sector 32, Chandigarh Dr. Naga Dharshan Devendra, MD (JIPMER), Associate Professor and Course Director, Department of Biochemistry and Genetics, Trinity School of Medicine, Saint Vincent and Grenadines Dr. Saseendar S, MS (Ortho), DNB, Dip SICOT (Belgium), MNAMS, Care Sports Injury, Chennai Dr. Srirangaraj S, MD, Professor, Department of Microbiology, MGMCRI, Puducherry Dr. Sri Vengadesh Gopal, MS (JIPMER), Assistant Professor, Department of Surgery, IGMC&RI, Puducherry Dr. Sumanth MM, MD (JIPMER), DNB, Associate Professor of Community Medicine, MMC&RI, Mysore, Karnataka Dr. Sentitoshi, MD (JIPMER) Forensic Medicine, Former Assistant Professor, MGMC&RI, Puducherry Dr. Asayas Bosco Chandrakumar, MS, Associate Professor of Surgery, SLIMS, Puducherry Dr. Mahesh Nagappa, MD Anaes (JIPMER), DNB, MNAMS, Assistant Professor, SLIMS, Puducherry Dr. Sinhasan SP, MD, Associate Professor of Pathology, IGMC&RI, Puducherry Dr. Amiya Kumar Nath, MD (JIPMER), Associate Professor of Dermatology, IGMC&RI, Puducherry Dr. Venkateswaran R, MD, Associate Professor of Medicine, JIPMER, Puducherry Dr. Niranjan G, MD Biochem (JIPMER), Associate Professor of Biochemistry, AIIMS Nagpur Dr. Vishnu Kanth, MD (JIPMER), Associate Professor, Department of Respiratory Medicine, JIPMER, Puducherry Dr. Dilli Kumar, MD (JIPMER), Associate Professor of Pediatrics, JIPMER, Puducherry Dr. Dilip Kumar R, MD (JIPMER), MRCP (UK), Dr. Mehta’s Hospitals, Chetpet, Chennai-31 Dr. Sachidananda Adiga, MD, Professor of Pharmacology, KS Hegde Medical Academy, Mangalore Dr. Giriyanna Gowda, MD, Associate Professor of Community Medicine, KIMS, Bangalore, Karnataka Dr. Gomathi Shankar V, MS (JIPMER), DNB, MNAMS, Associate Professor of Surgery, JIPMER, Puducherry Dr. Karthik, MD Physiology (JIPMER), Associate Professor of Physiology, JIPMER, Puducherry Dr. Lourdu Jafrin, MD, Associate Professor of Pharmacology, IGMC&RI, Puducherry Dr. Mahalakshmy T, MD PSM (JIPMER), Associate Professor of PSM, JIPMER, Puducherry Dr. Melvin George, MD, DM Clin Pharm (JIPMER), Assistant Professor, Cardiac Clinical Trials and Research, Department of Cardiology, SRM Medical College and Hospital, Potheri, Tamil Nadu Dr. Naveen Nair, MS Orthopedics (JIPMER), Associate Professor of Orthopedics, IGMC&RI, Puducherry Dr. Noyal Mariya Joseph, MD (JIPMER), Associate Professor of Microbiology, JIPMER, Puducherry Dr. Raveendranath, MS Anatomy (St Johns), Associate Professor of Anatomy, JIPMER, Puducherry Dr. Rupa Vani, DNB, Assistant Professor of Obstetrics and Gynecology, IGMC&RI, Puducherry Sincere Thanks to: Dr. Zubaida Begum A, MBBS, MGMC&RI, Junior Resident in Pediatrics, IGMC&RI, Puducherry Dr. Ramachandran M, MBBS, IGMC&RI, Puducherry Dr. Priyadharshini A, MBBS, SVMCHRC, Junior Resident in Pediatrics, IGMC&RI, Puducherry Dr. Maheswaran, MBBS, Government Stanley Medical College, Chennai Dr. Vishnu Venkatesan, MBBS, SVMCHRC, Puducherry Dr. Shivam Yadav, MBBS, New Delhi Dr. Brijesh Chandra Yadav, Anaesthesia Resident, Motilal Nehru Medical College, Allahabad

viii  TARGET JIPMER Dr. Supriya Jeevanthanam, MBBS, Government Vellore Medical College, Vellore Dr. Rachit Singhania, MBBS, North Bengal Medical College and Hospital, Darjeeling, West Bengal Dr. Renuga Devi, MBBS, Junior Resident in Pediatrics, MAPIMS, Melmaruvathur, Tamil Nadu Dr. Shahul Hamid, MBBS Intern, IGMC&RI, Puducherry Dr. Ashwin Reddy, MBBS, IGMC&RI, Puducherry Dr. Jayaram Saibaba, MBBS, IGMC&RI, Puducherry Dr. Immaneul Joshua, MBBS, IGMC&RI, Puducherry Dr. GK Raman, MBBS, IGMC&RI, Puducherry Dr. Ashok E, MBBS, DCH, Salem, Tamil Nadu Dr. Anandhasayanan Sriramalu, MBBS, Tirukkoyilur, Tamil Nadu and Mr. Thirunavukkarasu D, Government School English Lecturer (Retd), Puducherry Mrs. Sampurnam, Principal (Retd), SSVHSS, Puducherry Mr. Vijayan D, Cash Officer (Retd), SBI, Puducherry Mrs. Sagoundala, Under Secretary (Retd), Government of Puducherry Mr. Srinivasan Babu, PWD, Puducherry Mr. Dhinesh Shankar, EC Software, Chennai Mr. Rajkumar, System Engineer, Apple, CA, USA Write to Us Any observations, suggestions, criticisms are welcome. Write to the author at [email protected] Errata Please visit: ‘TARGET JIPMER Book Series’ Facebook page, www.drarunbabu.in & www.peepeepub.com Follow Author in Facebook: www.facebook.com/targetjipmer/and Dr Arun Babu’s Pediatrics Discussion group (TARGET Pediatrics by Dr Arun Babu)

CONTENTS 1. ANATOMY........................................................................................................................................................ 1 2. PHYSIOLOGY ............................................................................................................................................... 10 3. BIOCHEMISTRY............................................................................................................................................ 26 4. PHARMACOLOGY........................................................................................................................................ 37 5. PATHOLOGY................................................................................................................................................. 45 6. MICROBIOLOGY........................................................................................................................................... 58 7.

FORENSIC MEDICINE.................................................................................................................................. 64

8. PSM................................................................................................................................................................ 67 9. ENT................................................................................................................................................................ 71 10. OPHTHALMOLOGY...................................................................................................................................... 74 11. MEDICINE...................................................................................................................................................... 77 12. SURGERY...................................................................................................................................................... 94 13. OBSTETRICS AND GYNECOLOGY........................................................................................................... 125 14. ORTHOPEDICS........................................................................................................................................... 156 15. PEDIATRICS................................................................................................................................................ 161 16. DERMATOLOGY......................................................................................................................................... 195 17. ANESTHESIOLOGY.................................................................................................................................... 200 18. RADIOLOGY AND RADIOTHERAPY......................................................................................................... 203 19. PSYCHIATRY............................................................................................................................................... 205

JIPMER–December 2018  1

JIPMER–DECEMBER 2018 ANATOMY 1.

A midline protrusion in maxillary region is mostly due to which of the following? (a) Torus palatinus (c) Torus maxillarius

(b) Torus tubarius (d) Torus mandibularis

Explanation:

•

Torus means bony prominences

Torus palatinus:

• • • •

Painless bony growth on the roof of the mouth in the middle of the hard palate. 20 to 30 % of the population has torus palatinus. It occurs most frequently in women and those of Asian descent. Varies in size, 2 mm to 6 mm and varies in shapes — flat, nodular, spindle-shaped.

Torus maxillarius:

•



•

Maxillary tori is another meaning for palatal tori, and is composed of densely mineralized bones usually devoid of medullary cavity. Maxillary tori usually found bilaterally on both sides of the palate.

Torus tubarius:

•



•

The cartilaginous portion of the auditory tube lies directly under the mucous membrane of the nasopharynx, where it forms an elevation, the torus tubarius. The torus tubarius is very close to the tubal tonsil which is sometimes called the tonsil of torus tubarius.

Torus mandibularis:

•

Torus mandibularis is a bony growth that develops on the lower jaw, bilaterally beneath and on the sides of the tongue.

Torus palatinus

Torus maxillarius

Torus mandibularis

Ans: (a) Torus palatinus Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 533 & http://caringdentists.com

2  TARGET JIPMER 2.

Not true about Pterygopalatine fossa: (a) (b) (c) (d)

It contains pterygopalatine ganglion and third part of maxillary artery It inferomedially communicates with infra temporal fossa It communicates with middle cranial fossa through Vidian canal Foramen rotundum is located above the Vidian canal

Explanation: Pterygopalatine fossa:

• • •



•



• •



•

Shape: pyramidal space Location: just below the apex of the orbit on the lateral side of the skull Boundaries: o Laterally: infratemporal fossa [pterygomaxillary fissure] o Medially : nasopharynx [perpendicular plate of palatine bone, with its orbital and sphenoidal Processes] o Posteriorly: root of the pterygoid process and adjoining greater wing of the sphenoid [two openings in the posterior wall : 1.foramen rotundum, which transmits the maxillary nerve. 2. Vidian canal, which transmits the nerve of the pterygoid canal (Vidian nerve) o Foramen Rotundum is seen to lie above and lateral to the pterygoid canal o Anteriorly: posterior surface of the maxilla o Roof: body of the sphenoid Contents: third part of the maxillary artery, maxillary nerve and its branches and pterygopalatine ganglion. Functions: neurovascular conduit Communications: o with nasal cavity via sphenopalatine foramen o with orbit via medial end of inferior orbital fissure o with infratemporal fossa via pterygomaxillary fissure o with middle cranial fossa via foramen rotundum and the pterygoid canal o with oral cavity via greater palatine canal Applied Significance: Its proximity & communications to these adjacent areas permits the ready spread of both tumours and infection

Ans: (b) It inferomedially communicates with infra temporal fossa Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 552

JIPMER–December 2018  3 3.

Jersey finger is due to involvement of? (a) Extenser pollicis (c) Flexor digitorum profundus

(b) Flexor digitorum superficialis (d) Extensor digiti minimi

Explanation: Jersey Finger

•



• • • •



• •



•



•

Named Jersey Finger since typically associated with a sports player trying to grab the jersey of an opponent and injuring his finger. Jersey Finger is due to avulsion of the FDP (Flexor Digitorum Profundus) FDP inserts at the base of the distal phalanx Jersey Finger involves ring finger in a great percentage due to the anatomy of our fist. Ring finger tip is 5mm more prominent than the other digits when the hand is closed, which causes more exposure of the fingertip during a strong grasp. The area injured is known as flexor tendon zone 1 which involves the tip of the fingers. This zone is prone to avulsions and lacerations injuries to the tendons.

The Jersey Finger is classified from type I to type V based on the level of tendon retraction in the hand and the presentation of fracture on the distal phalanx Leddy and Packer Classification

Type

Description

Treatment

Type I

FDP tendon retracted to palm. Leads to disruption of the vascular supply 

Prompt surgical treatment within 7 to 10 days

Type II

FDP retracts to level of PIP joint

Attempt to repair within several weeks for optimal outcome

Type III

Large avulsion fracture limits retraction to the level of the DIP joint

Attempt to repair within several weeks for optimal outcome

Type IV

Osseous fragment and simultaneous avulsion of the tendon from the fracture fragment  (“Double avulsion” with subsequent retraction of the tendon usually into palm)

If tendon separated from fracture fragment, first fix fracture via ORIF then reattach tendon as for Type I/ II injuries

Type V

Ruptured tendon with bone avulsion with bony comminution of the remaining distal phalanx (Va, extra articular; Vb, intra-articular)

  Repair of fracture fragment and tendon repair

4  TARGET JIPMER

Ans: (c) Flexor digitorum profundus Ref: 1. https://www.orthobullets.com/hand/6015/jersey-finger 2. Avulsion Injuries of the Flexor Digitorum Profundus Tendon: Journal of the American Academy of Orthopaedic Surgeons, 2011, Vol 19, No 3; Page 152-162.



4.

Stellate ganglion is located: (a) Posterior to prevertebral fascia (c) Anterior to transverse process of C7

(b) Posterior to trachea (d) Anterior to transverse process of C5

Explanation:

•



• • • • • •

Inferior (or cervicothoracic/stellate) ganglion: fusion of the lower two cervical and first thoracic segmental ganglia [sometimes the second and even third and fourth thoracic ganglia]. The ganglion lies on or lateral to the lateral border of longus colli muscle The ganglion lies between the base of the C7 transverse process and the neck of the 1st rib Related anteriorly - vertebral artery & vein Related posteriorly - cervical pleura Related inferiorly - suprapleural membrane & costocervical trunk of the subclavian artery Laterally - superior intercostal artery

Ans: (c) Anterior to transverse process of C7 Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 469.

JIPMER–December 2018  5 5.

Which of the following hernias occurs through this opening (Shaded in red)? (a) Bochdalek hernia (c) Eventeration

(b) Morgagni hernia (d) Hiatus hernia

Explanation: Bochdalek’s hernia: (Posterolateral hernia)

•



• •

Posterolateral hernia is the most common (85–90%) and may be bilateral (5%) or unilateral. Left side is more commonly affected (80%). Embryological basis: failure of fusion of the pleuroperitoneal membrane Primary abnormality is lung hypoplasia, and the herniation of the abdominal contents is secondary

Morgagni hernias: (Hernias between the costal and sternal origins)

•

Morgagni hernias are rare (1–2%)

Antenatal measures:

• • • •



•



•

Diaphragmatic hernias can usually be diagnosed by antenatal ultrasound examination. The presence of bowel in the thorax and mediastinal shift may be seen sonographically The main causes of death in babies with diaphragmatic hernias are pulmonary hypoplasia and hypertension. Pulmonary hypoplasia is related to the abnormal branching of the airways both ipsilaterally and contralaterally, resulting in the formation of reduced numbers of alveoli. Pulmonary hypertension is related to pulmonary hypoplasia, and also to the increased muscularization and reactivity of the pulmonary circulation. Associated abnormalities, including trisomy 13 and 18

Diaphragmatic eventration:

•



• •

In which an abnormal diaphragmatic silhouette is seen on X-ray with an abnormal medial bulge into the thorax It is associated with paradoxical motion of the diaphragm during respiratory movements. Embryological basis: failure of formation and migration of mesenchyme over the pleuroperitoneal membrane.

Ans: (a) Bochdalek hernia [shaded region is posterolateral, developed from pleuroperitoneal membrane] Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring. 41st edition, 2016, Page 907

6  TARGET JIPMER 6.

Median lingual swelling was shaded. What is the special sensory supply the (red) shaded area? (a) Lingual nerve (c) Glossopharyngeal nerve

(b) Chorda tympani nerve (d) Hypoglossal nerve

Explanation:

• •



•



•

The sensory innervation of the tongue reflects its embryological development Anterior two-thirds (presulcal part) is derived from first arch mesenchyme [2 lingual swelling & tuberculum impar]- general sensation by lingual nerve and taste by chorda tympani nerve Posterior third (postsulcal part) from third arch mesenchyme [hypobronchial eminence]-both general and taste sensation by glossopharyngeal nerve Region of the valleculae is supplied by the internal laryngeal branch of the vagus nerve.

Ans: (b) Chorda tympani nerve [shaded structure is tuberculum impar, developmental source of presulcal part (anterior 2/3) of tongue] Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring. 41st Edition, 2016, Page 511-514 7.

Which nucleus of cerebellum is responsible for slow saccadic movement? (a) Dentate nucleus (c) Fastigial nucleus

(b) Emboliform nucleus (d) Globose nucleus

Explanation:

• •



•



•



•



•

Cerebellum plays an important role in the control of eye movements The cerebral hemispheres are extremely important for the programming and coordination of both saccadic and pursuit conjugate eye movements The vestibulocerebellum (flocculus and nodule) is involved in gaze holding, smooth pursuit and the vestibuloocular reflex. The dorsal vermis and fastigial nucleus play a major role in programming accurate saccades and smooth pursuit. To remember: 4 main cortical areas in the cerebral hemispheres involved in the generation of saccades. 1. Frontal eye field,(Brodmann area 8) 2. Supplementary eye field,(Brodmann area 6) 3. Dorsolateral prefrontal cortex, (Brodmann area 46) 4. Posterior eye field,(Brodmann areas 39 and 40) These cerebral cortical areas are interconnected and send projections to the superior colliculus and the brainstem areas controlling saccades.

Ans: (c) Fastigial nucleus Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 675

JIPMER–December 2018  7 8.

Which among the following is not a normal variant? (a) Inferior sagittal sinus (c) Marginal sinus

(b) Occipital sinus (d) Median prosencephalic vein

Explanation: Median prosencephalic vein

• •



• • •



•

Median prosencephalic vein is a precursor of the vein of Galen The vein of Galen develops from an arteriovenous fistula between primitive choroidal vessels and the median prosencephalic vein The vein of Galen malformation represents 1% of all vascular brain malformations. Abnormal flow through this fistula retards the normal involution of the median prosencephalic vein Therefore, the vein of Galen malformation is a misnomer as the vein of Galen is not formed and it is the median prosencephalic vein which is dilated. The median prosencephalic vein drains into the sagittal sinus usually via a persistent falcine vein and the straight sinus is absent

Inferior sagittal sinus

• •

Located in the posterior half of the free margin of the falx cerebri It ends in the straight sinus and receives veins from the falx cerebri and sometimes from the medial surfaces of the cerebral hemispheres.

Occipital sinus

• •



• •

Located in the attached margin of the falx cerebelli and is occasionally paired. It commences near the foramen magnum in several small channels, one joining the end of the sigmoid sinus. It ends in the confluence of the sinuses. Connects with the internal vertebral plexuses.

Marginal sinus

• • • •

Marginal sinus encircles the foramen magnum. It communicates anteriorly with the basilar plexus and with the occipital sinus posteriorly. It typically drains to the sigmoid sinus or jugular bulb by small sinuses May connect extracranially to the internal vertebral venous plexus or the paravertebral or deep cervical veins in the suboccipital region.

Ans: (d) Median prosencephalic vein Ref: 1. Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring. 41st edition, 2016, Page 434-439 2. https://radiopaedia.org/articles/median-prosencephalic-vein 9.

Which is not Superior mediastinum content? (a) Branchial cyst (c) Extraadrenal pheochromocytoma

(b) Thymoma (d) Dermoid cyst

Explanation: Branchial cysts

•



•



• •

Branchial cysts and fistulae usually present in the upper neck as fluctuant swellings at the junction of the upper and middle thirds of the anterior border of sternocleidomastoid. The cyst typically passes backwards and upwards through the carotid bifurcation and ends at the pharyngeal constrictor muscles Intimate association with the hypoglossal, glossopharyngeal and accessory nerves. Great care must be taken to avoid damage to these nerves during surgical removal of a branchial cyst.

8  TARGET JIPMER Thymoma

• •



•



•

Thymus located in the superior mediastinum During thymectomy, a careful inspection of the remaining tissue in the mediastinum is performed to identify any possible anatomical anomalies that might result in retained thymic tissue after the operation. The most common anomaly is the unanticipated location of the upper poles of the thymus behind the left brachiocephalic vein. The aortopulmonary window is also a common location for thymic tissue and this area is sometimes difficult to expose with a transcervical approach. Any suspicious foci of fat in the mediastinum are removed, and, if necessary, sent for frozen section to ascertain whether or not they contain thymic tissue.

Extra-adrenal pheochromocytoma

• •

Extra-adrenal pheochromocytomas may arise in any portion of the paraganglion system. Most commonly occur below the diaphragm. Common site of occurrence is the superior para-aortic region between the diaphragm and lower renal poles.

Dermoid cyst

• •



• •



•



•



•



•

Dermoid cysts of the mediastinum are rare tumors. A majority lie in the upper half of the mediastinum anteriorly and just behind the sternum. Here the mass may extend upward to protrude in the suprasternal notch. Less commonly the tumor is situated in the lower portion of the mediastinum. Mediastinal dermoids occur at all ages, but the great majority of cases are found in patients between the ages of 15-30. There is no sex preponderance. In an occasional case, a blow on the chest or an infectious disease has apparently incited the tumor activity. Symptoms- due to pressure of the enlarging mass upon the adjacent tissues or organs, or may be due to irritation of the tumor producing the clinical picture of an intrathoracic inflammatory process. Genesis- derived from the third branchial arch which produces the deep sinus cervicalis and the thymus. The intimate relations of ectodermal and endodermal layers of the third and fourth arches may explain the variety of the epithelium and the connection with the thymus and thyroid; while the descent of the heart may carry these structures deep into the thorax. Dermoids of the lower mediastinum may result from imperfect closure of the anterior chest wall.

Ans: (a) Branchial cyst Ref: 1.Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 449,986 10.

Which nerve is liable for injury on removing the fish bone from pyriform fossa? (a) Internal laryngeal nerve (c) Recurrent laryngeal nerve

(b) External laryngeal nerve (d) Superior laryngeal nerve

Explanation:

• • • • •



•



•



•

Piriform fossa lies on each side of the laryngeal inlet Boundaries: Medially - aryepiglottic fold, Laterally- thyroid cartilage and thyrohyoid membrane Branches of the internal laryngeal nerve lie beneath its mucous membrane. Internal laryngeal nerve is a branch from superior laryngeal nerve of vagus Superior laryngeal nerve (mixed nerve) divided into internal laryngeal nerve (sensory) & external laryngeal nerve (motor) Internal laryngeal nerve supplies the mucosa from the base of tongue (valleculla) upto the level of vocal cord. Internal laryngeal nerve accompanies superior laryngeal artery and pierces thyrohyoid membrane to supply the mucosa of larynx. External laryngeal nerve supplies the cricothyroid muscle of larynx.

Ans: (a) Internal laryngeal nerve Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 577

JIPMER–December 2018  9 11.

Maximum Coronal diameter (in mm) of trachea in male and female (a) 25 and 23 (c) 25 and 27

(b) 25 and 21 (d) 20 and 17

Explanation:

•

The external transverse diameter of trachea is typically 2 cm in adult males and 1.5 cm in adult females.

Note:

•



• • • •

Mean transverse diameter is greater than anteroposterior diameter up to the age of 6 years, after that the two diameters are nearly equal The lumen of trachea is about 12 mm in diameter (internal transverse diameter) In the first postnatal year, the tracheal diameter does not exceed 4 mm. Length of trachea : 10–11 cm Trachea consists of 16–20 “C” shaped incomplete rings of hyaline cartilage

Ans: (d) 20 mm and 17 mm Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st edition, 2016, Page 965 12.

Neuronal migration is complete at which month of gestation? (a) 4

(b) 5

(c) 6

(d) 7

Explanation:



“Neuronal migration is thought to be complete by 20 weeks’ gestation.” Pediatric Neuroradiology: Brain. Head, Neck and Spine - Page 206 “Neuronal migration to the human cerebral cortex roughly spans a period between 8 and 16 weeks of gestational age, tapering off after this period to its almost unmarked completion by 24–26 weeks of gestation”. Disorders of Neuronal Migration, Peter G Barth, Pg XI “But once the neuronal migration is complete by 20 weeks an asphyxial insult cannot damage the brain in the same way since all the neurons have completed the migration by then”. Recent Advances in Pediatrics; Neonatal Emergencies, Suraj Gupte, Page 123 • With the above references, it is safe to conclude that Neuronal migration is completed between 20 – 26 weeks. Fetal Neural Growth



•



• •



• •

By 28 weeks after conception, brain has virtually all the neurons it will ever have, .i.e. the proliferation and migration of neurons completed by this time. Neurogenesis is the proliferation of neurons through cell division, mostly from conception to 20 weeks. Migration – peaking between 12-20 weeks, neurons move to particular locations in the brain; innermost brain first, outermost brain last. Myelination begins in 4th month of prenatal development and continues into adulthood. Synaptogenesis: from 3 months before birth to 2 years of age, number of synapses increases

Ans: (d) 7 months Ref: Gray’s Anatomy, The Anatomical Basis of Clinical Practice, Susan Standring, 41st Edition, 2016, Page 255-263

10  TARGET JIPMER

PHYSIOLOGY 1.

Glomerular filtration barrier does not permit: (a) 4000 daltons (c) 40000 daltons

(b) 400 daltons (d) 40 daltons

Explanation:

•



•



•



•



•



•

The glomerular filtrate is nearly protein-free and contains most inorganic ions and low-molecular-weight organic solutes in virtually the same concentrations as in the plasma. Selectivity of the filtration barrier to the solute to be filtered is based on their molecular size and electrical charge. Solutes of molecular weight of less than 7000 Da are freely filtered through the filtration barrier. Small ions, glucose, urea, amino acids and many hormones are freely filtered. Filtration barrier does not filter plasma albumin of molecular weight 66,000 Da. However very small quantity of about 0.02 % of plasma albumin is filtered in the glomerulus. The amount filtered through the glomerulus become smaller as the molecular weight of the substance increases from 7000 to 70,000 Da. The surface of the filtration barrier contains polyanions which repels the negatively charged molecules from filtration. Negatively charged macromolecules are filtered to lesser extent. Positively charged macromolecules are filtered to a greater extent than neutral molecules. Almost all plasma proteins are negatively charged.

Ans: (c) 40000 daltons Ref: Guyton and Hall Textbook of Medical Physiology, 13th edition, Page 336 & Vander’s Renal Physiology, 7th edition, Page 26 2.

Ultra filtrate passes through all filtration barrier except: (a) Endothelial fenestra (c) Fenestra in podocytes

(b) Basement membrane (d) Filtration slit between podocytes

Explanation:

•

Glomerular capillary membrane consists of three layers o Capillary endothelium o Basement membrane o Layer of epithelial cells (Podocytes)

JIPMER–December 2018  11

•



•



•



•

The capillary endothelium is perforated by thousands of small holes called fenestrae. These fenestrations are endowed with negative charges that prevents filtration of plasma proteins. The basement membrane surrounding the capillary endothelium consists of a meshwork of collagen and proteoglycan fibrillae. Large amounts of water and small solutes are filtered through this layer. They prevent filtration of plasma proteins because of the presence of strong negative charges associated with proteoglycans. The outer surface of the glomerulus is lined by a layer of epithelial cells that contain foot processes called the podocytes. The podocytes are separated by slit pores through which the substances are filtered. They also contain negative charges which prevents passage of negatively charged particles. Blood is filtered through filtration barrier to form glomerular filtrate. The filtered fluid passes through the following layers of the glomerulus o Fenestrae in the glomerular capillary endothelial layer o Basement membrane o Slit diaphragm through podocyte foot processes.

Ans: (c) Fenestra in podocytes Ref: Ganong’s Review of Medical Physiology, 26th edition 3.

How much % of glucose gets reabsorbed in late PCT ( 3rd segment of PCT)? (a) 2

(b) 5

(c) 7

(d) 10

Explanation:

• •



•



•

Normally all filtered glucose are reabsorbed in proximal convoluted tubule. This involves removing glucose from the tubular lumen along with sodium via a sodium-dependent glucose symporter (SGLT) across the apical membrane of proximal convoluted tubule epithelial cells, followed by its exit across the basolateral membrane into the interstitium via a GLUT uniporter. Approximately 90 % of the filtered glucose is reabsorbed by SGLT 2 in the early part of proximal tubule and remaining 10 % is reabsorbed by SGLT1 in late part of Proximal Tubule. On the basolateral side, Glucose diffuses out of the cell via GLUT 2 is early PCT and GLUT 1 in late PCT.

Ans: (d) 10 Ref: Guyton and Hall, Textbook of Medical Physiology, 13th edition, Page 349 4.

Formula for calculating Oxygenation index (OI): (a) (FiO2 × PaO2)/ Mean Airway Pressure (c) (PaO2 × Mean Airway Pressure)/FiO2

(b) (FiO2 × Mean Airway Pressure)/PaO2 (d) FiO2 / (PaO2 × Mean Airway Pressure)

Explanation: Oxygenation index

•

Oxygenation index = MAP × FiO2 ÷ PaO2 o FiO2 = fraction of inhaled oxygen, % o MAP= mean airway pressure, mm Hg o PaO2 = Partial pressure of arterial oxygen, mm Hg



•



•

Oxygenation Index is considered to be a superior ‘integrated’ index of the oxygenation efficiency of the lungs during mechanical ventilation in Pediatric critical care. It is used to assess severity of hypoxic respiratory failure and persistent pulmonary hypertension of the newborn. Increase in Oxygenation index denotes worsening of the oxygenation status. Oxygenation index more than 40 signifies the need for ECMO.

Oxygen Saturation Index

•

Oxygen saturation index =Mean Airway Pressure × FiO2 ÷ SpO2 is an alternate method of assessing severity of hypoxic respiratory failure.

12  TARGET JIPMER Ans: (b) (FiO2 × Mean Airway Pressure)/PaO2 Ref: Rawat, Munmun et al. “Oxygen saturation index and severity of hypoxic respiratory failure” Neonatology vol. 107, 3 (2015): 161-6. 5.

Which of the following best describe ‘Anrep effect’? (a) Increased preload decreases cardiac contractility (c) Increased preload decreases cardiac relaxation

(b) Increased after load increases cardiac contractility (d) Decreased after load decreases cardiac relaxation

Explanation: Anrep Effect (Homeometric autoregulation)

•



•



•



•



• •



•

The Anrep effect is an autoregulation method in which myocardial contractility increases with afterload. It was experimentally determined that increasing afterload caused a proportional linear increase in ventricular inotropy* Sudden increase in afterload causes an increase in ventricular contraction. This is not only observed in intact hearts but also in denervated hearts and isolated cardiac muscle. A sudden increase in aortic pressure causes a rapid increase in left ventricular end-diastolic volume. This leads to an initial increase in force of contraction of the ventricle through Frank Starling’s mechanism. If the increased afterload is maintained for 10-15 minutes, the force of contraction increases further and the end-diastolic volume begins to decrease. Without Anrep effect, an increase in aortic pressure would result in sustained decrease in cardiac output. The initial increase in contractile force (Frank-Starling mechanism) is largely due to increased troponin C sensitivity to calcium. The delayed increase in contractility is likely promoted by increased release of calcium by the sarcoplasmic reticulum, mediated by endothelin-1 and angiotensin II released by cardiac cells in response to stretch.

Ans: (b) Increased after load increases cardiac contractility Ref: Joel A. Kaplan, Essentials of Cardiac Anesthesia for Noncardiac Surgery: A Companion to Kaplan’s Cardiac Anesthesia, Page 113 & www.cvphysiology.com/Cardiac%20Function/CF009 6.

When the HR is 72 beats per min, what would be the duration of cardiac cycle? (a) 445 ms (c) 700 ms

(b) 1450 ms (d) 833 ms

Explanation:

•



•

Cardiac Cycle refers to the cardiac events that occur from the beginning of one heartbeat to the beginning of the next. The duration of each cardiac cycle is calculated by diving 60 by the heart rate If the heart rate is 72 bpm. o Total duration of cardiac cycle = 60/72 = 0.833 seconds or 833 msec.

Events in cardiac cycle:

Phase

Duration

Atrial cycle Atrial Systole

0.1 sec

Atrial Diastole

0.7 sec

Ventricle Cycle Ventricular Systole

0.27 Sec

Ventricular systole consisting of the events such as:

• • •

Isometric contraction – 0.05 sec Rapid ejection – 0.1 sec Slow ejection – 0.15 sec Contd.

JIPMER–December 2018  13 Contd.

Ventricular Diastole

• • • • •

•

0.53 sec

Protodiastole – 0.04 sec Isometric relaxation - 0.06 sec Rapid passive filling phase – 0.11 sec Reduced filling phase or diastasis – 0.19 sec Last rapid filling phase – 0.1 sec

As the heart rate increases, the duration of each phase decreases.

Ans: (d) 833 ms Ref: Guyton and Hall, Textbook of Medical Physiology, 13th edition, Page 113 & Indu Khurana, Textbook of Medical Physiology, 2nd edition, Page 274 7.

Formula to calculate minute ventilation volume: (a) TV × RR (c) TV × (RR–dead space)

(b) Fio2/PEEP (d) TV + (RR–dead space)

Explanation: Minute Ventilation and Alveolar Ventilation

•



•

Minute ventilation or Respiratory Minute Volume is the amount of air inspired or expired per minute. It is calculated as tidal volume times breaths per minute i.e., o Minute Ventilation = Tidal Volume x Respiratory Rate o Normal Minute Ventilation volume is about 6 L. (MV = 500 mL × 12 breaths per minute) Alveolar Ventilation is the amount of fresh gas reaching the alveoli. It takes part in gas exchange. o Alveolar Ventilation = (Tidal Volume – Dead Space) × Respiratory Rate o Normal Alveolar Ventilation is about 4.2 L. [Alveolar Ventilation = (500-150) × 12]

Dead Space

•



•



• •

The anatomic dead space is the volume of air present in the conducting zone that does not take part in gaseous exchange. It can be measured by Single breath Nitrogen Technique. The physiologic dead space includes both anatomical dead space and alveolar dead space. It is calculated by Bohr’s equation. In healthy individuals anatomical dead space and physiological dead space are equal. Physiological dead space is higher in conditions such as Emphysema, Bronchiectasis, etc.,

Ans: (a) TV × RR Ref: John B West, Respiratory Physiology: The Essentials, 9th edition, Page 20 8.

Which of the following best describes Baroreceptors? (a) Stretch receptor (c) Chemo-receptor

(b) Ligand gated receptor (d) Enzyme receptor

Explanation:

•



•



•



• • • •

The arterial baroreceptors also called as pressoreceptors are the stretch receptors located in the carotid sinus and in the aortic arch. Baroreceptor nerve terminals in the walls of the carotid sinus and aortic arch respond to the vascular stretch and deformation induced by changes in arterial blood pressure. The frequency of firing of these nerves is enhanced by an increase in arterial blood pressure and diminished by a reduction in arterial blood pressure. Baroreceptors are sensitive to pulsatile pressure than constant pressure. Afferent from carotid sinus – Glossopharyngeal nerve (Carotid Sinus nerve or nerve of Herring) Afferent from wall of arch of aorta – Branch of vagus nerve (aortic depressor nerve). They are collectively called as sinoaortic nerves or buffer nerves. Most of these fibers end in Nucleus Tractus Solitarius (NTS) and secrete the excitatory neurotransmitter glutamate. These projections extend to Caudal Ventrolateral medulla (CVLM). Projections from CVLM in turn inhibits the Rostral Ventrolateral medulla (RVLM) by secreting γ-aminobutyric acid (GABA).

