Gastrointestinal Tract in the Aged [1 ed.] 9781612090191, 9781611225198

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Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

DIGESTIVE DISEASES - RESEARCH AND CLINICAL DEVELOPMENTS

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

GASTROINTESTINAL TRACT IN THE AGED

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Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

DIGESTIVE DISEASES - RESEARCH AND CLINICAL DEVELOPMENTS

GASTROINTESTINAL TRACT IN THE AGED

STEPHEN DH MALNICK EHUD MELZER Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

AND

SARI TAL EDITORS

————————————

Nova Biomedical Books New York Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com

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Library of Congress Cataloging-in-Publication Data Malnick, Stephen D. H. Gastrointestinal tract in the aged / authors, Stephen D.H. Malnick, Ehud Melzer, Sari Tal. p. ; cm. Includes bibliographical references and index. ISBN  (H%RRN) 1. Geriatric gastroenterology. I. Melzer, Ehud. II. Tal, Sari. III. Title. [DNLM: 1. Gastrointestinal Diseases. 2. Aged. 3. Gastrointestinal Tract. WI 140] RC802.4.A34M35 2010 618.97'633--dc22 2010041367

Published by Nova Science Publishers, Inc. † New York

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Contents

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Preface

vii

Chapter I

Epidemiology of the Elderly Gary Sinoff

1

Chapter II

The Physiology of GI Tract in the Aged Asif Bhutto

9

Chapter III

Gastrointestinal Motility Disturbances in the Elderly Christopher K. Rayner and Michael Horowitz

23

Chapter IV

Nutrition in the Elderly Yitshal N. Berner

43

Chapter V

Chronic Constipation in the Elderly Joseph Lysy

65

Chapter VI

Diseases of the Stomach in the Aged Huy Nguyen, Raziuddin Ali, Joshua Barocas and Marie L. Borum

79

Chapter VII

Small Bowel Diseases in the Elderly Bernd Lemos and Jörg C. Hoffmann

99

Chapter VIII

Disease of the Pancreas and Biliary Tract in the Elderly Henry Johnson and John Baillie

119

Chapter IX

Liver Diseases in the Elderly Yaacov Baruch

131

Chapter X

Inflammatory Bowel Disease in the Elderly Amir Klein, Yehuda Chowers and Rami Eliakim

151

Chapter XI

Diverticular Disease in the Elderly Adi Lahat and Simon Bar-Meir

181

Chapter XII

Cancer in the Geriatric Age: G-1 Cancer in the Aging Adi Shani

191

Index Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

197

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

Preface The elderly population is rapidly increasing in size as a result of the aging of the baby boomers following the Second World War. Since there is a greater morbidity and mortality with advanced age, it is not surprising that this group is becoming a major consumer of health care resources. Most of the organ systems of the body undergo significant changes during the aging process and the gastrointestinal system is no exception. The purpose of this book is to review the changes in the entire GI system as a result of aging and to provide a guide nto practicioners who are dealing with the care of the aged. Chapter I - The sociological changes of the world population are occurring rapidly not only in the more developed countries (MDCs) but also in the less developed countries (LDCs). At present, the world has over 6 billion persons and this number is expected to reach 10 billion within next 50 years, with the majority of the change occurring in the LDCs. In fact, by 2050 over half of the world’s population will be in eight countries, all LDCs except the United States of America. The greatest transformation occurring is the aging of the world’s population. Western Europe and North America now have about 14% of their population over the age of 65, which is expected to increase to 25% within 50 years. Even more alarming is the proportional increase in the eldest-old group over the age of 85. Concomitant with this aging phenomenon, is a greater expenditure on health as the elderly need more aid in their activities of daily living. The elderly presently utilize up to 30% of the medical services of a country and diseases of the gastrointestinal tract have become a major contributor to this burden. This chapter relates to the epidemiology of the elderly, relating also to the gastrointestinal tract. Chapter II - As the population of world is growing older there is a need for physicians to understand the physiological changes associated with aging in the gastrointestinal tract to help them better understand the mechanism of multiple co-morbidities affecting the graying population. The purpose of this chapter is to provide detailed overview of the different age related changes in the GI tract. Chapter III - The gastrointestinal tract is remarkable for the degree to which its motor function remains intact with healthy aging, while there appears to be a substantial decline in gastrointestinal sensory function. However, because gut motility is prone to be affected by a variety of co-morbidities that are prevalent in the elderly, or medications used to treat them, disordered gastrointestinal motor function occurs frequently. This chapter will focus on the esophagus and stomach, with relatively less emphasis on the small and large intestines, which are dealt with in more detail elsewhere. Particular attention is given to motor and sensory

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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viii

Stephen DH Malnick, Ehud Melzer and Sari Tal

function, rather than secretion or blood supply. The chapter does not discuss nutrition, constipation or fecal incontinence in depth, nor deal with the pancreas, biliary tree, cancer or pre-malignant conditions (eg. Barrett’s esophagus), which are the subject of other chapters. Chapter IV - The elderly population is growing with time in the developed as well as in the developing societies at a rate of about 5% a year. This population has higher morbidity then the general population. The elderly are characterized by changes in different physiological activities as well as multiple pathologies. Cellular function is based on hormones, cytokines and neurotransmitters acting through the cell’s receptors and altered cellular function. Dietary structure is considered as one of the components of health and wellbeing. Having a high morbidity together with a slower rate of cure, elderly are major consumers of nutrition support. It is important to differentiate between the role of nutrition as part of lifestyle, in aging and the role of nutrition in treatment of the sick elderly. Nutrition has an important role in the process of healthy aging, nevertheless aging has an impact on the nutrition of the person secondary to physiological changes. The recent developments in the technology of nutrition support give us the tools to supply every person with all nutrient compounds in different manners. The authors can modulate the dietary structure in any way that we think that can benefit the person. There are enriched solutions with different substances, that either bypass the swallowing mechanism in different ways supplying enteral nutrition or going parenterally directly to the circulation through different ports. Despite these various opportunities there are many questions about the efficacy of nutritional support in the elderly in certain conditions and an ethical debate regarding the indication with different opinions is current, questioning the medical indications, together with the techniques and the timing for the implementation of such support. Sarcopenia, a decline in muscle mass, is part of the aging process. The differentiation between low muscular mass resulting from diseaserelated starvation and that derived from different responses to disease consequent to the background effect of aging has has been recently determined. The role of the feeding process as part of the needs of the old person, reflecting empathy and psychosocial support, is becoming a more prominent part of the care of the elderly. Currently, the main challenge of clinical nutrition in the aged, is in the determination of the optimal time for intervention. Chapter V - Constipation occurs in all age groups but is more common in those older than 65 years (3). This age- specific increase in prevalence was observed in both whites and nonwhites in the U.S.A. Elderly patients tend to seek medical assistance for constipation more commonly than younger persons. Epidemiological studies show that up to 20% of community-dwelling and 50% of the institutionalized elderly, report symptoms of the disorder. Elderly patients most commonly describe constipation as excessive straining and hard stools rather than a decrease in stool frequency. Chapter VI - The elderly population presents unique difficulties in medical management and access to care. Polypharmacy is common and is associated with increased cost and potential drug-drug interactions. There is often limited data on adverse drug effects in elderly patients. Additionally, elderly individuals may have difficulty adhering to complex medication regimens. Regimens with numerous medications per day, varying frequencies, and instructions to avoid or take with food are more common in older patients and may be more difficult to manage. Chapter VII - Little and inconsistent data is available concerning the epidemiology of malabsorption in the elderly. Statements range from being an “uncommon problem” to a “major health problem” in the geriatric population. Information about the etiology of mal-

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Preface

ix

absorption in aged people discloses that half of the cases are related to small bowel disturbances. In the individual patient other causes of diarrhoea not involving the intestine must be considered, particularly pancreatic insufficiency, colon cancer, or biliary tract disease. Rarely intestinal parasites or obstruction of the intestinal lymphatic system turn out to be cause of diarrhea. Chapter VIII - Increasing numbers of the population are now surviving to an advanced age. Since the prevalence of hepatobiliary and pancreatic (HBP) diseases increase with age, gastroenterologists will be faced with an increasing number of patients with these disorders. Physicians have an arsenal of diagnostic and therapeutic tools to elucidate the etiology of HBP disorders and direct therapy as indicated. High-resolution computer tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) provide excellent diagnostic tools that the clinician may safely employ to delineate the extent of disease. Increasingly, therapeutic intervention is indicated and experts in the invasive fields of endoscopic retrograde cholangiopancreatography (ERCP) and interventional radiology must be called in. Chapter IX - With an aging population, chronic liver disease is becoming an increasingly significant cause of morbidity and mortality. The elderly population is different, not only because of the physiological changes occurring, but also because of issues such as cost benefit of treatments associated with life expectancy. The review will discuss some of the main liver diseases leading to liver transplantation today including HCV (viral hepatitis C), NASH (Non Alcoholic Steatohepatitis), HBV (viral hepatitis B) and AIH (Autoimmun Hepatitis) as well as issues of liver transplantation in the old age group. Chapter X - IBD in the elderly population is less studied and the literature on this subset of patients is incomplete. Most randomized clinical trials do not focus on this age group. Many decisions on management and treatment are therefore based on experience and information gathered from much younger cohorts, perhaps with different disease characteristics and behavior. This chapter will attempt to define the nature, clinical course and treatment of UC and CD in the patient over the age of 60 years. Chapter XI - Diverticulum of the colon is defined as a sac like protrusion of the mucosa through the muscular colonic wall. These diverticula are accurately pseudo (false) diverticula, since they contain only mucosa and submucosa covered by serosa, and not a full thickness projection. These protrusions typically occur where the vasa recta (blood vessels that supply the mucosa and submucosa) penetrate the bowel wall, thus making it more frail. The diverticulum's diameter is typically between 5-10 mm, though bigger diverticula can exist. The term diverticular disease of the colon applies to the presence of diverticula within the colon. Chapter XII - In the old aged, there are well known physiologic changes. These include deterioration in renal function, changes in bowel movement, limited bone marrow reserve and changes in cognitive function.In addition to a natural decline in physiological capabilities there are comorbid diseases which with the physiologic changes can alter the tolerance to chemotherapy. Changes of mental status and social situation can deeply affect the potential of treatment programs.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter I

Epidemiology of the Elderly Gary Sinoff* Head, Cognitive Clinic and Deputy Director Department of Geriatrics; Carmel Medical Center 7 Michal Street; Haifa 34362; Israel.

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Abstract The sociological changes of the world population are occurring rapidly not only in the more developed countries (MDCs) but also in the less developed countries (LDCs). At present, the world has over 6 billion persons and this number is expected to reach 10 billion within next 50 years, with the majority of the change occurring in the LDCs. In fact, by 2050 over half of the world’s population will be in eight countries, all LDCs except the United States of America. The greatest transformation occurring is the aging of the world’s population. Western Europe and North America now have about 14% of their population over the age of 65, which is expected to increase to 25% within 50 years. Even more alarming is the proportional increase in the eldest-old group over the age of 85. Concomitant with this aging phenomenon, is a greater expenditure on health as the elderly need more aid in their activities of daily living. The elderly presently utilize up to 30% of the medical services of a country and diseases of the gastrointestinal tract have become a major contributor to this burden. This chapter relates to the epidemiology of the elderly, relating also to the gastrointestinal tract.

Introduction Any textbook on the elderly will, initially, always have to relate to the aging of the general population and justifiably so. The issue starts with the defining of old-age. The classic definition relies on the chronological age, using 60 or 65 as the cut-off point, which is related somewhat to the age of retirement in the Western world. The question that crops up is that in some places such as Africa or Asia, accurate official recording of the actual birth date of the *

Gary Sinoff: Tel: +972-(0)4-8250559; Fax: +972 –(0)4- 8250548; E-mail: [email protected]

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

2

Gary Sinoff

person is lacking and therefore it is difficult to ascertain the true numbers of elderly. Also in many parts of the developing world, chronological age has little significance but rather the definition of old age relies on the societal requirements to have the capabilities to continue to function (usually interrelated with decreasing physical status), and in these countries old age is defined as 50 or 55 years. There have even been recommendations by organizations, such as the World Health Organization (WHO) to actually use this lower age of 50 years as the general definition of an aged person, in order to inform policy makers and program planners in the developing countries about the changes to be expected in the future [1]. For this chapter the classical chronological definition is used and the statistics will relate to persons over the age of 60 or 65 years. This chapter will relate to the epidemiology of the elderly in several aspects: the demographic changes in the world population, the demographic changes in the elderly population and, finally, relating to the gastrointestinal tract epidemiology in the elderly.

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Demographic Changes in the World Population The world has undergone changes in its demographic characteristics particularly over the last century. It took almost 50,000 years for the population of the Earth to reach 5 billion persons and the prediction is that within the next 50 years, by 2050, the world’s population will have doubled to almost 10 billion. This growth has come about not only due to a decrease in infant mortality but also related to an increase in the life span. Almost all of the growth is predicted to occur in the less developed countries (LDC ) with the population expected to enlarge from 5.3 billion in 2004 to 7.8 billion by 2050, whereas the more developed countries (MDC) will remain stable at about 1.2 billion [2]. When one examines the statistics, it becomes apparent that since the beginning of the present millennium in 2000 until 2008, the world’s population has grown at a rate of 76 million annually [3]. When one investigates the demographic changes in LDC, it indicates very rapid population growth in the coming years [4]. Up until the year 2050, the population in countries such as Afghanistan, Chad, Liberia, Uganda and many others is predicted to triple in numbers. By the year 2050 , the following eight countries: India, Pakistan, Democratic Republic of the Congo, Uganda, United States of America, Ethiopia and China (listed according to their contribution to the population growth), will account for over half of the world’s population [5]. There are expected to be changes in the fertility rates world-wide with a steady decrease in the rates from 2.6 children per woman in 2004 to just over 2 children per woman in 2050 but the bottom line is that the increase in the world’s population is inevitable [6]. When one looks into the differences between MDC and LDC, the explosion of the demographic changes becomes even more evident. In the MDC, the fertility rate now stands at 1.56 children per woman and actually is expected to rise to about 1.84 children per woman over the coming decades. Yet in the LDC, the fertility rate is expected to drop from 5 children per woman to 2.57 children per woman by 2050 but still the rate is well above the numbers for the MDC. In figure 1 below, the differences of the fertility rates for 1998 in different countries are shown. More Developed Countries such as in Western Europe and North America have reported rates

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Epidem miology of the Elderly

3

off 2 or less ch hildren per wooman but Lesss Developed Countries, esspecially in Africa, A have ovver 5 children per woman.

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Fiigure 1. Total Fertility F Rates inn 1998 [3].

Between th he years 2000 and 2004, the fertility rates r remaineed above 5 chhildren per woman in 35 of w o the 148 lesss developed countries c in thhe world, moostly marked in i the least deeveloped coun ntries. On thee other hand, in some 23 developing d couuntries includding China, annd in 44 MDC C, the fertility rates are actuaally below-repplacement leveels of the popuulation [2]. The end resultt is that less and less chiildren are being born in these t countriees and the t populatioon pyramid (Figure ( 2). poopulation is aging resultiing in the innversion of the Innterestingly, itt shows that by b 2050 the LDC L will havee a pyramid much m as the MDC M had in 19995. One can only surmise that in anotheer 50 years aft fter that, the LDC L will havee a pyramid w a dispropo with ortionate numbber of elderly. The chang ging fertility rates r are alsoo accompaniedd by changess in expectedd life span, inncreasing the aging of the world’s popuulation. Todayy the life expectancy rates vary from cllose to 75 yeaars in the moree developed coountries (MDC C), with Japann having ratess as high as 855.5 years for women and 78.7 years foor men, to levvels as low as a less than half h in less deeveloped coun ntries (LDC), such as Ethioopia. On the other o hand, thhe life expectaancy in the LDC, which is currently as loow as 50 yearrs, is anticipateed to rise to 66 years by 20550 [7]. The n aging of the population inn the LDC by the t middle of this century. efffect will be an

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Gary Sinoff

Key: MDCs = More Developed Countries LDCs= Less Developed Countries. Figure 2. Population pyramids in (a) 1995 and (b) prediction for 2050. Population in each group is expressed as a percentage of the total population in a region [8].