14  TARGET JIPMER

Ans: (a) Stretch receptor Ref: Ganong’s Review of Medical Physiology, 26th edition 9.

Features of Chronic mountain sickness are all except: (a) Hyperventilation (c) Increase in HCO3 excretion

(b) Increase erythropoietin (d) Decrease in mitochondria

Explanation: Chronic Mountain Sickness – other name: Monge’s disease

•



•



•



•

Chronic mountain sickness is seen in people living in high altitudes for long time. It usually occurs in native people living in high altitudes after 40 years of age. It is characterized by excessive erythrocytosis (Hb level >19 g/dl in females and > 20 g/dl in males), severe hypoxemia and in severe cases Pulmonary hypertension. MC symptoms includes headaches, dizziness, dyspnea, sleep disturbances, tinnitus, physical and mental fatigue, alterations of memory, loss of appetite, muscle pain. Laboratory parameters o Hemoglobin and hematocrit values are ↑↑. o The arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) are ↓↓. o Arterial partial pressure of carbon dioxide (PaCo2) levels are ↑↑.

JIPMER–December 2018  15



•



•



•

o Bicarbonate levels are higher than the people living in same altitudes which indicates mild respiratory alkalosis with partial renal compensation (i.e., increase HCO3 excretion). Patients with CMS were found to have blunted ventilator response to hypoxia and are found to be breathless. Prolonged exposure to extreme high altitude leads to loss of mitochondrial volume density in skeletal muscle. Modification of lifestyle and prevention from obesity and COPD seems to prevent chronic mountain sickness.

Acute Mountain sickness

•



•



•

People who ascend rapidly to high altitudes are at risk of developing certain sickness characterized by acute cerebral edema and acute pulmonary edema. Acute mountain sickness is characterized by dyspnea at rest, inability to walk, cyanosis, headache with sense of confusion, chest congestion, hemoptysis, decreased consciousness and pale appearance. It is prevented by slow ascent, breathing oxygen and descending to lower altitudes to sleep.

Ans: (a) Hyperventilation Ref: Ganong’s Review of Medical Physiology, 26th edition 10.

True about Bowditch’s effect of heart: (a) Increased in HR decrease relaxation (c) Increased in HR decrease contraction

(b) Increased in HR increase relaxation (d) Increased in HR increases contraction

Explanation: Bowditch effect

• • •

Increase in HR causes increase in contractility of the heart in human and mammalian heart. AKA treppe or frequency dependent activation. This phenomenon is due to an inability of the Na+/K+-ATPase to keep up with the sodium influx when the heart rate is increased. This leads to an accumulation of intracellular calcium via the sodium-calcium exchanger in the cardiac myocyte.

Factors affecting contractility of the heart: Factors that causes positive inotropic effect

•

Sympathetic nerves play a predominant role in inotropic regulation of the heart by releasing norepinephrine that binds to β1 receptors of the heart.

•

↑ Circulating catecholamines (Norepinephrine and Epinephrine)

•

↑ Heart rate (Bowditch effect)

•

↑ Afterload (Anrep effect)

Factors that causes negative inotropic effect

•

β receptor antagonists

•

Calcium channel blockers

•

Acetylcholine released from parasympathetic fibers decreases contractility of the heart. Ach inhibits opening of calcium channels by cGMP pathway.

•

Myocardial ischemia causing inhibition of calcium channels.

Ans: (d) Increased in HR increases contraction Ref: Rodney A Rhodes, Medical Physiology: Principles of Clinical Medicine, Fourth edition, Page 250. Richard E Klabunde, Cardiovascular Physiology concepts, Second edition, Page 82

16  TARGET JIPMER 11.

Histologic picture of anoxic damage is shown. The region in brain most susceptible to anoxic damage is: (a) Locus coeruleus (c) Amygdala

(b) Hippocampus (d) Basal ganglia

Explanation:

•



• •



• •



•



•

Anoxic Ischemic brain injury is the most devastating complication of cardiac arrest. Due to hemodynamic collapse, there is decrease in cerebral blood flow which leads to loss of consciousness. Neurons and glial cells may be saved if patient is resuscitated immediately and the circulation is restored. During decreased cerebral blood flow due to cardiac arrest, vulnerability of neuronal damage due to hypoxia is not the same in all areas of the brain. The CA1 neuronal cells of Hippocampus is found to be the most susceptible region to hypoxic damage. The Basal ganglia (caudate nucleus and putamen), cerebellar purkinje cells and the neocortex are the other areas susceptible to hypoxic brain damage. Presence of excitatory neurotransmitter receptors or high metabolic demands could be the reason for the susceptibility of these areas. When oxygen supply is disrupted the regulatory mechanisms that maintain the cerebral blood flow are activated to regulate the cerebral blood flow. These regulatory mechanisms are exhausted during prolonged hypoxia. At the neuronal level damage occurs due to release of excitatory neurotransmitters that causes an influx of sodium that leads to cellular swelling and injury.

Ans: (b) Hippocampus Ref: Alejandro A. Rabinstein, Neurocritical Care, An Issue of Neurologic Clinics, E-Book, Page 602 12.

Glucose is absorbed through apical membrane of PCT by which transporter? (a) SGLT-1 (c) GLUT-1

(b) SGLT-2 (d) GLUT-2

Explanation:

•

Glucose is filtered in the glomerulus at a rate of about 100 mg/min and essentially almost all the glucose is reabsorbed.

JIPMER–December 2018  17

•



•



•

Glucose is reabsorbed along with Sodium by secondary active transport in the early part of proximal convoluted tubule (PCT). Transport maximum is the limit to the rate at which the substances are reabsorbed. This limit is due to the saturation of the carrier proteins. Transport maximum for glucose is 375 mg/min in men and 300 mg/min in women.

Mechanism of Glucose transport:



•

Glucose is transported into the cell by binding to sodium-dependent glucose transporter (SGLT)-2 along with Na+. SGLT 2 specifically binds to D – Glucose and has less affinity towards L Glucose.



•

Glucose is carried into the cell as Na+ moves down its electrical and chemical gradient.



•

Glucose then transported to the interstitial fluid from the cell by facilitated diffusion via Glucose transporter – GLUT 2



•

Phlorhizin inhibits glucose reabsorption in the kidney.

Ans: (b) SGLT-2 Ref: Ganong’s Review of Medical Physiology, 25th edition, Page 681. & Guyton and Hall Textbook of Medical Physiology, 13th Edition, Page 350 13. IP3 facilitates the entry of which of the following ions into cytoplasm? (a) Na+ (c) Ca2+

(b) K+ (d) Mg2+

Explanation:

•



•



•



•



•

Intracellular Ca2+ as affected by IP3-DAG pathway is an important second messenger system affecting multiple physiologic processes IP3-DAG pathway can be activated by G-protein coupled signal transduction or via tyrosine kinase receptors In this pathway, binding of an appropriate ligand to its receptor results in activation of phospholipase C (PLC) enzyme (present in the inner aspect of cell membrane) which causes breakdown of a membrane phospholipid, phosphatidyl 4,5 disphosphate (PIP2) to inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG) IP3 binds to the IP3 receptor (a ligand-gated Ca2+ channel) on the endoplasmic reticulum and triggers release of Ca2+ into the cytoplasm DAG is also a second messenger, stays in the cell membrane, and activates protein kinase C (PKC) which is involved in protein phosphorylation.

18  TARGET JIPMER Trivia:

•



• • •



•

Ligands acting via this pathway: angiotensin II, norepinephrine via α1 receptor, vasopressin via V1 receptor Extracellular ligands are the first messengers Resting free intracellular [Ca2+] = 100 nmol/L = 1/12000 [Ca]ECF Transient Ca2+ release from internal stores opens calcium channels on cell membrane called store operated calcium channels Ca2+ is pumped back into ER by sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA)

EXTRA EDGE:

• •

Largest source of IP3 : membrane phospholipid : PIP2 The basic structure of the membrane recpetor to which the extracellular molecules bind has seven transmembrane domains

Second messengers mediating hormonal functions:

• • • • • •

cAMP cGMP IP3 DAG Ca++ Phospholipase C

Hormones using Phospholipase C second messenger system:

• • • • • •

Vascular smooth mucles – vasopressin I receptor, Angiotensin II GnRH GHRH Oxytocin a receptors of catecholamines TRH

Ans: (c) Ca2+ Ref: Ganong’s Review of Medical Physiology, 25th edition, Page 55, 57-59 & Guyton and Hall, Textbook of Medical Physiology, Second South Asian edition, Page 573-575 14.

IGF-1 acts through which of the following receptors? (a) Cytokine related receptor (c) Tyrosine kinase receptor (e) JAK/STAT

(b) G protein couple receptor (d) Nuclear or cytoplasmic

Explanation:

•

Insulin, IGF-1, IGF-2, EGF and PDGF act via tyrosine kinase receptors (TKRs). Binding of ligand to TKRs

JIPMER–December 2018  19 causes dimerization of receptor which in turn activates the intrinsic tyrosine kinase activity and cause cross-phosphorylation of the receptors and downstream effects thereof. General scheme of signal transduction of growth factors affecting gene expression (TKR: tyrosine kinase receptor)

Signal transduction for various peptide hormones: Agonists

Receptor

Linked Enzyme

Second Messenger

PTH

Coupled to Gas

Adenylyl cyclase

cAMP

ANG II

Coupled to Gai

Adenylyl cyclase (inhibited)

cAMP

AVP, ANG II, TRH

Coupled to Gaq

PLC

IP3 and DAG

ANG II

Coupled to Gi/ Go

PLA2

Arachidonic acid metabolites

ANP

Guanylyl cyclase

Guanylyl cyclase

cGMP

Insulin, IGF-1, IGF-2, EGF, PDGF

Tyrosine kinase

Tyrosine kinase

Phosphoproteins

GH, erythropoietin, LIF

Associated with tyrosine kinase

JAK-STAT family of tyrosine Phosphoproteins kinases

ANG II, angiotensin II; ANP, atrial natriuretic peptide; EGF, epidermal growth factor; JAK-STAT, Janus kinase/signal transducer and activator of transcription; LIF, leukemia inhibitory factor.

Ans: (c) Tyrosine kinase receptor Ref: Medical Physiology (A cellular and molecular approach) Updated 2nd edition by Boron & Boulpaep, Page 1021 & Ganong’s, Review of Medical Physiology, 25th edition, Page 61-62 15.

Neurotransmitter of inner hair cells: (a) GABA (c) Glycine

(b) Glutamate (d) Acetyl choline

Explanation:

•

Micro-iontopheretic techniques investigating various candidate neurotransmitters have shown that inner hair cells are connected to afferent type I auditory neurons by glutamate. The efferent lateral olivocochlear

20  TARGET JIPMER system has modulatory effects on this synapse via inhibitory GABA and dopamine, and excitatory acetylcholine. EXTRA EDGE: The inhibitory neurotransmitter GABA is found to be secreted by the amacrine cells – Substance P ganglion cells in retina Ref: Neurotransmitters in the retina by Helga Kolb. Ans: (b) Glutamate Ref: Ganong’s Review of Medical Physiology, 25th edition, Page No: 204 & Advances in Oto-Rhino-Laryngology 59 (2002): 131–39. 16.

False about funny current channel in heart: (a) (b) (c) (d)

It is a Na-K channel They are responsible for diastolic depolarization It is responsible for spontaneous rhythm producing tissue of heart They are voltage dependent channel only

Explanation: Pacemaker current /Funny current Funny current (If) is the pacemaker current found in SA node, AV node and Purkinje fibers



•



•



•



•

The unusual property (“funny”) is that they do not conduct in positive potentials but are activated by hyperpolarization at the end of phase 3, and is responsible for early part of prepotential



•

ICa contributes to later part of prepotential and thus to pacemaker activity



•

The channel is well-modulated by binding of cAMP (regulated)

A nonspecific cation channel called HCN (hyperpolarization activated, cyclic nucleotide gated) channel produces If Reversal potential of If is -20 mV (Nernst potential for Na is +50 mV and K is -90 mV)

EXTRA EDGE:

•

First described by H.F.Brown in 1979 – funny channel



•

Ivabradine – found to selectively bind to the funny channels – prolongs diastolic duration by reducing the diastolic depolarization. It causes only reduction in heart rate without affecting BP. This drug got approved by European Medical Agency and is used in India. It is teratogenic and can cause side effects like blurred vision and bradycardia.

Ans: (d) They are voltage dependent channel only Ref: Medical Physiology (A cellular & molecular approach) Updated 2nd edition by Boron & Boulpaep, Page 509; Nature 411, no. 6839 (June 14, 2001): 805–10. & “Funny Current and Cardiac Rhythm: Insights from HCN Knockout and Transgenic Mouse Models.” Frontiers in Physiology 3 (2012). 17.

All are related to negative lusitropy except: (a) Excess calcium within cell (b) Defective calcium removal through NCX exchanger (c) Improper functioning of SERCA pump (d) Excess catecholamines

Explanation:

• •

Lusitropy refers to speed of relaxation. Negative lusitropy means prolonged relaxation. Catecholamines are positively lusitropic as they increase the speed of relaxation by promoting rapid reuptake of free calcium from the cytosol.

JIPMER–December 2018  21 b, Adrenoceptor ↓ Activated as ↓ ↑ Adenylyl cyclase ↓ ↑ cAMP ↓ ↑ Protein kinase A ↓ Phosphorylation of phospholamban (PLN)

Phosphorylation of troponin 1 (TNNI 3)

↑ SR Ca2+ pump (SERCA2a)

↑ Off-rate of Ca2+ from Ca2+- TNNC1 complex

↑ Ca2+ reuptake into SR ↑ Ca2+ stores

↑ Speed of relaxation (lusitropic)

↑ Speed of relaxation (lusitropic effect)

↓ Duration of contraction

↓ Duration of contraction

Ans: (d) Excess catecholamines Ref: Medical Physiology (A cellular & molecular approach) Updated 2nd edition by Boron & Boulpaep, Page 563 18.

The mechanism responsible for sustained vascular smooth muscle contraction is: (a) Sustained calcium release from SERCA pump (c) Latch bridge mechanism

(b) Vascular smooth muscle tone (d) Henneman principle

Explanation:

•

Smooth muscles can maintain high force generation at low energy consumption. This low energy consumption/ high-tension state is called latch state. While the exact mechanism is unknown, sustained binding of Ca to calmodulin, and slower rate of detachment of cross-bridges are the proposed mechanisms

EXTRA EDGE: Hennemens size principle

•



• •

The muscles are recruited in the order of their size ie; one must engage in tasks that require high force outputs to recruit high threshold muscle motor units. Order of recruitment: type I > II A > II B Exceptions to the principle: o Eccentric exercises o Explosive movements.

Ans: (c) Latch bridge mechanism Ref: Medical Physiology (A cellular & molecular approach) Updated 2nd edition by Boron & Boulpaep, Page 259 & Ganong’s Review of Medical Physiology, 25th edition, Page 116 19.

Which of the following is true about TRPV channel? (a) Related to pain (c) Related to pleasure

(b) Related to pruritus (d) Related to fine touch

Explanation:

•

TRPV (transient receptor potential vanilloid) channels are a group of nonselective cation channels present on the endings of nociceptive sensory fibers that respond to noxious thermal, mechanical or chemical stimuli.

22  TARGET JIPMER

•

TRPV1 is activated by capsaicin (ingredient responsible for burning sensation in spicy foods). Chillies taste hot because they activate same ion channels that heat activates. Threshold for TRPV1: 43°C, and hence responsible for nociceptive aspects of heat. TRPV2-4 channels are activated at moderate temperatures and hence code warmth sensation.

Trivia:

•

TRPM8 receptor is a cold receptor beginning to get activated at 27°C, with maximal activation at 8°C. It is a menthol receptor and hence menthol evokes cold sensation.

Ans: (a) Related to pain Ref: Medical Physiology (A cellular & molecular approach) Updated 2nd edition by Boron & Boulpaep, Page 404 20.

Which of the following is correctly matched regarding memory? (a) Hippocampus- implicit memory (c) Medial temporal lobe – Declarative memory

(b) Neocortex - associative learning (d) Cerebellum - priming

Explanation: Long-term memory

Declarative: Things you know that you can tell others

Episodic: Remembering your first day in school

Semantic: Knowing the capital of France

Nondeclarative (procedural): Things you know that you can show by doing

Skill learning: Knowing how to ride a bicycle

Priming: Being more likely to use a word you heard recently

Conditioning: Salivating when you see a favorite food

Declarative/explicit memory

Semantic (facts)

Episodic (events)

Lateral and anterior temporal cortex, prefrontal cortex

Hippocampus, medial temporal lobe, neocortex

Nondeclarative/implicit memory

Procedural (skills, habits)

Priming and perceptual

Associative learning (classical conditioning

Nonassociative learning (habituation, sensitization

Striatum, cerebellum, motor cortex

Neocortex

Amygdala, cerebellum

Reflex pathways

Ans: (c) Medial temporal lobe – Declarative memory Ref: Ganong’s Review of Medical Physiology, 25th edition, Page 285

JIPMER–December 2018  23 21.

Alveolar exchange ratio 0.8 with PaO2 49 and PaCO2 48. Calculate the gradient between alveolar and arterial O2 (A- a oxygen difference). (a) 10 (c) 30 (e) 60

(b) 50 (d) 40

Explanation: Calculation of alveolar to arterial gradient of O2 concentration (A-a) O2:

= PAO2 – PaO2 = [FiO2(Patm-PH2O) – PaCO2/RER] – PaO2 (from alveolar gas equation) = [0.21(760-47) – (48/0.8)] – 49 = 0.21*713 – 60 – 49 @ 150 – 109 = 41 mmHg Ans: (d) 40 Ref: Respiratory Physiology, The Essentials 8th edition by John B West, Page 61 and 63

22.

Transthoracic compliance formula: (a) C = Vt × RR /PEEP (c) C = Vt/Pplt - PEEP

(b) C= V/Alv p – atmospheric pressure (d) C = Vt/Pk - Pplt

Explanation:

• • • • • •

Lungs are elastic structures. Its ability to expand (stretchability) is quantified in terms of compliance Like lung, chest wall is also an elastic structure Compliance is defined as “the change in volume per unit change in the pressure” Compliance = ΔV/ΔP Here Transthoracic pressure is the difference between alveolar pressure and atmospheric pressure So, C= V/Alv p – atmospheric pressure

Ans: (b) C= V/Alv p – atmospheric pressure Ref: Ganong, 25th edition, Page 631 & Pilbeam’s Mechanical Ventilation JM Cairo, 5th editon, Page 31 23.

Normal value of EPO (U/L) is: (a) 10-25 (c) 45-55

(b) 15-40 (d) 55-65

Explanation: Erythropoietin (Epo)

• •



•

Is a glycoprotein hormone whose normal level is 10–25 U/L Receptor for erythropoietin – Cytokine receptor that activates tyrosine kinase Jak/STAT signaling cascade Mechanism of action of EPO - inhibits apoptosis of red blood cells

Sources of erythropoietin

•



• •

Kidney is the major source. Approx 85% of the erythropoietin comes from peritubular capillary bed cells of the kidneys Remaining 15 % of erythropoietin comes from perivenous hepatocytes in the liver Erythropoietin is also found in brain, uterus and fallopian tube

Ans: (a) 10-25 Ref: Ganong, 25th edition, Page 555

24  TARGET JIPMER 24.

Normal cardiac index in an adult is: (a) 5.9 L/min/m2 (c) 3.2 L/min/m2

(b) 2.3 L/min/m2 (d) 4.6 L/min/m2

Explanation: Cardiac output is the product of heart rate (HR) and stroke volume (SV) Cardiac output = HR X SV Normal cardiac output values:

• •

Men - 5.6 L/min Women - 4.9 L/min

Cardiac index:

• • •

Cardiac index is expressing cardiac output per square meter of body surface area Cardiac index = Cardiac output / Body surface area Normal cardiac index for adults is 3.2 L/min/m2 of body surface area

Ans: (c) 3.2 L/min/m2 Ref: Ganong, 25th edition, Page 543 25.

When capillary and interstitial hydrostatic pressures are 3 mm of Hg and 0 mm of hg and colloid oncotic pressure of capillaries and interstitum is 25 mm of Hg and 5 mm of Hg, what is the Net filtration pressure? (a) 17 mm Hg (c) 23 mm Hg

(b) 33 mm Hg (d) 10 mm Hg

Explanation:

•

The rate of filtration at any point along a capillary depends on a balance of forces sometimes called the Starling forces which are o Hydrostatic pressure gradient (Difference between Capillary Hydrostatic pressure & Interstitial Hydrostatic pressure) o Osmotic pressure gradient (Difference between Capillary Osmotic pressure & Interstitial Osmotic pressure) Fluid movement across the capillary depends on Net filtration pressure which is the difference between the hydrostic pressure gradient and oncotic pressure gradient.



•



Net Filtration Pressure = k [(Pc - Pi) - (πc - πi)] k = capillary filtration coefficient Pc = capillary hydrostatic pressure Pi = interstitial hydrostatic pressure πc = capillary colloid osmotic pressure πi = interstitial colloid osmotic pressure

Replacing the values we get; Net Filtration Pressure = (3 - 0) - (25 - 5) = - 17 mm Hg The minus sign indicates that fluid movement is inward into the capillary. So the answer is 17 mmHg Ans: (a) 17 mm Hg Ref: Ganong’s Review of Medical Physiology, 25th edition, Page 578-579.

JIPMER–December 2018  25 26. A Trekker is at an altitude of 13000ft (4000 m) above the sea level where the barometric pressure is 447 mm Hg. Calculate the partial pressure of inhaled oxygen in moist air: (a) 100 mm Hg (c) 93 mm Hg

(b) 149 mm Hg (d) 84 mm Hg

Explanation: The composition of dry air is 20.98% O2, 0.04% CO2, 78.06% N2, and 0.92% other inert constituents such as argon and helium. The barometric pressure (PB) at sea level is 760 mm Hg (1 atmosphere). At this barometric pressure, the partial pressure of gases in dry air can be calculated as: The partial pressure of O2 PO2 in dry air = 0.21 × 760 = 160 mm Hg at sea level. Similarly, PN2 = 0.79 × 760 = 600 mm Hg at sea level PCO2 = 0.0004 × 760 = 0.3 mm Hg at sea level These are partial pressures of gases in dry air. When dry air is inspired, air gets equilibrated with water vaporized from respiratory surfaces and the inspired air is saturated with water vapour by the time it reaches the lungs. Hence, the water vapour reduces the partial pressures of gases, to a slight degree. Water vapour pressure in alveoli is around 47 mm Hg at body temperature. This value remains constant regardless of altitude, as long as body temperature is normal. Hence the partial pressure of O2 inspired air (Pi O2 ) would be; PiO2 = 0.21 × (760 - 47) = 150 mm Hg With increase in altitude, there is decrease in PO2 due to decrease in barometric pressure, though the percentage of oxygen remains same (21%). In this question, at increased altitude, the barometric pressure given is 447 mm Hg. The water pressure would be same as at sea level i.e. 47 mmHg, considering normal body temperature. Hence the partial pressure of O2 inspired air (Pi O2 ) would be; Pi O2 = 0.21 × (447 - 47) = 84 mm Hg Ans: (d) 84 mm Hg Ref: Ganong’s Review of Medical Physiology, 25th edition, Page 634 & Guyton & Hall, Textbook of Medical Physiology, 13th edition, Page 561-562. 27. In a measurement of cardiac output during exercise using the Fick principle, the O2 concentrations of mixed venous and arterial blood are 15 and 20 ml/100 ml, respectively, and the O2 consumption is 250 ml/min. The cardiac output in liters/min is: (a) 5.2 liters/min (c) 4.8 liters/min

(b) 5 liters/min (d) 6 liters/min

Explanation: Cardiac output fomula by Fick’s principle FICK C.O. =

•



• •

O2 consumption (VO2) mL/min AVO2 difference × 10

The Fick principle states that the cardiac output is equal to the oxygen consumption divided by the arterialvenous oxygen concentration difference. Here, its (20 - 15) ml per 100 ml or (200 - 150) ml /liter Therefore, the cardiac output is equal to 250/(200 - 150) or 5 liters/min

Ans: (b) 5 Ref: Ganong, 25th edition, Page 543

26  TARGET JIPMER

BIOCHEMISTRY 1.

True regarding FGF 23: (a) It activates 1 alpha hydroxylase

(b) It causes hyperphosphatemia

(c) Its deficiency causes osteomalacia

(d) It enhances phosphate excretion

Explanation:

•

Fibroblast growth factor 23 (FGF 23) is a bone-derived hormone that regulates systemic phosphate homeostasis and vitamin D metabolism 



•

FGF23 inhibits renal tubular reabsorption of phosphate through mechanisms independent of PTH



•

It reduces circulating 1, 25(OH)2D through its dual effects by suppressing its production and stimulating catabolism of 1,25(OH)2D

Ans: (d) It enhances phosphate excretion Ref: Darryl Quarles, Role of FGF23 in Vitamin D and Phosphate Metabolism: Implications in Chronic Kidney Disease, Exp cell research 2012;318(9):1040-8. 2.

‘I’ cell disease is due to: (a) Peroxisome

(b) Mitochondria

(c) Lysosome

(d) Golgi apparatus

Explanation:

•

I cell disease (inclusion cell disease) is due to faulty targeting of lysosomal enzymes



•

Synthesis of lysosomal enzymes is normal, but enzymes do not reach lysosomes → elevated enzyme levels in plasma



•

Mannose 6 phosphate serves to target enzymes in lysosomes



•

In this disease, cells lack Mannose 6 P recognition marker



•

Mutations in gene encoding golgi located N acetyl glucosamine phospho transferase, results in absence of Mannose 6 Phosphate signal for lysosomal localization of certain hydrolases



•

In this disease,



Cells lack lysosomal enzymes



Molecules are not degraded



↓

Accumulation of undegraded molecules in lysosomes



↓

↓

Inclusion body formation

Ans: (c) Lysosome Ref: Harper’s Illustrated biochemistry, 30th edition, chapter 40, Page 496, chapter 46, Page 581

JIPMER–December 2018  27 3.

All the following affect equilibrium in Hardy Weinberg criteria except: (a) Small population size

(b) Random mating and fertilization

(c) Migration, gene flow

(d) Mutations

Explanation:

•



•



•



•

Population genetics is the study of alleles of genes in populations and forces which maintain or change the frequencies of particular alleles and genotypes in populations. Hardy-Weinberg equilibrium or principle or law states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary factors. Seven assumptions underlying Hardy Weinberg equilibrium: o Organisms are diploid o Only sexual reproduction takes place o Generations are nonoverlapping o Mating is random o Population size is infinitely large o Allele frequencies are equal in the sexes o There is no migration, gene flow, admixture, mutation or selection Factors influencing deviation in Hardy-Weinberg equilibrium are: o Genetic drift o Assortative mating o Selection of mate o Mutations o Subpopulations within the sample

Ans: (b) Random mating and fertilization Ref: Instant Notes, Genetics, 2nd edition, section D3-Page 211 4.

True about thyroid hormones: (a) Thyroid peroxidases form T3 from T4 (c) T4 is more protein bound to TBG than T3

(b) Half-life of T4 is more than T3 (d) Affinity of TBG is more for T4 than T3

Explanation:

•

T4 is otherwise known as thyroxine and it forms about 90% of the total secretion, whereas T3 is only 9% to 10%. The potency of T3 is four times more than that of T4 . T4 acts for longer period than T3 . Duration of T4 action is four times more than T3 action. This is because of the difference in the affinity of these hormones to plasma proteins. T3 has less affinity for plasma proteins and combines loosely with them, so that it is released quickly. T4 has more affinity and strongly binds with plasma proteins, so that it is released slowly. Therefore, T3 acts on the target cells immediately and T4 acts slowly. T4 has a long half-life of 7 days. Half-life of T3 is varying between 10 and 24 hours. Deiodinase converts T4 to T3



• •



•



• •



Steps of thyroid hormone synthesis: 1. Iodine trapping 2. Organification



3. Coupling



4. Storage



5. Secretion

28  TARGET JIPMER

2

3

4

5

1

Ans: (a) Thyroid peroxidases form T3 from T4 Ref: Essentials of Medical Physiology by Shambhu Lingam, chapter 69, Page 389 5.

Phosholipase C is activated by: (a) Gq

(b) Gi

(c) Gs

(d) G12

Explanation:

• • • • •

Phospholipases are enzymes that allow degradation and remodeling of phosphoglycerols. Phospholipase C is activated by G proteins (Gq class). Vasopressin, Ach, TRH, GnRH etc., employ this pathway. Effector is Phospholipase Cβ. 2nd messengers are IP3 & Ca2 and DAG. IP3–IP3 receptor and DAG-Protein Kinase C Extracellular signals Receptor G protein Phospholipase C (PLC)

Cell surface membrane

Phosphatidyl Inositol bis-phosphate (PIP2) Inositol 1,4,5 trisphosphate (IP3) all isoforms

IP3 receptor IRBIT Cellular

Ca2+ Response

Diacyl Glycerol (DAG) Protein Kinase C (PKC) Phosphorylation Cellular Response

JIPMER–December 2018  29 Ans: (a) Gq 6.

Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 54, Page 702

IP3 facilitates which ion entry into cytoplasm? (a) Na+

(b) K+

(c) Ca++

(d) Mg++

Explanation:

Ans: (c) Ca++ Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 54, Page 702 7.

Which of the following is the most effective buffer for pH of 7.4? (a) Carbonic acid buffer with pkA- 6.1 (c) Glutamate buffer with pkA -8.7

(b) Phosphate buffer with pKA of 6.9 (d) Acetate buffer with pKa 4.5

Explanation:

•



• • • • •

The choice of buffer depends on the buffering capacity in the desired ph range with the ability to maintain constant pH during fixation. The buffering range of a buffer is +1 of pKa, Phosphate buffer is the most appropriate option. Phosphate buffer is most physiological of all buffers Mimics certain components of extracellular fluid pH varies little with temperature Stable for several weeks at 4 degree C

Ans: (b) Phosphate buffer with pKA of 6.9 Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 2, Page 11 8.

All are true about Chromosomal walking except: (a) (b) (c) (d)

It is a method to isolate an allele from chromosomal library For short segments of DNA Used to detect single nucleotide polymorphisms It cannot be stopped by unclonable sections of DNA

30  TARGET JIPMER

Explanation:

•

Chromosome walking is a method of positional cloning used to find, isolate and clone of a particular allele in a gene library.



•

In chromosome walking , a fragment representing one end of a long piece of DNA is used to isolate another that overlaps but extends the first.



•

The direction of extension is determined by restriction mapping, and the procedure is repeated sequentially until the desired sequence is obtained.



•

The technique of chromosome walking is as follows:

Intact DNA

Gene X

Fragments

Initial probe



•

Gene X is to be isolated from a large piece of DNA.



•

The exact location of this gene is not known, but a probe (*——) directed against a fragment of DNA ( 5’ end of ) is available, as is a library of clones containing a series of overlapping DNA insert fragments.



•

The initial probe will hybridize only with clones containing fragment 1, which can then be isolated and used as a probe to detect fragment 2. This procedure is repeated until fragment 4 hybridizes with fragment 5, which contains the entire sequence of gene X.

Application of chromosome walking:

1. Detection of genetically inherited diseases, especially X chromosome linked disorders as only single allele is expressed here.



2. Detection of single nucleotide polymorphisms(SNPs)



3. Disadvantage of this technique: It can be stopped by unclonable sections of DNA Ans: (d) It cannot be stopped by unclonable sections of DNA Ref: Harper’s Illustrated Biochemistry, 30th edition, Chapter 39, Page 463

9.

Limit dextrinosis: (a) Coris disease

(b) Her’s disease

(c) Mcardle’s disease

(d) Anderson disease

Explanation: Glycogen Storage Disorders (Glycogenoses)

•

Abnormal storage of glycogen (normal or abnormal type)



•

Liver or skeletal muscle affected in many types



•

Some are multisystem disorders



•

Most are autosomal recessive disorders

JIPMER–December 2018  31 Type

Disease

Enzyme Defective

Type 0

----------

Glycogen synthase

Type IA

Von Gierke disease

Glucose-6-phosphatase

Type IB

---------

Glucose-6-phosphate transporter-Endoplasmic reticulum

Type II

Pompe’s disease

Lysosomal α 1-4 and 1-6 glucosidase (acid maltase)

Type IIIA

Limit dextrinosis, Forbe, Cori disease

Liver and muscle debranching enzyme

Type IIIB

Limit dextrinosis

Liver debranching enzyme

Type IV

Amylopectinosis Anderson’s disease

Branching enzyme

Type V

McArdle disease Myophosphorylase deficiency

Muscle phosphorylase

Type VI

Hers disease

Hepatic phosphorylase

VII

Tauri’s disease

Muscle & RBC Phospho fructokinase 1(PFK1)

VIII

Liver phosphorylase kinase

IX

Liver & Muscle phosphorylase kinase

X

cAMP dependent Protein kinase A

Most important of all is Von Gierke disease* Type I -- Von Gierke’s disease is due to deficiency of Glucose-6–phosphatase. Clinical manifestations are:



• Fasting hypoglycemia • Hyperlipedemia • Ketosis • Hyperuricemia • Lactic acidosis • Enlarged liver Treatment: Small quantity of food at frequent intervals Ans: (a) Coris disease Ref: Harper’s Illustrated Biochemistry, 30th edition, Chapter 18, Page 179

10.

Regarding microdeletion of chromosome, all are true except: (a) FISH can detect (c) Usually involves 5Mb base pairs

(b) High resolution karyotyping can detect (d) Routine cytogenetic techniques cannot detect

Explanation:

•



•



• •



•



•

Microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs (5 Mb) Genes are too small to be detected by conventional cytogenetic methods or high resolution karyotyping (2–5 Mb). Detection is done by fluorescence in situ hybridization (FISH). FISH is a sensitive and specific cytogenetic technique in which a fluorescently labeled DNA probe hybridizes to the gene of interest. FISH is applied to detect genetic abnormalities like chromosomal deletions or duplications which are not detectable under microscope. It is also used in different research applications, such as gene mapping or the identification of novel oncogenes. It is a rapid technique, can be automated.

32  TARGET JIPMER Ans: (b) High resolution karyotyping can detect Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 39, Page 459 11.