Demographic Changes in the Elderly Population The transformation in the demographic characteristics of the world’s population when relating to the elderly is even more astounding. In 1995, it was estimated that 371 million persons were over the age of 65, constituting 6% of the world’s population, with differing percentage rates from region to region and by 2006, 485 million persons were over the age of 65 constituting about 7% of the world’s population [9]. Europe is now bordering on 14% of their population over 65, North America 13%, but in Latin America and Asia the rates are about 5% and Africa only 3%. The percentages are expected to rise in the coming years and it is estimated that by 2025, many countries will have about 20% of their population over the age of 65 years with Japan leading the list with an estimated 29.3% of the population over 65

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Epidemiology of the Elderly

5

[10]. By the year 2004, the global population over 65 years was estimated to be 672 million and the predictions are that by 2050, 1.9 billion persons will be over the age of 65. By 2006, almost half of the world’s elderly were living in 5 countries: India, China, United States of America, Japan and Russia. The more worrying statistics are that the old-oldest (those over the age of 85) are proportionately increasing more rapidly than any other subgroup of those over 65 and this is a phenomenon occurring across the whole world (Table 1).

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Table 1. Distribution of the Elderly in Different Countries in 2006 Countries

Population (millions)

% aged 65+

Sweden USA UK Japan Kazakhstan China

9 257 58 124 17 1130

17.6 12.7 15.7 13.0 6.0 5.6

% of those aged 65+ 65-74 75-84 53.9 35.6 56.8 32.9 55.8 33.9 60.0 32.1 60.3 32.2 70.5 25.8

85+ 10.5 10.3 10.2 7.9 7.5 3.7

From table 1, it is shown that in MDC countries such as Sweden, USA and UK the oldest-old (over 85) are over 10% of those aged 65 and the numbers are expected to grow in the coming years. In fact, this age group (85+ years) numbers 86 million now and is expected to increase by 4.6 times to 394 million in the next 50 years. Though in LDC the percentage at present is low in 2005, about 7.5% of the elderly, it is expected to rise above the average for the world, increasing by 6.6 times resulting in the absolute numbers escalating from 42 million to 278 million by 2050. The end-point is that by the middle of the present century, the majority of the oldest-old will be found residing in the less developed countries. On examining the sociological changes over time, the nuclear-family model of parents and children without the grandparents living in the same household has become the norm rather than the previous extended-family model. This has become apparent even in countries with a strong tradition of filial piety such as Japan. In many Western countries, between 3040% of the elderly are living alone. In Denmark, over 50% of the elderly are living alone, Germany and Sweden report that 40% of the elderly are living alone and in the UK the numbers living alone have increased from one in eight of the elderly after the Second Word War to one in three recently (33%). The aging of the population has also had a major effect on health expenditures with 9.8% of the gross domestic product (GDP) being spent on health care in 1995 [11]. The expenditures can only increase as one realizes that with the aging of the population there is a concomitant increase in disabilities. In the USA, around 40% of persons over 60 have some disability and the rates rise exponentially with increasing age groups, 240 per thousand in the age group 60-69, 408 per thousand in the age group 70-79 and 714 per thousand in the oldest old age group 80+. Using actuarial models, the health expenditure has been calculated to increase to 27.1% of GDP by 2050 [11]. The transformation has become even more apparent with those over the age of 80 in the oldest-old age group. When one realizes that the decline in the function of this oldest-old age group has rates as high as 39% for those 80+ compared to 7% to those in the age group

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Gary Sinoff

between 65-74, one becomes aware of the enormity of the problem of the aging of the population [2].

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Gastrointestinal Tract Epidemiology in the Elderly The population explosion, especially when relating to the aging of the world population, has resulted in the need to address the changes in the physiology of the elderly and to study the disease processes occurring as the population ages. In the Western world, the elderly have now become major consumers of medical services and are reported to use about 30% of the medical services of a country and constitute almost 40% of the admissions in tertiary care hospitals [12]. In Israel, the oldest-old group has a rate of 1,139 per thousand visits to the family physician compared to the national rate of 644 per thousand persons (which also includes children) [9]. So the burgeoning effect of the aging population in a MDC becomes apparent. Diseases of the gastrointestinal tract in the elderly have become a major contributor to the burden on the health services. Increasing numbers of the elderly are turning to physicians with unexplained gastrointestinal complaints and disorders and it is reported to be the third major reason for visits to the primary physician in the elderly in Western countries [13]. Amongst the disorders is also malnutrition, which is stated to occur in up to 10% of the elderly admitted to hospital. This is related to physiological changes in the mouth, the intestinal, and the pancreatic tract and, in fact, in the whole gastrointestinal tract [14], but is also due to sociological changes in the socioeconomic status of the elderly. This emphasizes the necessity to relate to disorders in the elderly on a multi-faceted approach combining the physiological and social aspects of old age together with the pathological aspects of aging. Often these changes are inevitable and the physicians of today need to be aware of the normal physiological changes occurring as well as the disease processes in the elderly. Physicians should therefore seek and actively treat disorders in the gastrointestinal tract and not just ascribe the changes to old age. These physiological changes in the elderly in the gastrointestinal tract are varied ranging from disturbances in motility, to changes in the structure of the mucosa, and to loss of reserve to adapt to situations of stress [15]. The end result of these processes is not only the development of common disorders in the elderly such as constipation, bleeding from the gastrointestinal tract or dysphagia, but also the loss of functional status, loss of independence and finally decreases in quality of life in the vulnerable older population [16]. Though the gastrointestinal diseases in the elderly were in the past neglected by clinicians and researchers [17], the demographic changes expected in the general population and, especially in the elderly, has created a need for a textbook on gastrointestinal disorders in the elderly.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Epidemiology of the Elderly

7

References [1]

[2]

[3] [4] [5] [6]

[7] [8]

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[9] [10]

[11]

[12] [13] [14] [15] [16] [17]

World Health Organization (WHO). Older Adult Health and Aging in Africa. Minium Data Set Project 2008. [Internet]. [Retrieved Feb 20, 2009 from WHO: Official Site Web site]. Available from :http://www.who.int/healthinfo/survey/aging/en/ World Health Organization (WHO). The Global Burden of Disease 2006. [Internet]. WHO, Geneva. [Retrieved Mar 20, 2009 from WHO: Official Site Web site]. Available from: http://www.dcp2.org/pubs/GBD U.S. Census Bureau. International Data Base 2008.[Internet]. [Modified 2008 Dec 15; cited 2009 Feb 20] Available from: http://www.census.gov/ ipc/www/idb/ Lunenfeld B. An aging world – demographics and challenges. Gynecol Endocrinol. 2008 Jan;24(1):1-3. Population Reference Bureau. 2008 - World Population Highlights. Popul Bull. 2008 Sep; 63 (3). Availabe from: http://www.prb.org/pdf08/63.3highlights.pdf. World Health Organization (WHO). World Health Statistics, 2007. [Internet]. [Retrieved February 20, 2009 from WHO: Official Site Web site]. Available from: www.who.int/whosis/en/ Babel B, Bomsdorf E, Schmidt R. Future life expectancy in Australia, Europe, Japan and North America. J Popul Res. 2007;24(1):119-131 Lutz, W. In The Future Population of the World. What can we assume today? (Ed. Lutz, W.) Earthscan, London, UK. 1996. 253-277. JDC-ESHEL. The Elderly in Israel: Statistical Abstract 2007. Eshel, Jerusalem. 2008. United Nations, Department of Economic and Social Affairs, Population Division World Population Prospects: The 2006 Revision. [Retrieved Feb 20, 2009 from UN, Official Site Web site]. Available from: http://www.un.org/esa/population/ publications/wpp2006/ wpp2006_aging.pdf Mayhew, L.D. Health and Elderly Care Expenditure in an Aging World. IIASA Research Report RR-00-021. 2000. [Internet]. [Retrieved February 20, 2009 from ILASA (International Institute for Applied Systems Analysis] Availabe from: http://www.iiasa.ac.at/Admin/ PUB/Documents/RR-00-021.pdf Demers M. Factors explaining the increase in cost for physician care in Quebec’s elderly population. CMAJ. 1996 Dec;55 (11):1555-1560. Durazzo M, Premoli A, Bo S, Pellicano R. Gastrointestinal problems in the elderly. Panminerva Med 2007 Dec;49(3): 151-158. Lovat LB. Age related changes in gut physiology and nutritional status. Gut 1996 Mar;38: 306-309. Salles N. Basic mechanism of the aging gastrointestinal tract. Dig Dis 2007 Apr;25(2): 112-117. Crane SJ, Talley NJ. Chronic gastrointestinal symptoms in the elderly. Clin Geriatr Med. 2007 Nov ;23(4):721-734. Holt PR. Intestinal malabsorption in the elderly. Dig Dis. 2007 Apr;25(2):144-150.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter II

The Physiology of GI Tract in the Aged Asif Bhutto Assistant Professor of Internal Medicine Division of Geriatric Medicine Saint Louis University St Louis, Missouri, U.S.

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Purpose of Review As the population of world is growing older there is a need for physicians to understand the physiological changes associated with aging in the gastrointestinal tract to help them better understand the mechanism of multiple co-morbidities affecting the graying population. The purpose of this chapter is to provide detailed overview of the different age related changes in the GI tract.

Highlights Gastrointestinal Tract changes with aging are variable and affect GI physiology and anatomy in different ways. Decreased salivary secretion, altered taste perception, changes in gastric fundal compliance and gastric emptying rates predispose elderly population to experience anorexia of aging and weight loss. Impaired relaxation of the lower esophageal sphincter leads to higher incidence of aspiration syndromes and further complicates the hospital course of elderly people admitted with pneumonia. Changes in secretion of different GI hormones leads to conditions like post-prandial hypotension and abnormal glucose absorption. Drug metabolism is also affected due to changes in the activity of cytochrome P450 enzyme related drug metabolism leading to increased incidence of adverse drug reactions in elderly patients. The incidence of infections like C. Difficile in elderly population is increasing due to age related changes in commensal bacteria in the gut.

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Summary Aging associated changes in gut physiology plays a major role in anorexia of aging, weight loss, early satiety, and frailty complicating the course of other co-morbid illnesses

Introduction The population of world is growing older. Over the past decade there has been a significant change in population dynamics with an increase in the number of patient population aged 80 and 90 years old. This change in population dynamics is attributed to improved overall environmental conditions and better health care system. There has been increased identification of multiple factors related to increased morbidity and mortality in older people. The number of elderly population is estimated to increase by 75 million by 2030. Other important factors for increases in baby boomer population are better survival rates and lower birth rates making health care needs of elderly people more challenging. As the population ages the incidence of malnutrition and weight loss increases because of cooccurrence of physiological processes such as anorexia of aging especially in elderly people living in long term care settings. Also as people age they feel less hungry and experience early satiety due to various age related phenomenon.

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Alteration in Chemosensory Function Aging affects chemosensory function in various ways. The changes in sense of smell and taste can result in decreased appetite and consumption of food changing energy requirements and over all well being of older folks. There is reduced sense of olfaction associated with aging [1]. Studies have shown that aging is associated with changes in smell detection, smell discrimination, and odor identification [2]. Histological changes occurring in olfactory epithelium include replacement of olfactory epithelium with respiratory epithelium [3]. Some Animal studies have shown thinning of olfactory epithelium, decrease in the number of olfactory neural cells, and alteration of olfactory mucosal border [4]. Human studies have indicated that these changes can affect both sexes, but women appear to identify odor better than men at all ages [5] These changes are mostly the combined result of physiologic changes as well as environmental insults affecting the olfactory tract. Chronis sinusitis, seasonal allergies, and cigarette smoking all contribute to reduced smell identification. Neurodegenerative diseases like Alzheimer’s, Parkinson’s disease and vascular dementia patients tend to experience physiologic as well as pathologic anorexia of aging related to loss of olfactory sensation further complicating weight loss and frailty observed in long term care residents with these chronic disorders. Several studies have demonstrated that Alzheimer disease patient have an accumulation of abnormal tau protein in the olfactory mucosa similar to changes seen in Alzheimer patient brain lesions [6]. Parkinson’s disease patients suffer significant changes in sense of smell which may be related to accumulation of Lewy bodies in olfactory bulb and lower brain stem of patient causing marked problems with odor recognition [7].

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Sense of taste is a major contributor to eating habits and andplays a major role in the process of satiation. Aging has been shown to be associated with decline in all four taste sensation [8]. The recognition threshold of all four sensations of taste are reported higher in elderly population in comparison to younger people[9]. Metabolic conditions like diabetes and mineral deficiencies such as zinc deficiency can also lead to altered taste perception of foods leading to malnutrition and weight loss seen in the population [10]. These effects seem to be minor. The different chemosensory changes associated with aging are summarized in table below Table 1. Changes in Chemosensory Sensation with Aging OLFACTION

TASTE SENSATION

Decreased sense of olfaction

Decline in all four taste senses

Decreased smell identification

Decreased taste intensity perception

Decreased smell discrimination Altered olfactory epithelium Decrease in the number of olfactory cells Decreased odor threshold

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Physiologic Anorexia of Aging: Physiological or Patholigical Process The concept of physiologic anorexia of aging is complex and has been investigated in detail [figure 1]. Physiological as well as pathological factors have been implicated in the pathogenesis of age related loss of appetite leading to cachexia and frailty seen in older adults. It is estimated that more than 5 million people In USA suffer from cachexia[11]. People experiencing Cachexia due to chronic illnesses like congestive heart failure have adverse outcomes when compared to people with chronic disease with-out cachexia [12]. Physiologic anorexia of aging on the other hand is the result of multiple changes seen in the GI tract with aging. Changes in the olfactory nasal mucosa, decreased sense of smell, altered antral emptying time, altered compliance of stomach musculature, abnormal secretion of different GI hormones, and early satiety related to abnormal CCK secretion all contribute to decreased appetite and weight loss experienced by aging population. Some studies seem to indicate that these changes are more marked in men than women. With aging there is impaired ability to identify different odors often leading to decreased desire to consume food. These changes are more marked in people 50 years or older with some studies showing incidence of olfactory impairment in up to 60% to 80 % in people 80 years or older [13]. Most of these changes are physiological as evidenced by changes in odor detection and identification as part of normal aging process but co-morbid disease processes plays an important part. Viral infections, medication use, toxin exposures, and smoking can all

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contribute to damage of olfactory epithelium resulting in reduced stimulation of olfactory receptors making food less desirable and enjoyable. Taste sensation declines with aging. Changes occur in all four basic taste types [14]. Aging has been associated with altered taste bud membrane function leading to altered food choices [15]. Older persons seems to loose the increased sensitivity of tongue tip to NaCl in comparison to younger people [16]. Zinc deficiency have been associated with changes in taste sensitivity as seen in diabetic patient, liver disease and with the use of diuretics[17]. Decreased salivation, excessive smoking, peri-odontal disease, and viral infections can contribute to altered taste sensitivity seen in aging population Changes in pharyngeal esophageal motility include prolonged peristaltic phase and decreased clearing of food in stomach causing increased incidence of dysphagia observed in elderly population [18] With aging there is decreased esophageal peristalsis and decreased trans-pyloric flows [19] contributing to increased incidence of aspiration pneumonia. Aging is associated with decreased compliance of fundus part of stomach caused by decreased nitric oxide levels after food ingestion [20] leading to early satiety seen in older people. All these changes can contribute to less food consumption and anorexia. Changes in GI hormone secretion are evidenced by increased levels of CCK in elderly after food consumption. CCK is released in the duodenum after consumption of fat, and the levels of CCK have been observed to be higher in elderly population [21][22]. CCK is considered a satiety hormone and is potent inhibitor of feeding in human and animal models [23]. Aging males have decreased levels of testosterone which leads to increased levels of letpin, which is a potent satiety hormone explaining the increased incidence of anorexia of aging seen in elderly males in comparison to females [24][25][26]. The effects of neuropeptides on gastrointestinal tract are still been investigated and have received attention as they seem to exert there effects centrally as well as peripherally. Some of the neurotrasmitters working centrally includes neuropeptide Y, the orexins, ghrelin, CCK, and noradrenaline. Research has demonstrated that most of the actions of neuropeptide Y are dependent on nitric oxide levels which seem to be declining with age contributing to anorexia of aging seen in elderly population [27][28][29]. The incidence of weight loss and malnutrition is higher in aging population residing in nursing homes as well as in community and it is important for physicians taking care of these elderly individuals to understand the basic mechanisms leading to the development of these complicated geriatric syndromes. It is also important to understand that physiologic anorexia of aging places elderly people at risk for falls, complicated post operative recovery, delayed wound healing, increased mortality risk , and possible hip fractures by contributing to weight loss, cachexia and sarcopenia seen in frail elderly [30][31][32]. The pathological causes of weight loss in elderly needs to be treated carefully as the incidence of weight loss related to depression, cancer, and medication use is higher in institutionalized elderly population and can be potentially reversible if underlying pathology is treated.