Deficiency of Acid lipase: (a) Fabry disease (c) Farber disease

(b) Gaucher disease (d) Wolman disease

Explanation:



Wolman disease is an autosomal recessive lysosomal storage disorder caused by a deficient activity of lysosomal acid lipase (LAL). • Human lysosomal acid lipase is essential for the metabolism of cholesteryl esters and triglycerides. • Clinical Features: in infants, poor weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of Wolman disease. • Hepatomegaly, hepatic steatosis often leads to fibrosis and cirrhosis. • Biochemical findings: high total cholesterol and LDL-cholesterol, elevated triglycerides, and low HDLcholesterol, elevation of liver transaminases • The diagnosis of LAL deficiency requires clinical experience and specialized laboratory tests. The diagnosis is based on finding deficient activity of acid lipase and/or molecular tests. Early diagnosis is particularly important for the enzyme replacement therapy. Other options of the question belong to group of diseases called sphingolipidoses: • Defects in lysosomal Enzymes concerned with the degradation of complex lipids • These lipids accumulate in lysosomes→ lysis→ tissue destruction • Since brain and nervous tissue have ↑concentration of sphingolipids, symptoms are usually severe • The diseases are listed in the below table •

Disease

Enzyme deficiency

Tay-Sachs disease

Hexosaminidase A

Fabry’s disease

alpha- Galactosidase

Metachromatic leukodystrophy

Aryl sulphatase A

Krabbe’s disease

Beta Galactosidase

Gaucher’s disease

Beta Glucosidase

Niemann-Pick disease

Sphingomyelinase

Farber’s disease

Ceramidase

Ans: (d) Wolman disease Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 24, Page 251 & Tylki-Szymańska A et al. Lysosomal acid lipase deficiency: wolman disease and cholesteryl ester storage disease, Pril 2014;35(1): 99-106. 12. Calculate the number of moles for 1 liter solution containing 6 g of urea (Molecular weight of urea = 60): (a) 0.1 (d) 0.5

(b) 0.2 (e) 0.6

(c) 0.3

Explanation: Molarity is the number of moles per liter of solution. i.e. Molarity = moles (gram molecular weight) of solute / liter of solution 1 mole of urea (1M) = 60 g/ liter 6 g of urea makes x moles? x= 6/60 = 0.1 M Ans: (a) 0.1 Ref: Clinical Chemistry by Kaplan, 5th edition, chapter 1, Page 33

JIPMER–December 2018  33 13.



Degeneracy of codon means: (a) Commaless (c) One amino acid having more than one codon

(b) Unambiguity (d) One codon coding for more than one amino acid

Explanation: • Codon - Sequence of 3 nucleotides, triplet code • Number of bases – 4 (adenine,guanine,cytosine and uracil) • So number of codons = 4 3= 64 • Out of 64, 3 codons donot code for any amino acid. So they are called as non sense codons or stop codons – UGA,UAG, UAA • Remaining 61 codons code for 20 amino acids. • Initiation codon – AUG - METHIONINE Characteristics Genetic Code • Unambiguity - 1 Codon codes for 1 specific amino acid • Degeneracy- 1 amino acid can be coded by more than 1 codon • Universality - Each amino acid coded by same codon in most species. • Non overlap- Consecutive codons are distinct from and independent of each other. • Commaless - No nucleotide or punctuations b/w 2 consecutive codons • Wobble hypothesis – Base pairing between the last nucleotide of codon and corresponding nucleotide of anticodon is not strictly by Watson and Crick rule. Ans: (c) One amino acid having more than one codon Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 37, Page 414-415.

14.





Which of the following has cyclic GMP mediated action? (a) Photochemical reactions of visual cycle (b) Steroidogenesis (c) Thyroid hormone action (d) Recruitment of glucose transporters to cell membrane Explanation: • Membrane-bound Guanylyl Cyclase are the group of single-transmembrane-segment receptors • Peptide hormones like ANP, BNP activate the membrane-forms Cyclic GMP: • Second messenger used by Nitric oxide (NO) which is a vasodilator • Involved in Phosphorylation of proteins. • Has a Role in the action of neurotransmitters. • cGMP allosterically activates PKG, which in turn phosphorylate specific proteins to produce SM relaxation, vasodilation, inhibition of platelet activation, reduced endothelial permeability, natriuresis, diuresis , etc. • Formation of cGMP GTP Guanylyl cyclase↓ Cyclic 3’, 5’- GMP (cGMP) Phosphodiesterase↓ 5’ GMP Role in vision: • When the rhodopsin is exposed to light it is bleached releasing the 11-cis-retinal and opsin • This triggers a series of conformational changes on the way to conversion all-trans-retinal metarhodopsin II activates transducin, leading to an increased GTP-binding

34  TARGET JIPMER

•

Drop in cGMP concentration at retina results in complete closure of the Na+ channels.



•

The closing of the channels leads to hyperpolarization of the rod cell with concomitant propagation of nerve impulses to the brain

Ans: (a) Photochemical reactions of visual cycle Ref: Harper’s Illustrated biochemistry, 30th edition, chapter 44, Page 551 15.

Copper is a cofactor for: (a) Glutathione peroxidase

(b) ALA synthase

(c) Prolyl oxidase

(d) Carbonic anhydrase

Explanation: Copper is a component of following enzymes:

•

ALA synthase



•

Ascorbic acid oxidase



•

Catalase



•

Cytochrome oxidase



•

Monoamino oxidase



•

Phenol oxidase



•

Superoxide dismutase



•

Tyrosinase

Other functions of copper:

•

Hb synthesis



•

Lysyl oxidase-conversion of lysine to allysine, collagen cross linking



•

Ceruloplasmin - ferroxidase- Fe+2 to Fe+3 transport of iron



•

Melanin & phospholipid synthesis



•

Bone & nervous system (myelin) development

Ans: (b) ALA synthase Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 52, Page 675 16.

Oxytocin receptor target cell: (a) Cytokine related receptor

(b) G protein coupled receptor

(c) Tyrosine kinase receptor

(d) Nucelar or cytoplasmic

Explanation:

•

The oxytocin receptor (OTR) belongs to the rhodopsin-type (Class 1) of the G-protein coupled receptor (GPCR) superfamily.



•

In the uterus, the Gαq/11 protein couples to phospholipase C-β (PLC-β), which controls the hydrolysis of phosphoinositide-bis-phoshate (PIP2) into inositol-tris-phosphate (IP3) and diacylglycerol (DAG).



•

In turn, these control the mobilisation of Ca2+ from intracellular stores such as the sarcoplasmic reticulum (SR) and activation of protein kinase type C (PKC), respectively.



•

Release of Ca2+ from the SR brings about smooth muscle contractions via stimulation of Ca2+-dependent calmodulin which in turn, activates myosin light chain kinase (MLCK).



•

Subsequent phosphorylation of the regulatory myosin light chains by MLCK brings about cross-bridge cycling and generation of force.

JIPMER–December 2018  35

Ans: (b) G protein coupled receptor Ref: Harper’s Illustrated Biochemistry, 30th edition, chapter 42, 521-23. 17.

Glucose is absorbed through apical membrane of PCT by which transporter? (a) SGLT-1 (c) GLUT-1

(b) SGLT-2 (d) GLUT-4

Explanation:

• • • •

Five facilitative bidirectional glucose transporters- GLUT1,2,3,4,5 Have different kinetic characteristics All consists of a single polypeptide with characteristic 12 Transmembrane - spanning domains Sodium dependent transporters are present in small intestine and kidney

Transporter

Tissue Location

Functions

Facilitative bidirectional transporters GLUT1

Brain, kidney, colon, placenta, RBC

Glucose uptake

GLUT2

Liver, pancreatic beta cell, small intestine, kidney

Rapid uptake or release of glucose

GLUT3

Brain, kidney, placenta

Glucose uptake

GLUT4

Heart & skeletal muscle, adipose tissue

Insulin mediated glucose uptake

GLUT5

Small intestine

Absorption of fructose

Sodium dependent unidirectional transporter SGLT1

Small intestine and kidney

Active uptake of glucose against conc gradient

36  TARGET JIPMER Ans: (a) SGLT-1 Ref: Harper’s Illustrated Biochemistry, 30th edition,chapter 19, Page191 18.

IGF 1 acts through which receptors: (a) Cytokine related receptor (c) Tyrosine kinase receptor (e) JAK/STAT

(b) G protein couple receptor (d) Nucelar or cytoplasmic

Explanation:

•



• • •



•



•

Insulin-like growth factor-1 (IGF-1) also called as somatomedin C, is a hormone that functions as the major mediator of growth hormone (GH)-stimulated somatic growth IGF-1 is synthesized in the liver and secreted into the blood is under the control of GH. IGF-1 is structurally similar to insulin but has different metabolic actions. IGF-1 binds to at least two cell surface receptor tyrosine kinases: the IGF-1 receptor (IGF1R), and the insulin receptor. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of many cell types in many tissues. Binding to the IGF1R initiates intracellular signaling following phosphorylation of tyrosine residues which in turn phosphorylate other proteins.

Ans: (c) Tyrosine kinase receptor Ref: David Clemmons, Metabolic actions of IGF-1 in normal physiology and diabetes, Endocrinol Metab clin north America 2012;41(2):425-443

JIPMER–December 2018  37

PHARMACOLOGY 1.

Temozolomide mechanism of action is: (a) Alkylation of DNA (c) Microtubule inhibition

(b) Crosslinking of DNA (d) Proteosome inhibition

Explanation: Temozolomide

• • •



•



• •

Is a triazene and a DNA alkylating agent Active metabolite: Methyltriazenoimidazole carboxamide (MTIC) Closely related to dacarbazine : but unlike dacarbazine it crosses blood brain barrier – so given orally and used in brain tumors and doesn’t require CYP 450 system for metabolic transformation Used in combination with radiation therapy for patients with malignant glioma, glioblastomas, metastatic melanomas and astrocytoma It is a oral drug with approximately 100% bioavailablity Requires hematological monitoring during therapy

Examples of other Anti–cancerous drugs: Class of drugs

Examples

Cross linkers of DNA

Carboplatin, cisplatin, platinum complexes

Alkylating agents

Dacarbazine, temozolomide

Microtubule inhibitors

Vincristine, Vinblastin paclitaxel, docetaxel

Proteosome inhibitors

Bortezomib, carfilzomib, ixazomib, Marizomib (Salinosporamide A)**

** - treatment of multiple myeloma under clinical trial Ans: (a) Alkylation of DNA Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 1175 2.

Monoclonal antibody used in Head and neck cancer is: (a) Pembrolizumab (c) Rituximab

(b) Cetuximab (d) Ocralizumab

Explanation: Pembrolizumab

• •

Humanized monoclonal antibody that blocks interaction between PD-1 and its ligands Approved for the treatment of patients with advanced melanoma, unresectable or metastatic melanoma in patients previously treated with ipilimumab, PD-L1–positive NSCLC (either prior to or after platinumcontaining chemotherapy) and chemotherapy-refractory head and neck cancer

NSCLC – Non Small Cell Lung Carcinoma Drug

Mechanism of Action

Therapeutic Uses

Rituximab

Targets HER 2 / neu

1. Rheumatoid arthritis 2. Non – Hodgkin lymphoma 3. ITP 4. Systemic lupus erythematosus (lupus) 5. Chronic Lymphocytic Leukemia (CLL) Mnemomic: R(E)NAIL/RENAL Contd.

38  TARGET JIPMER Contd.



Cetuximab*

Targets EGFR – Epidermal Growth Factor Receptor of tyrosine family

EGFR positive colorectal carcinoma

Ocrelizumab**

Acts against CD- 20 of B – Lymphocytes

Multiple sclerosis

* Causes hypomagnesemia and has increased risk of interstitial lung diseases ** Phase 3 trials reveal – patients have risk of developing infections like progressive multifocal leukoencephalopathy, herpes. Severe adverse effect: systemic inflammatory response syndrome

Ans: (a) Pembrolizumab Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 1222 3.

Which of the following drug should not be given with Midazolam? (a) Ritonavir (b) Indinavir (c) Zidovudine (d) Lamivudine

Explanation: Ritonavir is an CYP3A4 inhibitor which inhibits metabolism of Midazolam, so Ritonavir should not be given with Midazolam • Indinavir is a moderately potent CYP3A4 inhibitor • Zidovudine and Lamivudine are NRTIs, which doesn’t inhibit CYP3A4 Midazolam: A selective hypnotic among the barbiturates. EXTRA EDGE: Newer sedative / hypnotics: 1. Zopiclone – stimulates GABA receptors 2. Zolpidem – increases GABA action by binding to w1 subtype of BZD receptor 3. Zaleplon – increases GABA action by binding to w1 subtype of BZD receptor 4. Suvorexant – orexin receptor antagonist

•

Ans: (a) Ritonavir Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 342 4.

Mirabegron is a: (a) Beta 3 agonist (c) Beta 1 agonist

(b) Beta 3 antagonist (d) Beta 1 antagonist

Explanation:

Mirabegron • Is a Beta 3 agonist used in overactive bladder • Beta 3 stimulation in the bladder will relax detrusor muscle and increases bladder capacity Side effects • Increased blood pressure • Increased incidence of urinary tract infection • Headache Beta adrenergic receptors agonists: Receptor

Examples

Use

Beta 1

Prenalterol

Reversal of beta blocker overdose effect

Beta 2

Salbutamol, terbutaline, salmeterol, formoterol

Bronchial asthma

Isoxspurine

Tocolysis

Mirabegron

Overactive bladder

Beta 3

JIPMER–December 2018  39 Ans: (a) Beta 3 agonist Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 202 5.

Time dependent PK shown by all the following drugs except: (a) Linezolid (c) Lincosamide

(b) Daptomycin (d) Meropenem

Explanation: Concentration dependent PK

• • • • • • • •

Aminoglycosides Fluroquinolones Daptomycin Metronidazole Amphotericin B Colistin Azithromycin Ketolides

Time dependent killing

•



• • • •

Beta lactams o Penicillins o Cephalosporins o Carbapenems o Aztreonam Vancomycin Clindamycin Macrolides (except azithromycin) LINEZOLID

Ans: (b) Daptomycin Ref: Levison ME, Levison JH, Pharmacokinetics and pharmacodynamics of antibacterial agents, Infect Dis Clin North Am. 2009; 23(4): 791-815, vii. 6.

Concentration dependent PK followed by all except: (a) Amikacin (c) Linezolid

(b) Metronidazole (d) Daptomycin

Explanation: Refer previous explanation EXTRA EDGE: Prolonged Antibiotic Effect: Presence of inhibitory effect of an antibiotic over an organism even after the concentration of the antibiotic is far below the minimum inhibitory concentration Drugs having PAE:

• • •



•

Aminoglycosides Chloramphenicol Rifampicin – prolongs the effects of Isoniazid – that is why INH though given thrice weekly in the old regimen seems effective. Fluoroquinolones

Ans: (c) Linezolid Ref: Levison ME, Levison JH, Pharmacokinetics and pharmacodynamics of antibacterial agents, Infect Dis Clin North Am, 2009; 23(4): 791-815, vii.

40  TARGET JIPMER 7.

In a child of infantile spasm and visual defect, which drug is not used even though it is highly effective? (a) Lamotrigine (c) ACTH

(b) Topiramate (d) Vigabatrin

Explanation: Vigabatrin

Irreversible GABA transaminase inhibitor Used for partial seizures As orphan status for infantile spasms Infantile spasms due to tuberous sclerosis ( REMEMBER 4 S – triad of seizures, sub – normal intelligence, sebaceum adenoma , also associated with shagreen patch ) were particularly responsive to vigabatrin • Progressive and permanent bilateral vision loss occurs with vigabatrin as it causes retinal atrophy, that’s why it is not used even though it is highly effective in infantile spasms • It is reserved in resistant cases • It is available from those pharmacies which enroll themselves in REMS (Risk Evaluation and Mitigation Strategies) Program. Infantile spasms: Other name – West syndrome • I line DOC: Corticotropin(ACTH) > Vigabatrin • II Line DOC: BZD > Divalproex > Topiramate • Lamotrigine – not generally used in treatment of infantile spasms. Specifically used for GTCS, Lennox – Gastaut Syndrome ( childhood epileptic encephalopathy / syndrome ) characterized by seizures, mental retardation and abnormal EEG. • • • •

Ans: (d) Vigabatrin Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 320 8.

Not true about Tofacitinib: (a) (b) (c) (d)

Oral JAK inhibitor Studied for use in moderate to severe Crohn’s disease Increases triglycerides Dose reduction is required in renal and hepatic impairement

Explanation: Tofacitinib

• • • • • •



• • •

Is an oral Jak inhibitor Is a JAK inhibitor that primarily inhibits JAK1 and JAK3 and, to a lesser extent, JAK2. Approved for use in rheumatoid arthritis refractory to methotrexate in adults It has demonstrated efficacy for psoriasis in clinical trials and for atopic dermatitis in a pilot study Studied for use in moderate to severe Crohn’s disease Dose-dependent increases in the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol have been found in patients receiving tofacitinib Moderate hepatic or renal impairment patients require dose reduction to 5 mg once daily. Hemoglobin value of more than 9 g/dl is must to warrant the initiation of the therapy. Before initiation of therapy in these patients TB screening must definitely be done, especially in India where TB load is more.

Ans: (c) Increases triglycerides Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 1288 9.

False regarding volume of distribution is: (a) Proportional to t1/2 (c) Skeletal muscle relaxants have low Vd

(b) Calculated by t1/2 multiplied by log2 (d) High plasma protein bound drugs have low Vd

JIPMER–December 2018  41

Explanation:

To answer this question one should know pk formulas • t1/2 = log 2/ k (log 2 is the natural logarithm of 2 (or 0.693) and k is the elimination rate constant of the drug) • k = CL/ Vd • T1/2 = log 2 X Vd/CL • Vd = T1/2 x CL/ Log 2 So from above formula Vd is calculated by dividing t1/2 by log 2 • So option B is false statement



Other options Volume of distribution = CL × T1/2 / 0.693 • So from formula Vd is directly proportional to t1/2 if Clearance is constant High plasma protein bound drugs have low Vd • plasma protein binding confines drug to vascular compartment and less Vd



Skeletal muscle relaxants have low Vd. • These are polar quaternary compounds, so not absorbed orally and do not cross cell membranes • These Skeletal muscle relaxants have low volumes of distribution







Factors affecting volume of distribution (Vd): • Plasma protein binding o High Plasma protein binding decreases Vd o Low Plasma protein binding increases Vd • Tissue Perfusion o Decreased tissue perfusion implies decreased Vd • Water Soluble drugs have low Vd and Lipid soluble drugs have high Vd • Acidic drugs have low Vd • In edematous condition, water soluble drugs have high volume of distribution • Tissue binding. o High Vd with higher tissue binding • Low molecular weight drugs have high Vd Ans: (b) Calculated by t1/2 multiplied by log2 Ref: KD Tripathi, Essentials of Medical Pharmacology, 8th edition, Page 39

10. Eltrombopag is a: (a) Thrombopoietin agonist (c) Erythropoietin agonist

(b) Thrombopoietin antagonist (d) Erythropoietin antagonist

Explanation: Eltrombopag is a Thrombopoietin agonist Eltrombopag

• • • • •

Is an orally active small nonpeptide thrombopoietin agonist Used in chronic immune thrombocytopenia who have had an inadequate response to other therapies For treatment of thrombocytopenia in patients with hepatitis C to allow initiation of interferon therapy Peak platelet count responses are observed in approximately 2 weeks. Recently FDA has approved for the treatment of aplastic anemia

Ans: (a) Thrombopoietin agonist Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 756

42  TARGET JIPMER 11.

Which is not a bacterial drug resistance mechanism? (a) (b) (c) (d)

By synthesing enzymes against antibiotics By altering porin channels By actively effluxing the drug out By inhibiting DNA gyrase or topoisomerase activity

Explanation:



Inhibiting DNA gyrase or topoisomerase activity is a mechanism of action of fluroquinolnes, so it is not a mechanism for bacterial resistance The following are bacterial resistance Mechansims • Reduced entry of antibiotic into pathogen • Enhanced export of antibiotic by efflux pumps • Release of microbial enzymes that alter or destroy the antibiotic • Alteration of target proteins • Development of alternative pathways to those inhibited by the antibiotic Examples of drugs with different mechanisms of resistance: Due to alteration of target proteins

Due to decreased accumulation

Due to enzymatic inactivation

• Aminoglycosides • Fluroquinolones • Beta lactams (Pneumococci alters the penicillin binding proteins) • Clindamycin • Chloramphenicol

Decreased permeability: Beta lactams (by alteration of porin channels)

Beta lactams (action of penicillinases)

Increased efflux: 1. Tetracyclines 2. Macrolides 3. Fluoroquinolones

Ans: (d) By inhibiting DNA gyrase or topoisomerase activity Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 965 12.

Which of the following is an EGFR antagonist? (a) Sorafenib (c) Erlotinib

(b) Sunitinib (d) Pazopanib

Explanation: Tyrosine kinase inhibitors Against EGFR Erlotinib:

• • •

Used in metastatic NSCLC(Non-small cell lung cancer) Adverse effects: rashes - increases with increasing the dose, hepatotoxicity Should not be used with warfarin

Afatinib • Treatment of metastatic NSCLC • Should be administered only on empty stomach , can cause paronychia Osimertinib • Treatment of metastatic NSCLC • Use effective contraceptive action seen in females • Notable adverse effect: nail toxicity Monoclonal antibodies against EGFR

• • •

Cetuximab: used in Colorectal cancer, head and neck cancer ,non-small cell lung cancer Panitumumab: used in Colorectal cancer Necitumumab: used in squamous NSCLC

JIPMER–December 2018  43 Tyrosine kinase inhibitors Against VEGFR

• •

Sorafenib, Sunitinib and pazopanib All these are notable to cause hand – foot syndrome

Ans: (c) Erlotinib Ref: Katzung, Basic and Clinical Pharmacology, 7th edition, Page 968 13.

Correct order based on Volume of distribution is: (a) Haloperidol > Gentamicin > Phenytoin > Heparin (c) Phenytoin > Heparin > Gentamicin >Haloperidol

(b) Gentamicin >Haloperidol > Phenytoin > Heparin (d) Heparin < gentamicin < phenytoin < haloperidol

Explanation: Factors affecting volume of distribution (Vd):

• • • • • •



• •



•



•



•



• • •

Molecular weight of drug Lipid solubility Plasma protein binding Tissue binding Pathological conditions Large molecular size of drug ( remain in vascular compartment) o Heparin Low molecular weight drugs have high Vd Plasma protein binding o High Plasma protein binding decreases Vd o Low Plasma protein binding increases Vd Tissue Perfusion o Decreased tissue perfusion implies decreased Vd Water Soluble drugs have low Vd o Gentamicin Lipid soluble drugs have high Vd o Phenytoin, haloperidol, Thiopentone Acidic drugs have low Vd In edematous condition, water soluble drugs have high volume of distribution Tissue binding. o High Vd with higher tissue binding o Digoxin o Chloroquine

Vd of individual drugs

• • • •

Heparin: 0.058 L/Kg Gentamicin: 0.31 L/Kg Phenytoin: 0.64 L/Kg Haloperidol: 18 L/Kg

Note:

•

Its highly impossible to remember Vd of these drugs, so at least you should know that heparin has lowest Vd because of its molecular size. So option starting with heparin can be taken as a guess in choosing the right order of Vd of drugs

Ans: (d) heparin < gentamicin < phenytoin < haloperidol Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 1349 14.

Which drug can be used in patient with CML with T315I mutation? (a) Bosutinib (c) Interferon alpha

(b) Ponatinib (d) Omecetaxine

44  TARGET JIPMER

Explanation: Ponatinib

• • •

Third-generation BCR-ABL kinase inhibitor It can be used in patient with CML withT315I mutation Ponatinib is approved for resistant CML and Philadelphia + ALL.

Ans: (b) Ponatinib Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 13th edition, Page 1214 15. Which of the following drug is not needed to be present in tubular lumen for diuretic action? (a) Chlorthiazide (c) Mannitol

(b) Acetazolamide (d) Eplerenone

Explanation: MECHANISM OF ACTION OF DIURETICS Eplerenone

• Aldosterone acts by combining with an intracellular mineralocorticoid receptor • It induces the formation of aldosterone-induced proteins (AIP) . • These AIPs promote Na+ reabsorption and K+ secretion • Spironolactone is an aldosterone antagonist • It acts from the interstitial side of the tubular cell • It combines with Mineralocorticoid Receptor and inhibits the formation of AIPs Mannitol • It is freely filtered through glomerulus • Acts through entire nephron but mainly at PCT and loop of Henle • Acts through luminal side and acts by osmosis mechanism, withdrawing fluid into tubular lumen Chlorthiazide • Site of action in the cortical diluting segment or the early DT • Inhibit Na+–Cl¯ symport at the luminal membrane • They enter the proximal tubule via organic acid secretory pathway • From there they reach early DT, where they bind to specific receptors located on the luminal membrane Acetazolamide • Noncompetitively but reversibly inhibits Carbonic anhydrase in PT • Proximal tubular epithelial cells are richly endowed with the zinc metalloenzyme carbonic anhydrase, which is found in the luminal and basolateral membranes • Carbonic anhydrase inhibitors acts on the luminal and basolateral enzymes • Carbonic anhydrase plays a key role in NaHCO3 reabsorption and acid secretion EPLERENONE Uses



• • •

Heart failure – along with thiazides Refractory edema Adrenal hyperplasias /Aldosterone producing adenomas

Adverse Effects

• • • • •

Gynaecomastia Decreased libido/ Impotence Menstrual irregularities Hirsutism Increased risk of peptic ulcer disease

Ans: (d) Eplerenone Ref: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics, 12th edition, Page 692

JIPMER–December 2018  45

PATHOLOGY 1.

CD markers seen in Primary effusion lymphoma: (a) CD 30, CD 138 (c) CD 19, CD 20

(b) CD 20, CD 28 (d) CD 29, CD30

Explanation: Primary Effusion lymphoma (formerly body cavity lymphoma)

•



•



•

Rare type of diffuse large B cell lymphoma with lymphomatous effusions in pleural, pericardial and abdominal cavities but no tumor mass Strongly associated with HHV-8 (Kaposis Sarcoma associated) and advanced HIV (considered AIDS defining); usually EBV+ Also occurs in non immunosuppressed patients, often elderly

IHC

• • •

These display – typical ‘null’ lymphocyte phenotype Positive for – CD30, CD138, EMA, HHV8, CD 71, HLA DR(Plasma cell differentiation) Negative for – CD5, CD19, CD20, CD22

EXTRA EDGE: Common AIDS defining Non – Hodgkins Lymphoma’s:

• • • •

Burkitt’s Lymphoma Diffuse Large B – cell Lymphoma Plasmoblastic lymphoma – associated with multicentric castleman’s disease Primary effusion lymphoma

Ans: (a) CD 30, CD 138 Ref: WHO, Manual of Hematologic Malignancies, Page 323 2.

Emperioplosis seen in: (a) Alcohlic hepatitis (c) Chronic hepitis

(b) Acute hepatitis (d) Autoimmune hepatitis

Explanation: Emperioplosis

•

Active penetration of one cell by another cell which usually remains dormant / intact

Engulfment of hematopoietic cells 

• • •

The cell which eats is Megakaryocytes The cells which enter - erythroblast, myeloid cell, neutrophils Seen in normal marrows and in a varied variety of haematolymphoid malignancies, first described in : T – Cell Lymphoblastic lymphoma (mediastinal type)

Engulfment of inflammatory cells

• • •

The cell which eats is Macrophage The cells which enter - Lymphocyte and Plasma cell Seen in Rosai – Dorfman disease (Benign proliferative disorder of histiocytes), Autoimmune hepatitis

EXTRA EDGE:

•

Entosis

46  TARGET JIPMER



•

o Is homogenous cell in cell phenomenon due to imbalance in actinomycin contractions between neighboring cells o Associated with lower incidence of metastases in pancreatic adenocarcinoma. Cellular canabalism: o Ability of a cell to engulf another living cell. o Seen in breast carcinoma ( epithelial cells engulf WBC), lung carcinoma ( fibroblasts engulf WBC) and Thymoma (neural cells engulf WBC)

Ans: (d) Autoimmune hepatitis Ref: Silverman, Liver Pathology, Page 226 & J Oral Maxillofac Pathol, 2017 Jan – APR; 2(1): 92-8 3.

Co stimulatory factor for T cell include all except: (a) b7. 1 (c) b7. 3

(b) b7. 2 (d) Cd40

Explanation: Co-stimulatory molecules

•

Best characterized costimulatory receptors expressed by T cells is CD28, which interacts with CD80 (B7-1) and CD86 (B7-2) on the membrane of APCs. o CD28 is constitutively expressed on almost all T cells, and is the major costimulatory receptor for naive T cells. o The costimulatory molecules B7-1 and B7-2 are expressed mainly on APCs, including dendritic cells, macrophages, and B cells. o The expression of B7-1 and B7-2 on APCs is enhanced by the presence of microbes and by cytokines that are produced in response to microbes.

EXTRA EDGE:

•

The activation of T cells is generally a two step process: o Step 1 : T cell Receptor (TCR) binds to MHC bound antigen. Here CD4 / CD 8 act as co- receptors. o Step 2 : CD 28 interacts with co stimulatory molecules – B7-1 and B 7-2 present over the APC’s

Ans: (c) b7. 3 Ref: Robbins, Pathology, Page 190 4.

All are seen in Fragile X syndrome except: (a) Testicular enlargement is seen (c) Trinucleotide repeat

(b) Cause of mental retardation (d) Genomic imprinting

Explanation: Fragile X syndrome/Fragile X tremor / Fragile X ataxia

•



• • •



•

Genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment Fragile X is because of CGG repeats in FMR1 gene. It has X-Linked Recessive inheritance pattern. Affected males are mentally retarded (second most common genetic cause of mental retardation following downs syndrome), with an IQ in the range of 20 to 60 (extremely low IQ). They express a characteristic physical phenotype that includes a. o Long face with a large mandible o Large everted ears o Large testicles (macro-orchidism – most distinctive feature). o Hyperextensible joints o High arched palate o Mitral valve prolapse

JIPMER–December 2018  47 •

Sherman’s Paradox – the risk of mental retardation is higher in grandsons than brothers of the transmitting males, because the grandsons are seen to acquire a pre – mutation from their grandfathers which gets amplified in their mother’s ova. Ans: (d) Genomic imprinting Ref: Robbins Pathology, Page 170

5.

Which of the following is not a germ cell tumor? (a) Embryonal cell cancer (c) Germinoma

(b) PNET (d) Teratoma

Explanation:

Seminoma AFP– Dysgerminoma AFP–

GERM CELL

Tumors Embryonal carcinoma of totipotential cells with elements of seminoma AFP+ Embryonal carcinoma

Extra-embryonic structures Chorionepithelioma with elements of embryonal carcinoma AFP+ Endodermal sinus tumor AFP++

Chorioncarcinoma AFP–

Embryonal ectoderm, endoderm and mesoderm AFP+

Teratoma

AFP–

PNET

• • •

PNET – It’s an old terminology not used anymore. PNET included tumors from neuro ectodermal origin, not from germ cell origin Belongs to Ewing Family of tumors

Ans: (b) PNET Ref: WHO, Tumor of Genital System 6.

Antischkow cells seen in all except: (a) Systemic sclerosis (c) Iron def Anemia

(b) Rheumatic Fever (d) Recurrent aphthous stomatitis

Explanation: Rheumatic Fever

•



•

Distinctive lesions occur in the heart, called Aschoff bodies, consisting of foci of T lym- phocytes, occasional plasma cells, and plump activated macrophages called Anitschkow cells (pathognomonic for acute RF). These are usually binucleate and resemble a caterpillar and are hence named caterpillar cells Squamous epithelial cells with nuclear changes resembling Anitschkow cells have also been observed in recurrent aphthous stomatitis, iron deficiency anemia, children receiving chemotherapy

Other salient features of RHD:

•

Pancarditis: Characteristic of RHD

48  TARGET JIPMER

• • • • • • • •

Bread and butter pancarditis: due to fibrinous exudation Most commonly affected valve is: Mitral valve Least commonly affected is Pulmonary valve Most common lesion in Acute Rheumatic fever: Mitral regurgitation Most common lesion in chronic rheumatic heart disease: Mitral stenosis Non erosive arthritis Small verrucous vegitations Pathognomic of Chronic RHD: o Mac callum plaques (irregular thickening of left atrial valve attributed to mitral regurgitation) and o Fish mouth/ button hole stenosis (due to leaflet thickening, fusion of commisures and tendinous cords attributed to mitral stenosis)

Ans: (a) Systemic sclerosis Ref: Pathol Int. 1999 Jan;49(1): 85-7. 7.

False statement regarding Myelodysplasia: (a) (b) (c) (d)

Patient with 5q deletion have poor prognosis Erythroid cells with basophilic stippling are seen Micromegakaryocytes are seen in bone marrow Hypolobulated neutrophils are seen in peripheral blood

Explanation: Prognostic subgroup Very good - Loss of Y chromosome de1 (11q) Good - Normal, del (5q), 
del(12p), 
del(20q), 
Double, including del(5q) Intermediate

• • • • • •

del(7q) Gain of chromosome 8 Gain of chromosome 19 lsochromosome 17q Single or double abnormalities not specified in other subgroups Two or more independent non-complex clones

Poor

• • •

Loss of chromosome 7 inv(3), t(3q) or del(3q) Double including loss of chromosome 7 or del(7q) Complex (3 abnormalities)

EXTRA EDGE: Haematological features in Myelodysplasia

• • • • •

Macrocytic anemia with Howell jolly bodies are seen Band shaped neutrophils – pseudo Pelger Huet anomaly seen Nuclei: hyposegmented and ring nuclei are seen Eosinobasophilc granulations are seen Decreased Neutrophil alkaline phosphatase (NAP) score

Specific important cytogenetic abnormalities: 5q- syndrome • Seen mostly in old age • Bone marrow shows – bilobate megakaryocytes • DOC: Linolidomide

Monosomy 7 • Seen usually between 6 months to 2 years • Increases risk of infection in children

JIPMER–December 2018  49 Ans: (a) Patient with 5q deletion have poor prognosis Ref: WHO, Manual of hematology & Textbook of hematology, Tejinder Singh 8.

Most common site of GIST: (a) Small intestine (c) Stomach

(b) Colon (d) Liver

Explanation:

•

More than half of GIST tumors occur in stomach

Gastrointestinal stromal tumor (GIST)

• • • • •



• • • •



•

MC mesenchymal tumor of abdomen* Differentiates towards interstitial cell of Cajal/ pacemaker cells of GIT Carney’s triad (gastric GIST, paraganglioma, pulmonary chondroma) Associated with type -1 neurofibromatosis (Von – Recklinghausen Disease) in 1% population Carneys – Stratakis syndrome = germline mutation causing loss of SDH function – increased risk of GIST and paraganglioma (different from Carney’s triad) M/C site - Stomach (60%) Microscopy - Spindle shaped cells rarely even epitheloid cells may be seen IHC - DOG 1 (Discovered on GIST 1) better than CD117 (C-KIT) Molecular genetics - Most common - cKIT mutation. PDGFRA mutation seen in cases of absent cKIT, pediatric GIST and GIST associated with syndromes Responds well to Tyrosine Kinase inhibitors – imatinib

Ans: (c) Stomach Ref: WHO, Manual of Gastro Intestinal Tract & Robbins Pathology, Page 775-6 9.