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Figure 1. Overview of Anorexia of Aging [CCK= cholecystokinin].

Post Prandial Hypotension The history of postprandial hypotension dates far back to 1977 when it was reported in Parkinson disease patients. Postprandial hypotension is defined as a drop in systolic blood pressure after eating heavy meals especially carbohydrate rich leading to syncope or near syncope. It is an under recognized cause of syncope or near syncope in the community or institutionalized elderly population and seem to affect people with or without evidence of autonomic failure. The drop in blood pressure occurs after 30-90 minutes of eating and is thought to occur due to the release of calcitonin related peptide causing vasodilatation in peripheral vasculature [33]. The onset of symptoms is both dependent on the amount of carbohydrate as well rapid ingestion of meals as observed in certain studies [34][35]. The symptoms of postprandial hypotension range from dizziness, lightheadedness, angina, syncope, and falls. Postprandial hypotension is associated with increased mortality in nursing home residents. The symptoms of postprandial hypotension seem to improve with the use to alpha-glucosidase inhibitors like acarbose, which cause increase in the levels of glucagon like peptide 1 resulting in changes in gastric emptying [36]. The incidence of postprandial hypotension is reported higher in patients with diabetes mellitus with evidence of autonomic dysfunction.

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Silent Aspiration Syndromes Aging has been associated with changes in phases of swallowing leading to higher incidence of aspiration pneumonia seen in elderly population. This silent aspiration syndrome further predisposes elderly population to risk of developing bacterial or viral pneumonia. This risk is complicated by weak cough reflux seen in elderly people. Oropharyngeal and gastrointestinal motility changes further predispose to the aspiration of gastric contents into the bronchial tree [37]. Changes in swallowing and the resultant dysphagia occur frequently in elderly population. Decreased salivary production, impaired tongue muscle movements, increased oral transit times, and changes in dentition lead to pocketing of food in mouth leading to ineffective swallowing and resultant dysphagia [38][39]. These changes are further complicated if there is underlying memory problem such as dementia of the Alzheimer’s type leading to forgetfulness to swallow food. This can result in severe malnutrition observed in demented patients living in long term care settings. Other changes in pharyngeal swallowing mechanisms include decreased amplitude of pharyngeal peristalsis [40], changes in transsphincteric pressures, and changes in relaxation of lower esophageal sphincter [41] in response to food ingestion. All of these pharyngeal changes can contribute to the increased incidence of silent aspiration seen in aging population.

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Gastrointestinal Motility Changes in Aging Gut Knowledge about the physiological changes in gastro-intestinal motility is the key for understanding the impact of the aging gut on different aging related gastrointestinal complications as summarized in Table 2. Geriatric syndromes like weight loss, malabsorption, and constipation are common in aging people and can have a significant impact on quality of life and can lead to wide use of medical resources. Weight loss in elderly is common and is associated with decreased functional status, increased rates of hip fracture, institutionalization, and increased mortality [42][43][44]. Changes in esophageal motility include decreased esophageal peristalsis, decreased transpyloric flows, and reduced peristaltic efficiency [45][46].these changes can contribute to prolonged duration of acid reflux seen in older people [47]. Gastro-intestinal motility changes can lead to delayed gastric emptying for larger meals in elderly population [48][49] which can contribute to poor food intake seen in later life. Colon transit times have been noted to be increased in elderly population [50] possibly leading to increased incidence of constipation seen in residents of long term care settings. The incidence of fecal incontinence is reported to be 13% in community living elderly [51]. The increased incidence of fecal incontinence in institutionalized elderly is partly related to co-morbid illnesses like dementia syndromes, constipation, and certain drugs but also related to certain physiological changes like decreased anal sphincter tone which is more marked in women [52] and changes in thickness of internal anal sphincter.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Table 2. Summary of Gastrointestinal Motility Changes PHARYNGOESOPHAGEAL MOTILITY Prolongation of the oropharyngeal phase

GASTRIC MOTILITY

COLONIC MOTILITY

Reduced rate of gastric emptying

Prolongation of colon transit times

Reduced peristaltic velocity

Decline in the adaptive fundal compliance

Reduction in anal canal squeeze pressure

Decreased frequency of peristaltic contractions

Lower mean basal pressures in colon

Reduced peristaltic efficiency Altered upper esophageal sphincter pressure Delayed opening of the upper esophageal sphincter Reduced lower esophageal sphincter pressure

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Changes in Gastric Mucosa, Acid Production, and Gut Flora Knowledge about the physiological changes in the gastric mucosa, acid production, and gut flora helps us to better understand the increased incidence of certain infectious and noninfectious diseases prevalent in elderly population. Aging is associated with a decrease in the levels of PGE2 and PGF2 levels [53] predisposing to increased susceptibility for mucosal damage. The incidence of atrophic gastritis is reported higher in elderly. Thus elderly population have an overall increased incidence of H Pylori infection with prevalence rates of 40% to 60 % in asymptomatic individuals and about 70% in people with underlying duodenal ulcer disease [54][55]. The incidence is even higher in people living in long term care settings with duration of stay being a strong predictor for acquiring the disease [56][57]. Mucosal cell atrophy further increases the risk of other fungal and bacterial infections The physiological changes in gut micro-flora ranges from a decline in gut microorganism like bifidobacteria [58] with resultant increase in entero-bacteriace species[59]. These changes in gut flora can contribute to higher incidence of C Difficille infection seen in elderly population [60][61][62]. The other risk factors associated with development of C Dificille infection in elderly is prolonged hospital stay, excessive antibiotic usage, diverticular disease, and constipation. The increases in gut bacterial load contributes to the development of malnutrition, sarcopenia, and weight loss seen in elderly people with chronic diseases as the gut bacteria secretes lipopolysacchrides causing increased cytokine related activity [63][64].

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Intestinal Absorption Changes in intestinal absorption with aging are minimal with most of them complicated by co-morbid illnesses leading to mal-absorption of carbohydrates , vitamins and mineral. The absorption of fats and proteins seems to be unaffected in large part [65]. Much of the effects of aging on intestinal absorption are summarized in Table 3. Some of the significant changes associated with effects on overall health outcomes are discussed briefly in the next few paragraphs. Table 3. Effects of Aging on Absorption of Nutrients

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Nutrient Protein Fat Carbohydrate Vitamin B12 Vitamin D Calcium Vitamin A Zinc Magnesium Iron

Effects None None Possible decrease absorption Decreased with atrophic gastritis Decreased with malnutrition Decreased absorptio Increased absorption Decreased absorption Decreased absorption Decreased absorption

Vitamin D deficiency has been associated with muscle weakness, increased incidence of falls, increase incidence of hip fractures [66]. The higher incidence of vitamin D deficiency is the result of decreased absorption with aging in the gut as well as lack of sun exposure especially in people residing in nursing homes Vitamin B12 is mainly absorbed in the small intestine. There is no direct effect of aging on intestinal absorption of B12 but reduced gastric acid as seen in cases of achlorhydria is the causative factor for reduced absorption in most of the cases. Iron absorption is decreased with aging [67]. The association of chronic diseases such as cancer, renal disease, and chronic infections causes an increase in the levels of circulating cytokines like IL-6 with resultant mixed iron deficiency anemia and anemia of chronic disease [68].

Aging Liver: Regeneration Capacity and Effects on Drug Metabolism The changes in liver size, function and regeneration capacity with advancing age are significant and should be kept in mind when prescribing pharmacotherapy to older individuals as the altered activity of cytochrome enzyme system can have meaningful effects on drug absorption and elimination and subsequent side effects. The changes in liver weight are more marked in women than men with liver weight reduction of up to 14.3% in women and 6.57% in men [69]. Aging is associated with decreased ability of hepatic cells to regenerate in response to metabolic insults [70]. There are decreases in smooth endoplasmic reticulum

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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cells, decreased activity of liver microsomal enzymes [71][72]. There is a decline in mitochondrial volume in hepatocytes as well as decreased blood flow to hepatic cells [73]. Albumin synthesis decreases with aging. This effect is more marked in people who have chronic inflammatory condition with persistent cytokine activation [74]. Studies in some animal models have shown that regeneration capacity of liver to toxic insults is less in aged mice in comparison to young mice [75][76] explaining the time taken by older people to recover from environmental and toxic insults to liver. The liver plays a critical role in the metabolism and elimination of drugs through cytochrome P450 enzyme system. The activity of phase 1 reactions has been shown to be decreased in aging males as compared to fewer changes in females [77]. No changes in phase 2 reactions have been observed in the aging population.

Pancreatic Changes Observed with Aging: Effect on Carbohydrate Metabolism

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Aging is associated with changes in pancreatic endocrine function as well morphological changes. There is increase in the amount of fibrotic changes in pancreatic ducts and lobules causing pancreatic duct narrowing [78][79]. The amount of pancreatic secretions decreases but the effects are minimal on intestinal absorption [80]. The metabolism of carbohydrate is altered in aging people as evidenced by increased glucose intolerance seen in older people. Islet cell function decreases [81] with resultant decline in insulin secretion observed in animal models and humans [82][83]. The decrease in islet cell functioning leads to the development of late onset diabetes which is a combination of insulin deficiency and insulin resistance seen in elderly [84].

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[11] Morley JE, Thomas DR, Wilson MM. Cachexia: pathophysiology and clinical relevance. Am. J. Clin. Nutr. 2006 [12] Anker et al wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997 [13] Murphy C., Schubert C.R., Cruikshanks K.J., et al: Prevalence of olfactory impairment in older adults. J. Am. Med. Assoc. 288. 2307-2312.2002 [14] Weiffenbach JM, Cowart BJ, Baum BJ. Taste intensity perception in aging. J. Gerontol. 1986 [15] Sternini C, Anselmi L, Rozengurt E. Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr. Opin. Endocrinol. Diabetes Obes. 2008; [16] Matsuda T, Doty RL. Regional taste sensitivity to NaCl: relationship to subject age, tongue locus and area of stimulation. Chem. Senses. 1995 [17] Morley JE. Micronutrient status in diabetes mellitus. Am. J. Clin. Nutr. 1987 [18] Grande et al, deterioration of esophageal motility with age, Am. J. Gastroenterology, 1999 [19] O Donovan et al, Effect of Aging on Transpyloric Flow, Gastric Emptying, and Intragastric Distribution In Healthy Humans—Impact on Glycemia, digestive diseases and sciences April 2005 [20] Morley JE, Kumar VB, Mattammal MB, et al. Inhibition of feeding by a nitric oxidesynthase inhibitor: effects of aging. Eur. J. Pharmacol. 1996 [21] McIntosh et al. Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men. Am. J. Gastroenterol. 2001 [22] MacIntosh et al. Effects of age on concentrations of plasma cholecystokinin, glucagonlike peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am. J. Clin. Nutr. 1999 [23] McIntosh CG, Morley JE, et al. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging. J. Clin. Endocrinol. Metab. 2001 [24] Wilson MM, Morley JE. Aging and energy balance (review). J Appl Physiol 2003 [25] Rolland Y, Kim MJ, Gammack JK, et al. Office management of weight loss in older persons. Am. J. Med. 2006 [26] Morley JE, Perry HM 3rd, Baumgartner RP, et al. Leptin, adipose tissue and aging, is there a role for testosterone? J. Gerontol. A Biol. Sci. Med. Sci. 1999 [27] Morley JE, Kumar VB, Mattammal MB, et al. Inhibition of feeding by a nitric oxide synthase inhibitor: effects of aging. Eur. J. Pharmacol. 1996 [28] Morley JE, Flood JF. Evidence that nitric oxide modulates food intake in mice. Life Sci. 1991 [29] Farr SA, Banks WA, Kumar VB, et al. Orexin-A-induced feeding is dependent on nitric oxide. Peptides. 2005 [30] Cornoni-Huntley JC, Harris TB, Everett DF, et al. An overview of body weight of older persons, including the impact on mortality. The National Health and Nutrition Examination Survey I—Epidemiologic Follow-up Study. J. Clin. Epidemiol. 1991

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[31] Payette H, Coulombe C, Boutier V, Gray-Donald K. Nutrition risk factors for institutionalization in a free-living functionally dependent elderly population. J. Clin. Epidemiol. 2000 [32] Ensrud KE, Ewing SK, Stone KL, Cauley JA, Bowman PJ, Cummings SR. Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J. Am. Geriatr. Soc. 2003 [33] Jones KL, O’Donovan D, Russo A, et al. Effects of drink volume and glucose load on gastric emptying and postprandial blood pressure in healthy older subjects. Am. J. Physiol. Gastrointest. Liver Physiol. 2005 [34] Jansen RW, Lipsitz LA. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann. Intern. Med. 1995 [35] Edwards BJ, Perry HM 3rd, Kaiser FE, et al. Relationship of age and calcitonin gene related peptide to postprandial hypotension. Mech. Aging Dev. 1996 [36] Lee A, Patrick P, Wishart J, et al. The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics. Diabetes Obes. Metab. 2002 [37] Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest. 2003 [38] Steele CM, van Lieshout PM. Does barium influence tongue behaviors during swallowing? Am. J. Speech Lang. Pathol. 2005 [39] Connor N, Konopacki R. Alterations in contractile properties of tongue muscles in older rats. Ann. Otol. Rhinol. Laryngeal. 2005 [40] Tracy JF, Logemann JA, Kahrilas PJ, et al. Preliminary observations on the effects of age on oropharyngeal deglutition. Dysphagia. 1989 [41] Meier-Ewert HK, Van Herwaarden MA, Gideon RM, et al. Effect of age on differences in upper oseophageal sphincter and pharynx pressures between patients with dysphagia and control subjects. Am. J. Gastroenterol. 2001 [42] Cornoni-Huntley J.C., Harris T.B., Everett D.F., et al: An overview of body weight of older persons, including the impact on mortality. The National Health and Nutrition Examination Survey I—Epidemiologic Follow-up Study. J. Clin. Epidemiol. 1991 [43] Payette H., Coulombe C., Boutier V., Gray-Donald K.: Nutrition risk factors for institutionalization in a free-living functionally dependent elderly population. J. Clin. Epidemiol. 2000 [44] Ensrud K.E., Ewing S.K., Stone K.L., Cauley J.A., Bowman P.J., Cummings S.R.: Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J. Am. Geriatr. Soc. 2003 [45] Grande L, Lacima G, Roz E, et al. Deterioration of esophageal motility with age. Manometric study of 79 healthy subjects. Am. J. Gastroenterol. 1999 [46] Ren J, Shaker R, Kusano M, et al. Effect of aging on secondary esophageal peristalsis: presbyesophagus revisited. Am. J. Physiol. 1995 [47] Anggiansah R, et al. Effects of age on gastroesophageal junction, esophageal motility and acid reflux disease. Clin. Gastroenterol. Hepatol. 2007 [48] Brogan A, Loreno M, Catalano F, et al. Radioisotopic assessment of gastric emptying of solids in elderly subjects. Aging Clin. Exp. Res. 2006 [49] Chatterton BE, et al. Changes in gastric emptying rates with age. Clin. Sci. 1984 [50] Sarma SK. Physiology and pathophysiology of colonic motor activity. Dig. Dis. Sci. 1999 [51] Tariq SH. Geriatric fecal incontinence. Clin. Geriatr. Med. 2004

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[52] Rociu E, Stoker J, Eigkemans MJ, Lameris JS. Normal anal sphincter anatomy and ageand sex-related variations at high-spatial-resolution endoanal MR in aging. Radiology. 2000 [53] Goto H., Sugiyama S., Ohara A., et al: Age-associated decreases in prostaglandin contents in human gastric mucosa. Biochem. Biophys. Res. Commun. 1992 [54] Pilotto A, Malfertheiner P. Review article: an approach to Helicobacter pylori infection in the elderly. Aliment Pharmacol. Ther. 2002 [55] Pilotto A, Salles N. Helicobacter pylori infection in geriatrics. Helicobacter. 2002 [56] Regev A, Fraser GM, Braun M, et al. Seroprevalence of Helicobacter pylori and length of stay in a nursing home. Helicobacter. 1999 [57] Davidovic M, Svorcan P, Milanovic P, et al. Specifics of Helicobacter pylori infection/NSAID effects in the elderly. Rom. J. Gastroenterol. 2005 [58] Hopkins MJ, Sharp R, Macfarlane GT. Variation in human intestinal microbiota with age. Dig. Liver. Dis. 2002 [59] Hebuterne X. Gut changes attributed to aging: effects on intestinal microflora. Curr. Opin. Clin. Nutr. Metab. Care. 2003 [60] Hebuterne X. Gut changes attributed to aging: effects on intestinal microflora. Curr. Opin. Clin. Nutr. Metab. Care. 2003 [61] Hopkins et al, Changes in predominant bacterial populations in human faeces with age and with C Difficille infection. J. Med. Microbiol. 2002 [62] Makris et al. Clostridium difficile in the long-term care setting. J. Am. Med. Dir. Assoc. 2007 [63] Mookerjee RP, Hodges S, et al. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J. Hepatol. 2008 [64] Morley et al. Frailty and the aging male. Aging Male. 2005 [65] Russell RM. Bioavailability of nutrients and other bioactive components from dietary supplements: factors in aging that effect the bioavailability of Nutrients. J. Nutr. 2001 [66] Kamel HK. Update on osteoporosis management in long-term care: focus on bisphosphonates. J. Am. Med. Dir. Assoc. 2007 [67] Choudhurry MR, Williams J. Iron absorption and gastric operations. Clin. Sci. 1959 [68] Morley JE, Baumgartner RN. Cytokine-related aging process. J. Gerontol. A Biol. Sci. Med. Sci. 2004 [69] Popper H. Aging and the liver. In: Popper H, Schaffner F, editors. Progress in liver diseases, vol. 8. New York: Grune & Stratton; 1986 [70] Zoli M, Magalotti D, Bianchi G, et al. Total and functional hepatic decrease in parallel with aging. Age Aging. 1999 [71] Schmucker DL. Hepatocyte fine structure during maturation and senescence. J. Electron. Microsc. Tech. 1990 [72] Tauchi H, Sato T. Age related changes in size and number of mitochondria of human hepatic cells. J. Gerontol. 1968 [73] Tauchi H, Sato T. Age related changes in size and number of mitochondria of human hepatic cells. J. Gerontol. 1968 [74] Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons. Part II: laboratory evaluation. Nutrition. 2000

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[75] Sanz N, Diez-Fernandez C, Alvarez AM, et al. Age related changes on parameters of experimentally-induced liver injury and regeneration. Toxicol. Appl. Pharmacol. 1999 [76] Schmucker DL. Aging and the liver: an update. J. Gerontol. A Biol. Sci. Med. Sci. 1998 [77] Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin. Pharmacokinet. 2005 [78] Anand et al. Effect of aging on the pancreatic ducts: a study based on endoscopic retrograde pancreatography. Gastrointest. Endosc. 1989 [79] Detlefsen et al, pancreatic fibrosis associated with age and ductal papillary hyperplasia. Virschow Arch. 2005 [80] Laugier R, Bernard JP, Berthezene P, Dupuy P. Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly, digestion 1991 [81] Ihm et al, Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets. Diabetes Res. Clini. Prac. 2007 [82] Kim MJ, Rolland Y, Cepeda O, et al. Diabetes mellitus in older men. Aging Male 2006; [83] Morley JE. Diabetes mellitus: a major disease of older persons. J. Gerontol. A Biol. Sci. Med. Sci. 2000 [84] Mazza AD, Morley JE. Update on diabetes in the elderly and application of current therapeutics. J. Am. Med. Dir. Assoc. 2007

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter III

Gastrointestinal Motility Disturbances in the Elderly 1

Christopher K. Rayner*1 and Michael Horowitz2

Associate Professor, Discipline of Medicine, University of Adelaide, and Consultant Gastroenterologist, Royal Adelaide Hospital, Australia 2 Professor, Discipline of Medicine, University of Adelaide, and Director of the Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia

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Introduction The gastrointestinal tract is remarkable for the degree to which its motor function remains intact with healthy aging, while there appears to be a substantial decline in gastrointestinal sensory function. However, because gut motility is prone to be affected by a variety of comorbidities that are prevalent in the elderly, or medications used to treat them, disordered gastrointestinal motor function occurs frequently. This chapter will focus on the esophagus and stomach, with relatively less emphasis on the small and large intestines, which are dealt with in more detail elsewhere. Particular attention is given to motor and sensory function, rather than secretion or blood supply. The chapter does not discuss nutrition, constipation or fecal incontinence in depth, nor deal with the pancreas, biliary tree, cancer or pre-malignant conditions (eg. Barrett’s esophagus), which are the subject of other chapters.

*

Address for correspondence: Associate Professor Chris Rayner; Discipline of Medicine; Royal Adelaide Hospital; North Terrace; Adelaide; South Australia 5000; AUSTRALIA; Tel +61 8 8222 2916; Fax +61 8 8223 3870; Email: [email protected]

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Control of Upper Gastrointestinal Motility Motor function of the gut consists of contractions of the inner circular and outer longitudinal layers of smooth muscle that invest most of the length of the gastrointestinal tract. Basic patterns of contraction are coordinated by neurons distributed in plexuses within the gut wall, known as the enteric nervous system, containing in total as many neurons as the spinal cord (about 108) [1]. Efferent and afferent communication between the gut and the brain occurs via extrinsic nerves (sympathetic and parasympathetic), allowing for modulation of gut function by the central nervous system, and vice versa. In addition, peptide hormones released from the gut represent another mode of communication with higher centers.

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Age-Related Changes in the Enteric Nervous System In rodents, aging is associated with loss of about 40% of small intestinal and 60% of colonic neurons [2]; similar losses have been reported in the human esophagus and colon. In contrast to these changes in the enteric nervous system, the number of vagal nerve fibers in rodents appears to be unchanged. The relative preservation of gastrointestinal motor function with age, discussed in detail below, suggests a generous functional reserve. However, in the colon, where neuronal loss is greatest, transit does tend to be slowed with age [3]; this may be reflected in the high prevalence of constipation in the elderly. Neuronal loss in rodents preferentially affects neurons utilizing cholinergic transmission, which subserve a range of functions including sensation, in contrast to nitrergic neurons, which are mainly inhibitory [4]. Selective loss of intrinsic sensory fibers might account, for example, for the reduction in secondary peristalsis (defined in the next section) observed in the esophagus in the healthy elderly [5]. Furthermore, perception of distension in the esophagus [6], stomach [7] and rectum [8], and perception of acid in esophagus [9], are all reduced in healthy older subjects, in contrast to the relative preservation of motor function. Cerebral evoked potentials, elicited by esophageal distension and recorded from scalp electrodes, display diminishing amplitude and latency with increasing age, but the relative contribution of enteric neuronal loss, afferent nerve deterioration or changes in central processing have not been determined.

Esophagus Effects of Healthy Aging Normal swallowing requires the transfer of a bolus through the pharynx, coordinated with relaxation of the upper esophageal sphincter (UES), followed by transit through the esophageal body, propelled by an orderly sequence of contraction known as primary peristalsis. Relaxation of the lower esophageal sphincter (LES) allows entry of the bolus into

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the stomach. Esophageal peristalsis can also be stimulated by esophageal distension or reflux of gastric contents (secondary peristalsis), or can occasionally be spontaneous and uncoordinated (tertiary peristalsis). Barriers to reflux of gastric contents back into the esophagus include tonic contraction of the LES, and its position at the level of the diaphragmatic hiatus. Postprandially, episodes of transient LES relaxation can be triggered by gastric distension, as well as gut hormones released from the small intestine in response to nutrient exposure. These allow the expulsion of swallowed air, but are also the mechanism by which most acid reflux events occur [10]. In people with hiatus hernia, other mechanisms of reflux become prominent, including low basal LES pressure, swallow-associated LES relaxations, and straining [11]. Defence mechanisms against acid reflux include neutralization of acid by saliva, and clearance of refluxate by primary and secondary peristalsis. “Presby-esophagus” is the term commonly thought to describe changes in esophageal function with healthy aging, but in fact the original report documented radiologic and manometric observations in a group of nonogenerians who had a high prevalence of dementia and other chronic illnesses [12]. In these patients, the barium swallow showed tertiary contractions, esophageal dilatation and delayed clearance, while multi-peaked, non-peristaltic waves were evident on manometry. Other investigators have also reported disordered esophageal motility in the very old [13]. However, up to the age of 80, age-related changes appear modest, with slightly more simultaneous contractions, and lower peristaltic wave amplitude and velocity [14] compared to the young. Other subtle changes include a lesser propensity for esophageal distension to elicit secondary peristalsis [5], possibly accounted for, at least in part, by increased esophageal wall stiffness and impaired sensation of distension [15]. Indeed, changes in biomechanical properties and primary and secondary peristalisis are evident from as early as 40 years of age [16]. Sphincter function at either end of the esophagus is also affected with aging; while the length and resting pressure of the UES are diminished, relaxation during swallowing is delayed compared to the young [17], and the oropharyngeal phase of swallowing becomes protracted, with high intra-bolus pressures in the hypopharynx. Reflex relaxation of the UES in response to air in the pharynx remains intact with healthy aging, although contraction in response to fluid can be impaired, potentially predisposing to aspiration [18]. At the LES, there is minimal loss of length and tone with healthy aging, but the prevalence of hiatus hernia does increase with age (60% over 60 years) [19]. Although the frequency of reflux episodes does not increase with age, their duration is prolonged [20]; reports that the total percentage of time with pH less than 4 increases with age [21] have been inconsistent, perhaps because of varying prevalence of atrophic gastritis, and therefore hypochlorhydria, in different study populations. Nevertheless, even weakly acidic refluxate could cause injury due to its bile content [22]. Both impaired clearance of refluxate and reduced salivary flow could contribute to increased acid exposure. Neither the frequency of transient LES relaxations, nor mucosal repair mechanisms, have been formally compared between the healthy elderly and the young, although there is a greater frequency of postprandial reflux events induced by pharyngeal water stimulation (with attendant LES relaxation) than in the young, which could be relevant in individuals with retained food or secretions in the pharynx [23].

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Disorders of Esophageal Function in the Elderly Disorders of esophageal motor function typically present with difficulty swallowing (dysphagia) or chest pain. When specificially questioned, older subjects living in nursing homes (up to 60%) and those who are hospital inpatients (up to 30%) will report dysphagia [24]. Although dysphagia can be either oropharyngeal (difficulty initiating a swallow) or esophageal (impaired transit in the esophagus) in origin, this chapter will focus on esophageal causes, which can usually be differentiated from oropharyngeal pathology on history and examination. Common esophageal causes of dysphagia are outlined in Table 1. Benign or malignant strictures typically affect solids more than liquids, in contrast to motor disorders, which affect both [25]. A history of reflux symptoms suggests a peptic stricture, while dysphagia for solids that progresses over a relatively short period of time raises the concern of malignancy. Table 1. Esophageal Causes of Dysphagia Structural Neoplasia Peptic stricture Reflux esophagitis Eosinophilic esophagitis “Pill” esophagitis

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Schatzki ring Extrinsic compression (Vascular - aortic arch; Neoplastic) Functional Achalasia Diffuse esophageal spasm “Nutcracker” esophagus Non-specific motility disorder Systemic disorder (eg. Parkinson’s)

Contrast radiology is often a useful initial investigation for dysphagia, since it can indicate the presence of both structural and functional disorders, and therefore guides subsequent investigations. Even if endoscopy seems likely to be needed, a contrast swallow can help anticipate the need for possible therapeutic interventions (eg. esophageal dilatation), or indicate that particular caution is needed by the endoscopist (eg. pharyngeal pouch). The sensitivity of contrast videofluoroscopy for detecting motor disorders of the esophagus probably depends on the experience and dedication of the radiology team; in experienced centers, normal clearance of barium and bread can be highly predictive for excluding disorders of motor function [26]. Endoscopy has a good safety profile in the elderly [27], and in addition to its value for diagnosing and treating benign and malignant strictures and complications of reflux disease, provides the opportunity to biopsy the mucosa for evidence

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of eosinophilic esophagitis, which is increasingly being recognised in adults, even in older age groups [28]. Manometry, using either multilumen water perfused or solid state catheters, is restricted to specialized centers, but represents the gold standard for diagnosis of esophageal motor disorders, and is most useful for diagnosing or excluding achalasia. The motility disorders span a wide age range, with diffuse esophageal spasm and non-specific motility disorders tending to increase with age.

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Achalasia Achalasia is characterized by incomplete or absent swallow-induced relaxation of the LES, classically with absence of peristalsis in the esophageal body, although a minority have high amplitude pressure waves (“vigorous achalasia”). The basal LES pressure in achalasia tends to be higher with advancing age [29]. The etiology is unknown, but histologically there is myenteric plexus inflammation, neuronal loss, and fibrosis [30]. Although the peak incidence occurs in early to mid-adulthood, there is a smaller peak in the elderly [31]. In addition to dysphagia for both liquids and solids, there may be regurgitation, weight loss, and a risk of aspiration. The latter two complications are more common in the elderly [32], while presentation with chest pain is less common than in the young [33]. Contrast radiology typically shows tapering towards the distal esophagus (“bird’s beak” or “rat’s tail”), delayed emptying of the barium column, and a dilated esophageal body (Figure 1), but manometry is required for definitive diagnosis. The possibility of “pseudoachalasia”, associated with a distal esophageal or cardia tumor, needs to be considered in older patients, especially if the history is short and weight loss is prominent. Endoscopy, with or without endoscopic ultrasound, and computed tomography, are used to exclude this entity. Treatment is directed towards the LES, and aims to improve dysphagia, but cannot restore normal motility to the esophageal body. The main treatment options are pneumatic dilatation or surgery – the latter involving myotomy, often combined with an anti-reflux procedure and performed laparoscopically. Good symptomatic responses are reported for both [34], although the only randomized controlled trial favored surgery for completeness of symptom relief [35, 36]. Relief of dysphagia after surgery appears as good for older as for younger patients (about 80%) [37], while older patients my get better relief from pneumatic dilatation than the young [38]. Pneumatic dilatation can be complicated by perforation (3%) and reflux symptoms (10%), and often needs to be repeated, but is less expensive than surgery, and therefore may be more cost-effective in older patients. Injection of botulinum toxin into the LES represents a third treatment option with adequate symptom relief in about 60%, but a limited duration of effect (about 6 months). It is therefore usually reserved for the frail elderly [34]. Because more frequent procedures are needed, it is more costly than dilatation [39].

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Christopher K. Rayner and Michael Horowitz

Figure 1. Typical barium swallow appearance of achalasia.

Diffuse Spasm and “Nutcracker” Esophagus Diffuse esophageal spasm is defined manometrically as simultaneous pressure waves observed on some, but not all, swallows [40]. Sometimes the barium swallow shows a “corkscrew” pattern. So-called “nutcracker” esophagus, on the other hand, is characterized by high amplitude, but peristaltic, contractions. These disorders are sometimes associated with non-cardiac chest pain, as discussed below. However, a causal relationship is frequently not clear; often there is a poor response to smooth muscle relaxant drugs, and symptoms per se may need to be addressed, for example with a low dose tricyclic antidepressant as a pain modifying agent – with particular caution regarding the potential adverse effects of these drugs in elderly.

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Non-Specific Motility Disorders When the manometric features in the esophagus are outside the normal range, but not sufficient for the diagnosis of achalasia, diffuse esophageal spasm, or nutcracker esophagus, the label “non-specific motility disorder” is used. About a third of patients over 65 years of age presenting for investigation of dysphagia will be put in this category. The relationship between the manometric findings and symptoms is often unclear, and no specific therapy is available.