A wedge shaped area in the adrenal gland is affected. On HPE nucleus is not seen but cellular outlines are intact. Which type of necrosis is being described? (a) Coagulative (c) Fibrinoid

(b) Liquefactive (d) Caseous

Explanation: Coagulative

Liquefactive

Protein degradation

Lysosomal activation and tissue destruction

Architecture maintained

Architecture lost

Ghost cells seen

No ghost cells seen

Solid organ infarct

Brain infarct, Bacterial infection (suppuration)

Dry Gangrene

Wet Gangrene

EXTRA EDGE: Caseous Necrosis

• • •

Tomb stone appearance of tissues Classically seen in TB. Others: Syphilis, Histoplasmosis (because it has high lipid content in cell wall) Cheese like appearance

Fat Necrosis

• •

By action of lipases Seen where fat is more: Breast, Pancreas, Omentum

Fibrinoid Necrosis

• • •

By antigen – antibody complexes Necrotic material contains fibrinogen and plasma Seen in RHD, Poly arteritis Nodosa

50  TARGET JIPMER Gangrenous Necrosis:

•

Special ones: o Fourniers gangrene: scrotal gangrene o Noma: Vulval gangrene

Ans: (a) Coagulative Ref: Robbins Pathology, Page 46 10.

MYH 7 gene locus: (a) Chromosome 14 (c) Chromosome 11

(b) Chromosome 22 (d) Chromosome 9

Explanation: MYH7 gene

• • • •

The MYH7 gene provides instructions for making a protein known as the beta (β)-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers Cytogenetic Location: 14q11.2 Diseases caused o Familial hypertrophic cardiomyopathy o Laing distal myopathy o Left ventricular noncompaction o Myosin storage myopathy o Congenital fiber-type disproportion o Familial dilated cardiomyopathy o Familial restrictive cardiomyopathy

Some other important genes and their chromosomes Gene

Chromosome

Associated diseases

MHC

6p

Bare Lymphocyte syndrome (absence of MHC –II)

RB

13q

Retinoblastoma

BRCA - 1

17q

Hereditary breast – ovarian cancer syndrome

BRCA - 2

13 q

Prostate cancer > colorectal cancer Breast cancer

NF – 1

17q

Neurofibromatosis type 1

NF – 2

22q

Merlin deficiency – NF type II

p53

17p

Li – Fraumeni syndrome, sarcomas

Ans: (a) Chromosome 14 Ref: Genetic Home Reference 11.

Which of the coagulation factor is increased in hepatic necrosis? (a) Factor 5 (c) Factor 8

(b) Factor 9 (d) Factor12

Explanation: Favoring hemorrhage

Favoring thrombosis

Low platelet count Impaired platelet function and platelet-vessel wall interaction

Elevated levels of factors VIII and vWf

Enhanced platelet inhibition by nitric oxide (NO) and prostacyclin III, α2-antiplasmin

Decreased levels of protein C, protein S, anti thrombin

Decreased levels coagulation factors (II, V, VII, IX, X, XI)

Macroglobulin

Low level of α2-antiplasmin, TAFI, histidine-rich-glycoprotein

Decreased levels of plasminogen

JIPMER–December 2018  51 Ans: (c) Factor 8 Ref: Silverman, Liver Pathology, Chapter Coagulation Abnormalities in Liver Disease 12.

All the following cause thrombophilias through protein C except: (a) Factor 5 leiden mutation (c) Oestrogen contraceptive pill

(b) Tetrahydrofolate reductase polymorphism (d) Lupus anticoagulant

Explanation: Acquired Protein C Deficiency

•



• •



•

Acquired protein C deficiency has been observed in patients with o DIC o Acute leukemia o Hepatic disease o Nephrotic syndrome o Renal transplant patients o Patients taking warfarin or oral contraceptives Factor V leiden mutation will result in resistance to activated protein C. Lupus anticoagulant - The mechanism for thrombosis is incompletely understood but may involve IgG binding to phospholipids that are essential for the normal activating and degrading effects of protein C and protein S, thus shifting the balance in favor of thrombus formation. Pathogenesis: o The protein C deficiency leads to decreased inhibition, thereby predominance of factors Va & VIIIa, thus leading to prolonged thrombosis o Protein C – Vitamin K dependent Protein and synthesized in Liver

Ans: (b) Tetrahydrofolate reductase polymorphism Ref: T. Singh Hematology, Page 590 - 600 13.

Function of guardian of genome p53: (a) Increase in Cell proliferation (c) Inducer of necrosis

(b) Evasion of Apoptosis (d) Reduce cell mutation rate

Explanation: p53

•



•



•



•

TP53, a tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis Activation of normal p53 by DNA-damaging agents or by hypoxia leads to cell cycle arrest in G1 and induction of DNA repair by transcriptional upregulation of the cyclin-dependent kinase inhibitor CDKN1A (encoding the cyclin-dependent kinase inhibitor p21) and the GADD45 genes. Successful repair of DNA allows cells to proceed with the cell cycle; if DNA repair fails, p53 triggers either apoptosis or senescence. In cells with loss or mutations of the p53 gene, DNA damage does not induce cell cycle arrest or DNA repair, and genetically damaged cells proliferate, giving rise eventually to malignant neoplasms.

Corrected other statements:

• • •

P53 does not increase cell proliferation but triggers senescence It induces apoptosis and doesn’t evade It doesn’t induce necrosis

EXTRA EDGE: p53

• • •

Inactivated by viral oncoproteins like E6 of Human Papilloma Virus Defect in the gene can result in Li – Fraumeni syndrome and risk of sarcomas. Li – Fraumeni syndrome: Other name – tumor predisposition syndrome. o Soft tissue sarcomas

52  TARGET JIPMER o o o o

Bone sarcomas Acute leukemias Adrenal cortical carcinomas Glioblastomas

Ans: (d) Reduce cell mutation rate Ref: Robbins Pathology, Page 294 14.

Most common malignant tumour of parotid gland: (a) Warthin tumour (c) Acinic cell CA

(b) Mucoepidermoid CA (d) Adenoids cystic CA

Explanation: Neoplasms of Salivary Gland Benign

Malignant

Pleomorphic adenoma (50%) (mixed tumor)

Mucoepidermoid carcinoma (15%)

Warthin tumor (5%-10%)

Adenocarcinoma (NOS) (10%)

Oncocytoma (1%)

Acinic cell carcinoma (5%)

Other adenomas (5%-10%) Basal cell adenoma Canalicular adenoma

Adenoid cystic carcinoma (5%) Malignant mixed tumor (3%-5%) Squamous cell carcinoma (1%)

Ductal papillomas

Other carcinomas (2%)

Mucoepidermoid Carcinoma

•



• • •

Mucoepidermoid carcinomas can grow as large as 8 cm in diameter and although they are apparently circumscribed, they lack well-defined capsules and are often infiltrative at the margins. t(11;19) balanced translocation Pale and gray-white on transection, they frequently contain small, mucin-containing cysts. The basic histologic pattern is that of cords, sheets, or cystic configurations of squamous, mucous, or intermediate cells

OTHERS: Acinic cell tumor

• •

Mostly arise from parotid gland. Mostly have clear cytoplasm. Spaces between tumor cells are filled with hyaline material

Adenoid cystic Carcioma:

• • •

Uncommon tumor If found usually seen in the palate Involves perineural spaces too

Ans: (b) Mucoepidermoid CA Ref: Robbins Pathology, Page 745-46 15.

Histology for type 2 autoimmune pancreatitis: (a) Igg4 more than 10/HPF (c) Storiform fibrosis

(b) Granulocytic infiltration (d) Microvascular thrombosis

Explanation: There is no granulocyte infiltration in IgG4 mediated disorder

JIPMER–December 2018  53 Diagnostic criteria for IgG4-RD (modified after Umehara et al.) 1 Organ involvement: dysfunction, localized or diffuse swelling

+

2

+

Serum IgG4 >135 mg/dl

= Diagnosis of IgG4-RD

3 Histopathology: IgG4/ IgG Ratio > 0.4 and > 10 IgG4 + cells per HPF

Organ specific criteria for IgG4-RD (e.g., AIP, Mikulicz’ disease)

Definite

Definite

Organ involvement: dysfunction, localized or diffuse swelling

Serum IgG4 0.4 and > 10 IgG4 + cells per HPF

Probable

Organ involvement: dysfunction, localized or diffuse swelling

Serum IgG4 >135 mg/dl

Histopathology: Not available or not diagnostic

Possible

Organ involvement: dysfunction, localized or diffuse swelling

Serum IgG4 1 crore Limitation Period



 Case need to filed within 2years Also Know Consumer Protection Bill, 2018 (Passed by Lok Sabha) Salient Features



•

Proposes setting up a Central Consumer Protection Authority (CCPA)

66  TARGET JIPMER

• • • • • •

Class action suit (Liability for all affected customers) Punishment for all parties involved if product causes injury, death or physical damage Disputes to be heard by a single entity (consumer mediation cell) and not at separate levels E-commerce liability increased Accountability of personalities endorsing products in fake advertising Punishment for fake complaints

Ans: (b) 2 years Ref: KSN Reddy, Essentials of FMT, 33rd edition, Page 649 4.

A child presents with hard neck lymph nodes with a strong suspicion of lymphoma. Resident orders for a biopsy without revealing the reason for biopsy or suspected condition. What are the ethical reasons for this behavior? (a) Judgemental (c) Non-maleficence, beneficence

(b) Non-maleficience, autonomy veracity (d) Autonomy, Justice

Explanation:

• Medical ethics is a system of moral principles that apply values to the practice of clinical medicine and in scientific research. • Medical ethics is based on a set of values that professionals can refer to in the case of any confusion or conflict. Principles of Medical Ethics



• Respect for Autonomy – Respect for decision making capacities of autonomous person • Non-maleficence – Not causing harm to others • Beneficence – Prevent harm, provide benefits and balance benefits against risks & costs • Justice – Appropriate distribution of benefits, risk and costs fairly “In above case, resident ordered biopsy for the benefit of the patient without causing any harm to him. However if he had informed the patient and did the biopsy inspite of patient’s refusal then it would have been breach of medical ethics as patients Autonomy is not respected.” Ans: (c) Non-maleficence, beneficence Ref: Richard Edmund Ashcroft, Angus Dawson, Heather Draper, John McMillan; Principles of Health Care Ethics, 2nd edition

JIPMER–December 2018  67

PSM 1.

Quality control agent for sterilization in autoclave: (a) Bacillus subtilis (c) Bacillus stearothermophilus

(b) Bacillus pumilus (d) Bacillus globigi

Explanation: Biological indicators are mainly used to assess sterilization by various methods. Concept: If the process of sterilization is proper, then the organisms (biological indicators) should have been destroyed and should not grow in inoculation in culture media. Biological indicators of sterilization Methods

Indicator

Autoclave

Bacillus stearothermophilus

Filtration

Brevundimonas diminuta or Serratia

Ionizing radiation

Bacillus pumilus

Ethylene oxide

Bacillus globigi

Hot air oven

Clostridium tetani (nontoxigenic strain). Bacillus subtilus subsp.niger.

Plasma sterilization

Bacillus stearothermophilus or bacillus subtilis subsp.niger

Ans: (c) Bacillus stearothermophilus Ref: Apurba Sastry, Textbook of Microbiology, Page 266 2.

Programme for screening developmental delay, deficiency and neonatal genetic defects: (a) JSY (b) JSSK (c) Rashtriya bal swasthya karyakaram program(RBSK) (d) Ayushman bharat

Explanation: The 4 D’s that are covered in RBSK are: Defects of Birth

Childhood Diseases

1. Neural Tube Defect

15. Skin condition (Scabies, Fungal Infection and Eczema)

2. Down’s Syndrome

16. Otitis Media

3. Cleft Lip and Palate/Cleft Palate alone

17. Rheumatic Heart Disease

4. Talipes (club foot)

18. Reactive Airway Disease

5. Developmental Dysplasia of the Hip

19. Dental Caries

6. Congenital Cataract

20. Convulsive Disorders

7. Congenital Deafness

Developmental Delays and Disabilities

8. Congenital heart Diseaes

21. Vision Impairment

9. Retinopathy of Prematurity

22. Hearing Impairment

Deficiencies

23. Neuro-Motor Impairment

10. Anemia especially in servere cases

24. Motor Delay

11. Vitamin A Deficiency (Bitot spot)

25. Cognitive Delay

12. Vitamin D Deficiency (Ricket)

26. Language Delay

13. Severe Acute Malnutrition

27. Behaviour Disorder (Autism)

14. Goiter

28. Learning Disorder 29. Attention Deficit Hyperactivity Disorder 30. Congenital Hypothyroidism, Sickle Cell Anaemia, Beta Thalassemia (Optional)

68  TARGET JIPMER JANANI SURAKSHA YOJANA (JSY)

•



•



•



•



•



•

Janani Suraksha Yojana (JSY) is a safe motherhood intervention under the National Rural Health Mission (NRHM) The objective is to reduce the maternal and neonatal mortality by promoting institutional delivery among the poor pregnant women. The Yojana, launched on 12th April 2005, by the Hon’ble Prime Minister, is being implemented in all states and UTs with special focus on low performing states. JSY is a 100 % centrally sponsored scheme and it integrates cash assistance with delivery and postdelivery care. The Yojana has identified ASHA, the accredited social health activist as an effective link between the Government and the poor pregnant women in l0 low performing states. In other eligible states and UTs, wherever, AWW ((Anganwadi workers )and or ASHA  like activist has been engaged in this purpose, she can be associated with this Yojana for providing the services.

Important features of JSY

•



•



•

The Scheme Focuses on the Poor Pregnant Woman with special dispensation for states having low institutional delivery rates namely the states of Uttar Pradesh, Uttaranchal, Bihar, Jharkhand, Madhya Pradesh, Chhattisgarh, Assam, Rajasthan, Orissa and Jammu and Kashmir. While these states have been named as Low Performing States (LPS), the remaining states have been named as High performing States (HPS). Tracking Each Pregnancy: Each beneficiary registered under this Yojana should have a JSY card along with a MCH card. ASHA/AWW/ any other identified link worker under the overall supervision of the ANM and the MO, PHC should mandatorily prepare a micro-birth plan.  This will effectively help in monitoring Antenatal Check-up, and the post delivery care. Eligibility for Cash Assistance: BPL Certification – This is required in all HPS states. However, where BPL cards have not yet been issued or have not been updated, States/UTs would formulate a simple criterion for certification of poor and needy status of the expectant mother’s family by empowering the gram pradhan or ward member.

JANANI SHISHU SURAKSHA KARYAKARAM (JSSK)

Government of India has launched Janani Shishu Suraksha Karyakaram (JSSK) on 1st June, 2011. • The scheme would benefit pregnant women who access Government health facilities for their delivery. It will motivate those who still choose to deliver at their homes to opt for institutional deliveries. • It is an initiative to ensure that benefits under JSSK would reach every needy pregnant woman coming to government institutional facility. All the States and UTs have initiated implementation of the scheme. Free Entitlements for Pregnant Women • • • • • • • • • •



Free and cashless delivery Free C-Section Free drugs and consumables Free diagnostics Free diet during stay in the health institutions Free provision of blood Exemption from user charges Free transport from home to health institutions Free transport between facilities in case of referral Free drop back from Institutions to home after 48 hrs stay

Free Entitlements for Sick Newborns Till 30 Days After Birth • • • • • • • •

Free treatment Free drugs and consumables Free diagnostics Free provision of blood Exemption from user charges Free Transport from Home to Health Institutions Free Transport between facilities in case of referral Free drop Back from Institutions to home

AYUSHMAN BHARAT–The scheme aims to provide healthcare facilities to over 10 crore families covering urban and rural poor. The scheme has been renamed as PM Jan Arogya Yojana (PMJAY). • Ayushman Bharat is the biggest government-sponsored healthcare scheme in the world • The scheme offers an insurance cover of Rs 5 lakh, which will cover almost 50 crore citizens

JIPMER–December 2018  69 Ans: (c) Rashtriya bal swasthya karyakaram program Ref: Park, Textbook of Preventive & Social Medicine, Page 568 3.

A PHC was created with goal of creating community based health care system integrated with community. For achieving this what did Indian govt do? (a) International acceptance (c) NGOs involvement

(b) Getting WHO standards to PHC (d) Comprehensive Health Services

Explanation:



Bhore committee – Comprehensive health care (1946) Preventive, curative and promotional health services from womb to tomb to all Principles of Primary Health Care 1. Equitable distribution 2. Intersectoral co-ordination 3. Appropriate Technology 4. Community participation Ans: (d) Comprehensive Health Services Ref: Park, Textbook of Preventive & Social Medicine, Page 721

4.

According to Indian newborn action plan (INAP) - Neonatal mortality rate target for 2035 is: (a) 12

(b) 15

(c) 9

(d) 11

Explanation: Indian Newborn action plan targets to achieve Single Digit Neonatal mortality rate by 2035. Milestones in Child Survival Programmes in India 1992 – Child Survival and Safe Motherhood Programme (CSSM) 1997 – RCH I 2005 – RCH II 2005 – National Rural Health Mission 2013 – RMNCH+A Strategy 2013 – National Health Mission 2014 – India Newborn Action Plan (INAP) Current NMR is 29/1000 live births

India Newborn Action Plan – Six pillars are:

1. 2. 3. 4. 5. 6.

Preconception and antenatal care; Care during labour and child birth; Immediate newborn care; Care of healthy newborn; Care of small and sick newborn; Care beyond newborn survival.

Ans: (c) 9 Ref: Indian Newborn Action Guidelines 2018 5.

Single disease control strategy done by / programme known as: (a) Horizontal program (c) Interventional program

Explanation: Types of National Health Programmes in India

1. Vertical 2. Horizontal

(b) Vertical program (d) Volunteer programme

70  TARGET JIPMER Vertical Programs: These are often disease-specific, hospital-based, medically-driven programs. Horizontal Programs: These are community-owned and community-directed programs Vertical Programmes

Horizontal Programmes

They are special Health programmes run by Government of India

They are run by state governments

Target oriented cash programmes

Routine programmes in PHC

All national programmes are vertical except RNTCP

RNTCP

Ans: (b) Vertical programme Ref: Suryakantha Community Medicine with recent advances, Page 897 6.

If first Quartile is 34, how much % of observations will be more than this? (a) 25

(b) 75

(c) 37

(d) 66

Explanation: First quartile is 25 % of observations. Third quartile is 75 % of observations A quartile is a statistical term describing a division of observations into four defined intervals based upon the values of the data and how they compare to the entire set of observations. Each quartile contains 25% of the total observations.

• • • • •

Generally, the data is arranged from smallest to largest with Observations falling below 25% of all the data analyzed allocated within the 1st quartile Observations falling between 25.1% and 50% and allocated in the 2nd quartile Observations falling between 51% and 75% allocated in the 3rd quartile Remaining observations allocated in the 4th quartile.

Ans: (b) 75 Ref: Textbook of Biostatistics by Mahajan, Page 121

JIPMER–December 2018  71

ENT 1.

Kashima’s operation done for all conditions except: (a) Vocal cord dysplasia (c) Nasopharyngeal carcinoma

(b) Ca larynx (d) Bilateral abductor palsy

Explanation:

•



•



•



• •

Kashima operation also known as transverse cordotomy is primarily done for bilateral abductor paralysis, which is due to bilateral recurrent laryngeal nerve paralysis. The idea is to widen the airway, which helps in decannulation [removal of tracheostomy tube] in tracheostomy dependant patients It is done by removing soft tissue at the junction of the membranous cord and the vocal process of the arytenoids It can also be used to treat dysplastic lesions and localized malignancies of the vocal cord However it is contraindicated in extensive malignanciesof the vocal cord as it may increase the risk of metastasis

Figure showing kashima operation

Ans: (c) Nasopharyngeal carcinoma Ref: Diseases of the Ear Nose and Throat by PL Dhingra, 6th edition, 2010, Page 300 2.

WHO recommendation cut off for noise in industrial city: (a) 70 dB (c) 45 dB

(b) 60 dB (d) 120 dB

Explanation:



•

The permissible limits of noise as per the Noise Pollution (Regulation and Control) Rules 2000, Ministry of Environment and Forest, Govt. of India are as follows

Zone

Limits during 6 am to 10 pm

Limits during 10 pm to 6 am

Industrial

75

70

Commercial

65

55

Residential

55

45

Silence

50

40

•

Silence zone is 100m around premises of hospitals, nursing homes, educational institutions and courts

72  TARGET JIPMER Ans: (a) 70 dB Ref: Diseases of the Ear Nose and Throat by PL Dhingra, 6th edition, 2010, Page 35 3.

All are done for recurrent laryngeal papillomatosis except: (a) Zinc therapy (c) Interferon alpha-2a

(b) Intralesional cidofovir (d) Steroids

Explanation: Recurrent laryngeal papillomatosis

• • •



•

Caused by Human papilloma virus* (Refer figure below) Most common are type 6 and 11* There are two types a. Juvenile papillomatosis – seen in children o Most common 3 to 5 years o Present with hoarseness of voice or stridor o Multiple papillomas most commonly over Supraglottis and glottis o Subglottis, trachea and bronchus can also be affected o Recurrence is common o Rarely undergo malignant change b. Adult onset papilloma – more common in 30-50 years of age o Single o Smaller size o Less recurrent o More common in males (M:F = 2:1) o Usually arise at the anterior commissure or anterior half of vocal cord o Increased malignant potential The mainstay treatment is removal either surgically by forceps, debrider or by using Laser [Most commonly CO2 laser] o Medical therapy is adjuvant and can delay recurrences or used in patients unfit/unwilling for surgery o Adjuvant include – Interferon alpha-2a, Acyclovir, Ribavirin, Intralesional cidofovir, COX-2 inhibitors, Retinoids, Anti-reflux medications, Zinc, Indole-3-carbinol and therapeutic/preventative vaccines.

Laryngeal papillomatosis

Ans: (d) Steroids Ref: Diseases of the Ear Nose and Throat by PL Dhingra, 6th edition 2010, Page 306 & Expert Opin Pharmacother, 2009 Mar;10(4): 645-55.

JIPMER–December 2018  73 4.

Sistrunk operation is for: (a) Branchial cyst (c) Thyroglossal cyst

(b) Branchial fistula (d) Thyroglossal fistula

Explanation: Thyroglossal cyst

• • • • • •

Presents as a midline neck swelling They can occur at anywhere in the course of thyroid duct They are common in children but can affect any age It moves with deglutition because of attachment to foramen caecum at the base of of tongue In some patients it may be the only functioning thyroid tissue Simple excision of the cyst leads to recurrence and therefore the cyst is excised along with the body of hyoid bone and core of tongue tissue around the tract – Sistrunk Surgery

Ans: (c) Thyroglossal cyst Ref: Diseases of the Ear Nose and Throat by PL Dhingra, 6th edition, 2010, Page 390-391

74  TARGET JIPMER

OPHTHALMOLOGY 1.

Most radioresistant layer of retina: (a) Layer of Rods and cones (c) Inner plexiform layer

(b) Retinal Pigment epithelium (d) Ganglion cell layer

Explanation:



• • • • •



• •

The most radioresistant layer in the retina is Ganglion cell layer* The most radiosensitive layer in the retina is vascular endotheliumà Radiation retinopathy* The most radiosensitive part of the eye is the lens* The most radioresistant part of the eye is the sclera* Radiotherapy may cause acute ophthalmic complications such as o Dry eye syndrome (also known as “ocular surface disorder” and/or “keratoconjunctivitis sicca”) o Conjunctivitis o Keratitis o Cataract o Secondary glaucoma o Radiation optic neuropathy o Retinopathy o Maculopathy o Retinal vascular occlusions o Chorioretinal atrophy. Orbital bones, muscle, and fat can tolerate relatively high doses The lens, eyelashes, retina, and lacrimal system are more radiosensitive 

Ans: (d) Ganglion cell layer Ref: Radiation hazards to eyes J Fr Ophtalmol, 2001 Nov; 24(9): 993-1003. [Radiation induced retinopathy] by Grange JD; Ophthalmic and adnexal complications of radiotherapy 2.

Blood retinal barrier is formed by: (a) Muller cells (c) Bipolar cells

(b) Amacrine cell (d) Horizontal cell layer

Explanation:

•



•

Müller glial cells (MGC) and astrocytes participate in the formation and maintenance of the inner blood–retinal barrier Although the endothelium of the retinal capillaries forms the inner blood retinal barrier, the glial cells may play a role as metabolic intermediaries between the retinal capillaries and retinal neurons.

OCULAR BARRIERS

Anterior Segment: Blood aqueous barrier Posterior Segment: Outer & Inner blood retinal barrier Blood aqueous barrier

Tight junctions between the non-pigmented epithelial cells and by the endothelium of the iris vessels

Outer Blood retinal barrier

Tight junctions between the Retinal pigment epithelium

Inner blood retinal barrier

Retinal capillary endothelium, Muller cells

Ans: (a) Muller cells Ref: Basak’s Essentials of Ophthalmology, 6th edition

JIPMER–December 2018  75 3.

Mizou-nakamura phenomenon in fundus is seen in (a) Congenital rod absence (c) Congential cone defect

(b) Congenital stationery night blindness (d) Best disease

Explanation: Congenital stationary night blindness (CSNB)

•

Refers to a group of disorders characterized by early onset of night blindness in the infancy itself but the retinal dysfunction is not progressive.

Types

• •

With normal fundus With abnormal fundus – Oguchi’s disease & fundus albipunctatus

Oguchi’s Disease

•



•

The fundus has an unusual golden-yellow colour in the light-adapted state , which becomes normal after prolonged dark adaptation . This is called Mizuo or Mizuo–Nakamura phenomenon* Rod function is absent after 30 minutes of dark adaptation but recovers to a near-normal level after a long period of dark adaptation.

Fundus Albipunctatus

•

Characterized by multiple tiny yellow spots at the posterior pole.

Ans: (b) Congenital stationary night blindness Ref: Kanski, Clinical Ophthalmology, 8th edition, Page 658 4.

Universal Limbal stem cell marker: (a) C-Cadherin

(b) Pax6

(c) Abcg2

(d) P63

Explanation: Limbal stem cell markers are p63 gene, ABCG2, ABCB5, Vimentin, K19 and connexin. P 63:

•



•



•

P63 gene belongs to P53 gene family - a tumor suppressor gene, p63 protein functions as a transcription factor. P63 gene plays a key role especially in the development, differentiation, morphology and connections between the epithelial cells. P63 gene products are accepted as a marker for limbal epithelial stem cells (LEKH); especially ΔNp63α isoform is accepted as a real marker and functions in LEKH activation.

ABCG2

•



• •

Also known as breast cancer resistance protein 1 (BCRP1), it is the ATP-binding cassette subfamily G, member 2 (ABCG2). It is a marker defined for hematopoietic stem cells and was proposed as a universal stem cell marker These markers are utilized to culture Limbal stem cell in In-Vitro.

Ans: (d) P63 Ref: Limbal Stem Cells in Review - PMC3448387 5.

Not true about Epiblephron is: (a) Seen in Hypertelorism (c) Trauma to epicanthus can cause

Explanation: Epiblepharon

•

Congenital condition.

(b) Congenital epicanthus (d) Fold of skin and conjunctiva turned inwards

76  TARGET JIPMER



There is an extra horizontal fold of skin stretching across the anterior lid margin The hypertrophic preseptal orbicularis oculi fibres overrides the pretarsal fibres, commonly seen in lower lid • Associated with orbital hypertelorism • Spontaneous resolution with age is usual. • •

Ans: (c) Trauma to the epicanthus can cause Ref: Kanski, Clinical Ophthalmology, 8th edition, Page 59

JIPMER–December 2018  77

MEDICINE 1.

All are new markers for ‘Acute Kidney Injury (AKI)’ except: (a) Plasma IL 18 (c) Plasma NGAL

(b) Urinary IL 18 (d) Urinary NGAL

Explanation: Novel Biomarkers for AKI Detected in Urine

Detected in Plasma

•

•

• • • • • • • •

Neutrophil gelatinase associated lipocalin (NGAL, lipocalin-2 or siderocalin) Kidney injury molecule-1 (KIM-1) Insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) Interleukin (IL) 18 L-type fatty acid binding protein Netrin-1 N-Acetyl-β-D-glucosaminidase (NAG) β2-Microglobulin α1-Microglobulin

•

Neutrophil gelatinase associated lipocalin (NGAL,lipocalin-2 or siderocalin) β2-Microglobulin

Novel Biomarkers for CKD Detected in Urine

Detected in Plasma

•

•

• • •

Neutrophil gelatinase associated lipocalin (NGAL,lipocalin-2 or siderocalin) Kidney injury molecule-1 (KIM-1) L-type fatty acid binding protein Urinary Monocyte Chemoattractant Protein-1 (UMCP-1)

• •

Neutrophil gelatinase associated lipocalin (NGAL lipocalin-2 or siderocalin) Plasma Asymmetric Dimethylarginine Fibroblast Growth Factor 23

EXTRA EDGE: Plasma IL-18 is linked with oxidative stress in preeclampsia. It is in a way co-related to coenzyme Q -10 involved in the oxidative stress in preeclampsia. Ans: (a) Plasma IL 18 Ref: Harrison’s Principles of Internal Medicine 19th edition, Page 1808, Harrison’s Principles of Internal Medicine, 20th edition, Page 2108, Brenner & Rector’s The Kidney, 9th edition, Page 1024; Acta Obstet Gynecol Scand, 2010 Mar; 89(3):360-6 and J Nephropathol, 2016 Jan; 5(1): 28–33 2.

True regarding managing a patient with atrial fibrillation: (a) (b) (c) (d)

NOACs require bridging therapy Check for accessory conduction in atrial fibrillation with rapid ventricular rate Absence of fibrillary waves excludes diagnosis TTE better than TEE to detect atrial thrombus

Explanation: ECG in Atrial fibrillation:

•

Characterized by Fibrillatory or ‘f’ waves from the fibrillating atria and an irregularly irregular ventricular rhythm.

78  TARGET JIPMER

In some patients, f waves are very small and not perceptible on the electrocardiogram, and the diagnosis of AF is based on the irregularly irregular ventricular rhythm • In typical untreated AF - Ventricular rate -100 to 160 beats/min • Patients with the ventricular rates - exceeding 250 beats/min- Consider Wolff -Parkinson-White (WPW) syndrome because of conduction over the accessory pathway – bundle of kent . • Transesophageal echocardiogram more sensitive and specific means of assessing left atrial thrombi and spontaneous echo contrast than transthoracic echocardiogram. NOACs – Non Vitamin K antagonist Oral Anticoagulants - Advantages over warfarin: • Eliminates the need for laboratory monitoring • Fewer drug interactions • No food interactions • Rapid onset of action that obviates the need for bridging therapy •

Limitations or contraindications for using NOACs:

• • • • •

Disorders of haemostasis Active bleeding Liver disease Prosthetic heart valves Renal impairment

Ans: (b) Check for accessory conduction in atrial fibrillation with rapid ventricular rate Ref: Hursts the Heart, 14th edition, Page 1954 3.

Liepzig criteria used in: (a) Wilson disease (c) Primary biliary cirrhosis

(b) Hemochromatosis (d) Autoimmune hepatitis

Explanation: Scoring system developed at the 8th International Meeting on Wilson’s disease, Leipzig 2001 Typical clinical symptoms and signs Other tests KF rings Liver copper (in the absence of cholestasis) Present 2 >5x ULN (>4 mmol/g) Absent 0 0.8-4 mmol/g Normal (2x ULN Normal, but >5x ULN after D-penicillamine Serum ceruloplasmin Mutation analysis Normal (>0.2 g/L) 0 On both chromosomes detected 0.1-0.2 g/L 1 On 1 chromosome detected 1:40 > 1:80 LKM > 1:40 SLA positive IgG Upper normal limit > 1.1 times upper normal limit Liver histology Compatible with AIH Typical of AIH Absence of viral hepatitis

+1 +2 +2 +2 +1 +2 +1 +2 +2

Adapted from Hennes et al. (Hepatology 2008; 48:169-76) with permission.

Ans: (a) Wilson disease Ref: EASL Clinical Practice Guidelines: Wilson’s disease, Journal of Hepatology, 2012 Vol. 56 j 671–685 4.

Which among the following extra intestinal manifestations of IBD does not correlate with disease severity? (a) Pyoderma gangrenosum (c) Peripheral arthritis type 1

(b) Episcleritis (d) Recurrent aphthous stomatitis

Explanation: Extra Intestinal manifestation Axial arthropathy

Parallel course of IBD

Perpheral neuropathy

ü Type 1

Erythema nodosum

ü

Separate course of IBD

May or may not parallel disease activity

ü

Pyoderma gangrenosum

ü Type 2 ü

Sweets syndrome

ü

Oral apthous ulcers

ü

Episcleritis

ü

Uveitis

ü

Primary Sclerosing cholangitis

ü

Ans: (a) Pyoderma gangrenosum Ref: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 10th edition, Page 2058 5.

Cause of pruritus in primary biliary cholangitis? (a) TGR 4 (c) Vanilloid receptor

(b) Glucagon like peptide (d) Gastrin releasing peptide

Explanation: Pruritus in primary biliary cholangitis

•

Increased levels of the endogenous ectonucleotide pyrophosphatase/phosphodiesterase autotaxin in cholestatic patients. These mediate pruritus, by catalysing the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which acts as a pruritogen.

80  TARGET JIPMER

•

The transient receptor potential vanilloid 1 (TRPV1) is a capsaicin receptor that plays an important role in sensory transmission of itch and pain and activated by lysophosphatidic acid (LPA).

EXTRA EDGE:

• •

Vallinoid receptor Agonists: Capsaicin and Olvanil* Vallinoid receptor Antagonists: Capsazepine*

Ans: (c) Vanilloid receptor Ref: Sherlock’s Diseases of the Liver and Biliary System, 13th edition, Page 332; Schiff’s Diseases of the Liver, 12th edition, Page 527 6.

Delta gap compares: (a) Change in Anion gap wrt chloride only (c) Change in Anion gap wrt bicarbonate

(b) Change in Anion gap wrt sodium and potassium (d) Change in Anion gap wrt to Sodium only

Explanation:

Delta ratio is a formula that can be used to assess elevated anion gap metabolic acidosis and to evaluate whether a mixed acid base disorder is present. • Changes in AG and HCO3 can be useful in unmasking occult metabolic disorders. Delta gap = (change in anion gap) - (change in bicarbonate); Δ gap = Δ AG – Δ HCO3 •

Normally, increase in anion gap=decrease in serum bicarbonate

< -6 = Mixed high and normal anion gap metabolic acidosis

Delta gap = (change in anion gap)(change in bicarbonate) Δ gap = Δ AG – Δ HCO3

> +6 = Mixed high anion gap acidosis and metabolic alkalosis

Ans: (c) Change in Anion gap wrt bicarbonate Ref: Harrison’s Principles of Internal Medicine, 20th edition, Page 316 7.

APRV stands for: (a) Adult pressure release ventilation (c) Air pressure reverse ventilation

(b) Airway pressure release ventilation (d) Airway pressure reduction ventilation

Explanation: Nonconventional Ventilatory Strategies:

Ability to improve gas exchange and survival rates in severe hypoxemic respiratory fail­ure. • High-frequency oscillatory ventilation (HFOV) • Airway pressure release ventilation (APRV) • Partial liquid ventilation (PLV) using perfluorocarbons Ans: (b) Airway pressure release ventilation Ref: Harrison’s Principles of Internal Medicine, 20th edition, Page 2037

8.

Chance of acquiring hepatitis by eye splash with hepatitis B positive patient blood: (a) 10% (c) 30%

(b) 20% (d) 0.3%

JIPMER–December 2018  81

Explanation:

•



•



•

For a susceptible person, the risk from a single needle-stick or cut exposure to HBV-infected blood ranges from 6-30% and depends on the hepatitis B e antigen (HBeAg) status of the source individual. The average risk for infection after a needle-stick or cut exposure to HCV-infected blood is approximately 1.8%. HIV transmission risk of different routes:

Exposure route

HIV

Blood transfusion

90-95%

Perinatal

20-40%

Sexual intercourse

0.1-10%

Vaginal

0.05-0.1%

Anal

0.065-0.5%

Oral

0.005%-0.01%

Injection drug use

0.67%

Needle stick exposure

0.3%*

Mucous membrane splash to eye, oro-nasal

0.09%

Ans: (d) 0.3% Ref: Exposure to What Healthcare Personnel Need to Know CDC 2003, Management of Occupational Exposure Including Post-exposure Prophylaxis, NACO guidelines 9.

Which is a risk factor for sudden death in HOCM ? (a) Presence of MYH7 mutation (c) LV apical aneurysm

(b) Hypertension on exercise (d) LV thickness >30mm

Explanation: Risk Factors for Sudden Death in Hypertrophic Cardiomyopathy History of cardiac arrest or spontaneous sustained ventricular tachycardia Family history of sudden cardiac death Spontaneous non sustained ventricular tachycardia LV thickness >30 mm Abnormal blood pressure response to exercise Syncope

Ans: (d) LV thickness >30mm Ref: Harrison’s Principles of Internal Medicine 20th edition, Page 1796 10.

Hypernatremia can be rapidly corrected by all except: (a) 5% Dextrose (c) Loop diuretics

(b) RL (d) Dialysis

Explanation: Hypernatremia

•

Defined as a plasma [Na+] >145 mEq/L and represents a state of hyperosmolality

82  TARGET JIPMER ECF volume

Hypervolemic • •

•

>1000 mL

Urine osmolality

Urine osmolality

40 mm

DCIS Grade

Grade 1 to 2

Grade 1 to 2 + necrosis

Grade 3

Excision Margin

> 10 mm

1 to 9 mm

< 1 mm

Patient Age

> 60 years

40 to 60 years

< 40 years

Tumour description

Prognosis

Invasive ductal carcinoma not otherwise specified, high grade

Poor

Invasive lobular carcinoma, pleomorphic type, high grade

Poor

Metaplastic or myeloblastic carcinoma, high grade

Poor

High-grade oat-cell neuroendocrine tumours

Poor

Apocrine breast cancers (some may be HER2 )

Depends on grade: Grade 1 = good Grade 2 = intermediate Grade 3 = poor

Medullary

Good

Adenoid-cystic

Good

Metaplastic low-grade (low-grade adenosquamous, fibromatosis like)

Good

+

Involvement of subdermal lymphatics makes the tumor T4, and carries a poor prognosis. Ans: (b) Medullary CA with high mitotic index has poorest prognosis Ref: Sabiston, 20th edition, Page 836 to 860 6.

Patient becomes completely symptom-free after surgery. Likely diagnosis: (a) Diffuse esophageal spasm (c) Nutcracker esophagus

(b) Achalasia cardia (d) Hiatus hernia

100  TARGET JIPMER

Explanation:

•

Among esophageal diseases, outcome is best following Achalasia cardia surgery (Heller’s myotomy with antireflux procedure)

Hiatus Hernia

• • • •



• •



•



•

Greater than 95% of HHs is type I or sliding hernias Of all PEHs, type III is the most common* PEHs are more common in females and have an autosomal dominant mode of transmission. MC structure to herniate is the fundus of the stomach; other structures that may be located in the hernia sac include the spleen, colon, and omentum Type IV PEH has a higher incidence of serious results, with 50% of patients presenting emergently Clinical Features o Most common preoperative symptom and finding is the typical heatburn o Others are chest pain, epigastric pain, dysphagia, postprandial fullness, regurgitation, vomiting, weight loss, anemia, and respiratory symptoms. o Hematemesis or anemia is evident in about a third of patients with PEH. Diagnosis o Barium swallow is the most important diagnostic test o Endoscopy helps to identify mucosal erosions as a source of gastrointestinal blood loss. o Manometry is needed to determine the motor function of the esophageal body. Treatment o Surgical approach: Transabdominal (laparoscopic or open) or transthoracic. o Transabdominal laparoscopic approach is preferred

Achalasia Cardia

• • •



•

Achalasia means “failure to relax,” (sphincter remains in a constant state of tone with periods of relaxation) Both the muscle of the esophagus and LES are affected Prevailing theory: Destruction of the nerves to LES is primary pathology and degeneration of neuromuscular function of the body of esophagus is secondary Premalignant condition leading to squamous cell carcinoma

Treatment

•



•



•



• • •



•

Early stage: Sublingual nitroglycerin, nitrates, or calcium channel blockers may offer hours of relief of chest pressure before or after a meal. Bougie dilation up to 54 French may offer several months of relief but requires repeated dilations to be sustainable Botulinum toxin: o Injection of botulinum toxin (Botox) directly into the LES blocks acetylcholine release, preventing smooth muscle contraction, and effectively relaxes the LES. o With repeated treatments, Botox may offer symptomatic relief for years o Symptoms recur more than 50% of the time within 6 months. Laparoscopic Heller myotomy is now the operation of choice. Extent of Heller’s myotomy: 2 cm above GE junction to 1 cm below, over stomach. Partial antireflux procedure (Toupet or Dor fundoplication) will restore a barrier to reflux and decrease postoperative symptoms. Esophagectomy is considered megaesophagus, sigmoid esophagus, failure of more than one myotomy, or an undilatable reflux stricture.

Diffuse Esophageal Spasm

• •



• •

Esophageal contractions are repetitive, simultaneous, and of high amplitude Basic pathology is related to a motor abnormality of the esophageal body that is most notable in the lower two thirds of the esophagus. More common in women and is often found in patients with multiple complaints. Clinical Features o Clinical presentation: Chest pain and dysphagia (may be related to eating or exertion and may mimic angina)

JIPMER–December 2018  101



•



•

o Complain of a squeezing pressure in the chest that may radiate to the jaw, arms, and upper back. o The symptoms are often pronounced during times of heightened emotional stress. Diagnosis o Barium swallow: – Corkscrew or rosary-bead esophagus, segmental spasm or pseudodiverticulosis appearance – Due to presence of tertiary contractions – Indicative of advanced disease o Manometry is gold standard test for diagnosis. – Classic manometry findings: Simultaneous, multipeaked contractions of high amplitude (>120 mm Hg) or long duration (>2.5 sec). – These erratic contractions occur after more than 20% of wet swallows. Treatment o Mainstay of treatment for DES is nonsurgical, and pharmacologic (Nitrates, calcium channel blockers) or endoscopic intervention (Bougie dilation) is preferred. o Indications of surgery (long esophagomyotomy):− – Incapacitating chest pain or dysphagia who have failed medical and endoscopic therapy – Presence of a pulsion diverticulum of the thoracic esophagus

Nutcracker Esophagus

• • • • •



•



•

Hypermotility disorder also known as supersqueeze esophagus Esophagus with hypertensive peristalsis or high-amplitude peristaltic contractions. MC and most painful esophageal hypermotility disorder Associated with hypertrophic musculature resulting in high-amplitude contractions of the esophagus Clinical Features o Chest pain and dysphagia are typical symptoms. Diagnosis o The gold standard of diagnosis is the subjective complaint of chest pain with simultaneous objective evidence of peristaltic esophageal contractions 2 standard deviations above the normal values on manometric tracings. o On manometry, amplitude >180 mmHg and duration of contraction >6 seconds Treatment o The treatment of nutcracker esophagus is medical (Calcium channel blockers, nitrates, and antispasmodics)

Ans: (b) Achalasia cardia Ref: Bailey and Love, 27th edition 7.

Treatment of anal cancer stage 2: (a) APR (c) Concurrent chemoradiation

(b) APR followed by chemoradiation (d) Neoadjuvant chemotherapy followed by Surgery

Explanation: TNM Staging of Anal Cancer (American Joint Committee for Cancer) Primary tumor (T)

TNM

Explanation of stage

TX T0 Tis T1 T2 T3 T4

Primary tumor cannot be assessed No evidence of a primary tumor Carcinoma in situ Tumor 2 cm or less in greatest dimension Tumor >2 cm but < 5 cm in greatest dimension Tumor > 5 cm in greatest dimension Tumor of any size invading adjacent organs Contd.

102  TARGET JIPMER Contd. Regional lymph nodes (N)

NX N0 N1 N2 N3

Regional nodes cannot be assessed No regional node metastases Metastasis in perirectal lymph node(s) Metastasis in unilateral internal iliac &/or inguinal LNs Metastasis in perirectal/inguinal LN &/or bilateral II LN

Matastasis (M)

MX M0 M1

Distant metastasis cannot be assessed No distant metastasis Distant metastasis present

Anal Cancer Staging Stage

Ta

Nb

Mc

Stage 0

Tis

N0

M

Stage I

T1

N0

M0

State II

T2

N0

M0

State II

T3

N0

M0

Stage IIIA

T1, T2, T3

N1

M0

Stage IIIA

T4

N1

M0

Stage IIIB

T4

N1

M0

Stage IIIB

Any T

N2, N3

M0

Stage IV

Any T

Any N

M1

Treatment of anal cancer:

• • • •

Anal canal Stages I to III : radiation + chemotherapy with mitomycin and fluorouracil Anal margin Stage I : Wide local excision Anal margin Stage II to III : radiaton + chemotherapy Stage IV : Cisplatin based chemotherapy with/without radiation

Ans: (c) Concurrent chemoradiation Ref: Sabiston, 20th edition, Page 1414 8.

Pancreaticoduodenectomy is not indicated in: (a) (b) (c) (d)

Multiple cyst and calcifications in head of the pancreas carcinoma Duodenal cancer Failed drainage procedure for chronic pancreatitis Ampullary carcinoma with secondaries in peritoneum

Explanation: Pancreaticoduodenectomy

• •



•



•

AKA pancreatoduodenectomy, Whipple procedure or Kausch-Whipple procedure It consists of complete removal of the pancreatic and hepatoduodenal ligament lymph nodes, the duodenum with a short segment of the proximal jejunum and the distal half to two-thirds of the stomach with the right half of the greater omentum Whipple’s Procedure involves resection of o Distal stomach o Gall bladder o CBD o Head of pancreas o Duodenum o Proximal jejunum o Regional lymphatics Restoration of GI continuity requires

JIPMER–December 2018  103



•



•

o Pancreaticojejunostomy o Hepaticojejunostomy o Gastrojejunostomy Pylorus Preserving Pancreaticoduodenectomy (PPPD) or Longmire-Traverso Procedure is the preferred surgery for carcinoma head of pancreas The Whipple procedure is now reserved for situations in which the entire duodenum has to be removed (e.g. in FAP) or where the tumour encroaches on the 1st part of the duodenum or the distal stomach and a PPPD would not achieve a clear resection margin.

Medical Indications for Pancreaticoduodenectomy

•



• • • • • •

Pancreatic cancer – Head of pancreas o Adenocarcinoma o Ampullary carcinoma Cystic tumours of pancreas Chronic pancreatitis Duodenal carcinoma Common bile duct cancer (Cholangiocarcinoma) Mucinous cytadenoma Trauma

Contraindications

•

Metastatic disease in abdominal cavity or nearby organ

Ans: (d) Ampullary carcinoma with secondaries in peritoneum Ref: Bailey and Love, 27th edition. 9.

Maggot used for wound debridement: (a) Black fly (c) Green bottle fly

(b) House fly (d) Blue bottle fly

Explanation:

• • • • •



•



•



•

Maggots can either feed only on dead tissue, only on living tissue or both on living and dead tissue. The infestation by maggots of live animals is called myiasis. The flies used most often for the purpose of maggot therapy are blow flies of the Calliphoridae. The blow fly species used most commonly is Lucilia sericata, the common green bottle fly. Another important species, Protophormia terraenovae, is also notable for its feeding secretions, which combat infection by Streptococcus pyogenes and S. pneumoniae. Secretions from maggots believed to have broad-spectrum antimicrobial activity include allantoin, urea, phenylacetic acid, phenylacetaldehyde, calcium carbonate, proteolytic enzymes, and many others In vitro studies have shown that maggots inhibit and destroy a wide range of pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), group A and B streptococci, and Grampositive aerobic and anaerobic strains. Bacteria like Pseudomonas aeruginosa, E.coli or Proteus spp. are not attacked by maggots, and in case of Pseudomonas even the maggots are in danger.

The maggots have 4 principal actions:

• • • •

Debridement Disinfection of the wound Stimulation of healing Biofilm inhibition and eradication

Ans: (c) Green bottle fly Ref: Acute wound care: The Surgeon’s Perspective, John Mitchell, Page 108

104  TARGET JIPMER 10.

Treatment for acute bleeding esophageal varices are all except: (a) Beta blockers (c) Sclerotherapy

(b) Banding (d) Surgery

Explanation:

•

Beta blockers are used for prevention of re-bleeding (prophylaxis). Somatostatin (IV Octreotide) and vasopressin are used in acute bleeding episode.

Refer table and flowchart below: Treatment of Acute Variceal Hemorrhage Regimen

Options

General Management

Admit to intensive care unit Resuscitation but limit transfusion to hemoglobin level of 7 g/dL Secure intravenous access Consider intubation and mechanical ventilation

Vasoconstrictor

IV octreotide (50 mg bolus then 50 mg/hour infusion × 2 to 5 days) IV terlipressin (2 mg every 4 hours for first 48 hours, followed by 1 mg every 4 hours × 2 to 5 days)

Antibiotic Prophylaxis

IV ceftriaxone 1 gm daily × 7 days (preferred in Child class B and C) Oral norfloxacin 400 mg twice a day × 7 days

Endoscopic Therapy

Endoscopic variceal ligation (preferred) Endoscopic variceal sclerotherapy

Salvage Therapy

Balloon tamponade (only temporary, maximum 24 hours) Transjugular intrahepatic portosystemic shunt UGI bleed ? varices Endoscopy available ? Yes

No

UGI endoscopy

Glypressin Somatostatin Octreotide

Oesophageal variceal bleed Variceal band ligation/ sclerotherapy Uncontrolled Balloon tamponade

TIPSS/surgery

Controlled

Gastric variceal bleed Gastro-oesophageal varices Treat as oesophageal varices

Banding eradication programme Recurrent Eradicated variceal bleeding FU at 3 and 6 months and then Consider referral for yearly TIPSS/surgery

Isolated gastric varices TIPSS

JIPMER–December 2018  105 Thus, as we can see above all of the four choices are options for control of acute variceal hemorrhage. Ans: (a) Beta blockers Ref: Sabiston, 20th edition, Page 1138 11.

A person was found unconscious following a RTA. Patient was deeply comatose with decerebrate and decorticate rigidity. MRI shows small hemorrhages on corpus callosum and nothing else. Person dies after a week in coma. Cause of death: (a) Axonal injury (c) EDH

(b) Subdural hematoma (d) Infarct

Explanation:

•



•



•

Diffuse axonal injury (DAI), also known as traumatic axonal injury (TAI), is a severe form of traumatic brain injury due to shearing forces. It is a potentially difficult diagnosis to make on imaging alone, however, it has the potential to result in severe neurological impairment.  The diagnosis is best made on MRI where it is characterized by several small regions of susceptibility artifact at the grey-white matter junction, in the corpus callosum, and in more severe cases in the brainstem, surrounded by FLAIR hyperintensity. 

Clinical presentation

•



•

Typically, patients who are shown to have diffuse axonal injury have loss of consciousness at the time of the accident. Post-traumatic coma may last a considerable time and is often attributed to coexistent more visible injury (e.g. cerebral contusions). As such the diagnosis is often not suspected until later when patients fail to recover neurologically as expected. 

Pathology

Diffuse axonal injury is the result of shearing forces, typically from rotational acceleration (most often a deceleration). • In the majority of cases, these forces result in damage to the cells and result in edema. Actual complete tearing of the axons is only seen in severe cases.  MRI is the modality of choice for assessing suspected diffuse axonal injury even in patients with entirely normal CT of the brain. MRI, especially SWI or GRE sequences, exquisitely sensitive to paramagnetic blood products may demonstrate small regions of susceptibility artefact at the grey-white matter junction, in the corpus callosum or the brain stem. Some lesions may be entirely non-hemorrhagic (even using high field strength SWI sequences). These will, however, be visible as regions of high FLAIR signal.  •

MR spectroscopy

MRS can be of benefit in identifying patients with grade I injury which may be inapparent on other sequences. • Features typically demonstrate elevation of choline peak and reduction of NAA  The other options i.e EDH, SDH and infarcts present with more overt radiological findings. •

Ans: (a) Axonal injury Ref: Greenberg, Handbook of Neurosurgery, Page 864 12.

All are true about Chronic SDH except: (a) (b) (c) (d)

Immediate recovery after surgery Presents weeks after trivial injury Patient can be completely asymptomatic Use of a subdural drain is associated with a decreased need for repeat surgery

Explanation:

•

Chronic subdural hematomas can be treated by burr hole craniotomies, twist drill craniostomy with subdural drains etc.

106  TARGET JIPMER

•



•

There is clinical improvement when subdural pressure is close to zero, which usually occurs after almost 20 percent of the collection has been removed. Residual subdural fluid collections are common and may take upto 6 months for complete resolution.

Complications of surgical treatment:

• Seizures including intractable status epilepticus. • Intracerebral hemorrhage. • Failure of brain to expand. • Tension pneumocephalus. • Subdural empyema. Patients can present weeks after trivial injury and can be completely asymptomatic. Risk factors: Alcohol abuse, seizures, CSF shunts, coagulopathies etc.

Ans: (a) Immediate recovery after surgery Ref: Greenberg, Handbook of Neurosurgery, Page 823 13. A RTA patient presents with multiple fractures. He develops respiratory distress and dies after few days. CT brain shows petechial hemorrhage. Most likely diagnosis is: (a) Fat embolism (c) Hemorrhage

Explanation:

(b) Stroke (d) Hypoxic ischaemic encephalopathy

JIPMER–December 2018  107 Fat embolism syndrome (FES)

• • •



•



•



•



•



•



•

Generally associated with displaced long-bone fractures of the lower extremities Occur in 0.5–3.5% of cases. Fat emboli may reach the brain through a right-to-left cardiac shunt or through an intact pulmonary circulation in patients without a shunt.  The major clinical characteristics of FES include respiratory insufficiency, neurologic symptoms, and a petechial skin rash. Neurologic symptoms may vary considerably, ranging from a subclinical presentation to confusion to coma and seizures; in rare cases, death may result. The number of white matter lesions on MR images is correlated with the patient’s score on the Glasgow coma scale. In most cases, neurologic function is gradually recovered over days to months. The pathologic hallmarks of cerebral fat embolism (CFE) include petechia or purpura distributed throughout the white matter of the cerebrum and cerebellum, with relative sparing of the gray matter. Fat globules occlude the microvasculature, with necrosis and hemorrhage in the surrounding parenchyma. Infarcts may range from a few millimeters to 4 cm in diameter. The chronic sequela of CFE is extensive demyelination of the white matter. Recent animal model studies suggest that fat embolism can result in the breakdown of the capillary endothelium and the blood-brain barrier, causing focal vasogenic edema without infarction or hemorrhage.

Ans: (a) Fat embolism Ref: Greenberg, Handbook of Neurosurgery, Page 868 14.

All the following factors are included in qSOFA except: (a) HR >100 (c) Altered mental status

(b) RR>22 (d) SBP22, Altered mental status & SBP 204

Cardiovascular Hypotension

No hypotension

MAP 5 or epi < 0.1* or norepi < 0.1*

Dopamine > 15 or epi >0.1* or norepi >0.1*

Central nervous system Glasgow coma score

15

13–14

10–12

6–9

14.2

Cardiovascular (PARd)

< 10.0

10.1–15.0

15.1–20.0

20.1–30.0

> 30.0

Hematologic (platelet count × 10-3)

> 120

81–120

51–80

21–50

25% contusion may likely needs intubation

Explanation:

•



• • •

Lung contusions may be present on the initial chest radiograph but typically require time to become visualized- So it can be missed Inadequate pain relief leads to hypoventilation, promotion of atelectasis & worsening hypoxemia. Intubation should be reserved for the classical indications only- It can result in pneumonia CECT- Investigation of Choice*

Pulmonary Contusion: Etiology: Caused by transfer of energy through chest wall to renal parenchyma Pathology:

• • • • •

Tissue damage along with hemorrhage into alveolar & interstitial spaces Manifested as physiologic shunt with hypoxemia Occurs with flial segment & is often more clinically important than rib fractures. Occurs in 75% of patients with flail chest Morbidity is secondary to a profound inflammatory response that can progress to multiple organ dysfunction or failure.

Clinical features:

• •

Natural progression of pulmonary contusion is worsening hypoxaemia for the first 24-48 hours. Clinical manifestations of pulmonary contusion vary from mild dyspnea to overt pulmonary failure with development of acute respiratory distress syndrome.

Signs of pulmonary contusion:

• • • • • • •

Hypoxemia (PaO2 60 mm Hg) on room air Hypercarbia Increased work of breathing Hemoptysis Loss of lung compliance Elevated intrapulmonary shunting Ventilation/perfusion mismatch

Radiological aspects:

•

Pulmonary contusion is identified by radiographic findings of an irregular interstitial pattern or frank consolidation in the lung parenchyma

X ray:

•



•

Lung contusions may be present on the initial chest radiograph but typically require time to become visualized. If identified early on chest film are frequently severe & often rapidly progress to respirator failure. Chest radiographic findings may be typically delayed- So it can be missed

CT scan:

•

Contrast CT scanning is confirmatory. o Injured lung tissue on CT appears as higher density o Thoracic CT is valuable for the identification of pulmonary contusion

JIPMER–December 2018  111

CT scan showing a pulmonary contusion (red arrow) accompanied by a rib fracture (blue arrow) Differentiate from Atelectasis: Atelectasis- Doesn’t cross pulmonary fissures, Contusions- Limited by ventilator segments. “Injured pulmonary tissue in the vicinity of chest wall injuries, especially when it is not in dependent areas is highly suggestive of pulmonary contusion” Treatment:

•



• • • •

Patients should be monitored for hypoxemia, increased work of breathing, and agitation that indicate respiratory decompensation that often requires intubation and mechanical ventilation. Mechanical ventilatory support permits adequate alveolar ventilation and reduces work of breathing. Pulmonary contusions will resolve with time Early intubation in these patients is controversial at present. Intubation should be reserved for the classical indications, although the need for intubation and mechanical ventilation can lead to a 44% incidence of pneumonia.

Pain Control:

Pain control with IV narcotics is often adequate in mild and moderate cases Severe cases, patients benefit from epidural analgesia. • Control of pain is critical in patients with limited chest excursion as a result of pain from rib fractures, chest wall contusion, and other injuries. • Inadequate pain relief can lead to hypoventilation, promotion of atelectasis, and worsening hypoxemia. • Epidural analgesia or patient-controlled analgesia using opioids and fentanyl patch should be considered, especially in the setting of rib fractures. • Haemoptysis or blood in the endotracheal tube is a sign of pulmonary contusion. • Mild contusion-- Treatment is oxygen administration, pulmonary toilet & adequate analgesia. • More severe cases require mechanical ventilation. • Normovolaemia is critical for adequate tissue perfusion and fluid restriction is not advised. About 15% of patients with pulmonary contusion die. Ans: (d) >25% contusion may likely needs intubation Ref: Sabiston, 20th edition, Page 428, Bailey, 27th edition, Page 371, Greenfeld, 5th edition, Page 377

17.

All are risk factors for Barretts esophagus except: (a) (b) (c) (d)

Overproduction of epidermal growth factor receptors in saliva Decreased esophageal pain Decreased esophageal motility Duodenogastric reflux

Explanation:

•

Factors predisposing to development of Barrett esophagus include: o Early-onset gastroesophageal reflux disease o Abnormal lower esophageal sphincter and esophageal body physiology o Mixed reflux of gastric and duodenal contents into the esophagus.

112  TARGET JIPMER BARRETT’S ESOPHAGUS: • Metaplasia of esophageal squamous epithelium into columnar in distal esophagus PATHOGENESIS BARRETT’S ESOPHAGUS

Reflux of gastric contents (Acid and Duodenal Juice) into Esophagus

Shorter and weaker LES and Reduced amplitude of esophageal peristalsis

Amount of reflux is greater and esophageal clearance is slower



• •

Consequence of severe reflux esophagitis Barrett’s esophagus requires both endoscopically visible segment of columnar lining of distal esophagus and intestinal metaplasia showing goblet cells on biopsy

Columnar Type Of Epithelium In Barrett’s Esophagus

• • • • • •

Intestinal type: Most common type (Most commonly associated with dysplasia & carcinoma). Junctional type Fundic type Metaplasia characteristically affects distal esophagus More common in men, whites and with increasing age Premalignant condition for adenocarcinoma

Clinical Features:

• • •

Patients with Barrett esophagus typically have a long history of GERD. Most patients have both typical and atypical symptoms of GERD Others–Asymptomatic over time due to decreased sensitivity of metaplastic epithelium

Investigations:

•



•

Endoscopy shows presence of “salmon pink” epithelium above gastroesophageal junction, replacing whitish squamous epithelium. Esophageal manometry often shows a short and hypotensive LES and abnormal esophageal peristalsis (decreased amplitude of peristaltic waves, simultaneous waves). Barrett's esophagus

JIPMER–December 2018  113 Direct measurement of esophageal bilirubin exposure as a marker for duodenal juice has shown that GERD patients have increased esophageal exposure to duodenal juice and that this exposure is most dramatically related to Barrett esophagus. Complications:

• • •

Can lead to chronic peptic ulceration of esophagus (Barrett’s ulcer) Can lead to high (midesophageal) and long strictures Progression of nondysplastic Barrett epithelium occurs with 5% to 10% of patients per year progressing to dysplasia & 0.5% to 1% per year progressing to adenocarcinoma.

Treatment: Early adenocarcinoma

Esophagectomy

Fit for surgery–Esophagectomy

High grade dysplasia

Unfit for surgery–Ablative therapy

Barrett’s esophagus

Close follow up every 3 months

Follow up every 1 year Low grade dysplasia Re endoscopy 6 monthly

No dysplasia

Follow up every 2-3 years

Role of epidermal growth factor & EGFR in barrett’s esophagus:



EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. • In normal oesophageal mucosa the distribution of EGF does not alter from proximal to distal oesophagus. • EGF is also found in the superficial epithelial cells in Barrett’s oesophagus, distribution which is quite different to that in the squamous mucosa. • Trophic and antisecretory effects of EGF are mediated by the luminal route in the stomach. • Luminal EGF may be involved in the proliferative abnormalities of Barrett’s mucosa because EGF receptors have been found throughout the glands of Barrett’s mucosa. • EGFR Over expression expression & amplification is relatively common in Barrett’s

114  TARGET JIPMER Role of Nitric Oxide In Barrett’s Esophagus: Exogenous NO

Exdogenous NO

Salivary nitrite Acid refluxant

Bacterial composition Gastro-esophageal reflux

Inflammatory reaction

NO production

Normal esophageal squamous epithelium

Barrett’s esophagus

Esophageal adenocarcinoma

Ans: (b) Decreased esophageal pain Ref: CSDT, 13th edition, Page 469, Greenfeld, 5th edition, Page 377 18.

Gall bladder carcinoma is M1 stage when which of the following lymph nodes are involved? (a) Superior mesenteric lymph nodes (c) Celiac lymph nodes

(b) Aortic lymph nodes (d) Pancreato-duodenal lymph nodes

Explanation:

•

Presence of tumor in the periaortic lymph nodes of the celiac axis indicates that the tumor is beyond the limits of normal resection.



•

Regional lymph nodes are the hepatic hilus nodes (including nodes along common bile duct, hepatic artery, portal vein & cystic duct), celiac & superior mesenteric artery nodes.



•

Lymphatic drainage of pancreas normally occurs into the peripancreatic nodes located along the veins.

STAGING OF GALL BLADDER CANCER: T1

T1a- Invades Lamina propria T1b- Invades Muscular layer (Water shed area for Gallbladder cancer management)

T2

T2a- Invades Perimuscular connective tissue on peritoneal side without serosal involvement T2b- Invades Perimuscular connective tissue on hepatic side with no extension into liver

T3

Perforates serosa (visceral peritoneum) and/or directly invades liver or adjacent organ like stomach, duodenum, colon, pancreas, omentum or extrahepatic bile ducts

T4

Invades main portal vein/hepatic artery or invades two/more extrahepatic organs/structures

N1

1-3 Regional lymph nodes

N2

4/more Regional lymph nodes

JIPMER–December 2018  115 N0 T1

I

T2a

IIa

T2b

IIb

T3

IIIA

T4

IVA

N1

N2

M1

IIIB

IVB

IVB

Management: > 1 cm Open Cholecystectomy Gallbladder polyp < 1 cm Serial USG Incidental finding

T1a Cholecystecomy sufficeObserve At time of/after cholecystectomy

T1b, Perineural, lymphatic or vascular invasion Extended cholecystectomy T2 Radical cholecystectomy

GBC

Suspected of gallbladder cancer preoperatively

Advanced locoregional disease Extended Liver resection (T3/T4)

Metastatic disease at presentation

Palliative Jaundice-Endoscopic biliary stenting Pain-Narcotics, Percutaneous neurolysis of celiac ganglion Intestinal obstruction-Endoscopic duodenal stent

Ans: (b) Aortic lymph nodes Ref: CSDT, 13th edition, Page 600, Greenfeld, 5th edition, Page 377 19.

Panda sign: (a) Unilateral & sign of anterior cranial fossa fracture (c) Unilateral & sign of posterior cranial fossa fracture

(b) Bilateral & sign of anterior cranial fossa fracture (d) Bilateral & sign of posterior cranial fossa fracture

116  TARGET JIPMER

Explanation: Panda sign–Raccoon eyes:

• •

Sign of anterior cranial fossa fracture It is mostly bilateral

RACCOON EYES/PANDA EYES:

Periorbital ecchymosis- Sign of basilar skull fracture (Mostly associated with Fractures of anterior cranial fossa). • It may also be a sign of disseminated neuroblastoma or multiple myeloma, Kaposi sarcoma & Amyloidosis, Subgleal hematoma or craniotomy that has ruptured meninges • Clinically, one may suspect a basilar skull fracture in presence of Battles sign, which is retroauricular ecchymosis, or “raccoon eyes,” which is bilateral periorbital ecchymosis. Raccoon eyes may be bilateral or unilateral- Mostly bilateral Bilateral- Highly suggestive of basilar skull fracture (Positive predictive value- 85%) •

Skull base fractures

Anterior cranial fossa

Middle cranial fossa

CSF Otorrhea/rhinorrhea Hemotympanum Ossicular disruption Battle sign–Bruise behind ear 7th and 8th cranial nerve palsies

Subconjunctival hematoma CSF Rhinorrhea Carotico-cavernous fistula Periorbital ecchymosis/ Raccoon eyes

Ans: (b) Bilateral & sign of anterior cranial fossa fracture Ref: CSDT, 13th edition, Page 867; Greenfeld, 5th edition, Page 347 20.

All are true about retained antral syndrome except: (a) Tech 99 scan is used for diagnosis (c) Positive pentagastrin test

(b) Seen after bilroth II surgery (d) Calcium provocation test was negative

Explanation:

• • •

Tc99m Scan is used for Diagnosis Seen usually after Billroth II gastrectomy -ve Pentagstrin test & -ve Calcium Provocation test (No antral cells to get stimulated)

JIPMER–December 2018  117 Retained-antrum syndrome:

• • •

Rare condition, occurring in Billroth II gastrectomised patients Ulcer recurs & is associated with high levels of circulating gastrin. Mechanism involved is inadequate removal of the distal antrum and pylorus during resection of the antrum and gastrojejunostomy. Lack of usual acid secreting gastric glands

Antral segment gets continually exposed to alkaline environment of duodenum

Reflex secretion of excessive acid and prone to form recurrent ulcers

Pathophysiology of retained antrum syndrome:

(A) Normal stomach with antrum. A segment of incompletely resected antrum bathed in the alkaline environment of the duodenum during distal gastrectomy with (B) Billroth II or (C) Roux-en-Y reconstruction results in intense gastrin secretion by retained antrum and causes marginal ulceration as depicted in (B) and (C).



• • • •

Fasting gastrin levels are 2 to 4 times above normal range Secretin tests won’t produce rise in gastrin levels as it occurs in Zollinger Ellison syndrome Treatment for retained antrum is revision surgery to excise the remaining tissue. Frozen section should be performed to look for Brunner glands at distal resection margin.

Extra Edge: Hypergastrinemia without gastric acid hypersecretion • •

Pernicious anemia Gastric atrophy

Hypergastrinemia with gastric acid hypersecretion • • • • • •

Gastrinoma (ZES) Retained antrum syndrome Antral G cell hyperplasia Gastric outlet syndrome Partial small bowel resection Renal insufficiency

118  TARGET JIPMER

•

Hypergastrinemia & gastric acid hypersecretion may occur in patients with gastric outlet obstruction, retained antrum after Billroth II gastrojejunostomy, and antral gastrin cell hyperactivity (hyperplasia). These conditions are differentiated from gastrinoma by use of secretin test.