“Pill” Esophagitis Impaction of medications in the esophagus with resultant mucosal injury needs to be considered as a cause of dysphagia or odynophagia (painful swallowing) in the elderly, and has been termed “pill” esophagitis. Contributing factors include reduced salivary flow, delayed esophageal transit, immobility, and polypharmacy. Capsules, which have slower esophageal transit, are generally more prone to cause problems than tablets. Potassium chloride, tetracycline, aspirin and non-steroidal drugs, quinidine, theophylline, iron, and the oral bisphosphonates are the most commonly implicated medications [41]. “Pill” esophagitis typically manifests as small ulcers in the esophagus, but bleeding, stricture and perforation are potential complications. Treatment involves stopping any drugs that might be implicated, and this alone may be sufficient. Sucralfate, which can form a protective barrier, has also been advocated. Prevention is important; older individuals in particular should be advised to drink a full glass of water after taking oral medications.

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Gastro-Esophageal Reflux Disease The prevalence of gastro-esophagheal reflux disease (GERD), based on typical symptoms like heartburn and acid regurgitation occurring at least weekly, is reported to be similar (up to 20%) in older people compared to young adults [42]. However, GERD in the elderly is more often atypical than in the young [43], so that the true prevalence may be difficult to determine. Atypical presentations can include dysphagia, cough, respiratory difficulty, vomiting and weight loss. Furthermore, the severity of heartburn is an unreliable indicator for the presence of erosive disease [44], which together with other GERD complications, is more common in older groups [45, 46], perhaps due to delayed acid clearance, as discussed in the “esophageal function” section above. In particular, elderly patients with Barrett’s esophagus often have few symptoms [47]. So-called “alarm” symptoms (dysphagia, weight loss, or evidence of bleeding) are indications for prompt endoscopic investigation. However, diagnostic procedures such as endoscopy or pH monitoring in the frail elderly are often limited by co-morbidities, such as cardiac disease or dementia. A therapeutic trial of double dose proton pump inhibitor for 8 weeks can be useful in atypical presentations in the absence of alarm symptoms [48]. Healing in response to standard doses of acid suppressive therapy seems similar to the young, although symptoms may be a less useful guide to dose titration in the elderly. Long term use of proton pump inhibitors has generally been regarded as safe, although an increased

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risk of osteoporotic hip fracture [49], and community acquired pneumonia [50] (each about 1.5 fold) have recently been reported, while Clostridium difficile infection [51], malabsorption of vitamin B12 [52], and interstitial nephritis are other potential adverse effects. Concerns about an increased risk of gastric or colon cancer have not been substantiated [53]. Long term therapy with acid suppression is thought to increase the risk of atrophic gastritis, and therefore gastric cancer, in Helicobacter pylori infected individuals, so many clinicians test and treat for H pylori prior to long term treatment; however, this approach may be less cost-effective in the elderly than in younger groups. Healthy older patients experience comparable benefits to the young after laparoscopic anti-reflux surgery [19], and the safety of these procedures seems as good in patients aged 65 years and over, as in younger individuals [54, 55]. Therefore, age in itself should not be an exclusion criterion for surgery, but careful consideration of co-morbidities is important. The indications for surgical therapy include intolerance of proton pump inhibitors, and symptoms that are refractory to medical therapy and can be attributed to weakly acidic reflux events.

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Stomach The primary role of the stomach is to store an ingested meal (predominantly in the proximal stomach), break down solids into small particles (in the antrum), and empty its content to the small intestine in a regulated manner (between 1 and 3 kcal/min) to optimize digestion and absorption of nutrients [56]. Tonic and phasic contraction of the pylorus acts as a brake to gastric outflow. These processes are under feedback control from neural and hormonal signals originating from the interaction of nutrients with the small intestine. This feedback is altered by prior patterns of nutrient exposure, for example the gastric emptying of glucose is accelerated after a period of glucose supplementation, and slowed after starvation [57, 58]. Gastric distension interacts with the signals arising from the small intestine to influence appetite. Age-related changes in stomach function could therefore be relevant to understanding the “anorexia of aging”, a reduction in energy intake out of proportion to diminished energy expenditure [59]. Scintigraphy, which entails imaging of a radiolabelled meal using a gamma camera, is recognised as the “gold standard” for measuring gastric emptying, and with the use of dual isotopes, the emptying of solids and liquids can be studied concurrently. Alternative methods for quantifying the rate of gastric emptying include breath tests and ultrasound (either 2 or 3 dimensional) [60]. Manometry, allowing measurement of pressures in the antrum and pylorus, and the electronic barostat, which can be used to evaluate proximal gastric tone and accommodation, are specialized research tools for evaluating gastric motor function. With healthy aging, there is a modest slowing of gastric emptying, more evident with higher caloric loads (>500kcal), though the rate generally remains within the normal young range [61-63]. This could potentially delay absorption of orally administered medications, as has been shown for paracetamol, but in practice the effect is likely only to have a small impact, and absorption of benzodiazepines, tetracycline and L-dopa is not significantly affected. Both diabetes, which is discussed subsequently, and a number of drugs (Table 2), have the potential to slow gastric emptying.

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Table 2. Drugs that Alter the Rate of Gastric Emptying

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Slowed gastric emptying Anticholinergics Calcium channel antagonists Clonidine GLP-1 analogs (eg. exenatide) L-dopa Nitrates Opiates Phosphodiesterase inhibitors Sumatriptan Tricyclic antidepressants Accelerated gastric emptying Beta adrenoreceptor antagonists Cisapride Domperidone Erythromycin Metoclopramide Tegaserod

Under fasting conditions, the compliance of the proximal stomach in the healthy elderly is similar to the young, but the perception of distension is markedly less [7]. After a meal, relaxation of the proximal stomach is delayed compared to the young, while antral distension after a nutrient drink is greater [64], suggesting a redistribution of gastric content. This is potentially important in relation to appetite, because in both healthy young and older subjects, meal consumption is inversely related to antral distension. Small intestinal feedback is altered in the healthy elderly compared to the young; concentrations of cholecystokinin, both fasting and in response to an intraduodenal nutrient infusion, are greater, while intraduodenal glucose infusions are more satiating [59]. This enhanced feedback could contribute to both slowing of emptying and increased satiation. For example, intraduodenal lipid produces greater stimulation of phasic pyloric contractions in the healthy elderly compared to the young [65]. Postprandial hypotension is an important clinical problem in the elderly, with the potential to contribute to syncope and stroke, and can be viewed as a gastrointestinal disorder [66]. Carbohydrate ingestion has potent effects in decreasing blood pressure, but fat also contributes [67]. The rate of entry of nutrient to small intestine is important in determining the magnitude of the postprandial fall in blood pressure [68], and the release of gut peptides (including calcitonin gene-related peptide [69]), increased mesenteric blood flow, or both, are likely to be important, since postprandial hypotension is ameliorated by octreotide [70]. Slowing of gastric emptying and carbohydrate absorption with acarbose or dietary interventions appears likely to be beneficial [71], while gastric distension, for example by drinking a glass of water, can attenuate the postprandial fall in blood pressure [72].

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Small Intestine

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Small intestinal motility is characterized by cyclical fasting motor activity (the “migrating motor complex” (MMC)), consisting of about 40 minutes of motor quiescence (phase I), a similar period of irregular contractions of increasing frequency (phase II), followed by 5 – 10 minutes of regular contractions at a rate of 10 – 12 per minute (phase III). The MMC is interrupted by meal ingestion, which converts the motor pattern to one of irregular pressures that facilitate digestion and absorption. The MMC cycle length is unchanged with aging, although propagation of phase III down the gut is slower in the healthy elderly than in the young. Increased propagated clusters of pressure waves are observed in both fasting and fed states [73], similar to what is observed in irritable bowel syndrome, although the functional significance of these changes is uncertain [3]. The rate of small bowel transit similar to the young [3], while the absorptive function of the gut remains largely intact except for calcium, due to reduced production and response to 1, 25 hydroxycholecalciferol. Atrophic gastritis, a complication of longstanding Helicobacter infection, can also impair absorption of vitamin B12. Small intestinal bacterial overgrowth is unusual in the healthy elderly, but can occur with co-morbidities that are associated with altered small intestinal motility (eg. diabetes), reduced acid secretion (eg. atrophic gastritis), or jejunal diverticula, with consequences of malnutrition, vitamin B12 deficiency, and diarrhea [19]. Breath tests, such as measurement of breath hydrogen after ingestion of glucose or xylose, are a non-invasive means of detecting bacterial overgrowth, but reports as to their sensitivity and specificity vary widely. Typically, treatment involves 1 to 4 weeks of an antibiotic such as metronidazole, tetracycline, a quinolone, or the non-absorbed antibiotic rifaximin [74], which may need to be repeated on a cyclical basis, but there is a paucity of randomized controlled trial evidence to guide practice in this area.

Specific Disorders that Affect Gastrointestinal Function in the Elderly Parkinson’s Disease Gastrointestinal dysfunction is common in Parkinson’s disease [75]. Involvement of the dorsal motor nucleus of the vagus affects parasympathetic function, while the enteric nervous system can be affected by Lewy bodies and loss of dopaminergic neurons. Dysphagia in parkinsonian patients can be due to problems with either the oropharyngeal phase of swallowing, or with esophageal transit. Both L-dopa and anticholinergic agents may either improve or worsen symptoms, while there is one report that apomorphine might be a helpful agent [76]. Gastric emptying may be delayed due either to the disorder itself, or to L-dopa therapy, and may be associated with nausea and bloating, impaired nutrition, and delayed absorption of oral medications including L-dopa; if the latter drug remains in the stomach for extended periods, it is metabolised to dopamine, which cannot be absorbed systemically. In parkinsonian patients who display the “on-off” phenomenon, the rate of gastric emptying can

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fluctuate with “on” and “off” phases, and the resultant fluctuating rate of L-dopa absorption can further contribute to the phenomenon. Metoclopramide (a dopamine antagonist) is contraindicated in Parkinson’s disease, but domperidone, which does not cross the bloodbrain barrier, can be used safely if a prokinetic drug is required. Small intestinal, colonic and anorectal motor function can all be impaired in Parkinson’s disease. For example, orocecal transit is prolonged when compared to age-matched controls. Constipation and pseudo-obstruction are potential clinical sequelae of this phenomenon.

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Diabetes Mellitus The prevalence of type 2 diabetes is increasing worldwide, and the disease is common in older individuals, with about 20% of those over 65 years being affected in Western societies. Normal aging is associated with decreased glucose tolerance, related to increasing peripheral insulin resistance, decreased beta cell function, and possibly impaired postprandial suppression of hepatic glucose output [77]. Gastrointestinal function is frequently affected in diabetes, and any segment of the gastrointestinal tract can be involved. Since the gastrointestinal tract regulates the emptying and absorption of ingested carbohydrate and secretes peptide hormones that stimulate insulin secretion, it is central to glycemic control. Conversely, acute changes in the blood glucose concentration influence gut function; for example, gastric emptying is markedly slower during acute hyperglycemia compared to euglycemia [78]. There is, however, no information regarding gut involvement in diabetes that is specific to the elderly [77]. In the esophagus, diabetes is associated with reduced amplitude and abnormal forms of pressure waves in the esophageal body, accompanied by failed peristalsis and delayed transit, while LES pressure is lower than healthy controls, and the prevalence of GERD is modestly increased. Up to 50% of outpatients with longstanding type 1 or 2 diabetes have delayed gastric emptying for solids, liquids or both. This is often attributed to the presence of gastrointestinal autonomic neuropathy, but methods of assessing the latter in humans are indirect. Measures of cardiac autonomic neuropathy are often used as a surrogate marker; however, the presence of cardiac autonomic neuropathy correlates only weakly with delayed gastric emptying [79]. Numerous pathological abnormalities have been documented in animal models, which are not always found in humans. However, studies in patients with gastroparesis refractory to medical treatment do reveal loss of both interstitial cells of Cajal, which are responsible for generating the electrical rhythm of the stomach, and myenteric neurons, while staining for inhibitory nerotransmitters is reduced, and gastric myopathy is evident in a few [80]. Gastric motor abnormalities associated with diabetes include reduced fundic tone, and diminished antral motility and antro-duodenal coordination of pressure wave sequences, and in some cases excessive pyloric contraction. Disordered gastric emptying potentially has clinical sequelae of upper abdominal symptoms, impaired absorption of nutrients and drugs, and deranged glycemic control, particularly in insulin-treated patients (of which the majority have type 2 diabetes), in whom cabohydrate absorption may not match the action of exogenous insulin. The relationship between the rate of gastric emptying and the presence of symptoms is relatively weak [79]. Patients with suspected diabetic gastroparesis should be investigated to exclude other causes,

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including endoscopy and possibly contrast radiology to exclude obstruction. The rate of emptying for solids and ideally also nutrient liquids should be evaluated with scintigraphy. Prokinetic drugs, such as metoclopramide or domperidone, are commonly used as first line treatment. The role of pyloric injections of botulinum toxin in refractory patients is unclear, as this therapy is yet to have proven benefit over placebo in controlled trials, and a recent retrospective analysis suggests that older patients (50 years or greater) are less likely to benefit than the young [81]. Gastric electrical stimulation with an implantable device for medically refractory gastroparesis has yielded promising outcome data in open label follow up studies, although the limited controlled trial data available to date are less favorable. Most large series contain a few patients in their 60s, but no subgroup analysis is available for older patients treated with this device. Small intestinal motility is often abnormal in diabetes. A reduction of duration of phases of the MMC is reported during fasting, while bursts of non-propagated pressure waves may be observed postprandially, with abnormal patterns of chyme flow, and variable rates of small intestinal transit, either normal, slow or rapid. Diarrhea and constipation both appear to be prevalent in people with diabetes. In those with diarrhea, small bowel bacterial overgrowth, pancreatic exocrine insufficiency, and celiac disease should be considered. Loperamide may be helpful, but prescribers must be alert to the potential adverse effects of constipation, urinary retention, dry mouth, sedation, and glaucoma in older patients. The alpha agonist, clonidine (with side effects of hypotension, bradycardia, drowsiness, dry mouth, fatigue and headache) and in extreme cases, the somatostatin analog, octreotide, can also be helpful.

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Functional Gastrointestinal Disorders in the Elderly Functional gastrointestinal disorders are manifest as recurrent or persistent symptoms referable to the gut, in the absence of a structural or biochemical explanation. Functional dyspepsia and irritable bowel syndrome (IBS) are common functional disorders, but there is much overlap between the different functional syndromes. These disorders are prevalent in the general community, and more common in women than men. In the young, they are associated with increased sensitivity to gastric and rectal distension – this phenomenon has not been studied in the elderly; as discussed, healthy elderly subjects have diminished perception of gut distension compared to healthy young controls. However, tolerance (defined as the threshold at which subjects ask for a stimulus to stop) for somatic stimuli decreases with aging; tolerance for visceral stimuli has not been studied in the elderly. IBS is defined by the Rome III criteria as two or three of (i) abdominal discomfort or pain relieved by defecation, (ii) change in stool form (looser or harder) and (iii) change in stool frequency, for at least 3 months [82]. The prevalence of IBS appears to be less in the elderly than the middle aged [83], although the incidence in a US study was reported to increase with age [84], possibly due to increased health care seeking behavior. De novo presentation in the elderly seems less likely than in the young or middle aged, but data on this point are limited [43]. The elderly seem less prone to developing IBS after a bout of gastroenteritis compared to the young, in whom 10% of patients have this pattern of onset. A Danish study reported that IBS prevalence at 70 years of age was between 6 and 18%, depending on the definition

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used, with symptoms resolving in about half of these subjects by five years [85]. Both these prevalence and resolution rates are similar to those reported in the young, suggesting a similar prognosis in the older group. However, elderly IBS patients are more likely to experience a decline in their functional status than the elderly without IBS. Functional (or “non-ulcer”) dyspepsia can be defined as epigastric discomfort, not including heartburn, in the absence of a structural or biochemical explanation. Unlike IBS, it may slightly favor males. About 30% of patients have delayed gastric emptying (relatively modest in most), and 40% have impaired accommodation of the proximal stomach [86]. There is even less information for functional dyspepsia than for IBS that is specific to the elderly, but the prevalence of the former appears similar in old and young people in the general population [85]. Functional dyspepsia impairs health-related quality of life in the young, but no impact data are available for older patients [43]. In managing patients presenting with gastrointestinal symptoms, it is important to exclude organic disease, which is more common in the old than the young. For example, entities such as peptic ulcer, malignancy, mesenteric ischemia, infection (eg. Clostridium difficile if there is a history of recent antibiotic use), medication side effects, thyroid disease, diabetes, depression (of which anorexia or constipation can be symptoms), and small intestinal bacterial overgrowth are more common in the elderly than the young [87]. Therefore, there should, for instance, be a low threshold for colonoscopy to investigate a change in bowel habit. Analysis of therapies for functional dyspepsia or IBS must take into account the high placebo response observed in these disorders (20 to 70%). Good randomized controlled trial evidence is only available for a handful of medications. For IBS, ispaghula fiber, the antispasmodics otilonium, hyoscine, and peppermint oil [88], and antidepressants have a good evidence base, although psychological therapies may be of comparable efficacy [89]. Selective serotonin reuptake inhibitors may be as good as tricyclic antidepressants for IBS, although venlafaxine is apparently not as helpful as tricyclics in functional dyspepsia [90]. No trials have focused specifically on the elderly, and the potential for adverse effects (eg. sedation, urinary retention, postural hypotension, blurred vision, or glaucoma with tricyclics or hyoscine) is likely to be greater in this group. Therapies are selected on the basis of the predominant symptoms, for example antispasmodics for crampy pain, and fiber supplements for constipation. Osmotic laxatives, or lubiprostone (a locally acting type-2 chloride channel activator, which induces intestinal fluid secretion), are other options for the latter [91]. Diarrhea may be treated with loperamide. Alosetron, which with withdrawn in 2000 due to an excess of cases of ischaemic colitis, was reintroduced for restricted use in 2002; only a few trial patients have been elderly, and ischemic colitis could be a particular concern in this group.