Ans: (c) Positive pentagastrin test Ref: Shackelford, 8th edition, Page 730; Manual of Gastroenterology, 4th edition, Page 161 21.

What is false regarding wandering spleen? (a) Chronic torsion leads to splenomegaly (c) Infarction & torsion are common

(b) Treatment of choice is splenectomy only (d) It is encapsulated with Long vascular pedicle

Explanation:

•



•



• • •

Wandering spleen is an unusual condition with normal spleen having a long loose & vascular splenic pedicle but lacks ligamental attachments Intermittent abdominal pain, splenomegaly resulting from venous congestion & severe persistent painSuggestive of wandering spleen & tension/ intermittent torsion of splenic pedicle. May lead to splenic torsion and infarction. Chronic torsion typically causes venous congestion and splenomegaly. Spleen removal or splenopexy is treatment of choice

WANDERING SPLEEN

(Displaced spleen, drifting spleen, splenoptosis, floating spleen, or splenic ptosis). • Wandering spleen is a normal spleen that has either extreme laxity or absence of the normal ligaments to keep it in left upper quadrant. • This allows spleen to move within the peritoneum • 13 times more frequently in women than in men. • More common in adults than children Etiology



• •

Wandering spleens in children arise from congenital atresia of the dorsal mesogastrium. Acquired tissue laxity associated with pregnancy (Hormonal changes)- Multiparous

Presentation

•

Symptomatic if there is torsion of pedicle (Acute ischemia & Acute pain).

Acute torsion manifests as acute abdominal pain, fever, vomiting, acute pancreatitis, and gastric compression. Persistent torsion more than 180° or without detorsion, splenic infarction and gangrene ensue.

Chronic torsion typically causes venous congestion & splenomegaly.

Lack of radiotracer uptake in a previous demonstrated wandering spleen indicates TORSION.



•

Diagnosis: Palpable lower abdominal mass confirmed by CT scan Nuclear imaging spleen scan finding of splenic tissue.

JIPMER–December 2018  119 Whirl Sign: Presence of whirl appearance of splenic vessels & surrounding fat at splenic hilum- Pathognomonic of Wandering spleen. Rim Sign: High density of splenic capsule compared to normal parenchyma is seen with splenic infarction Treatment



•



• •



•

Children

Adults

Associated with Infarction

Splenopexy Suturing spleen to diaphragm, abdominal wall or omentum

Splenectomy

Splenectomy

Treatment for a wandering spleen as an incidental finding at laparotomy or if the torsion can be corrected and the spleen appears to be viable is to do a splenopexy, affixing it to its native position in the left upper quadrant. If the spleen is infarcted, a splenectomy must be performed Wandering spleen is ideally suited for laparoscopic splenectomy as it is generally free from ligaments or attachments to other organs. Acute torsion of the pedicle occurs occasionally, necessitating emergency splenectomy, and elective removal of wandering spleens in the pelvis is recommended.

Ans: (b) Treatment of choice is splenectomy only Ref: Greenfeld, 5th edition, Page 1235; CSDT, 13th edition, Page 600; Sabiston, 20th edition, Page 1564 22.

According to Spetzler Martin criteria, how much SMC score is given for a 5 cm nidus with AV malformation. (a) 3 (c) 2

(b) 4 (d) 5

Explanation:

•

5 cm nidus indicates size of 3-6 cm and is assigned 2 points

Spetzler Martin Criteria

•

Points are assigned based upon o Size (< 3 cm→1 Point; 3-6 cm→2 Points; > 6 cm→3 Points) o Venous drainage (Superficial→0 points; Deep→1 point), o Eloquence of the surrounding brain, (Absent→0 points; Present→ 1 point) Spetzler-Martin AVM grading scale

Graded Feature

Points Assigned

Size of AVM 6 cm

1 2 3

Eloquence1 of adjacent brain Noneloquent Eloquent

0 1

Venous drainage Superficial Deep

0 1

Eloquent areas include: visual, language and sensorimotor cortex; the thalamus and hypothalamus; the internal capsule; the brainstem; the cerebellar peduncles; and the deep cerebellar nuclei.

1

120  TARGET JIPMER This criteria yields I-V grades THREE TIER MODIFICATION: Class A

Class B

Class C

Grade I & II

Grade III

Grade IV & V

Ans: (c) 2 Ref: Sabiston, 20th Edition, Page 1904, CSDT, 13th edition, Page 913 23.

Which branch of portal vein is usually involved in chronic pancreatitis? (a) Superior mesenteric vein (c) Left branch of portal vein

(b) Splenic vein (d) Inferior mesenteric vein

Explanation:

• • •

Chronic Pancreatic inflammation can produce vascular thrombosis Most commonly involved vein is Splenic vein Variceal formation can occur as a consequence of either portal or splenic venous occlusion, and splenic vein thrombosis with gastric variceal formation is referred to as left-sided or sinistral portal hypertension. Chronic inflammation Vascular thrombosis

Portal vein

Splenic vein

Severe cases Occurs by inflammatory mass in head of pancreas

4-8% of cases (Most common)

Ans: (b) Splenic vein Ref: Sabiston, 20th edition, Page 1531; Shackelford, 8th edition, Page 1088 24.

Structure preserved in radical neck dissection are all except: (a) Vagus nerve (c) Internal jugular vein

(b) Accessory nerve (d) Sternocleidomastoid

Explanation: Standard Radical Neck Dissection (Crile’s)

Structures removed include • Nodal levels I through V • Sternocleidomastoid muscle • Internal jugular vein • Cranial nerve XI • Cervical plexus • Submandibular gland. Modified RND (Brocca’s)



•

Preservation of the sternocleidomastoid muscle, internal jugular vein, or cranial nerve XI in any combination is referred to as a modified RND (MRND).

JIPMER–December 2018  121 Type of Neck Dissection Comprehensive

Nodal levels removed

Structures preserved

Indications

Radical neck dissection

Levels I-V

None

N+ neck for SCC where SAN involved

Modified radical neck dissection type I

Levels I-V

SAN

N+ neck for SCC where SAN free of disease

Modifed rediacal neck dissection type II

Levels I-V

SAN, SCM

N+ neck for SCC where IJV involved but SAN free of disease

Modified radical neck dissection type III

Levels I-V

SAN, SCM IJV

Metastatic differentiated thyroid carcinoma

Supraomohyoid neck dissection

Levels I-III

SAN, SCM, IJV

N 0 neck for SCC of oral cavity and oropharynx (include level 4); N 0 neck maliganant melanoma where primary site is anterior to ear (include parotidectomy for face and scalp)

Extended supraomohyoid neck dissection

Levels I-IV

SAN, SCM, IJV

N 0 neck for SCC of lateral tongue

Lateral neck dissection

Levels II-IV

SAN, SCM, IJV

N 0 neck for Scc of larynx and hypotharynx

Posterolateral neck dissection

Levels II-V, subocciptial, retroauricular notes

SAN, SCM, IJV

N 0 neck malignant melanoma where primary site is posterior to ear

Selective

SAN, spinal accessory nerve; SCM, sternocleidomastoid muscle; IJV, internal jugular vein

Ans: (a) Vagus nerve Ref: Sabiston, Textbook of Surgery, 19th edition, 796-8 & Mastery of Surgery, 5th edition, Page 324 25.

Most common early complication of TIPSS procedure? (a) Hepatic encephalopathy (c) Shunt stenosis

(b) Capsule rupture and hemorrhage (d) Recurrent variceal bleed

Explanation: Portal Hypertension

• Defined when portal venous pressure is more than 5mm of Hg. • Due to prehepatic, hepatic and posthepatic conditions causing Portal hypertension, patients present with variceal bleeding. • Treatment of acute variceal bleed includes airway, breathing and circulation, cross matching and blood transfusion. • Initial Endoscopy should be done within first 24 hours and the treatment options are o Endoscopic Band ligation o Sclerotherapy • Endoscopic Band ligation is considered more effective and associated with less complications. • When both these are not available or failure is seen, Balloon tamponade using Sengstaken-Blakemore tube is done for 48 hours. • Medical management of variceal bleed includes Octreotide and then vasopressin in severe bleeding.

122  TARGET JIPMER

• Endoscopic band ligation and Octreotide is the combination therapy that is considered more effective. • TIPSS (Transjugular Intrahepatic Porto Systemic Shunts) – percutaneous invasive procedure where a stent which passes through the Right hepatic vein and connects Right portal branch thereby shunting both. Done in patients with resistant Ascites, End stage liver disease needing liver transplant as a standby procedure. Complication of TIPSS can be divided into:



• • • •

Intra op complication: Capsular hemorrhage Early Complication: Hepatic Encephalopathy ( 34%) Late Complication: Recurrent Variceal bleed ( 19%) Delayed Complication: (6 months- 1 year) Shunt stenosis due to neo intimal hyperplasia > shunt thrombosis. Shunt stenosis can be dilated by Balloon. Total occlusion is seen in 15%.

Ans: (a) Hepatic encephalopathy Ref: Sabiston, Textbook of Surgery, 20th edition; Page 1439-1440 26.

Cause of nausea and vomiting in carcinoma head of Pancreas: (a) Involvement of celiac plexus (c) Duodenal infiltration

(b) Superior mesenteric artery syndrome (d) External compression of duodenum

Explanation: Pancreatic adenocarcinoma

•

Develops in the ductal cells and are called Ductal Adenocarcinoma.



•

They most commonly occur on the Right side, ie, Head and Uncinate Process (60-70%) than left side, ie, Body and Tail of pancreas (20-25%)



•

Features of Carcinoma Head of Pancreas are o Jaundice 75% o Weight loss 51% o Abdominal pain 39% o Nausea/vomiting 13% o Pruritus 11% o Fever 3% o Gastrointestinal bleeding 1% For tumors at the body and tail of pancreas, Pain(most common) and weight loss are the presenting features as they present at a late advanced stage



•



• Regarding Nausea and vomiting, they occur due to tumor extrinsic compression of duodenum C loop presenting a state of Gastric outlet obstruction.



•

In unresectable cases, these patients should be offered Endoluminal duodenal metal stent as palliation.

Ans: (d) External compression of duodenum Ref: Blumgarts, 6th edition, Page 979; Sabiston, 20th edition, Page 1544 27.

Treatment of choice for bleeding gastric ulcer: (a) Distal Gastrectomy (c) Under running of ulcer

(b) Antrectomy (d) Vagotomy and drainage

Explanation:

• Patients with bleeding gastric ulcers presents in the emergency setting as Hematemesis or in the mild chronic setting as Melena. • Most of the bleeding stops spontaneously and requires no intervention. However, persistent bleeding is associated with mortality. • In the Emergency setting, patient treatment algorithm is as follows:

JIPMER–December 2018  123 Large bore IV access IV fluids and blood products NG Lavage Close monitoring of signs of rebleeding

Upper GI Scopy – source of upper GI bleeding

Assess Risk of rebleeding using Forrest classification and Scoring systems

Lower risk Ulcers

IV PPI bolus followed by intermittent doses for 72 hours

High risk of rebleeding or active bleeding

Endoscopic intervention

Hemodynamically unstable - Surgery

Vasoconstrictor injection Sclerosant Clip application

Laparotomy, Duodenotomy and Oversewing the ulcer with three point U stitch

Cathether directed angiography and Endovascular Embolization



• Rebleeding risk is assessed by commonly used scoring systems – Blatchford and Rockall Prediction scores Ans: (c) Under running of ulcer Ref: Sabiston’s, Textbook of Surgery, 20th editon, Page 1202 – 1204.

28.

Best suitable graft for repairing dissecting aortic aneurysm: (a) Dacron (c) Autologous vein

(b) Teflon (d) PTFE graft

Explanation: Grafts in Vascular surgeries

•

Bypass surgeries are done for peripheral arterial occlusive diseases which are several enough (i.e, more than rest pain) and not eligible for Endovascular approaches (i.e., TASC C or D lesions meaning long segment occlusive disease or occlusion at trifurcation or bifurcation of vessels)

124  TARGET JIPMER

•



•



•

Another important criteria for bypass is, there should be sufficient length of normal distal vessel to allow for bypass anastomoses. For Bypass, two most common conduits used are o PTFE (Polytetrafluroethylene) – synthetic graft, used for larger vessels like iliac and axillary vessels o Autologous vein (most commonly saphenous vein) – Autograft, so innate antithrombotic properties, most preferred for infrainguinal bypass as they size match well, better patency rates than PTFE o Other graft is Dacron (polyethylene terephthalate or polyester) used in Aortic aneurysm repair Saphenous vein used should be reversed, as they have valves which allow unidirectional flow. So saphenous vein should be reversed (turned upside down) for bypass to allow any interruption to blood flow. (Reversed saphenous vein graft)

Aortic dissection



Aortic dissection occurs when there is a defect in the intimal layer which permits blood to create false channel within the aortic wall between media and adventitia. • Stanford classification* is most commonly used o Type A (any involvement of ascending aorta) – surgical emergency o Type B dissection mostly treated with Hypertensive control followed by endovascular stenting called TEVAR (thoracic endovascular aneurysm repair) • As mentioned above, all aortic surgeries are replaced with a synthetic graft – Dacron (woven/knitted polyester) sutured with 2-0 polypropylene •

Ans: (a) Dacron Ref: Sabiston, 20th edition, Page 1730

JIPMER–December 2018  125

OBSTETRICS AND GYNECOLOGY 1.

A 28 year old G2P1L1, with last child birth 1 year back, wants immediate contraception following vaginal delivery. Which of the following is the most ideal method? (a) Post placental IUCD (c) OCP

(b) Sterilization (d) Female condoms

Explanation:

Female sterilization or tubectomy is the most widely opted contraceptive method by women who have completed their family. • Previous one child of one year is enough as a criteria for permanent sterilization • Child norm for sterilization in India : 1 child of atleast 1 year of age • Consent of the husband is not necessary for sterilization Case Selection (Self-declaration by the client will be the basis for compiling this information.) • Clients should be married (including ever-married). • Female clients should be below the age of 49 years and above the age of 22 years. • The couple should have at least one child whose age is above one year unless the sterilization is medically indicated. • Clients or their spouses/partners must NOT have undergone sterilization in the past (not applicable in cases of failure of previous sterilization). • Clients must be in a sound state of mind so as to understand the full implications of sterilization. • Mentally ill clients must be certified by a psychiatrist, and a statement should be given by the legal guardian/spouse regarding the soundness of the client’s state of mind. • The basic principle in female sterilization is breaking the continuity of both the fallopian tubes by removing a small segment of both tubes •

TIMING OF FEMALE STERILIZATION

• • • •

Postpartum – within 48 hours upto 7 days of delivery After MTP With cesarean section (concurrent sterilization) Interval sterilization – Following a waiting period of 6 weeks after delivery

ROUTE OF STERILIZATION Female sterilization can be done by minilaparotomy (incision of less than 5 cm in length) or laparoscopy (procedure of choice these days). Postpartum sterilization is done by minilaparotomy Laparoscopic sterilization can be performed in following:

• •

With 1st trimester MTP As interval sterilization

Surgical technique of minilaparotomy: Points to be noted are:

• •



• • •

The fallopian tubes are identified by following it up to the fimbrial end The site of occlusion should be 3-4 cm from the uterine cornua in the isthmic portion- ie., at the junction of proximal 1/3rd and middle 1/3rd of the tube (improves the possibility of reversal if required in future) Atleast 1 cm of tube should be excised. Use of cautery and crushing should be avoided Pomeroy technique is the most commonly performed minilaparotomy method: After bringing out the fallopian tube through the incision, a Babcock’s clamp is placed about 3-4 cm lateral to the uterine cornua (isthmus portion) and the tube is pulled up so as to form a loop.

126  TARGET JIPMER



o The Pomeroy operation is the most simple and safe procedure of tubal ligation and is recommended by Govt. of India, Family welfare services. o It has got a failure rate of 1 in 400 cases (0.4%). o Length of tube destroyed is 3-4 cm • Parkland technique: This is another common method and the failure rate is about 1 in 400 procedures. • Irving technique: This technique has a very low failure rate, less than 1 in 1000 cases. • Uchida technique: Uchida claims no failure in 19,000 cases. • Fimbriectomy (Kroener’s technique): This technique is abandoned due to high failure rate (2–3%). • Madlener technique: High failure rate of 0.3–2% and has been practically abandoned. Least failure rate (among laparotomy techniques) = Uchida followed by Irving. Laparoscopic sterilization



NOTE: • Laparoscopic sterilization should not be done during post partum period upto 6 weeks and with II trimester MTP • Most common method of female sterilization is by laparoscopic sterilization The methods of occlusion in laparoscopic sterilization include: Falope rings or silastic band

Filshie clips (Titanium silicon clip) or Hulka clemens clip (sping loaded clip)

• •

• •

Tubal length destroyed is 2-3 cm Most common laparoscopic method in India

Tubal length destroyed is 4-5 mm (least destruction) Success rate for future recanalization is best with clips

NOTE: Unipolar cautery – least failure rate but abandoned due to risk of intestinal burns injury. Success rate for recanalization is least with cautery



• •



Hysteroscopic sterilization • Can be done using cauterization or using sclerosants – failure rate is 30%



Essure • It is a spring like device containing an outer coil of titanium and nickel and an inner coil of stainless steel. • It can be introduced via hysteroscopic route into the fallopian tubes • It acts by inciting tissue inflammatory reaction and blocking the fallopian tube • Success rate of 99% Ans: (b) Sterilisation Ref: Standards of Female and Male Sterilization Services, Ministry of Family Welfare

2.

Which of the following is not used for emergency contraception? (a) Mifepristone (b) IUCD (c) Levonorgestrel (d) None of the above

Explanation:

Emergency contraception (EC) • Emergency contraceptives are used as an emergency procedure in order to prevent pregnancy following unprotected intercourse or expected failure of contraception, before menstruation is missed,. • ECs are used after intercourse but before the potential time of implantation. • Mechanism of action- Prevents ovulation, interferes with fertilization and corpus luteal function, and prevents implantation of fertilized ovum • Various available EC options are as follows:

JIPMER–December 2018  127 Various regimens used for Emergency contraception Drug

Dosage

Time to be taken

Levonorgestrel

0.75 mg two doses, 12 hours apart or a single stat dose of 1.5 mg

Upto 72 hours following unprotected intercourse

Yuzpe regimen

OCPs - 100 μg of ethinyl estradiol + 500 μg Levonorgestrel in each dose given twice, 12 hours apart

Upto 72 hours following unprotected intercourse

Mifepristone

10 mg single dose

Upto 72 hours following unprotected intercourse

Ulipristal acetate

Single oral dosage of 30 mg

Upto 120 hours following unprotected intercourse Upto 5 days following unprotected sexual intercourse

Copper IUCD



•

Ulipristal suppresses follicular and endometrial growth

Ans: (d) None of the above Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 510 3.

Sperm interaction with cervical mucous is assessed by: (a) Friedman (c) Rubins

(b) Huhner (d) Papanicolau

Explanation: The postcoital test (PCT) (also known as Sims test, Huhner test or Sims-Huhner test)

• •

It is a test in the evaluation of infertility. The test examines interaction between sperm and mucus of the cervix.

Procedure

• •



• • • • •

The PCT is scheduled close to ovulation when cervical mucus is abundant. The couple is asked to have sexual intercourse and several hours later (usually 2 hours), the woman is examined and the mucus is aspirated from cervical canal and spread on a glass slide and examined. Presence of 10-50 progressively motile sperms per high power field is considered normal. Rotatory or shaky motion of sperms indicates presence of antispermal antibody. Cervical mucus is examined for quality, viscosity and fern test. The test is not done in presence of cervical infection. The role of the PCT has been questioned and its use has become controversial. Post-coital test (Sims-Huhner, 1866) : 3 samples taken

Specimen

Result

Diagnosis

Post. vag. wall. without prior PV

No sperms

Failure of deposition azoospermia

Dead sperms

Necrospermia Hostile vag. sec.

Shaking mov.

Anti-sperm Ab

> 20/HPF

Normally accepted

10-20/HPF

Satisfactory

5 mg/dl



•

Low platelets in late pregnancy should prompt one to perform liver function tests to rule out AFLP.



• There is hemolysis evidenced by leukocytosis, nucleated red cells, thrombocytopenia, and raised lactate dehydrogenase (LDH)

JIPMER–December 2018  129

•

Hypoglycemia is characteristic and is a poor prognostic feature. Other biochemical abnormalities are metabolic acidosis, renal dysfunction, high ammonia, and biochemical pancreatitis.



•

Swansea diagnostic criteria for diagnosis of acute fatty liver of pregnancy- Six or more of the following features in the absence of other explanation:

Vomiting

Abdominal pain Polydypsia/polyuria Encephalopathy High bilirubin (>14 μmol/L) Hypoglycemia (340 μmol/L) Leucocytosis (>11 × 106/L) Ascites or bright liver on ultrasound High AST/ALT (>42 IU/L) High ammonia (>47 μmol/L) Renal impairment (creatinine >150 μmol/L) Coagulopathy (PT >14 s or aPTT >34 s) Microvesicular steatosis on liver biopsy

•

Management - prompt delivery of the fetus, regardless of gestational age. Treatment is otherwise largely supportive with the goals of maternal stabilization and recovery of liver dysfunction.



•

Acute fatty liver can recur in subsequent pregnancies. Women with a H/o AFLP who are contemplating another pregnancy should be co-managed with a maternal-fetal medicine specialist.

Ans: (b) Acute fatty liver of pregnancy Ref: High Risk Pregnancy by Fernando Arias, 3rd edition, Page 298 5.

A 20-year-old female primi, 14 weeks of gestation with 2 episodes of seizures. Treatment of choice? (a) Nifedipine

(b) Carbamazepine

(c) Mannitol

(d) Furosemide

Explanation: EPILEPSY IN PREGNANCY

•

Epilepsy is the most common neurological disorder encountered in pregnancy.



•

The most common cause for epilepsy in pregnant women is idiopathic.



•

Seizure frequencies is unchanged in 50%, increased in 30% and decreased in 20% of pregnant females



•

Risk of congenital anomalies is about 4% and there is 5–10% risk of epilepsy in the child, if parents are affected.



•

All anticonvulsant drugs are associated with congenital anomalies as they interfere with folic acid metabolism



•

The common malformations include: Cleft lip and/or palate, mental retardation, cardiac abnormalities, limb defects and hypoplasia of the terminal phalanges. Sodium valproate is associated with neural tube defects.



•

There is chance of neonatal hemorrhage and is related to anticonvulsant induced vitamin K dependent coagulopathy.



•

In epilepsy during pregnancy: o Mono drug therapy is preferred

130  TARGET JIPMER o Lowest possible dose of the chosen drug is given o Therapeutic drug monitoring is done.

As per ACOG and RCOG guidelines, there is no particular drug of choice for epilepsy in pregnancy



•



•

Valproate increases chances of birth defects much more than phenytoin, carbamazepine or phenobarbitone and hence if valproate is being used, it should be substituted by a lesser teratogenic drug



•

Considering the teratogenicity, the safe drugs used in pregnancy are lamotrigine, leviteracetam and carbamazepine o Carbamazepine 0.8-1.2 mg/day in divided doses

o Lamotrigine 300-500 mg/day in two divided doses o Leviteracetam 1-3 gm/day in divided doses

All women on anticonvulsants should take folic acid: 4 mg/day for 12 weeks in the preconception period and throughout pregnancy.



•



•

Prenatal screening: Maternal Serum Alpha fetoprotein (MSAFP) at 16 weeks + level II USG (To detect neural tube defects)



•

Vitamin K 10 mg/day orally from 36 weeks onward to prevent hemorrhagic disease of newborn.



•

Postpartum Management: o The newborn is given vitamin K (1 mg IM)

o There is no contraindication to Breast feeding. Antiepileptic medications are excreted into breast milk to variable degree. Given the overall benefits of breast feeding and the lack of evidence of long term harm to the infant, by being exposed to antiepileptic drugs, mothers on antiepileptic drugs can be encouraged to breast feed.

• Contraception: If OCPs are prescribed, ACOG has recommended oral contraceptives containing 50 mg of estrogen (high dose) in women on anticonvulsants. Anti epileptic Drugs

Abnormalities Described

Valproate

Neural-tube defect, clefts, cardiac anomalies; developmental delay

Phenytoin

Fetal hydantoin syndrome-craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac anomalies, clefts

Carbamazepine; oxcarbazeoine

Fetal hydantoin syndrome; spina bifida

Phenobarbitone

Clefts, cardiac anomalies, urinary tract malformations

Lamotrigine

Increased risk for clefts (registry data)

Topiramate

Increased risk for clefts

Levetiracetam

Theoretical— skeletal abnormalities; impaired growth in animals

Ans: (b) Carbamazepine Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 273 6.

A 38-year-old woman is diagnosed HPV DNA positive on cervical screening. Next line of management? (a) HPV Testing after 1 year

(b) Colposcopy

(c) Trachelectomy

(d) Conization

Explanation: HIGH RISK HPV DNA TESTING IN CERVICAL SCREENING

•

High risk types: 16 18 31 33 35 45 56



•

Hybrid capture method detects HPV DNA within hours

JIPMER–December 2018  131

•

Only 2-5% women with positive HPV DNA will develop CIN



•

80% women < 30 years, clear HPV DNA with their own immunological defence within 1 year



•

Positive test in women > 30 years suggests colposcopic examination



•

If colposcopy is positive -> take biopsy



•

If HPV DNA is negative, repeat smear after one year

Management strategies of various cytological report of PAP smear PAP report

Next step

Normal/ reactive/ infective

Resume PAP test as per ACOG guidelines

ASCUS

Options available are: • Repeat PAP after 6 months or If >= 30 years, do HPV DNA testing • If PAP is >= ASCUS, or if HPV DNA is positive –> colposcopy is done • Best method of follow up of ASCUS is by immediate colposcopy

LGSIL

Colposcopy +/_ endocervical curettage If lesion is visible -> punch biopsy

HGSIL

Colposcopy +/_ endocervical curettage If lesion is visible -> punch biopsy

NOTE: Colposcopy is the gold standard technique for evaluation of abnormal cervical smear Indications for colposcopy

•

Abnormal PAP smear cytology



•

To locate abnormal areas



•

To obtain directed biopsies



•

Conservative therapy under colposcopy guidance



•

Follow up of cases treated conservatively

Ans: (b) Colposcopy Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 266 7.

Corpus luteum is maintained by which hormone? (a) LH

(b) Progesterone

(c) GnRH

(d) Inhibin

Explanation: CORPUS LUTEUM

•

After ovulation, the ruptured graafian follicle develops into corpus luteum



•

In non pregnant state, corpus luteum is maintained by hormone LH



•

Life span is 10-12 days



•

Maximum activity occurs 8 days after ovulation ie., day 22 of menstrual cycle



•

If pregnancy doesn’t occur, it degenerates on 22-23 rd day



•

If pregnancy occurs, corpus luteum is maintained by hormone hCG



•

Hormones secreted by corpus luteum are progesterone, estrogen, inhibin and relaxin



•

Life span of corpus luteum in pregnant state is about 10 weeks after which the function is taken over by placenta

132  TARGET JIPMER Flowchart Showing Events In Ovarian Cycle

JIPMER–December 2018  133 Pictorial Representation of the Events of Menstrual Cycle

Ans: (a) LH Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 70 8.

Risk factors for ectopic pregnancy: (a) IUCD (c) Infertility

(b) Previous h/o ectopic (d) All the above

Explanation: Risk factors for ectopic pregnancy

• •



• •



• • • • •

Tubal surgeries (for prior tubal pregnancy or recanalization surgery) M/C Risk factor- Prior salpingitis due to STDs such as gonococcal and chlamydial infection or salpingitis that follows septic abortion and puerperal sepsis.” Peritubal adhesions subsequent to salpingitis, appendicitis or endometriosis Salpingitis isthmica nodosa. (it is a noninflammatory condition in which tubal epithelium forms a diverticulum in the myosalpinx – in which fertilized ova can lodge) Developmental defects of the tube In utero DES exposure Infertility treatment: IVF, Ovulation induction using clomiphene and gonadotropin Current cigarette smoking (> 20 cigarettes per day) Contraception use: With any form of contraceptive, the absolute number of ectopic pregnancies is decreased because pregnancy occurs less often. However with some contraceptive failures, the relative number of ectopic pregnancies is increased.

134  TARGET JIPMER

• Examples include tubal sterilization > Progestasert > Mirena > Cu T > progesterone only pill. • Least risk is with OCPs NOTE: MC cause of ectopic pregnancy is PID but Maximum risk of ectopic pregnancy is after tubal damage, either due to previous ectopic pregnancy or tubal surgery Ans: (d) All of the above Ref: DC Dutta, Textbook of Gynecology

9.

Semen examination of a man showed counts of 25 million/cu.mm, volume – 1.5 ml; motility – 15%; Morphology – 15%. What is the diagnosis? (a) Azoospermia

(b) Asthenospermia

(c) Oligospermia

(d) Teratospermia

Explanation:

•

Asthenospermia refers to Decreased sperm motility (recommended normal sperm motility 32 % progressive motility, 40% total motility) Lower Reference Limits (WHO 2010) and Reference Value (WHO 1999) for Semen Characteristics

Parameter

Lower Reference Limits (WHO 2010)

Reference Value (WHO 1999)

Semen Volume

1.5 ml

> 2.0 ml

Sperm Concentration

15 million sperm/ml

> 20 million sperm/ml

Progressive Motility

32%

> 50%*

Total Motility

40%**

n/a

Vitality

58% live

> 75% live

Morphology (Strict criteria)

4% normal form

(> 15% normal form)#

* Grade a + baccording to the WHO 1999 manual. ** Progressive motile + non-progressive motile sperm according to the WHO 2010 manual. # No actual value given. Value was concluded from multi-centre studies. Nomenclature for Semen Variables (WHO 2010) Aspermia

No semen

Asthenozoospermia

Percentage of progressively motile sperm Do karyotyping.: AIS: Karyotyping is 46, XY; MRKHS: Karyotyping is 46, XX. If breast development is present and uterus is present: It implies that the patient has been exposed to estrogen in the past. Workup is similar to a case of secondary amenorrhea If breast development is absent and uterus is present: It implies that the patient has never been exposed to estrogen. It could be due to primary ovarian failure or failure of pituitary gonadotropin secretion -> An endocrine evaluation is done. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and prolactin are checked. Elevated FSH and LH levels (hypergonadotropic hypogonadism) imply gonadal dysgenesis or premature ovarian failure (POF). Turner syndrome (45, XO karyotype) is the most common cause of gonadal dysgenesis. Low FSH and LH levels imply constitutional delay of puberty or hypothalamic or pituitary failure (hypogonadotropic hypogonadism). – Do MRI brain: Detects CNS tumors or empty sella syndrome where pituitary is affected causing decreased gonadotropin secretion. – Do bone age radiograph: Helps to distinguish a case of constitutional delay from hypogonadotropic hypogonadism. If signs or symptoms of hyperandrogenism are present, check serum testosterone, dehydroepiandrosterone sulfate (DHEAS), and 17-hydroxyprogesterone—to assess for congenital adrenal hyperplasia (CAH) or any androgen-secreting tumor of the ovary.

Flowchart for evaluation of primary amenorrhea

136  TARGET JIPMER Ans: (c) Serum FSH Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 375 11.

Bart test is: (a) HCG + AFP + Estriol (c) HCG + AFP + Estriol

(b) AFP + Uric acid (d) HCG + AFP + PAPP-A

Explanation: Triple test

•



•

The triple test, also called triple screen, the Kettering test or the Bart’s test, is an investigation performed during pregnancy to detect neural tube defects The Triple screen measures serum levels of AFP, estriol, and beta-hCG, with a 70% sensitivity and 5% false-positive rate.

AFP

UE3

hCG

Associated conditions

Low

Low

High

Down syndrome

Low

Low

Low

Trisomy 18 (Edward’s syndrome)

High

N/A

N/A

Neural Tube Defects  (like  spina bifida  that may have associated increased levels of  acetylcholinesterase  in the amniotic fluid), omphalocele, gastroschisis, multiple gestation (like twins or triplets), or an underestimation of gestational age.

Double test

•

Free beta hCG and PAPP-A are measured.

Quadruple test

• A test of levels of dimeric inhibin A is sometimes added to the other three tests, under the name “quadruple test.” Other names used include “quad test”, “quad screen”, or “tetra screen.” • Inhibin A will be found high in cases of trisomy 21 and low in cases of trisomy 18. Inhibin A

Associated conditions

High

Trisomy 21 (Down syndrome)

Low

Trisomy 18 (Edwards syndrome)

Variable

Trisomy 13 (Patau syndrome)

Ans: (c) HCG, AFP, Estriol Ref: DC Dutta, Textbook of Obstetrics, 9th Edition, Page 103 12.

Placenta with cord attached to margin. What is your diagnosis? (a) Battledore placenta (c) Circumvallate placenta

(b) Placenta succenturiata (d) Velamentous cord insertion

Explanation: PLACENTAL PATHOLOGY Placental infarction:

• •

These are the most common placental lesion; may lead to placental insufficiency or abruption Infarcts may be associated with preeclampsia or lupus anticoagulant.

Placentomegaly (big placenta) seen in:

• •

Multiple pregnancies Diabetes mellitus

JIPMER–December 2018  137

• • • • •

Maternal anemia Macrosomia Hydrops fetails (immune and nonimmune) Syphilis Toxoplasma, CMV infection.

Small placenta seen in:

• • •

Postdatism IUGR Placental infarcts

Placental abnormalities Abnormality

Feature

Significance

Succenturiate placenta

A small part of placenta is separated from the rest of placenta and a leash of vessels connect the placenta to the small lobe, traversing through the membranes. In case the communicating blood vessels are absent, it is called as Placenta spuria. Note: The accessory lobe in succenturiate placenta is developed from the activated villi on the chorionic levae.

It can be retained following delivery leading to PPH, sub involution, uterine sepsis and polyp formation

Circumvallate placenta

The peripheral edge of the placenta is covered by a circular fold of amnion and chorion. Fetal surface of such a placenta presents a central depression surrounded by a thickened, grayish-white ring. Circum marginate placenta-  The ring does not have the central depression with the fold of membranes

It can lead to abortion, APH, IUGR, Preterm, delivery and hydrorrhea gravidarum

Battle dore placenta

Placenta with umbilical cord attached to its margin rather than in centre

Velamentous Insertion of the cord

Vessels of cord separate at a distance away from the margin of the placenta surrounded only by a fold of amnion.