Non-Cardiac Chest Pain Chest pain often represents a diagnostic dilemma, especially in the elderly, where the prevalence of coronary artery disease is high. Once ischemic heart disease has been excluded, chest pain is often attributed to the esophagus, but can also potentially arise from pericardial, pulmonary, gastric, biliary, or musculoskeletal disease, or as part of a panic disorder (92).

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Christopher K. Rayner and Michael Horowitz

Atypical GERD could be the cause of pain in a proportion of patients, since a slight majority have excessive esophageal acid exposure on pH monitoring. Since the absence of esophagitis does not exclude this possibility, endoscopy is not necessarily helpful in the investigation of chest pain [93]. Rather, a 2 to 8 week trial of double dose proton pump inhibitor can be advocated, with subsequent downwards dose titration in responders, and esophageal manometry and pH studies in non-responders [94]. Diffuse esophageal spasm and nutrcracker esophagus are sometimes found on manometry in patients presenting with chest pain, but as discussed, the relationship of the manometric findings to pain episodes is often unclear, particularly as the patient is often pain-free during the manometry study. Moreover, the response to muscle relaxants (nitrates, calcium channel antagonists, or sildenafil) is often disappointing. Pain modifying agents such as tricyclic antidepressants may be more helpful.

Summary Healthy aging is associated with remarkably little impairment of gastrointestinal motor function, but a decline in sensation. Co-morbid illnesses occur commonly in older individuals, and a number of illnesses and medications can impair gastrointestinal function, with implications for swallowing, appetite control, absorption of nutrients and drugs, and altered bowel function. Functional gut disorders are probably common in older individuals, but the clinician should be alert to the possibility of organic disease.

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Acknowledgment The authors wish to thank Professor Richard Holloway, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, for providing the radiograph depicted in figure 1.

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[77] Kuo P, Rayner CK, Horowitz M. Gastric emptying, diabetes, and aging. Clin. Geriatr. Med. 2007;23:785-808, vi. [78] Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001;24:371-81. [79] Horowitz M, Maddox AF, Wishart JM, Harding PE, Chatterton BE, Shearman DJ. Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus. Eur. J. Nucl. Med. 1991;18:229-34. [80] Khoo J, Rayner CK, Jones KL, Horowitz M. Pathophysiology and management of gastroparesis. Expert Rev. Gastroenterol. Hepatol. 2009;3:167-81. [81] Coleski R, Anderson MA, Hasler WL. Factors Associated with Symptom Response to Pyloric Injection of Botulinum Toxin in a Large Series of Gastroparesis Patients. Dig. Dis. Sci. 2009. [82] Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480-91. [83] Bennett G, Talley NJ. Irritable bowel syndrome in the elderly. Best Pract. Res. Clin. Gastroenterol. 2002;16:63-76. [84] Locke GR, 3rd, Yawn BP, Wollan PC, Melton LJ, 3rd, Lydick E, Talley NJ. Incidence of a clinical diagnosis of the irritable bowel syndrome in a United States population. Aliment Pharmacol. Ther. 2004;19:1025-31. [85] Kay L. Prevalence, incidence and prognosis of gastrointestinal symptoms in a random sample of an elderly population. Age Aging. 1994;23:146-9. [86] Lee KJ, Kindt S, Tack J. Pathophysiology of functional dyspepsia. Best Pract. Res. Clin. Gastroenterol. 2004;18:707-16. [87] Bharucha AE, Camilleri M. Functional abdominal pain in the elderly. Gastroenterol. Clin. North Am. 2001;30:517-29. [88] Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313. [89] Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. GUT. 2009;58:367-78. [90] Van Oudenhove L, Tack J. Is the antidepressant venlafaxine effective for the treatment of functional dyspepsia? Nat. Clin. Pract. Gastroenterol. Hepatol. 2009;6:74-5. [91] Morley JE. Constipation and irritable bowel syndrome in the elderly. Clin. Geriatr. Med. 2007;23:823-32, vi-vii. [92] Eslick GD, Fass R. Noncardiac chest pain: evaluation and treatment. Gastroenterol. Clin. North Am. 2003;32:531-52. [93] Richter JE. Oesophageal motility disorders. Lancet. 2001;358:823-8. [94] Fass R, Fennerty MB, Ofman JJ, Gralnek IM, Johnson C, Camargo E, et al. The clinical and economic value of a short course of omeprazole in patients with noncardiac chest pain. Gastroenterology. 1998;115:42-9.

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In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter IV

Nutrition in the Elderly Yitshal N. Berner* Professor and Head, Geriatric Medicine, Meir Medical Center Kfar Saba, Affiliated to the Sackler School of Medicine, Tel Aviv University, Israel

Abstract

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The elderly population is growing with time in the developed as well as in the developing societies at a rate of about 5% a year. This population has higher morbidity then the general population. The elderly are characterized by changes in different physiological activities as well as multiple pathologies. Cellular function is based on hormones, cytokines and neurotransmitters acting through the cell’s receptors and altered cellular function. Dietary structure is considered as one of the components of health and well-being. Having a high morbidity together with a slower rate of cure, elderly are major consumers of nutrition support. It is important to differentiate between the role of nutrition as part of lifestyle, in aging and the role of nutrition in treatment of the sick elderly. Nutrition has an important role in the process of healthy aging, nevertheless aging has an impact on the nutrition of the person secondary to physiological changes. The recent developments in the technology of nutrition support give us the tools to supply every person with all nutrient compounds in different manners. We can modulate the dietary structure in any way that we think that can benefit the person. There are enriched solutions with different substances, that either bypass the swallowing mechanism in different ways supplying enteral nutrition or going parenterally directly to the circulation through different ports. Despite these various opportunities there are many questions about the efficacy of nutritional support in the elderly in certain conditions and an ethical debate regarding the indication with different opinions is current, questioning the medical indications, together with the techniques and the timing for the implementation of such support. Sarcopenia, a decline in muscle mass, is part of the aging process. The differentiation between low muscular mass resulting from disease-related starvation and that derived

*

Correspondence: Yitshal N. Berner MD MPH; Meir Hospital, 57 Tchernichovski st Kfar Saba 44281 Israel; Tel: 972-9-7471003; Fax: 972-97471314; e-mail: [email protected]; [email protected]

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Yitshal N. Berner from different responses to disease consequent to the background effect of aging has has been recently determined. The role of the feeding process as part of the needs of the old person, reflecting empathy and psychosocial support, is becoming a more prominent part of the care of the elderly. Currently, the main challenge of clinical nutrition in the aged, is in the determination of the optimal time for intervention.

Keywords: Aging, Nutrition deficiencies, Nutrition support, Elderly nutrition, Elderly care.

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Life expectancy is rapidly increasing in the Western world. Throughout history people have been concerned with the well-being of the youthful and in being able to have a prolonged good quality of life. Nutrition has a significant impact on physiological function, and thereby on health and well-being. The elderly are an important segment of the total population, and they are more frail and more sick. In addition, it takes them longer to recover and they therefore consume more health services. Nutrition is an adjuvant to medical treatment. Swallowing disorders are common in the sick elderly. The may be a manifestation of different neurological disorders, but the most common swallowing disorder is de-conditioning during acute illness. There are different forms of enteral nutrition support bypassing the swallowing system, using nasogastric tubes or percutaneous gastric and enteric tubes. These feeding technologies can supply the needs of the elderly patient. Nevertheless our main task is rehabilitation of the swallowing system bringing the elderly to optimal functions. The role of a logo-therapist is crucial for swallowing rehabilitation, in addition to the medical treatment. Enteral nutrition is an essential part of geriatric medicine.

The Aging Population and its Special Health Problems An increase of about 2.5 years per decade has been observed in the life span of Israelis during the second half of the 20th century. This growth in the elderly population has led to over 10% of the population in Israel being over the age of 65 (750,000), and about 100,000 elderly over the age of eighty and over 1000 centenarians. A similar trend has been found in other Western societies (e.g., 1.8 years per decade in the United States). Consequently, the elderly population (defined as 65 year old and older) is constantly growing, with elderly people over 85 year old representing the fastest growing segment. Morbidity prevalence in this specific age group is of greater magnitude. Nutritional status derived from the intake of different nutrients is one of the components determining the physiological, medical and functional states of the elderly. Nutritional status is assessed as part of the CGA – Comprehensive Geriatric Assessment [1]. Most clinical professionals would agree that in the care of sick or frail elderly patients, nutritional and hydration concerns often rank far too low on the list of evaluation and treatment priorities. In hospitals and nursing homes [2,3], and in the community, elderly patients often receive a variety of costly and complex medical treatments, e.g., extensive drug therapy [4] and mechanical ventilatory support [5], while

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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routine provision of adequate food and fluids is neglected. Compared with the many serious maladies already established and diagnosed in elderly patients, being at risk of malnutrition sometimes seems less than urgent. The need for nutritional assessment and intervention is particularly crucial in this age group because of a higher incidence of chronic diseases and a myriad of socioeconomic factors that increase the likelihood of malnutrition [6]. Though this age group has particular needs, only relatively minor-scale research has been conducted.

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The Impact of Nutrition on the Aging Process Since the work of McCay in 1935, demonstrating the effect of an energy-restricted diet of about 30% of the “ ad libitum” eating on median and maximal life span in a cohort of rats [7], many other investigators have confirmed these findings in different species: rat, mice, hamsters, fish, flies, protozoa, worms, water fleas and partially in several mammals. Some reports have demonstrated a minor effect of lower protein intake, but the major effect was of restricted energy intake starting in young adult life or even in early middle age. [8]. Several possible mechanisms may explain energy restriction effects on the lifespan extension in animals, including altered glucose utilization [9], decreased oxygen radical damage [10], reduced glycation or oxidation of macromolecules [11], changes in gene expression [12] and increase in stress hormones [13]. There are numerous important intracellular and intercellular factors, which decrease with aging, the decreases of which, have been shown to be attenuated by energy restriction, some of them with increase in the expression of several genes of metabolic response. Decreased energy intake, in most of the studies, was associated with a decline in cellular and tissue metabolism. These metabolic changes could be explained with intracellular changes in the release of calcium from the endoplasmic and sarcoplasmic reticulum stimulated by inositol-triphosphate, the mitogen-activated protein kinase activities. Decrease sensitivity of receptors as the effect on beta-adrenergic receptors. The expression of several genes of the metabolic response as: including the heat shock protein − hsp 70, superoxide dismutase − SOD, catalase, calnexin, IL-2 in rat spleen T-cells and p53. Changes in the hormone secretion regulation (including gonadotropins, neuropeptide-Y, TSH, GH, steroids like dehydroepiandrosterone − DHEA, dehydroepiandrosterone sulphate − DHEAS, insulin, prolactin, but not proopiomelanocortin). Oxidative damage manifested as in increase in the exhalation of aldehydes, increased lipid peroxidation, and elevated glutathione concentration and scavenger enzyme activity. Definitive conclusions regarding the effect of energy restriction are expected to be deduced from studies in non human primates but will not be forthcoming for at least another 20 years [9]. There is, however, one epidemiological observation from Okinawa in Japan, showing increased longevity of the inhabitants of this island. The rate of centenarians there is about 40 times higher than in the rest of Japan with the people being shorter by about 4.1 cm. The average energy intake in the island was shown to be about 83% of the average consumption in Japan [15]. Recently, it was found in a human aging cohort, in the Baltimore Longitudinal Study of Aging, men with lower temperature and insulin and those maintaining higher DHEAS levels have greater survival than their respective counterparts with lower

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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levels of these biomarkers, consistent with the effects of energy restriction on aging and lifespan observed in monkeys [16]. Mammalian aging is associated with a reduced ability to activate prosurvival signaling pathways in response to oxidative stress, leading to cell oxidative damage [17]. The purpose of this article is to show the impact of energy restriction on the changes in cell metabolism and impulse transduction, observed in aging.

The Impact of Energy Restriction Many theories have been proposed to explain the process of aging. These theories may be divided into several groups including stochastic and genetic theories, environmental theories and intra- and intercellular theories [18]. Two of the theories of the aging process may provide some explanation for the effect of energy restriction on the lifespan extension and the reduction of age-related degenerative diseases: 1. The Free Radical Theory of Aging [19]; 2. The Neuroendocrine Theory of Aging [18].

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Age Related Physiological Changes Leading to Nutritional Deficiencies Weight loss may reflect changes in appetite, dentition, taste, depression, comorbidity, poverty, isolation, constipation and other factors. According to data collected for healthy nonsmoking subjects aged 18 to 100 years, between the age of 30 to 70 there is a continuous decline of about 0.1% to 1% (on average about 0.5%) per year in the function of many tissues and organs [20], which is manifested in the shape, needs and metabolism of the older person. However, regardless of cause, loss of lean body mass is an inevitable consequence of this age-related weight loss. Physical activity declines with age, especially in developed societies, depriving muscles of what is probably their most important environmental stimulus to maintaining their mass and function, as was previously discussed.

Gastrointestinal Changes and Nutrition with Aging Changes in the gastrointestinal system also affect nutritional status in the older man. The dental status deteriorates, i.e., there is loss of teeth, the remaining teeth are unsteady and artificial dentures may be ill fitting and disturbing. Only one study of the elderly describes the impact of dentures on nutritional intake. Out of 247 well educated Bostonian elderly of high socioeconomic status, those with artificial dentures consumed more refined carbohydrates and sucrose. With a decrease in the number of teeth, vitamin A, crude fiber and calcium intake decreased [21]. The swallowing process is less synchronized due to changes in the pharyngeal structure and deterioration in its neural control because of a decrease in neural conductivity which affects neural response.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Another factor affecting swallowing is atrophy of the saliva glands resulting in dryness of the mouth (xerostomia), which is aggravated by some drugs. Changes in taste and smell reduce appetite and food intake. In addition, there are alterations in brain food-intake control. Because of atrophic changes there is a decrease in normal stomach acid secretion, which in turn reduces the extent of initial protein degradation as well as iron, calcium and vitamin B12 absorption. There are changes in peristalsis which adversely influence gastric emptying and cause early sensation of satiety. The intestinal surface area decreases and blood supply to the intestine is reduced, affecting absorption and nutrient transport. Changes occurring in mucosal secretion have a detrimental effect primarily on disaccharide digestion [22, 23].