If the vessels traverse the membranes overlying the internal os, it can lead to vasa previa

138  TARGET JIPMER Ans: (a) Battledore placenta Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 204 13.

A 37 years old women presents with abdominal mass. On USG, solid Tumor is seen and presents with elevated LDH and HCG. What is the diagnosis? (a) Teratoma (c) Dysgerminoma

(b) Fibroma (d) Brenner

Explanation: DYSGERMINOMA

•

Dysgerminoma is the commonest (30–40%) malignant germ cell tumor.



•

It arises from undifferentiated germ cells.



•

75% unilateral



•

It is often (5%) associated with dysgenetic gonads



•

The counterpart of dysgerminoma in male is seminoma.



•

Majority (75%) of dysgerminomas occur before the age of 30 years.



•

Can be found at gonadal as well as extra gonadal sites



•

hCG assays may be positive, confusing the diagnosis with pregnancy.



•

Most common ovarian malignancy detected during pregnancy



•

Tumor markers α-fetoprotein (AFP) and LDH may be positive in dysgerminoma



•

Karyotyping is needed specially when a premenarcheal girl presents with a pelvic mass



•

Pathalogically, it is a solid neoplasm with areas of softening due to degeneration. Consistency is fleshy



•

Histologically, it mimics the pattern of primitive gonad, lymphocytic infiltration may be seen (good prognostic sign)



•

Most common route of spread is lymphatics, however hemotogenous and direct spread are also seen



•

Most cases are identified at an early stage



•

It can metastasize to opposite ovary and an uncommon site of metastasis seen is lower vertebra



•

Most radiosensitive tumor

Management of Dysgerminoma

Best prognosis among all germ cell tumors Treatment of early stage dysgerminoma (Stage IA)–Surgical: Unilateral salpingo – oophorectomy without post op. chemotherapy • Rest all cases – fertility sparing ie., removal of the affected ovary or debulking followed by chemotherapy Chemotherapy Regimens Used for Germ Cell Tumors are: • •

Regimens

Drugs

BEP

Bleomycin, Etoposide, Cisplatin

VBP

Vinblastin, Bleomycin, Cisplatin

VAC

Vincristin, Actinomycin, Cyclophosphamide

In case of recurrence:

• •

If primary therapy was surgery – then chemotherapy can be given If primary therapy was chemotherapy – radiation therapy can be given (disadvantage -loss of fertility) or chemotherapy in the form of POMB –ACE regimen (Cisplatin, Vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide) is given

JIPMER–December 2018  139 Tumor Markers In Germ Cell Tumors

Tumor Markers in Ovarian Tumors Ovarian Tumor

Tumor Marker

Endodermal sinus tumor/yolk sac tumor

AFP

Non mucinous Epithelial ovarian tumors (serous tumors)

CA-125

Sertoli cell, Leydig cell, Hilus cell tumors

Testosterone

Dysgerminoma

LDH, alkaline phosphatase

Choriocarcinoma

hCG

Mucinous tumors

CEA

Granulosa cell tumor

Inhibin

Hitological Characteristics of Ovarian Tumors Feature

Associated tumour

Call exner bodies and coffee bean nuclei

Granulosa cell tumour

Schiller duval bodies

Endodermal sinus tumour

Reinke’s crystal

Hilus cell tumour

Psammoma bodies

Serous epithelial tumours

Walthard cell nest

Brenner tumour

Signet ring cell

Krukenberg tumour

Hobnail cell

Clear cell tumour

Large polygonal cell with lymphocytic infiltration and fibrous septa

Dysgerminoma

Skin, teeth, cartilage

Teratoma

Ans: (c) Dysgerminoma Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 314

140  TARGET JIPMER 14.

23-year-old Female presents with 42 days of amenorrhea and vaginal spotting. Which of the following is the most useful diagnostic test? (a) Transvaginal USG (c) Beta HCG

(b) Urine pregnancy test (d) Serum Progesterone

Explanation:

The causes of amenorrhea followed by spotting P/v in a woman of reproductive age group could be due to pregnancy related causes such as: • Implantation bleeding • Threatened/ inevitable/ incomplete or missed abortion • Ectopic pregnancy • Molar pregnancy Uses of USG in first trimester



• Diagnosis of pregnancy • Dating of gestational age • To confirm cardiac activity and fetal viability • Diagnosis of multiple pregnancy • Diagnosis of molar pregnancy • Diagnosis of ectopic pregnancy • Pelvic mass diagnosis and follow up • Diagnosis of uterine malformations Transvaginal ultrasound is very useful in cases with hemorrhage in early pregnancy • It gives information about gestational sac, cardiac activity, blighted ovum, ectopic pregnancy, retained products, complete or incomplete abortion • The first definitive sonographic finding to suggest pregnancy is visualization of the gestational sac. • The first sign of intrauterine pregnancy is presence of yolk sac within the gestational sac. • Critical titre of HCG at which gestational sac can be visualized within uterus TVS = 1000 micro IU/ ml TAS = 6500 micro IU/ ml • True gestational sac is eccentric in position and double decidual sac sign or intradecidual sign is present. • Pseudo gestational sac is seen in ectopic pregnancy. It is irregular in outline, usually centrally located and has no double decidual sac sign and uterine cavity is empty.



• • • • • • • •

Fetal structure

Detected by TVS

Detected by TAS

Gestational sac

4.5 weeks

5.5 weeks

Yolk sac

5 weeks

6 weeks

Cardiac activity

6 weeks

7 weeks

Best time to assess gestational age by USG is 9-12 weeks (by crown rump length) CRL of embryo increases by 1 mm per day. CRL (in mm) + 42 = gestational age in days. Mean sac diameter (MSD) is used to determine gestational age before CRL can be measured MSD = Length + height + width/3 Normal MSD (in mm) + 30 = Days of pregnancy Fetal anomaly which can be earliest detected by USG- Anencephaly. Ultrasonographic markers of Down syndrome in first trimester: o Absent or hypoplastic nasal bone o Increased nuchal translucency

Ans: (a) Transvaginal ultrasound Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 154

JIPMER–December 2018  141 15.

G2P1, Rh negative mother, previous history of hydrops fetalis. Now ICT is positive at 20 weeks. What is the next line of management? (a) MCA Doppler (c) Exchange transfusion

(b) Amniocentesis and bilirubin estimation (d) Cordocentesis

Explanation: ICT POSITIVE at 20 weeks requires MCA Doppler. Refer flowchart below:

142  TARGET JIPMER Ans: (a)) MCA Doppler Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 318 16.

A primigravida at term presents with recurrent urination, and on examination there is suprapubic flattening on palpation, fetal heart sounds heard on extreme left lateral position. What is the presentation? (a) Occipito-posterior (c) Face

(b) Shoulder (d) Brow

Explanation: Occipito-Posterior Position

•



• • • •

In vertex presentation, when the occiput is placed posteriorly over the sacroiliac joint or directly over sacrum, it is called occipito-posterior position. Occipito-posterior is an abnormal position of the vertex rather than an abnormal presentation. At the onset of labor, the incidence is about 10% of all the vertex presentations. Right occipito-posterior is 5 times more common than the left occipito-posterior. Dextrorotation of the uterus and the presence of the sigmoid colon on the left, disfavor LOP position.

The following are the responsible factors:

• •



•

Shape of the pelvic inlet: OPP is associated with either an anthropoid or android pelvis. Fetal factors: Marked deflection of the fetal head, often favors posterior position of the vertex. The causes of deflexion are: (1) High pelvic inclination. (2) Attachment of the placenta on the anterior wall of the uterus— (3) Primary brachycephaly Uterine factor: Abnormal uterine contraction may lead to persistent deflexion and occipito-posterior position.

Diagnosis Abdominal Examination

Findings

Inspection

The abdomen looks flat, below the umbilicus.

Umbilical grip

• • •

Pelvic grips

The head is not engaged. The cephalic prominence (sinciput) is not felt so prominent as found in well flexed occipito-anterior.

Auscultation

The maximum intensity of the fetal heart sounds is heard on the flank and often difficult to locate

Vaginal Examination

• •

The fetal limbs are more easily felt near the midline on either side. The fetal back is felt far away from the midline on the flank. The anterior shoulder lies far away from the midline.

Posterior fontanelle is felt near the sacroiliac joint. The anterior fontanelle is felt more easily because of deflexion of the head

Salient parameters in occipito-posterior position Parameter

Finding in occipitoposterior position

Lie

Longitudinal

Presentation

Cephalic

Presenting part

Vertex

Attitude of the head

Deflexed head

Denominator

Occiput

Position OP

ROP is the most common OP position

Engaging diameter

Occipitofrontal (11.5 cm) or suboccipitofrontal (10.5 cm)

Diameter of engagement

Right oblique in ROP

JIPMER–December 2018  143 Outcome of Labor In Occipito-posterior Position

•



•

In the presence of favorable factors such as adequate pelvis, good uterine contractions, good flexion of the fetal head, and average size of the fetus- the occiput may undergo a complete anterior rotation by 3/8th of a circle and there is 90% chance of successful vaginal delivery Under unfavorable circumstances, the chance of vaginal delivery is less (10%). Depending on the degree of flexion of the fetal head, uterine contractions, pelvic adequacy, and fetal size, the occiput may fail to undergo complete anterior rotation, resulting in the outcomes as mentioned in the flowchart below: o Short anterior rotation by 1/8th of circle may result in deep transverse arrest o Short posterior rotation by 1/8th of circle may result in face to pubis delivery o Non rotation and Persistent OP position may result in OP arrest

Ans: (a) Occipito-posterior Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 343

144  TARGET JIPMER 17.

Chances of conception are maximum at: (a) 14 days prior to next menses (c) 14 days after last LMP

(b) Immediately after menses (d) Just prior to menstruation

Explanation:

•



•



•

In a regular 28 day cycle, on day 12 -14 after LMP, LH surge occurs . Ovulation occurs 10-12 hours after LH surge and the graffian follicle is converted into corpus luteum. The chances of conception are maximum during the time of ovulation and couples are advised to have sexual intercourse during this time to maximize the chances of conception. If fertilization does not occur, corpus luteum degenerates and menstruation occurs 14 days after ovulation. However, the duration of proliferative phase is variable ie, from the start of mensus to the time of ovulation may be variable in some women. The post ovulatory phase is always fixed. ie., from ovulation to the start of next mensus is always fixed to be 14 days. Hence the exact day of ovulation is 14 days prior to the next periods

Diagram Depicting Ovarian and Menstrual Cycle Luteal phase

Follicular phase

14 days

1 day Proliferative phase

FSH

20 mm

–v

Ovulation

Primordial Primary Antral Graafian Just before 10-12 hrs ovulation follicle follicle follicle follicle

e on fee FS dba H ck

Estrogen Proliferates Endometrium

+ve feedback on LH

22 days

28 days

Secretory phase CL formed Corpus Luteum Secretes

Maximum activity

Progesterone

32-36 hrs LH peak LH Surge

Inhibin B Secretory = Follicular phase (1st peak midfollicular phase 2nd peak near ovulation Nadir midluteal phase)

Inhibin A Estrogen Progesterone (levels begin (mainly) to rise in late follicular phase and maximum during midluteal phase)

Menstruation

LH

Corpus Luteum degenerates Estrogen New cycle

Ans: (a) 14 days prior to next mensus Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 196 18.

Uterine myoma does not derive blood supply from: (a) Uterine artery (c) Ovarian artery

(b) Vesical artery (d) Artery to round ligament

Explanation:

•



•

The uterus and uterine fibroid tumors are mainly supplied by the uterine artery, but ovarian arteries and round ligament arteries also may play a role Uterine fibroid tumors derive their main peripheral blood supply almost exclusively from the uterine arteries. The uterine artery is a branch of the anterior division of the internal iliac artery

JIPMER–December 2018  145



•



•



• •

The presence of uterine fibroids usually results in distortion and enlargement of the uterine arteries , which supply both normal myometrium and the fibroids . Usually, the flow to the fibroid tumor is substantially increased; perifibroid arteries are larger in diameter than are those that supply normal myometrium. The tumor itself is relatively hypovascular, and its interior is supplied by small centripetal arteries that originate in a rich perifibroid arterial plexus Even in the presence of two apparently normal uterine arteries, an additional supply to the fibroid may come from the ovarian artery in about 5%–10% of cases  Other sources of supply may be the round ligament artery and the lumbar artery Uterine artery embolisation targets mainly the uterine arteries for treatment of uterine fibroids

Ans: (b) Vesical artery Ref: Uterine Fibroid Vascularization and Clinical Relevance to Uterine Fibroid Embolization Jean-Pierre Pelage, Julien Cazejust Oct 1 2005https://doi.org/10.1148/rg.25si055510 19.

Isotretinoin to be stopped before pregnancy: (a) 3 days (c) 3 month

(b) 2 week (d) 3 years

Explanation: Isotretinoin in Pregnancy

•



• •

This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations. The baseline population risk of malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Although effective for treating severe acne, isotretinoin is a potent human teratogen.  Continued use of contraception for 1 month after the end of isotretinoin therapy has been advocated to provide an adequate safety margin to prevent fetal exposure, based on more than 5 elimination half-lives of the drug. However, there is evidence of greater variability in isotretinoin elimination half-life (from 5.3 h to 7 d); thus, 1 month may not allow clearing of the drug in all women. Indeed, there have been reports of isotretinoin-induced fetal malformations despite stopping treatment 1 month before pregnancy. A 3-month window may be more appropriate.

146  TARGET JIPMER Category

Examples

A

Adequate and well-controlled studies have failed to demonstrate a risk to the fetus

Levothyroxine folic acid

B

Adequate human studies are lacking, but animal studies have failed to demonstrate a risk to the fetus (or) Adequate studies in pregnant women have failed to demonstrate a risk to the fetus, but animal studies have shown an adverse effect on the fetus

Amoxicillin Paracetamol Cefaclor

C

No adequate studies in pregnant women and animal studies are lacking or have shown and adverse effect on fetus, but potential benefit may warrant use of the drug in pregnant women despite potential risk

Atropine Codeine Thiopentone

D

There is evidence of human fetal risk, but the potential benefits from use of the drug may be acceptable despite the potential risk

Carbamazepine Lorazepam

X

Studies in animals or humans have demonstrated fetal abnormalities, and potential risk clearly outweighs possible benefit

Estrogens Isotretinoin

Ans: (c) 3 months Ref: Choi JS, Koren G, Nulman I. Pregnancy and isotretinoin therapy. CMAJ. 2013;185(5):411-3 20.

Labour is said to be prolonged when the duration of first and second stage extend arbitrarily beyond: (a) 12 hours (c) 24 hours

(b) (d)

18 hours 36 hours

Explanation: First stage of labor:



• Two phases of cervical dilatation are defined: o Latent phase o Active phase • The latent phase corresponds to the preparatory division, and the active phase, to the dilatational division. • Friedman subdivided the active phase into the: o Acceleration phase o Phase of maximum slope o Deceleration phase • Latent Phase o The onset of latent labor, as defined by Friedman, is the point at which the mother perceives regular contractions. The latent phase for most women ends at between 3 and 5 cm of dilatation. • Prolonged Latent Phase o Friedman defined this by a latent phase exceeding 20 hours in the nullipara and 14 hours in the multipara • Active Labor o Cervical dilatation of 3 to 5 cm or more, in the presence of uterine contractions, can be taken to reliably represent the threshold for active labor • Protracted dilatation or descent - slow rate of cervical dilatation or descent o For nulliparous, it is less than 1.2 cm dilatation per hour or less than 1 cm descent per hour. o For multiparous, protraction is defined as less than 1.5 cm dilatation per hour or less than 2 cm descent per hour Second Stage of Labor



• This stage begins with full cervical dilatation and ends with fetal delivery: • The median duration is highly variable but is approximately o 50 minutes for nulliparas o 20 minutes for multiparas

JIPMER–December 2018  147

• The mean length of first- and second-stage labor was approximately o 9 hours in nulliparous women without regional analgesia, and the 95th percentile upper limit was 18.5 hours. o Corresponding times for multiparous women was a mean of 6 hours, with a 95th percentile maximum of 13.5 hours. Prolonged labour:



•



• •



•



•



• •



• •

Labour is said to be prolonged when the combined duration of first and second stage is more than 18 hours Labour is prolonged if cervical dilatation is less than 1cm/hr for minimum 4 hours First stage of labour–average duration is 12 hours in primi and 6 hours in multi normally. Labour is said to be prolonged when first stage is more than 12 hours Second stage of labour– average duration is 2 hours in primi and 30 min in multi normally. Labour is said to be prolonged when second stage exceeds 2 hours in primigravida and 1 hour in multigravida Causes of prolonged labour: o Abnormal uterine action o Malposition o Malpresentation o Macrosomia o Fetal malformation o Contracted pelvis o Cephalopelvic disproportion o Uterine inertia o Cervical dystocia Prolonged latent phase–in primi more than 20 hours and in multi more than 14 hours Prolonged active phase–most common. Cervical dilatation less than 1.2cm/hour in nullipara and less than 1.5cm/hour in multipara Secondary arrest of dilatation–there is arrest in cervical dilatation for atleast 2 hours Arrest of descent–there is arrest of descent of fetal head for atleast one hour

Ans: (b) 18 hours Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 376 21.

Cordocentesis is done at: (a) 9-11 weeks (c) 18-20 weeks

Explanation:

(b) 11-14 weeks (d) After 28 weeks

148  TARGET JIPMER Cordocentesis:

• • • • • •



• • •

Percutaneous cord blood sampling with a fine needle under ultrasound guidance It is performed under local anesthesia Performed after 18 weeks gestation 0.5 to 2 ml fetal blood collected Common site is the umbilical vein at the placental cord insertion Indications –Assessment and treatment of Rh isoimmunization, rapid karyotyping, hemoglobinopathies, genetic disorders, chromosomal anomalies, fetal infection, intravascular transfusion Fetal loss 1-2% Highly accurate It is an invasive procedure for prenatal diagnosis Chorion Villus Sampling

Amniocentesis

Cordocentesis

Time

Transcervical -10-12 weeks Transabdominal- 10 weeks to term

14-16 weeks (early 12-14 weeks)

18-20 weeks

Materials for study

Trophoblast cells

Fetal fibroblasts Fluid for biochemical study

Fetal white blood cells (others-infection and biochemical study)

Karyotype Result

Direct preparation-24-48 hrs Culture-10-14 days

Culture 3-4 weeks

Culture: 24-48 hrs

Fetal Loss

0.5-1%

0.5%

1-2%

Accuracy

Accurate ,may need amniocentesis for confirmation

Highly accurate

Highly accurate

Termination of pregnancy when indicated

Ist trimester-safe

2nd trimester-risky

2nd trimester-risky

Maternal effects following termination of pregnancy

Very little

More traumatic: Physically and psychologically

Same as amniocentesis

Ans: (c) 18-20 weeks Ref: Textbook of Obstetrics by Sheila Balakrishnan, 2nd edition, Page 503 22.

A child with tetrology of Fallot and polydactyly is diagnosed to have vaginal atresia. Likely diagnosis: (a) Meyer Rokintansky Kuster Hauser syndrome (c) Mckusick Kaufman Syndrome

(b) Kallman syndrome (d) Testicular feminization syndrome

Explanation: Mckusick Kaufman Syndrome

•



•



•



• •

McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly, congenital heart disease, and hydrometrocolpos in females and genital malformations in males (most commonly hypospadias, cryptorchidism, and chordee) Hydrometrocolpos can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. Cardiac malformations that have been described at least once in individuals with MKS include atrioventricularis (AV) communis with a left-sided superior vena cava, atrial septal defect, ventricular septal defect, AV canal, small aorta and hypoplastic left ventricle, tetralogy of Fallot, and patent ductus arteriosus. Treatment: Surgical repair of the obstruction MKS is inherited in an autosomal recessive manner

JIPMER–December 2018  149 McKusick-Kaufman Syndrome 

• • • • •

Autosomal recessive disease Postaxial polydactyly (PAP) Congenital heart disease (CHD) In Females: Hydrometrocolpos In Males: Hypospadias or Cryptorchidism.

Polydactyly Post-axial

Extra finger or toe present on the ulnar border of the hand

Pre-axial

Extra finger or toe present on the radial border of the hand

Common Syndromes Associated with Polydactyly

• • • • •

Carpenter syndrome Ellis-van Creveld syndrome Meckel-Gruber syndrome Trisomy 13 Rubinstein-Taybi syndrome.

Option A: Ellis-van Creveld syndrome

• • • •

Short limb dwarfism Polydactyly Abnormal development of fingernails Single common atrium is MC cardiac defect

Option B: Rubinstein-Taybi syndrome

• • • • •



•

Growth delays Intellectual disability Abnormally broad and often angulated thumbs and great toes (halluces) Feeding difficulties (dysphagia) The characteristic facial features: o Downward slanted eyes (downslanted palpebral fissures) o Long eyelashes o High-arched eyebrows o Low-hanging nasal septum (columella) o High palate o Grimacing smile o Extra cusp on the lingual side of a front tooth (talon cusps). Patent ductus arteriosus is the MC cardiac anomaly

Option D: Bardet-Biedl syndrome

• • • • • • • •

Polydactyly Cardiomyopathy is the MC cardiac anomaly Congenital heart disease Nyctalopia Obesity Anosmia Dental anomalies Renal anomalies

150  TARGET JIPMER Ans: (c) Mckusick kaufman syndrome Ref: https://www.ncbi.nlm.nih.gov/pubmed/20301675; Nelson textbook of Paediatrics, 20th edition, Page 2214 23.

Twin peak sign seen in: (a) Monochorionic Monoamniotic (c) Dichorionic Diamniotic Placenta

(b) Monochorionic Diamniotic (d) Dichorionic Monoamniotic

Explanation: Twin Peak Sign or Lambda Sign:



•



•



•

The chorion and amnion from the placenta reflect away from the fused placenta to form the intertwin membrane A potential space exists in the intertwin membrane,which is filled by proliferating placental villi giving rise to twin peak sign In monochorionic diamniotic placenta ,the intertwin membrane is composed of two amnions only. This is called T sign

TWIN VARIETIES Dizygotic twins

• Aka Fraternal or binovular twins • Commonest 80% cases • Results from fertilization of two ova Monozygotic twins



• Aka identical or Uniovular twins • Results from fertilization of single ova • Twinning may occur at different periods after fertilization o Division 13 days: Conjoint or Siamese twins – 1% - MC Thoracophagus Remember Mnemonic: DAD –>DAM -> MAM Problems specific to Monochorionic Twins



• • • • • •

Twin to twin transfusion syndrome Twin reverse arterial perfusion (TRAP) or Acardiac twin Monoamnionicity – High mortality due to cord problems Dead fetus syndrome Conjoint twins Discordant twins

JIPMER–December 2018  151 Diagnosis of Chorionicity:

• Best diagnosed by USG of Placenta at 6 – 9 weeks • In dichorionic twins, there is a thick septum identified at the base of the membrane as a triangular projection (Lambda or Twin peak sign) Ans: (c) dichorionic diamniotic placenta Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 192

24. Misoprostol: (a) PGI2 analogue (c) PGE2 analogue

(b) PGE1 analogue (d) PGF2 alpha analogue

Explanation: MISOPROSTOL

• •

Misoprostol is a synthetic PGE1 analogue Misoprostol tablets are available in different doses—25-, 50-, 100-, 200-, and 400-μg tablets.

Indications

• • • •

Medical abortion Cervical priming before surgical abortion Induction of labor at term Treatment of PPH

Route of administration Misoprostol can be administered by oral, sublingual, vaginal, and rectal routes. Advantages of misoprostol over other prostaglandins

• • • • • •

Is cheap Has a longer shelf life Is stable at room temperature (no need of refrigeration) Is easy to administer (can be given via oral, vaginal, sublingual, rectal routes) Is ideal for use in low-resource settings Is selective for uterus and has no effect on bronchus, hence not contraindicated in bronchial asthma

Contraindications

• • •

Previous uterine scar Hypersensitivity to the drug For treatment of gastric ulcers in pregnancy (misoprostol increases uterine contractions resulting in abortion)

Adverse effects

• • • •

Nausea, vomiting, and diarrhea Chills and rigors, and fever Uterine hyperstimulation Meconium staining of amniotic fluid

DINOPROSTONE GEL Dinoprostone is a prostaglandin E2 (PGE2) analogue. Dinoprostone gel contains 0.5 mg of PGE2 in 2.5 mL of gel Indication

•

For cervical ripening and induction of labor

Route of administration

Dinoprostone is available in the form of gel (Prepidil or Cerviprime) or a vaginal insert (Cervidil).

152  TARGET JIPMER Adverse effects

• • • •

Nausea and vomiting Hyperstimulation of uterus Fetal distress Rupture of uterus

CARBOPROST

It is a synthetic prostaglandin F2 alpha (PGF2α). Each ampoule of carboprost contains PGF2α 250 μg/mL Mechanism of action: It predominantly acts on the myometrium causing uterine contractions. •

Indications Management of atonic PPH Medical termination of second‑trimester pregnancy (It has been shown that prostaglandins are not preferable over conventional uterotonics such as oxytocin for the active management of third stage of labor and prevention of PPH. However, if PPH occurs, administration of parental prostaglandins serves as an effective form of treatment). Route of administration: It is administered as intramuscular injection.

• •

Dosage

•



•

Atonic PPH: Carboprost 250 μg IM injection can be repeated at 15-minute interval up to a maximum of eight doses. In severe cases of PPH,intramyometrial carboprost can be administered. Second-trimester MTP: Carboprost 250 μg IM injection, that can be is repeated every 4 hours until the patient aborts. A maximum of four injections are usually given.

Contraindications Carboprost should be used with caution in patients with asthma, hypertension, hepatic, or renal diseases. Adverse effects

• • •

Nausea, vomiting, and diarrhea Bronchoconstriction Hypertension, headache, flushing and pyrexia

Ans: (b) PG E1 analogue Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 469 25.

Spiegelberg criteria is used for: (a) Abdominal pregnancy

(b) Cervical pregnancy

(c) Ovarian pregnancy

(d) Uterine pregnancy

Explanation: OVARIAN ECTOPIC PREGNANCY Spiegelberg Criteria : Four criteria for differentiating ovarian from other ectopic pregnancies:

•

The gestational sac is located in the region of the ovary.



•

The ectopic pregnancy is attached to the uterus by the ovarian ligament.



•

Ovarian tissue in the wall of the gestational sac is proved histologically.



•

The tube on the involved side is intact.



•

USG Criteria 1. Uterine cavity empty 2. Gestational sac in ovary 3. Negative “sliding organ sign”– gestational sac cannot be separated from ovary on gentle probing 4. Corpus luteum can be seen separately

JIPMER–December 2018  153



Note: • Studdiford’s criteria – for diagnosis of abdominal ectopic pregnancy o Both the tubes and ovaries should be normal (without evidence of recent pregnancy). o Absence of uteroperitoneal fistula. o The pregnancy must be related exclusively to the peritoneal surface • Rubin’s criteria – for diagnosis of cervical ectopic pregnancy o The uterus is smaller than the surrounding distended cervix. o The internal os is not dilated. o Curettage of the endometrial cavity is nonproductive of placental tissue. o The external os opens earlier than in spontaneous abortion Ans: (c) Ovarian pregnancy Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 177

26.

Clue cells seen in: (a) Trichomonas vaginalis (c) Gardenella infection

(b) Candida (d) Treponema pallidum

Explanation: Bacterial Vaginosis

• • • •



• •

This is caused by Gardnerella vaginalis or haemophilus vaginalis Bacteroides , peptococcus, mobilincus, mycoplasma hominis also act synergistically Alteration in normal vaginal flora Decrease in number of lactobacilli in vaginal discharge - lactobacilli reduce pH and release hydrogen peroxide toxic to other bacteria 100 fold increase in anerobic bacteria Patient presents with Creamy white discharge with fishy odour

Amsel’s criteria–At least three of the four criteria should be present for a confirmed diagnosis.

1. 2. 3. 4. •

Homogenous, thin, white vaginal discharge Vaginal pH > 4.5 Positive whiff test Presence of clue cells >20% on microscopy Whiff test- fishy odor when a drop of discharge is mixed with 10% KOH due to release of amino metabolites from various organisms • Clue cells – vaginal epithelial cells are stippled with coccobacilli which gives a stippled or granular appearance Treatment: Metronidazole 200 mg tds for 7 days ; Clindamycin 2% intravaginal gel for 7 days

154  TARGET JIPMER Feature

Candidiasis

Trichomonal vaginitis

Bacterial vaginosis

Etiology

Candida albicans

Trichomonas vaginalis

Gardnerella vaginalis Ureaplasma urealyticum

Discharge amount

Scant

Profuse

Moderate (malodorous)

Color

Curdy/cheesy white

Greenish-yellow frothy

Grayish white homogenous

pH of vagina

4.7

10% KOH + secretions

Fishy odor (due to release of amines, acridine and putredine) = Whiff test

Microscopy

Pseudohyphae

Flagellate motile organism (Hanging drop preparation)

Clue cells (vaginal epithelial cells loaded with coccobacilli)

Usual treatment

Locally: Clotrimazole and miconazole Oral: fluconazole

Metronidazole

Metronidazole

Ans: (c) Gardnerella vaginalis Ref: DC Dutta, Textbook of Gynecology, 7th edition, Page 125, CDC Criteria 2010 27.

Snow storm appearance is seen in: (a) Ectopic pregnancy (c) Incomplete abortion

(b) Molar pregnancy (d) Heterotopic pregnancy

Explanation:

HYDATIFORM MOLE • Hydatiform mole is a gestational trophoblastic disease; otherwise termed vesicular mole • Incidence in India 1 in 400 • Pathology – degenerative and proliferative changes in chorionic villi • Hydatiform mole can be partial or complete • Complete moles have 46xx karyotype • Partial moles have 69XXY or XYY karyotype • Clinical features: vaginal bleeding, expulsion of grape like vesicles, thyrotoxicosis, pain abdomen, excessive vomiting, preeclampsia • Investigations: USG –snow storm appearance, elevated beta HCG> 100000Miu/ML, X-ray, CT,MRI • Theca lutein cysts in ovary present in 20-25% cases • Risk of developing choriocarcinoma is 2-10% • Management – suction evacuation • Follow up–every week till HCG becomes normal. It will take around 4 to 6 weeks. Then the patient is followed every month till one year • If HCG plateaus or re-elevates, prophylactic chemotherapy with methotrexate started after ruling out pregnancy • Secondary metastasis in lung in chorocarcinoma shows “cannon ball appearance” in chest X-ray

JIPMER–December 2018  155 Partial Mole

Complete Mole

Fetus, fetal vessels, placenta

Present

Absent

Karyotype

69 XXY (triploid) The extra haploid set of chromosomes usually is derived from father.

46 XX The chromosomes are entirely of paternal origin as an empty ova is fertilised by a single sperm that undergoes reduplication (process called as androgeniesis).

Hydropic changes

Focal

Marked

Trophoblastic proliferation

Focal Trophoblastic inclusion body present.

Diffuse Absent

Villi proliferation

Focal. Scalloping of chorionic villi present.

Diffuse Absent

Malignant potential

Rare

15-20%

USG:

Focal cystic spaces in placenta Fetus and placenta are seen Often confused with missed abortion

Snowstorm appearance

Clinical features:

Most common presenting feature is bleeding per vagina following a period of amenorrhea

Same

Passage of grape like vesicles Ht of uterus equal to or less than the period of gestation.

Height of uterus more than period of gestation

Thyrotoxicosis Preeclampsia Hyperemesis gravidarum

Less marked

More marked

Gold standard for diagnosis:

Histopathological examination

Histopathological examination

hCG levels:

Raised but not markedly raised.

Markedly raised (≥ 105 mIu/ml)

Theca lutein cysts

Not seen in ovary

Common

Persistent Gestational Trophoblastic Disease or (GTN)

Chances 3-5% Risk of choriocarcinoma=< 1%

15-20% 4%

Ans: (b) Molar pregnancy Ref: DC Dutta, Textbook of Obstetrics, 9th edition, Page 182

156  TARGET JIPMER

ORTHOPEDICS 1.

Judet view is used for fracture of: (a) Acetabulum (c) Calcaneum

(b) Coccyx (d) Scaphoid

Explanation:

•

Judet views are two special views of the pelvis (Obturator oblique and Iliac oblique) that are clicked to study acetabular fractures.

Some important X-ray views to remember:

• • • • • • • • • • • • • • • • • • • • •



•

Axillary view: Lateral view of shoulder joint. West point axillary view: For Bankart’s lesion. Internal rotation view and Stryker notch view: For Hill-Sachs lesion. Zanca view: Acromioclavicular joint. Serendipity view: Sternoclavicular joint imaging to detect dislocation. Green span view: Fractures of radial head and capitellum. Jones (AP) view elbow: Evaluation of reduction in supracondylar humerus fractures. Oblique view wrist and PA view wrist in ulnar deviation: Scaphoid fractures. Brewerton view: Used to see metacarpal head fractures. Robert’s view: Used for thumb CMC joint. Carpal tunnel view: For hook of hamate fractures. Ball catcher’s view: For visualizing erosions in RA hand. Judet views (Obturator oblique and Iliac oblique views): Acetabular fractures. Frog leg view: A modified method of taking lateral view of hip joint intraoperatively. Von Rosen view: CDH. Axial view, Skyline view and Merchant’s view: Patellar subluxation. Mortise view (ankle AP view in 15° internal rotation): Ankle injuries evaluation. Canale view: Talar neck fractures. Harris view of hind foot: Calcaneum fractures. Broden views: Intraoperative assessment in calcaneal fractures. Swimmer’s view: Cervical spine lateral view (shoulder pull down) to assess lower cervical spine (C6, C7 and T1 can be visualized). Ferguson view: This is 20° caudocephalic AP view of lumbar spine used to detect compression of L5 by a large transverse process of L5 vertebra against sacrum (called as Far out syndrome).

Ans: (a) Acetabulum Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 116. 2.

Gallows traction is applied for fracture of which bone: (a) Tibia (c) Humerus

(b) Radius (d) Femur

Explanation:

•



• •



•

Gallows traction (overhead Bryant skin traction) is useful for children younger than 2 years who weigh 10-12 kg for Fracture shaft of femur. The traction should be enough to just lift the buttocks of the child off the bed. Careful examination of the neurovascular status of the extremity is mandatory in the early period after application of traction. Older children have a risk of compartment syndrome , vascular insufficiency, peroneal nerve palsy, and skin breakdown when treated with this method.

JIPMER–December 2018  157

Gallows traction

Ans: (d) Femur Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 140. 3.