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Changes in Other Systems Affecting Nutrition with Aging Older men suffer from many disorders in the skeletal and muscular systems. These disorders make it difficult for them to purchase, prepare and serve food and often also to eat it. Changes in the central neural system, peripheral lesions, paralysis and changes in vision also make it difficult to eat. Many studies have tried to prove a cause and effect relationship between low intake of different vitamins and normal brain function [24]. One recent prospective study showed no correlation between a decrease in folate consumption and further cognitive deterioration [25]. A German study demonstrates that cognitive impairment leads to a decrease in micronutrient intake [26] which may then contribute to further cognitive and functional impairments but does not cause them. Mood is an important component of well being. Bereavement is a life event which affects the individual’s well being for a long time. Two studies have demonstrated the influence of recent bereavement on nutritional status [27] and food consumption [28]. The latter provides some explanation to the first. Both studies demonstrate how life events affect the nutritional status of many subjects and how this condition might be reversible with only a little effort by the health care professionals. Changes in the gastrointestinal system also affect nutritional status in the older man. The dental status deteriorates, i.e., there is loss of teeth, the remaining teeth are unsteady and artificial dentures may be ill fitting and disturbing. An inadequate intake of energy and nutrients is a common problem in demented patients. Undernutrition may be caused by several factors including anorexia (common cause: polypharmaco-therapy), insufficient oral intake (forgetting to eat), depression, and apraxia of eating or, less often, enhanced energy requirement due to hyperactivity. In advanced stages of dementia, dysphagia may develop and might be an indication for enteral nutrition in a few cases. The most common swallowing disorder in the elderly, is part of deconditioning after acute illness which may be cured with the cure of the acute illness, rehabilitation of swallowing mechanism and adjuvant nutrition support. It is of the greatest interest of the elderly patient that the correct diagnosis of the swallowing disorder is made and that he will receive the adequate treatment. The swallowing process is less synchronized due to changes in the pharyngeal structure and deterioration in its neural control because of a decrease in neural conductivity which affects neural response. The swallowing mechanism is affected in different neurological

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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disorders like CVA, Parkinson disease and others and if medical and rehabilitation treatment can not overcome it there is a need to bypass the swallowing system for feeding by use of a naso-gastric tube or percutaneous gastrostomy (endoscopic or surgical). Patients with dysphagia due to acute neurological damage secondary to a cerebrovascular accident may have reversible dysphagia and benefit from rehabilitation treatment or it remains as permanent stable damage. In this case bypassing the disturbed swallowing mechanism remains the only solution for feeding these patients. Nevertheless theses patients remain in a stable neurological condition in contrast to the dementia patients in whom dysphagia represents further disease progression . Another swallowing disorder is taking place In patients with advanced dementia the swallowing problem is a reflection of advancement of a progressive disorder.

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The Role of Illness and Comorbidity Increased consumption of some nutrients during illness may lead to low levels of other nutrients. Low zinc, vitamin A, carotene and vitamin E concentrations were found in elderly subjects with leg ulcers [29]. Forty Scandinavians with hip fractures had lower plasma vitamin C concentrations than 102 age-matched controls [30]. This nutrient deficiency may affect the immune response in the elderly, as was previously demonstrated by Chandra [31]. A significant decline with aging in the delayed cutaneous hypersensitivity (DCH) response to seven antigens was found in a population of elderly subjects with a high prevalence of low and deficient serum values of vitamin C, vitamin E, riboflavin, pyridoxine, iron and zinc. Vitamin supplementation for a period of 10 weeks significantly improved the biochemical parameters for those vitamins and the age related decline in the DCH test was no longer statistically significant [32]. Drugs may reduce appetite and use of medication may change the consumption of a variety of foods and reduce intake. Moreover, drugs may affect the nutritional status by altering the patterns of absorption and/or nutrient utilization and excretion, e.g.: 1. 2. 3. 4. 5.

diuretics cause excess potassium and magnesium excretion; antacids decrease phosphorus absorption; H2 blockers reduce vitamin B12 and iron absorption; laxatives affect intestinal nutrient transport and absorption; antibiotics have an influence on the gut microflora that indirectly affect some nutrient absorption.

Alternatively, drug metabolism may be changed by diet [33]. In a recent study on 149 hospitalized elderly subjects, low thiamin plasma concentration was the most prevalent vitamin deficiency and it correlated with consumption of diuretics (mainly furosemide) which increase the urinary excretion of thiamin [34]. In four studies, mild thiamin supplementation was found to improve mood in the elderly [35].

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Determination of Nutritional Deficiencies in the Elderly It is only in the present century that the American Food and Nutrition Board has issued nutritional recommendations, the DRI (Dietary Reference Intakes), which also include allowances for those aged 70 years and older [36-38]. Despite the different determinations of nutritional deficiency, nutrient deficiencies do not consist only of the classical Protein Energy Malnutrition (PEM), but also of marginal, borderline or subclinical micronutrient deficiencies caused by inadequate micronutrient intake. There is some confusion about the terminology used to express nutritional status. Nutritional status studies do not always discriminate between ‘malnutrition’ and ‘the risk of being undernourished’ or ‘being at nutritional risk’. For some, being at risk of malnutrition is different from actually being malnourished: being malnourished certainly sounds worse than being at risk of it. Others think that these two terms are one and the same. The terminology of nutritional risk can also cause difficulties in certain research situations, especially when nutritionists collaborate with clinical investigators from other disciplines. That a particular demographic or physiologic factor might increase or decrease the risk of being at nutritional risk can be a difficult concept to convey, and the selection of statistical methods can be hampered by the seemingly circular logic [39]. The sequence of events which leads from the healthy state to nutritional morbidity and mortality consists of a preliminary latent phase, through subclinical physiological to marginal clinical and clinical stages (Table 1). The two first stages represent the concept of ‘borderline nutritional deficiency’ which is of great importance in the fields of health promotion and prevention, especially in the elderly.

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Table 1. Stages of Micronutrient Deficiencies

I

II II I

Stage Prelatent: Preliminary, biochemical Latent: Subclinical, physiological Overt: Clinical

Pathophysiologic Meaning Decrease in micronutrient concentrations in different tissues Decrease in metabolite and enzyme activities Morphological and functional disorders

Detection Methods Dietary intake inquiry and chemical studies of different tissues Biochemical and physiological studies Clinical signs and symptoms Functional evaluation

Protein and Energy Deficiencies in Elderly The elderly eat considerably smaller amounts of food and eat less often than younger adults. Especially at times of acute or chronic illness, this lower intake leads to energy deficit and general malnutrition accompanied by deteriorated mood, a condition often defined as Failure To Thrive (FTT) [40]. Forty percent of elderly hospital admissions in the United Kingdom are undernourished, half severely so. In a recent study Allison et al. [41]. Showed that elderly patients consume less than 70% of their energy (recommended intake, 30 to 35 kcal/kg/d) and protein (recommended intake, 1 g/kg/d) requirements.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Hypoalbuminemia is found in more than 60% of malnourished geriatric patients and albumin remains one of the most sensitive markers of malnutrition. Hypoalbuminemia arises because diseases and multiple morbidity are frequent in the elderly and they regularly result in the release of cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The cytokines initiate a catabolic phase which is characterized by breakdown of muscle cells as well as rapid loss of appetite. The aversion to meat consumption of diseased elderly people is well known. Illness and lack of appetite preserve the catabolic state. This is a common phenomenon in geriatric patients. Lack of appetite and the specific cytokine pattern [42], lead to significantly decreased food consumption. Because the albumin deficit is hardly noticed at its early stage or if noticed, is not attributed to preexisting malnutrition [43], malnutrition persists and often gets worse after the patient’s admission to the hospital [44]. Without prompt diagnosis and appropriate countermeasures, the patient’s nutrition parameters will continue to deteriorate from day to day. In such a situation, refeeding to restore normal nutrition parameters can take days or weeks [45].

Protein Energy Malnutrition and Sarcopenia of Aging

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Definition of Sarcopenia in the Elderly Sarcopenia is a common phenomenon in elderly subjects. Its pathophysiology is not yet well understood. Because it is prevalent in the elderly, it is most important to differentiate it from PEM. Loss of body weight in older adults may be caused by many factors, of which some may be part of biological aging but others are definitely related to disease. The quantitative definition of sarcopenia is very difficult, and therefore the measurement of its prevalence is quite hard. However, if one defines it according to a boundary condition, such as 2 SD below the mean appendicular muscle mass of young healthy adults, one can determine its prevalence according to this level of severity [46]. Data are available from the New Mexico Elder Health Survey by Baumgartner et al. [47], who measured appendicular muscle mass in 883 randomly selected elderly Hispanic and white men and women by dual energy x-ray absorptiometry. Sarcopenia was defined as a muscle mass ≥2 SD below the mean for young healthy participants in the Rosetta Study [48], a large cross-sectional study of body composition in New York. The prevalence of sarcopenia according to this definition increased from 13-24% in subjects aged 65 to 70 years to over 50% in those older than 80. The prevalence increases in both men and women, though it is actually higher in men above 75 years old (58%) than in women (45%) of the same age. The higher prevalence of sarcopenia in men noted is consistent with the greater change in the quality of lean mass that occurs in men, as stated earlier [48]. However, the results of Baumgartner et al. [47] as well as of Ellis [49] imply that the biological process of sarcopenia occurs in both sexes, although perhaps to a greater extent in men [44].

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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The Causes of Sarcopenia in the Elderly

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Although the causes of sarcopenia are not yet clearly understood, there are many possible mechanisms. The role of protein deficiency in the development of sarcopenia is problematic. Castaneda et al. [50] showed that eating half the recommended dietary allowance (RDA) for protein of 0.8 g/kg/d, led to a significant decline in strength, body cell mass and insulin-like growth factor-1 (IGF-1) levels in postmenopausal women, but it is not clear whether moderate reductions in protein consumption also contribute to sarcopenia [44]. Overall, aging can be considered as the withdrawal of or resistance to several anabolic stimuli to muscle ─ central nervous system (CNS) input, growth hormone, estrogen, testosterone, dietary protein, physical activity, insulin action ─ and possibly the development of several catabolic ones ─ subclinical inflammation and production of catabolic cytokines, e.g. TNF-α, IL-6 and possibly IL-1β. In addition to the decline in anabolic stimuli that occurs with age there is also evidence of an increase in catabolic stimuli. Roubenoff et al [51] found that production of IL6 and IL-1Ra (IL-1 receptor antagonist) by peripheral blood mononuclear cells (PBMC) of ambulatory elderly participants (72–92 years old) in the Framingham Heart Study was significantly higher than that of younger controls (40 years old). Whether the anabolic or catabolic stimulants are more important, or even paramount, remains to be examined [44]. If there is a single most important cause of sarcopenia, it is probably the loss of motor neuron input to muscle that occurs with age [52]. Because innervation is crucial to the maintenance of muscle mass as well as muscle strength, it is possible that this decline is at the heart of sarcopenia. It is still unknown what role physical activity, hormone levels or genetic factors have in preserving motor unit numbers in older subjects [44]. 1. Endocrine and Metabolic Causes of Sarcopenia Of the hormonal anabolic inputs that decline with age, the sex hormones are probably the most important. Between the ages of 25 and 75 years, mean serum testosterone levels decline by about 30% and free testosterone levels decline by up to 50% and continue to decline with advancing age [53, 54]. The action of insulin, one of the major anabolic hormones related to muscle, also appears to decline with aging. In the pre-insulin era, diabetes mellitus was associated with severe muscle wasting. Insulin increases body cell mass and body nitrogen in diabetics [55, 56]. Its main action on muscle tissue appears to be in inhibiting protein breakdown, though it has been difficult to show its sustained effect in increasing muscle protein synthesis [57, 58]. Insulin resistance could also play a role in the development of sarcopenia. This resistance increases with age due to fat mass (especially visceral fat mass) accumulation and physical inactivity [59-63]. The diminution in insulin action that occurs in many older adults may well have a procatabolic effect on muscles [44]. Growth hormone (GH) begins to decline in the fourth decade and declines progressively thereafter. However, it is not clear at all whether GH deficiency is an important contributor to sarcopenia. Roubenoff et al, [64] found that among postmenopausal women 24-hour GH secretion was highest in those with the lowest body cell mass, which is the opposite of what is predicted by a straightforward GH-deficiency hypothesis.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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2. Physical Activity and Sarcopenia Physical activity is considered an anabolic activity and it is used as the main means of body building. Baumgartner et al. [65], using the New Mexico data, recently performed a cross-sectional analysis which evaluated the relative contributions of physical activity, dietary energy and protein, health status, serum testosterone, estrone, sex hormone-binding globulin and IGF-1 to sarcopenia in 121 men and 180 women aged 65 to 97 years. The authors found that muscle mass in men was significantly associated with free testosterone, physical activity, heart disease and IGF-1. In women, muscle mass was only associated with total fat mass and physical activity. The most convincing evidence of the importance of physical activity probably comes from the demonstrated capacity of exercise to reverse sarcopenia [44].

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Micronutrient Deficiency and Borderline Deficiency Elderly people are at particular risk for marginal deficiencies in vitamins and trace elements. Early detection of deficiencies and appropriate treatment are an important challenge. We can prevent deficiency by adequate micronutrient recommendations, thereby promoting health, increasing longevity and improving quality of life. Concerning micronutrients, the previously discussed concept of ‘borderline micronutrient deficiency’ is of utmost importance for the elderly. Food intake decreases with aging, resulting in lower micronutrient consumption [40, 41] . Inadequate intake of microelements and vitamins of varying degrees in the elderly has been described in many studies [66]. In many of the studies there is no data for several micronutrients, in particular for pantothenic acid, biotin, vitamin K, manganese, copper and iodine. For most of the micronutrients except for vitamin B12 (where one extreme value substantially increased the average value), median values are close to the average ones [66].

Zinc Deficiency Mild zinc deficiency is common in the elderly, but frequently cannot be confirmed because there are no conclusive criteria for the definition of zinc status. In order to evaluate such criteria, 15 elderly were put on a moderately zinc deficient diet and then on a zinc repletion diet, for 15 days each. Alkaline phosphatase, red blood cells methallothionein, Cu and Zn did not change in response to dietary alterations as expected. Only 5’-nucleotidase significantly decreased after depletion and increased after 6 days of repletion [67]. Low plasma zinc levels are more prevalent in the elderly ill [68, 69] and they are detected early in the course of malnutrition. Lymphopenia and thymic atrophy, which are early markers of zinc deficiency, are known to be caused by high losses of precursor T and B cells in the bone marrow [70]. Because of this, zinc deficiency is considered a causative factor of immune impairment in the elderly.

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Iron Deficiency Iron deficiency is prevalent in geriatric patients [71], but less common in ‘apparently’ healthy elderly subjects. Low iron intake in the elderly was observed in only 2 out of 38 studies [66]. Evaluation of 1016 subjects from the Framingham study aged 67 to 96 [72], found a prevalence of only 2.7% of iron deficiency while 12.9% had elevated iron stores, of which only 1% could be explained by chronic disease. In a study of 163 hospitalized elderly no correlation was found between iron stores and iron consumption [73]. Anemia is one of the most fascinating problems in geriatrics medicine, but recent data suggests a more complicated etiology than just iron intake and loss. Discriminant analysis of iron deficiency in 51 women in their seventies could not clearly differentiate between iron deficiency anemia and anemia of chronic disease [74]. In another study, anemia was prevalent in 25% of the subjects with elevated CRP (C-reactive protein) [75]. In a study of 1268 British elderly with low iron status, interactions with other nutrients were found. Alcohol, vitamin C, protein and fiber consumptions were positively associated with iron status while calcium, dairy products and tea consumption were nearly all negatively associated with iron status [76].

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Vitamin B12 and Folate Deficiencies Folic acid and vitamin B12 deficiencies, prevalent in about 10% and 14% respectively of the US population, may explain 25% of the genetic mutations occurring in the US [77]. However, low consumption of vitamin B12 was not found in any of 38 studies performed on the elderly, though in 15 of these studies low folate intake was observed [66]. Folate depletion was associated with increased DNA methylation in elderly women [78]. It has been recently shown that the prevalence of low plasma concentrations of vitamin B12 and antioxidants is lower with better intake of the vitamins [79]. The prevalence of vitamin B12 deficiency is about 40% in hospitalized ill elderly subjects in subacute care [80]. However, there is mounting evidence that vitamin B12 malabsorption increases with age, probably as a result of autoimmune atrophic gastritis [81, 82]. The primary manifestations of vitamin B12 deficiency in the elderly are peripheral neuropathy and reduced nerve-conduction velocity [83], reversible psychiatric illnesses, particularly delirium and cognitive disturbances including dementia [84, 85], Slight macrocytosis is often present, but macrocytic anemia is relatively uncommon.