Nexus criteria is used for: (a) Traumatic cervical spine injury (c) Traumatic knee injury

(b) Traumatic ankle injury (d) Traumatic hip injury

Explanation:

•



•



•

Polytrauma patients may have head injury and cervical spine injuries which are particularly difficult to evaluate when the level of consciousness is low. The criteria for imaging in cases with neck trauma (NEXUS) and head injury (Canadian CT head rule) are given in table 1 below. When all of NEXUS points are met, there is no need to go with cervical spine imaging.

NEXUS criteria and Canadian CT rule Criteria for cervical spine imaging and CT head in polytrauma NEXUS criteria for cervical spine imaging

Canadian CT head rule

No posterior mid-line tenderness

GCS 1 episode of vomiting Age >64 years Dangerous mechanism of injury (e.g., fall > 1 m height)

No need of cervical spine X-rays if all above conditions are met

Undertake a CT head study if any of the above condition is met

Abbreviations: NEXUS, National Emergency X-Radiography Utilization Study; GCS, Glasgow Coma Scale; CSF, cerebrospinal fluid.

Ans: (a) Traumatic cervical spine injury Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 55.

158  TARGET JIPMER 4.

Not seen in osteogenesis imperfecta: (a) Wormian bones (c) Coxa vara

(b) Thick cortex (d) Saber shin

Explanation:

• •



•



•



•

Osteogenesis imperfecta is a genetic disorder transmitted as both AD and AR patterns Defects in COL1A1 and COL1A2 genes results in abnormal collagen cross linking and defective Collagen type I (major collagen of bone tissue). As a result, there is marked osteopenia (with thin bone cortex) that leads to frequent fractures after trivial trauma. Saber shin, a tibial malformation presenting as a sharp anterior bowing, or convexity (classically seen in syphilis) may be seen. Wormian bones (intra sutural skull bones) are classical.

Ans: (b) Thick cortex Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 393. 5.

Ewing’s sarcoma peak incidence: (a) 1st decade (c) 3rd decade

(b) 2nd decade (d) 4th decade

Explanation:

•



• •



• • •



•

Ewing sarcoma (named after James Ewing, who first described), is the third most common nonhematologic primary malignancy of the bone It is the second most common (after osteosarcoma) in patients younger than 30 years of age Classically it affects children in the age group of 5–15 years with those in their second decade being more commonly affected. There is a slight male preponderance. Most common bones affected include the femur (diaphysis) and pelvis. The tumor is also commonly found in the diaphysis (often extending into metaphysis) of humerus, tibia and the flat bones like the vertebrae, ribs and scapula. Multicentric lesions have also been reported.

Ans: (b) 2nd decade Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 328. 6.

Identify the deformity in picture: (a) Mallet finger (c) Boutonniere deformity

(b) Swan neck deformity (d) Jersey finger

JIPMER–December 2018  159

Explanation:

Mallet finger (also called as Baseball finger) refers to rupture of common flexor tendon (Flexor digitorum profundus) from the base of distal phalanx. • Consequently there is inability of active extension of the distal phalanx. • It is the commonest closed tendon injury in athletes. OTHER OPTIONS GIVEN Swan neck deformity



•



•

It is a deformed position of the finger, in which the joint closest to the fingertip is permanently bent toward the palm while the nearest joint to the palm is bent away from it (DIP flexion with PIP hyperextension). It is commonly caused by injury or inflammatory conditions like rheumatoid arthritis or sometimes familial (like Ehlers–Danlos syndrome).

Boutonniere deformity

•



•

It is a deformed position of the fingers or toes, in which the joint nearest to the knuckle (the proximal interphalangeal joint, or PIP) is permanently bent toward the palm, while the farthest joint (the distal interphalangeal joint, or DIP) is bent back away (PIP flexion with DIP hyperextension). Causes include injury, inflammatory conditions like rheumatoid arthritis, and genetic conditions like Ehlers-Danlos syndrome.

Jersey finger

• •



•

It is an injury to an FDP tendon at its point of attachment to the distal phalanx. This injury often occurs in American football when a player grabs another player’s jersey with the tips of one or more fingers while that player is pulling or running away. Although it is a common football injury, this injury can occur during other sports or activities as well. A person who suffers a jersey finger injury in which the FDP tendon is completely ruptured cannot flex the affected digit at the DIP joint without assistance.

Jersey finger

Ans: (a) Mallet finger Ref: Fundamentals of Orthopedics by Mohindra and Jain (Jaypee Publishers), 2nd edition, Page 177 7.

Sun burst appearance of skull not seen in: (a) Paget’s disease (c) Metastasis due to neuroblastoma

(b) Osteosarcoma (d) Hemangioma

Explanation:

•



•

Sunburst pattern of periosteal reaction refers to bone formation by aggressive lesions leading to periosteal lifting and bone formation along sharpey’s fibers. All the above mentioned conditions can exhibit the sun burst pattern on a skull x ray. However, if to choose one option, Choice (c) can be marked because sun burst pattern has been mentioned to be a rare finding in neuroblastoma metastasis.

160  TARGET JIPMER

Sunburst pattern

Ans: (c) Metastasis due to neuroblastoma Ref: Egelhoff JC1, Zalles C. Unusual CNS Presentation of Neuroblastoma, Pediatr Radiol, 1996;26(1):51-4.

JIPMER–December 2018  161

PEDIATRICS 1.

In exhausted child with severe bronchiolitis, for every 10 mm Hg increase in PCO2, how many milliEq of bicarbonate will increase? (a) 2 (c) 8

(b) 4 (d) 1

Explanation:

• • •

Severe Bronchiolitis with exhaustion – implies ‘acute’ respiratory acidosis with compensation Respiratory Acidosis (inappropriate increase in the blood carbon dioxide (PCO2)). Secondary to - pulmonary diseases (as severe bronchiolitis), or non-pulmonary disease (as narcotic overdose).

Causes of Respiratory Acidosis



Pulmonary Causes

Non Pulmonary Causes

Upper airway Disease • Aspiration • Laryngospasm • Angioedema • Obstructive sleep apnea • Tonsillar hypertrophy • Vocal cord paralysis

Central Nervous System Depression • Encephalitis • Head trauma • Brain tumor • Central sleep apnea • Primary pulmonary hypoventilation (Ondine curse) • Hypoxic brain damage • Obesity-hypoventilation (Pickwickian syndrome) • Increased intracranial pressure

Pulmonary Disease • Pneumonia • Pneumothorax • Asthma • Bronchiolitis • Pulmonary edema • Pulmonary hemorrhage • Acute respiratory distress syndrome

Medication • Narcotics • Barbiturates • Anesthesia • Benzodiazepines • Aminoglycosides • Organophosphates (pesticides)

Miscellaneous • Flail chest • Cardiac arrest • Kyphoscoliosis

Disorder of spinal cord / Nerves / Neuro Muscular Junction • Diaphragmatic paralysis • Guillain-Barré syndrome • Poliomyelitis • Spinal muscular atrophies • Botulism • Myasthenia • Spinal cord injury

Acute Respiratory acidosis: • Plasma bicarbonate increases by 1 for each 10 mm Hg increase in the PCO2 (acute compensation). • Metabolic compensation for chronic respiratory acidosis - the kidneys increase acid excretion. (Occurs over 3-4 days) Chronic Respiratory acidosis:



•

Plasma bicarbonate increases by 3.5 for each 10 mm Hg increase in the PCO2 (chronic compensation).

Clinical Manifestations

•

Tachypnea (effort to correct the inadequate ventilation).

162  TARGET JIPMER

Acute respiratory acidosis more symptomatic than chronic respiratory acidosis. Central nervous system manifestations – anxiety, dizziness, headache, confusion, asterixis, myoclonic jerks, hallucinations, psychosis, coma and seizures. • Arterial pH < 7.20 - impairs cardiac contractility and the normal response to catecholamines, both in the heart and the peripheral vasculature. • Hypercapnia - causes vasodilation (cerebral vasculature), produces vasoconstriction (pulmonary circulation). A-a gradient (gradient between the alveolar oxygen concentration and the arterial oxygen concentration) • Useful for distinguishing between poor respiratory effort and intrinsic lung disease. • A-a gradient - increased if the hypoxemia is due to intrinsic lung disease • •

EXTRA EDGE: Normal levels of blood pH, PCO2 and HCO3 Blood levels Criteria

Venous

Arterial

PH

7.35-7.40

7.38-7.45

PCO2

45-50 torr

35-45 torr

HCO3

24-25 mEq/L

23-27 mEq/L

Normal ABG Values H+ (35−45 nmol/L) < 35 = alkalaemia, > 45 = acidaemia pH (7.35−7.45) < 7.35 = acidaemia, > 7.45 = alkalaemia PO2 (> 10.6 kPa or > 80 mm Hg in arterial blood on room air) PCO2 (4.7−6.0 kPa or 35−45 mm Hg in arterial blood) SpO2 (> 96%on room air)’ HCO3 (22−28 mmol/L) BE (-2 to +2) Lactate (0.4−1.5 mmol/L)

Stepwise approach for acid base disorders pH < 7.35 = acidosis; pH > 7.45 = alkalosis Primary change in HCO3 → metabolic • If the change in HCO3 is in keeping with the pH (i.e. acidosis + decreased HCO3) the problem is metabolic • If the change in HCO3 is opposite with the pH (i.e. acidosis + increased HCO3) the problem is compensatory metabolic Primary change in CO2 → respiratory • If the change in CO2 is in keeping with the pH (i.e. acidosis + increased CO2) the problem is respiratory • If the change in CO2 is opposite with the pH (i.e. acidosis + decreased CO2) the problem is compensatory respiratory

Mixed Acid base disorders

• •

Present when compensation is not appropriate Compensation never over-corrects the primary disturbance Expected Compensation

Limit of Compensation

Metabolic Acidosis

PCO2 = 1.5 × [HCO ] + 8 ± 2

PCO2 does not fall below 10 mm Hg

Metabolic Alkalosis

PCO2 increases by 7 mm Hg for each 10 mEq/L increase in serum [HCO3−]

PCO2 does not rise above 55 mm Hg

Acute Respiratory Acidosis

[HCO3−] increases by 1 for each 10 mm Hg increase in PCO2

HCO3 does not rise above 30 mEq/L

− 3

Contd.

JIPMER–December 2018  163 Contd. Chronic Respiratory Acidosis

[HCO3−] increases by 3.5 for each 10 mm Hg increase in PCO2

HCO3 does not rise above 45 mEq/L

Acute Respiratory Alkalosis

[HCO3−] falls by 2 for each 10 mm Hg decrease In PCO2

HCO3 does not fall below 18 mEq/L

Chronic Respiratory Alkalosis

[HCO3−] falls by 4 for each 10 mm Hg decrease In PCO2

HCO3 does not fall below 12 mEq/L

Ans: (d) 1 Ref: Nelson, Textbook of pediatrics, 20th edition, Page 381 2.

Not true regarding Prune belly syndrome: (a) Macroglossia (c) Anterior abdominal wall defect

(b) Hydrouretronephrosis (d) Crytorchidism

Explanation:

• •

Macroglossia is not a part of prune belly syndrome Triad of prune belly syndrome which includes o Deficient abdominal muscles o Undescended testes o Urinary tract abnormalities

Prune Belly Syndrome/Eagle-Barrett syndrome:

• • •



• •



•



•



•

1 in 40,000 births; (95% are male), many affected infants are stillborn. Maternal history of oligohydraminos* is usually present Severe urethral obstruction in fetal life leads to the characteristic association of o Deficient abdominal muscles o Undescended testes (testes are usually intra-abdominal), and o Urinary tract abnormalities Frequent complications - Oligohydramnios and pulmonary hypoplasia* Urinary tract abnormalities - includes massive dilatation of the ureters and upper tracts and a very large bladder, with a patent urachus or a urachal diverticulum with vesicoureteral reflux. The prostatic urethra (dilated), hypoplastic prostrate, dilatation of anterior urethra leads to megalourethra (result from underdevelopment of the corpus spongiosum and support structures of the urethra), rarely urethral stenosis or atresia. The kidneys - various degrees of dysplasia. Associated abnormalities: o Malrotation of the bowel o Cardiac abnormalities (10%) o Dimple over the lateral aspects of the knees & elbow o Musculoskeletal abnormalities (50%) like limb abnormalities (club foot) and scoliosis.

164  TARGET JIPMER

• •

In females, anomalies of the urethra, uterus, and vagina are usually present without any gonadal anomaly. Neonates - have difficulty with effective bladder emptying (because the bladder musculature is poorly developed and the urethra is narrowed).

Treatment options:

• •



• • •

If Obstruction absent - prevention of urinary tract infection with antibiotic prophylaxis. If obstruction of the ureters or urethra present a. Temporary drainage procedures – vesicostomy (to preserve renal function until the child is old enough for surgery). b. Orchidopexy for correction of the undescended testes-difficult (testes are located high in the abdomen) and done in the first 6 mo of life. Reconstruction of the abdominal wall offers cosmetic and functional benefits Prognosis - depends on the degree of pulmonary hypoplasia and renal dysplasia. Survivors - develop end-stage renal disease from dysplasia or complications of infection or reflux and require renal transplantation (result of transplantation are favorable).

EXTRA EDGE:

• • • •

Prune Belly Syndrome can occur in association with trisomy 18 & 21 Ratio of collagen to smooth muscle in prune belly ureters is elevated. Decreased myofibrils contributes to the poor peristalsis of ureter. Commonly the medial and inferior musculature of the abdominal wall is more deficient.

Ans: (a) Macroglossia Ref: Nelson, Textbook of Pediatrics, 20th edition, Page 2572 - 2573 3.

All are diagnostic criteria for ‘Severe acute malnutrition’ (SAM) except: (a) Mid- upper arm circumference (MUAC) 60 mm/hr, CRP) 2. ECG: Prolonged PR interval > 0.16 sec (in the absence of carditis as major criteria)

Pan carditis Polyarthritis Chorea Subcutaneous nodule Erythema marginatum

Essential Criteria - Supportive evidence of preceding streptococcal infection 1. Positive throat culture or rapid streptococcal antigen test (Streptozyme test) 2. Elevated or increasing streptococcal antibody titer • Anti streptolysin O (ASO titer: >333 unit for children and > 250 for adults) • Anti-deoxyribonuclease B (Normal values 1:60 unit in preschool, 1:480 units in school children & 1:340 in adults)

Diagnosis: 2 Major Criteria OR 1 Major and 2 Minor criteria Plus Essential criteria.

•

2 major is more specific than 1 major and 2 minor manifestations.



•

Arthralgia should not be taken as minor criteria in the presence of arthritis. Prolonged PR interval should not be taken as minor criteria if carditis is present.



•

History of sore throat without substantial lab support is not adequate evidence of GAS infection.

Exceptions of Jones Criteria*

•

Chorea



•

Indolent Carditis



•

Recurrences of ARF

Recent changes by American Heart Association 2015*

1. Categorizing the population as low risk (incidence < 2 per 100000 school children per year or prevalence of RHD < 1 per 1000 population) and moderate/high risk (most developing countries).



2. Different criteria for both populations.



3. The major manifestation: a. Carditis now includes sub clinical evidence of carditis (ECHO evidence of MR valvulitis without murmur) in high risk population.



4. Major manifestation of poly arthritis, now includes mono arthritis or polyarthralgia (in the absence of prior anti-inflammatory drugs) in high risk population.

176  TARGET JIPMER

5. Minor manifestation of polyarthralgia now includes monoarthralgia and polyarthralgia can be considered as major manifestation after excluding other causes.



6. Other changes in the minor manifestation like fever decreased to at least 38 deg C from 38.5 deg C, ESR decreased to 30 mm/hr from 60 mm/hr and CRP at least 3mg/dL in high risk population.



7. In high risk population - recurrence of rheumatic fever can be made with 3 minor manifestations alone. Treatment:



•

Principles of treatment: o Treatment of group A streptococcal infection.

o Control of inflammation with anti-inflammatory drug.

•

o Treatment of complications.

General measures and symptomatic relief: o Analgesics for pain relief (Aspirin should be avoided till diagnosis is confirmed). o Indications for Hospitalization is needed for – Moderate to severe carditis – Severe arthritis – Chorea. o Rest is individualized according to symptoms.

Specific measure: Control of inflammation with Anti Inflammatory Agents:

•

Total duration of anti-inflammatory therapy - 12 weeks



•

Aspirin and steroids are primarily used to control inflammation. Naproxen and methylprednisolone can be used alternatively.

Drugs for control of Inflammation In acute Rheumatic fever: Arthritis ± mild carditis

Responders: Aspirin - Starting doses: children 100mg/kg/day for 2-3 weeks once symptoms resolved, taper to 60-70mg/kg/day If aspirin intolerance detected - Naproxen - 10-20mg/kg/day If no response to aspirin in four days - Switch over to steroid. After ruling out chronic inflammatory/myelo-proliferative disorders.

Moderate to severe carditis or CCF

Responders: Steroids; Prednisolone: 2mg/kg/d, maximum 80mg/day till ESR normalizes – usually 2 weeks. Taper over 2 - 4 weeks, reduce dose by 2.5 – 5 mg every 3rd day. Start aspirin 50-75mg/kg/day simultaneously, to complete total 12weeks Non-responders: IV methyl prednisolone 30mg/kg/day for 3 days

Sydenham chorea

Sedative like phenobaribital, haloperidol or chlorpromazine if phenobarbital is ineffective

Treatment of group A streptococcal infection (GAS) and secondary prevention drugs. Drugs

Dose

Pharyngotonsillitis treatment (duration)

Secondary prophylaxis (interval)

Benzathine Penicillin G (deep IM inj)

1.2 million unit (> 27 Kg) After sensitivity test (AST)

Single dose

21 d

0.6 million unit (2 per 100,000 school-age children per year Ref: Nelson, Textbook of Pediatrics, Page 1332–36 & Arun Babu, T, ‘Concise Textbook of Pediatrics’, 1st edition, Elsevier, Page 218 9.

Most oxygenated foetal vessel: (a) Umbilical artery (c) Umbilical vein

(b) (d)

Ductus arteriosus Ductus venosus

Explanation: Fetal Circulation



In fetal circulation, the right and left ventricles exist in a parallel circuit, whereas in children and adults, it is in series.   • Ductus venosus, foramen ovale, and ductus arteriosus are the important structures needed for maintaining this parallel circulation. • Placenta provides gas and metabolites for exchange while the lungs do not provide gas exchange, and vessels in the pulmonary circulation are constricted. Fetal circulatory flow: • Oxygenated blood from the placenta flows to the fetus through the umbilical vein (UV). Approximately 50% of UV blood enters the hepatic circulation while the rest bypasses liver and joins the inferior vena cava via the ductus venosus. • This combined lower body plus umbilical venous blood flow enters the right atrium and is preferentially directed across the foramen ovale to the left atrium. The blood then flows into the left ventricle and is pumped into the ascending aorta. • From fetal superior vena cava blood enters the right atrium and preferentially traverses the tricuspid valve, rather than the foramen ovale, and flows primarily to the right ventricle. From the right ventricle, the blood is ejected into the pulmonary artery. • Since the pulmonary arterial circulation is vasoconstricted, only about 10% of right ventricular outflow enters the lungs. The major portion of this blood bypasses the lungs and flows through the ductus arteriosus into the descending aorta to perfuse the lower part of the fetal body, after which it returns to the placenta via the two umbilical arteries. EXTRA EDGE •

Oxygen Saturation of Inferior Vena Cava

70%

Oxygen Saturation of Superior Vena Cava

40%

Partial pressure of oxygen in Umbilical Vein

32 mm Hg (Highest)

Partial pressure of oxygen in Umbilical Artery

24 mm Hg

Partial pressure of oxygen Aorta

28 mm Hg

Partial pressure of oxygen Pulmonary artery

19 mm Hg

178  TARGET JIPMER Circulatory adjustments at birth

Removal of placenta - Increase in systemic vascular resistance (SVR) and closure of ductus venosus Lung expansion results in o Decrease in pulmonary vascular resistance (PVR) o Functional closure of foramen ovale o Closure of Patent ductus arteriosus As a result of increase in SVR and decrease in PVR, there is reversal of shunt in ductus arteriosus from aorta to pulmonary artery, which was from pulmonary artery to aorta in fetal circulation. • •

PERINATAL CHANGES INFLUENCING LEFT TO RIGHT SHUNT Before birth:

• •

Gas exchange in the fetus is primarily a placental function Minimal pulmonary blood flow (PBF), higher pulmonary vascular resistance (PVR) and low systemic vascular resistance SVR (resistance in placental circuit is low) are characteristic.

After birth:

•



•



•



•



•

Increase in arterial PaO2 decreases the PVR through arteriolar dilation but pulmonary artery pressure (PAP) remains elevated. Pulmonary smooth muscle regression and a postnatal increase in cross-sectional area of the pulmonary vascular bed allows progressive reduction in PVR over the initial 8–12 weeks and then till 4–5 years of age. Elimination of the low resistance placental circuit increases systemic vascular resistance (SVR) thereby promoting left–to–right shunting. Timing of changes in vascular resistances in the perinatal period dictates the onset of clinical symptoms. Hemodynamically significant left-to-right shunting starts at approximately 8–12 weeks. Size of defect is the primary determinant of the magnitude of shunting, larger defects allowing larger shunts leading on to earlier heart failure.

Ans: (c) Umbilical vein Ref: Parks, Cardiology for Practitioners, 5th edition, Page 119–121 10.





A 5-year-old presents with renal mass. Considering the most common cause in this age group, which of the following is not true? (a) Triphasic histology (b) Risk of WAGR (c) Bilateral involvement (d) Increased urine VMA levels

Explanation: • •

Wilms tumour accounts for 87% of pediatric renal masses (3–5 years of age) Increased vanillylmandelic acid (VMA) in urine is seen in Neuroblastoma

Wilms tumor (nephroblastoma) • MC primary malignant renal tumor of childhood • Second MC malignant abdominal tumor in childhood • Nephrogenic rests* are the putative precursor lesions of Wilm’s tumor • Complex mixed embryonal neoplasm of the kidney is composed of three elements • Triphasic histology: o Blastema o Epithelia o Stroma. • Bilateral Wilms tumor is 7%.

Pathogenesis Majority – sporadic Etiology – Mutation of following genes

JIPMER–December 2018  179

– Wilms tumor gene (WT1) on chromosome 11 – CTNNB1 gene (encoding β-catenin) – p53. Familial cases (family history positive in 2%, autosomal dominant manner) - genes have been localized to 19q13 and 17q, present at younger age, often bilateral and absent associated other congenital anomalies. Wilms tumor gene (WT1) located at 11p13, encodes a zinc finger transcription factor that is critical for normal kidney development, mutation seen in 20% of all Wilms tumors. Histologically: Favorable and unfavorable. Favorable histology

Unfavorable histology

•

• • • •

• • •

Comprises blastoma, epithelial and stromal elements. Devoid of anaplasia or ectopia. Brain and bone metastasis is rare. Metastasis may occur to lung

Marked enlargement of nuclei Hyperchromatism and multipolar mitotic figures Anaplasia is present Clear cell Sarcoma is a subtype and usually metastasizes to bone.

Rhabdoid tumor, which may metastasize to the brain, is no longer classified as a subtype.*



Clear cell carcinoma (histological subtype of Wilms tumour) – frequently metastasize to bone* Clinical Features: Usual age of diagnosis is 2-5 years. – Triad of abdominal mass, fever and microscopic hematuria – Presents as an abdominal mass (common). Rarely with abdominal pain, vomiting, hematuria, hypertension (due to renal ischemia), rapid abdominal enlargement and anemia ( due to bleeding into the renal parenchyma or pelvis). – Acquired deficiency of von Willebrand factor and factor VII Syndromes associated with Wilm’s tumor: Syndrome

Clinical Characteristics

Genetic anomalies

WAGR syndrome

Willm’s tumor Aniridia Genitourinary abnormalities Mental Retardation

Del 11p12 (WT1 and PAX6)

Denys-Drash syndrome

Early onset renal failure with renal mesangial sclerosis Gonadal dysgenesis (Male pseudohermaphrodism) Gonadoblastoma

WT1 missense mutation

Beckwith Wiedemann syndrome

Somatic overgrowth syndrome in which predisposition to embryonal tumors is observed Hemihypertrophy Organomegaly Omphalocele Abnormal large cells in adrenal cortex (Adrenal cytomegaly*)

Genomic imprinting Unilateral paternal disomy, duplication of 11p15 Microdeletions within the IGF2 imprinting control region.

Increased risk of Wilms tumor Pearlman syndrome, Sotos syndrome, neurofibromatosis and von Willebrand disease. Diagnosis:

• •



• • •

USG – First investigation – to differentiate solid from cystic CT scan - confirmation of the intrarenal origin of the mass, extent of tumor, involvement of the inferior vena cava, and contralateral kidney. Calcification* – Crescent shaped, discrete and peripheral .Enhance after injection of contrast medium Bone scans - for clear cell sarcoma of the kidney Radiographic of chest - presence of pulmonary metastases.

180  TARGET JIPMER STAGING

Developed by the National Wilms Tumor Study Group, correlates with prognosis 1. Stage I – Tumor is confined to the kidney (excised with the capsular surface intact). 2. Stage II – Tumor is also confined to the kidney, (although the capsule is penetrated or tumor is present in the perirenal soft tissue). 3. Stage III – Tumor has postsurgical residual nonhematogenous extension present. (Confined to the abdomen – Perirenal bed or draining lymph nodes, or surrounding tissue and organs by contiguity). 4. Stage IV – Tumor is characterized by hematogenous metastases. The metastases generally involve the lungs, liver. 5. Stage V – Tumor with bilateral renal involvement. Treatment Surgical extirpation of the tumor if inferior vena cava is patent (if not patent - preoperative chemotherapy) Stage

Treatment

I and II

Vincristin + Dactinomycin

III

Vincristin + Dactinomycin + Doxorubicin + radiotherapy to tumor bed

IV

Vincristin + Dactinomycin + Doxorubicin + radiotherapy to all sites

Unfavorable histology

Vincristin + Dactinomycin + Doxorubicin + cyclophosphamide + radiotherapy

Inoperable Wilms Tumor - Chemotherapy Bilateral Wilms Tumor - unilateral nephrectomy and contralateral partial nephrectomy or bilateral partial nephrectomies. Postoperatively - chemotherapy, radiation therapy are administered.



• •



The prognosis is worse - larger tumor (>500 g), advanced stage (III and IV), and unfavorable histologic subtype. OTHER KIDNEY TUMORS IN CHILDREN Congenital Mesoblastic Nephroma



• • •

Tumor is a massive, infiltrative, solitary renal mass. Considered benign, rarely metastasizes. often in males , producing renin. Resembles a leiomyoma or a low-grade leiomyosarcoma with trapped nephrons.

Nephroblastomatosis

• •



•

Abnormal persistence of embryonal renal tissue (associated with the development of Wilms tumor). Bilateral Wilms tumor has a strong relationship with the nodular renal blastema nephroblastomatosis complex. Brief course of relatively nontoxic chemotherapy (vincristine and dactinomycin) may be beneficial Wilm’s tumor

Neuroblastoma

Age

Mean age 3 years

retroperitoneum

Clinical Features

Unillateral flank massasymptomatic abdominal mass

Abdominal mass, GI or genitourinary obstruction, proptosis, fever, bone pain, spinal cord compression etc

Calcification

Less common

More common (85%) and punctate

X-ray abdomen

Curvilinear calcification

Stippled

Site of metastasis

Liver

Bones

Midline

Not crossed

Crossed

Aortic/IVC invasion

Absent

Present Contd.

JIPMER–December 2018  181 Contd. Spinal Extension

Absent

Present

Distribution of calyces

Very common (90%)

Not seen

Hydronephrosis

More common (40%)

Less common

Extrarenal

No

May occur

Retroperitoneal lymphadenopathy

Less common (13%)

More common (73%)

Prognostic Factor

Most important is staging

Good prognosis- Age 1-5 years, Stages I, II and IV, Normal serum ferritin, absence of n-myc gene amplification.

Ans: (d) Increased urine VMA levels Ref: Nelson, Textbook of Pediatrics, 20th edition, Page 2465-67 11.

Administration of PGE1 infusion will deteriorate condition in which of the following: (a) (b) (c) (d)

TGA with intact ventricular septum and restrictive foramen ovale HLHS with restrictive foramen ovale Mitral atresia with restrictive patent foramen ovale Supracardiac total anomalous pulmonary venous connection

Explanation:

•



•

PGE1 infusion in obstructive total anomalous pulmonary venous return (left to right shunt via a PDA) results in o Decrease systemic blood flow and o Increase blood flow to the pulmonary bed (pulmonary vascular congestion) Thus the clinical condition (cyanosis) of the neonate worsens.

Prostaglandin E1 (PGE1) Indications 1. Maintains patency of ductus arteriosus in neonates with ductal – dependent congenital heart lesions until surgery can be done. (a) Ductal depended systemic circulation condition – Critical Aortic Stenosis, Coarctation of Aorta, Interupted Aortic arch – Hypoplastic left Heart Syndrome (b) Ductal depended pulmonary circulation condition – Pulmonary Stenosis – Pulmonary atresia with intact Interventricular septum (Hypoplastic Right Heart Syndrome), Tricuspid Atresia, Ebstein anomaly.



2. Improve shunting after balloon septostomy has failed to improve oxygenation in certain cases of complete transposition of the great arteries

Contraindications and Precautions: 1. Total anomalous pulmonary venous return with obstruction 2. Persistent pulmonary hypertension (PPHN) 3. Hypersensitivity to prostaglandin E 4. Caution use in presence of bleeding tendencies or seizure disorders. Common Adverse Reactions:



1. Apnea (in up to 15% of patients)



2. Hypotension and Bradycardia

182  TARGET JIPMER

3. Fever and flushing



4. Hypoglycemia, hypocalcaemia



5. Thrombocytopenia



6. Seizure Ans: (d) Supracardiac total anomalous pulmonary venous connection Ref: Manual of Neonatal Care, 7th edition, Page 486

12.

Most common cause of craniosynostosis: (a) Plagiocephaly

(b) Brachycephaly

(c) Scaphocepahly

(d) Trigonocephaly

Explanation: Craniosynostosis

•

Premature closure of the cranial sutures and is classified as primary or secondary.



•

Primary craniosynostosis - closure of one or more sutures due to abnormalities of skull development o Incidence 1/2,000 births



•



•

o genetic syndromes account for 10-20% of cases.

Secondary craniosynostosis - from failure of brain growth and expansion. Mutations of the fibroblast growth factor receptor (FGFR) gene family have been shown to be associated with phenotypically specific types of craniosynostosis

Development and Etiology

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•



•



•

In early development - the brain is enveloped by a film of mesenchyme. By 2nd month - osseous tissue is evident in that portion of the mesenchyme corresponding to the cranium, and cartilaginous tissue is formed at the base of the skull. By 5th month - bones of the cranium are well developed (frontal, parietal, temporal, and occipital) and are separated by sutures and fontanels. Prevailing hypothesis suggests that abnormal development of the base of the skull creates exaggerated forces on the dura that act to disrupt normal cranial suture development. Dysfunctional osteoblasts or osteoclasts are not responsible for craniosynostosis.

Clinical Manifestations and Treatment

• •

Skull deformity that is a direct result of premature suture fusion. Palpation of the suture reveals a prominent bony ridge, and fusion of the suture may be confirmed by plain skull roentgenograms.

JIPMER–December 2018  183 Type of Head

Suture involved

Phenotype

Scaphocephaly (most common form)

Premature closure of the sagittal suture

• • •

Long and narrow skull. Prominent occiput, a broad forehead, and a small or absent anterior fontanel Difficulties during labor because of CPD Does not produce increased ICP or hydrocephalus neurologic examination of affected patients are normal

Frontal plagiocephaly 2nd common form more common in females

Premature fusion of a coronal and sphenofrontal suture

Unilateral flattening of the forehead, elevation of the ipsilateral orbit and eyebrow, and a prominent ear on the corresponding side

Occipital plagiocephaly more common in an immobile or handicapped child

Positioning during infancy or sclerosis of the lambdoid suture

Can cause unilateral occipital flattening and bulging of the ipsilateral frontal bone

Trigonocephaly

Premature fusion of the metopic suture

Keel-shaped forehead and hypotelorism and are at risk for associated developmental abnormalities of the forebrain.

Turricephaly

Premature fusion of the coronal and often sphenofrontal and frontoethmoidal sutures

Cone-shaped head

Kleeblattschädel deformity



•



•

• •

Skull that resembles a cloverleaf Prominent temporal bones, and the remainder of the cranium is constricted. Hydrocephalus is a common complication.

Premature fusion of only one suture rarely causes a neurologic deficit (sole indication for surgery is to enhance the child’s cosmetic appearance) Neurologic complications - hydrocephalus and increased ICP, are more likely to occur when two or more sutures are prematurely fused, in which case operative intervention is essential.

Genetic disorders associated with craniosynostosis



Crouzon Syndrome (autosomal dominant trait): • Shape of the head depends on the timing and order of suture fusion but most often is a compressed backto-front diameter or brachycephaly due to bilateral closure of the coronal sutures. • The orbits are underdeveloped, and ocular proptosis is prominent. • Hypoplasia of the maxilla and orbital hypertelorism are typical facial features



Apert Syndrome (sporadic condition, mutation of the FGFR2 gene) • Features in common with Crouzon syndrome + syndactyly of the 2nd, 3rd, and 4th fingers / toes • Facies tend to be asymmetric, and the eyes are less proptotic than in Crouzon syndrome • Premature fusion of multiple sutures, including the coronal, sagittal, squamosal, and lambdoid sutures • Have progressive calcification and fusion of the bones of the hands, feet, and cervical spine.



Carpenter Syndrome (autosomal recessive condition) • Produces kleeblattschädel skull deformity. • Soft-tissue syndactyly of the hands and feet is always present, and mental retardation is common. • Other associations - congenital heart disease, corneal opacities, coxa valga, and genu valgum.





Chotzen Syndrome (most prevalent / autosomal dominant trait) • Asymmetric craniosynostosis and plagiocephaly • Facial asymmetry, ptosis of the eyelids, shortened fingers, and soft tissue syndactyly of the 2nd and 3rd fingers.

184  TARGET JIPMER

Pfeiffer syndrome (Mutations of the FGFR1 gene located on chromosome 8): • Associated with turricephaly • Eyes are prominent and widely spaced, and the thumbs and great toes are short and broad • Partial soft tissue syndactyly Ans: (c) Scaphocepahly Ref: Nelson, Textbook of Pediatrics, 20th edition, Page 2917

13.



While treating a child with head injury by giving mannitol how much osmolarity should be maintained? (a)