Pyridoxine Low pyridoxine (vitamin B6) intake was observed in 18 out of 38 studies [66]. According to a recent evaluation of 546 elderly subjects in Europe as part of the SENECA study, 27% of the males and 40% of the females had low vitamin B6 intake as well as lower plasma concentrations of PLP (Pyridoxal Phosphate), a vitamin B6 derivative [86].

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Riboflavin Deficiency Riboflavin deficiency has no specific clinical signs. Eight out of the 38 studies reviewed in Table 3 demonstrate low consumption of riboflavin, which is usually associated with lower consumption of other vitamins [66]. In a recent study, it was found that in 75% of rural elderly Malays [87], riboflavin deficiency was associated with other deficiency states.

Fat Soluble Vitamins The densities of vitamins E and D were markedly lower in 13 and 10 studies, respectively, and far below the calculated RDA density values [66]. The lower vitamin E value may be partly due to the fact that the database used in the study takes into account a 50% loss of vitamin E during cooking [66,88]. Vitamin D density is lower because milk and milk products contain only traces of vitamin D and as in an Austrian study [66, 89], the elderly did not consume marine fish. Thus the main sources of vitamin D were eggs and meat, which contain only small amounts of this micronutrient. Vitamin A density in most of the studies exceeded the calculated RDA density value. Nutrient density appears to better reflect inadequate intake. It is a powerful tool for evaluating adequacy of micronutrient consumption because it is almost unaffected by individual under- or over-estimation of food intake. This is particularly true with the densities of vitamins D and E (fat soluble) as well as biotin, folic acid and vitamin B6 (water soluble) [66].

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Antioxidant Vitamins In one of the recent surveys on the elderly nutritional status [90], which compared antioxidant vitamin status in elderly cachectic (n=21) and non cachectic (n=106) subjects, the authors could not demonstrate differences in routine clinical laboratory tests but could show significant differences in plasma concentrations of ascorbic acid and carotenoids. This study demonstrates the significance of clinical evaluation of PEM in further identifying nutritional deficiencies in the elderly. In another study, 10% of 416 hospitalized elderly subjects suffered from atrophic glossitis, which correlated with lower plasma albumin as well as serum cholesterol, ascorbic acid, cholcacidiol and vitamin B12 concentrations [91].

Clinical Symptoms of Malnutrition All early symptoms of nutritional deficiencies are nonspecific and progress slowly (Table 3). Malnutrition is often considered as a normal age-associated phenomenon and is regarded as a “sign of aging.” Thus, an early diagnosis of malnutrition is difficult. The most typical early signs observed at the onset of malnutrition are diminished appetite and dislike of meat [92].

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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Table 3. Clinical Symptoms of Malnutrition in the Elderly Early symptoms

Diminished appetite Dislike for meat Reduced nutrition intake by 1/3 of the daily needs General restlessness Permanent fatigue Reduced mobility

Late clinical symptoms

Loss of appetite Avoidance of meat consumption Reduced nutrition intake by 2/3 of the daily needs Muscle wasting and weakness Permanent severe fatigue Significant weight loss Dry, thin, and cracked skin Immobility Dependence

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Prevalence of Deficiencies in Different Populations Stanga and Allison have recently stated that PEM, either accompanied or not by micronutrient deficiencies, is prevalent in up to 38% of elderly patients; 12% of the homebound, up to 65% of hospitalized patients and up to 85% of institutionalized elderly [93]. Inadequate intakes have been observed in many countries: in free-living pensioners with additional anthropometric and biochemical findings [94] and in institutionalized elderly [95] in Perugia, Italy; in the SENECA all European study [96, 97]; in distinct populations in France [98]; in the USA [99]; and in Israel [100]. According to the USDA Survey of Food and Nutrient Intakes by Individuals in the United States [101], approximately one third of men and women over 60 year of age eat less than 0.8 g/kg of protein per day, and approximately 15% eat less than 75% of the RDA. Recent meta-analysis on protein consumption [102] confirms that the RDA for protein for the elderly is set more or less at the optimal level. There is some data supporting the benefit of higher protein intake for increasing bone strength. However, with higher protein consumption a certain risk to the kidney is quite evident.

Active Enteral Nutrition Support Active nutritional support using the technique of tube feeding is a common practice in elderly with advanced dementia and other neurological disorders in Israel. [46]. In 2008 there

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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were approximately 1600 elderly patients, receiving active enteral nutritional support 800through a naso-gastric tube-, through and an additional 800percutaneous endoscopic gastrostomy. Nutrition support is a medical treatment that by definition supports living efforts and other medical and surgical treatments. It has several levels of intervention starting with dietary manipulation to improve quantity and quality of nutritional intake, swallowing rehabilitation, addition of specific nutrients in different forms like iron, other minerals and vitamins, energy and protein to running diet, using artificial formulas of food consisting all the nutritional ingredients in recommended amounts- defined as medical foods. When medical foods is delivered through tube feeding, whether naso-gastric, gastrostomy or jejunostomy, bypassing the swallowing mechanism, nutrition support becomes active enteral feeding. Parenteral Nutrition is the other form of nutrition support, delivering the nutritional component in active form using intravenous solutions when gastro-intestinal insufficiency is present and there is a need to bypass this system in order to supply the patient with sufficient nutrition. Recently a meta-analysis of protein and energy supplementation in older patients has provided the information that current evidence does not support routine supplementation at home or at any setting, except for undernourished elderly in the acute care setting. [103] This study supports the American College of nutrition National Institute of Health and the American Society of Parenteral and Enteral Nutrition conclusions from 1997 [104] that there are no published observations providing direct evidence that wasting is a cause of death and that reversal of wasting improves outcomes.

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Ethical Consideration in Making the Decision on Active Enteral Nutrition Support Some studies with ONS (Oral Nutrition Support) have shown improvements in body weight [105, 106, 107]. In tube-fed (TF) demented elderly patients, two studies reported weight gain [108, 109], but two others reported no change [21, 14]. Most of the available trials regarding the effects of ONS [105, 106] or TF [110, 111] on functional status, report no improvement in terms of survival [111, 112, 113]. On the other hand, Rudberg et al [114] described lower mortality, compared to controls, at 30 days and 1 year in enterally fed patients with severe swallowing disorders including patients with cognitive impairment. Very low mortality rates have been reported in PEG fed demented nursing home residents [115, 116]. In the Israeli study [116] differences have been shown between those with progressive dementia and the others. On the other hand, in one retrospective study comparing mortality rates in different diagnostic groups, outcome was worst among the demented [117]. According to the European Society of Parenteral and Enteral Nutrition (ESPEN) for the placement of PEG, published in 2005 [118], dementia is the most controversial indication. The stated aims of tube feeding in advanced dementia included improvement of functional status, avoiding hunger, improving comfort, preventing nutritional decline and its consequences’ preventing aspirations and reducing the incidence of pressure ulcers and infection. Decision on active enteral feeding, as any other medical treatment has to be done according to the four principles of medical ethics as were postulated in the Helsinki treaty:1.

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Patient’s autonomy, 2. Social justice. 3. Beneficence 4. Non-mal efficience to the patient. In order to consider these principles it is suggested to divide them into two groups: the first two are those which are not dependent on the physician, while the last two are dependent only on the knowledge and experience of the physician and his individual evaluation of each patient. Since most demented patients who need active nutrition support are not in a condition to express their wishes according to the first principle and the society gives the possibility for active nutritional support to these patients, the decision has to be done according to our medical experience and knowledge using the two principles of patient’s beneficence and non mal efficience. The specific questions have to be: 1. Does the patient suffer from a condition that is likely to benefit from EN? 2. Will nutritional support improve outcome and/or accelerate recovery? 3. Does the patient suffer from an incurable disease, but one in which quality of life and well-being can be maintained or improved by EN? 4. Does the anticipated benefit outweigh the potential risks? These questions are discussed in details, answering detailed questions concerning the evidence for beneficence and non mal efficience in ESPEN guidelines for enteral nutrition support in elderly [119]. Nevertheless it remains the main task of the clinician to evaluate and decide if the treatment is adequate or not for each individual patient.

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Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter V

Chronic Constipation in the Elderly Joseph Lysy Hadassah University Hospital, Jerusalem, Israel

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Epidemiology Chronic constipation is among the most common symptoms reported to physicians, affecting 2 -27% of the population [1]. Constipation accounts for more than 2.5 million office visits in the USA and over 500 million dollars spent on laxatives per year. The cost of testing alone in patients with constipation has been estimated to be $ 6.9 billion annually [2]. Constipation occurs in all age groups but is more common in those older than 65 years (3). This age- specific increase in prevalence was observed in both whites and nonwhites in the U.S.A. [4]. Elderly patients tend to seek medical assistance for constipation more commonly than younger persons [5]. Epidemiological studies show that up to 20% of community-dwelling and 50% of the institutionalized elderly, report symptoms of the disorder [6, 7]. Elderly patients most commonly describe constipation as excessive straining and hard stools rather than a decrease in stool frequency [6]. In Olmsted County, Minnessota, constipation was significantly more prevalent in old residents, 65 –93 years of age than in those aged 30-64 years. 12.5% of elderly persons entering a nursing home had constipation and furthermore constipation developed in 7% over 3 months of follow up [8]. Fecal impaction is very common among elderly patients. In one study among patients hospitalized in a geriatrics ward in the United Kingdom, up to 42% of the patients had fecal impaction [9]. Bowel dysfunction in the elderly and in particular chronic constipation have a significant negative impact on functional status, quality of life, daily activity and adversely affects the health care system in terms of resource utilization and cost.

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Definition of Chronic Constipation The broad range in the prevalence of constipation reflects differences in how it is defined and, in particular, a lack of agreement between patients and physicians regarding how they perceive it. Physicians mainly define constipation on the basis of stool frequency, considering fewer than three bowel movements per week to be abnormal. In contrast, patients typically define it on the basis of bothersome symptoms such as straining, passage of hard stool, unproductive urges, inability to defecate at will, and sensation of incomplete evacuation or abdominal bloating. Most patients with a complaint of constipation have a functional disorder that affects the colon and/or anorectum. "Functional" is used to describe symptoms or problems that have no underlying anatomic abnormalities, yet, their normal function has changed. The accepted diagnostic criteria for chronic functional constipation are those agreed by the Rome Working Group on Functional bowel Disease. The most recent Rome III criteria were developed to provide a consistent diagnostic approach for use in clinical practice and clinical trials. The Rome III criteria define functional chronic constipation as a chronic bowel disorder characterized by two or more of the following:

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• • • • • •

Straining Lumpy or hard stool Sensation of incomplete evacuation Sensation of anorectal obstruction or blockage Use of manual maneuvers to facilitate defecation during at least 25% of defecations Fewer than three bowel movements per week

In addition, loose stools should rarely occur without the use of laxatives. Chronic constipation is defined, when symptom onset occurred within the previous 6 months and symptom duration is at least 3 months. It was found that that stool consistency and form correlate best with colonic transit time. The Bristol Stool Scale or Bristol Stool Chart is a medical aid designed to classify the form of human feces into seven categories [10]. Type 1 and 2 indicate constipation and are described as follows: • •

Type 1: Separate hard lumps, like nuts (hard to pass) Type 2: Sausage-shaped, but lumpy

Risk Factors for Constipation in the Elderly There are several potential mechanisms or risk factors for chronic constipation in the elderly: increased mobility, inappropriate diet, depression, medications, neuromuscular disorders, change in gastrointestinal function and co-morbidities, or degeneration of the enteric nerves and poor rectal sensation and evacuation dynamics [11]. Increased prevalence of straining in the elderly is probably secondary to reduced mobility, weakening of abdominal and pelvic wall muscles, chronic illness and psychological

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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factors [12]. In general, there is an increase in drug consumption with age because elderly subjects often suffer from multiple chronic disease states and organ dysfunctions [13]. Opioids, diuretics, antidepressants, antihistamines, antispasmodics, anticonvulsants, and aluminum antacids have been found to be significantly associated with constipation [14]. The use of aspirin or other nonsteroidal anti-inflammatory drugs in the elderly population is associated with a small but significantly increased risk of constipation [15].

Types of Constipation Primary or Idiopathic Constipation There are three types of primary or idiopathic constipation,

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1. Normal transit 2. Slow transit 3. Outlet dysfunction Normal transit constipation: includes functional chronic constipation and irritable bowel syndrome that is constipation predominant. It presents with abdominal discomfort and bloating, difficult evacuation and hard stools. In chronic functional constipation, pain and discomfort may be present but are not the primary symptom. On the other hand, the major symptom of constipation-predominant irritable bowel syndrome, is severe discomfort or pain. Transit time and stool frequency is normal or slightly delayed in this type of constipation. Slow transit constipation: Can be simply defined, as a functional constipation characterized by delayed colonic transit. Its symptoms include low stool frequency, lack of urge to defecate, abdominal distention and bloating and abdominal discomfort. This is a motor disorder of the large bowel, characterized by ineffective colonic propulsion. No increased motor activity was seen following intake of a stimulant drug such as Bisacodyl or administration of a cholinergic drug such as neostigmine, or postprandially. Fewer high amplitude propagating contractions were seen in patients with STC, which may indicate enteric nerve system disruption. Indeed, decreased interstitial cells of Cajal were seen in the myenteric plexus of patients with this disorder [16]. Dysfunction of the neuroendocrine system is also present in aging, characterized by: decreased release of acetylcholine from colonic tissue and increased nitric oxide in ICC preparations from the distal colon. Serotonin has a role in regulating visceral pain perception and intestinal motility, as well as secretion. Clinical trials have shown that activation of serotonin receptors in the gut enhances gastrointestinal motility, inhibits visceral sensitivity, and stimulates intestinal secretion [17]. A decrease in serotonin immunoreactivity in the muscular mucosa and circular muscle was identified in patients who underwent subtotal colectomy for colonic inertia [18]. Age related anatomic changes of the colon may contribute to delayed transit time. These changes can include intestinal wall atrophy, reduced blood supply and intrinsic neuronal changes. The decrease in neuron density in the aged, is accompanied by an apparent increase

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in the fibrous components of the myenteric ganglia. These findings suggest that neurodegenerative changes may contribute to the disturbed colonic motility in the aging population. Secretion and absorption remain relatively stable over time. Colonic function in the old age appears to be more influenced by factors associated with aging (e.g. chronic disease, immobility and medications) than aging itself. Elderly people with chronic illness and constipation have a prolonged total gut transit time of 4-9 days (normal < 3days). Nursing home residents, mainly those who are least mobile, have even more prolonged transit times of up to 3 weeks [19]. Outlet dysfunction called also dyssynergic defecation and anismus, results from a functional defect in coordinated evacuation. Defecation involves the coordinated relaxation of the puborectalis and external anal sphincter muscles together with increased intraabdominal pressure. In patients with this disorder, ineffective defecation is associated with failure to relax, or inappropriate contraction of the puborectalis and the external anal sphincter muscles. The characteristic symptom is a feeling of being unable to adequately empty the rectum. Other symptoms are straining, sensation of incomplete evacuation and manual disimpaction which are not unique to pelvic floor dyssynergia. Older people have reductions in pelvic floor muscle strength as well as in rectal sensitivity and anal function [20, 21]. Failure to straighten the rectoanal angle during attempts to defecate, contributes to constipation in elderly women and may be a factor in the development of constipation associated with perineal laxity [22]. Combined forms: patients may have more then one type of primary constipation and presentation, and pelvic floor dyssynergia has been shown to prolong intestinal transit, which may improve with the treatment of dyssynergia. Fecal impaction is very common among elderly patients. It is considered to be a complication of chronic constipation, and is an important risk factor for fecal incontinence caused by overflow diarrhea. In one study elderly patients with constipation and a history of impaction had impaired rectal and perineal sensation and required significantly larger volumes of rectal distention to stimulate the normal urge to defecate [23]. Immobility, and inadequate toileting facilities are further risk factors for this condition in the elderly. Disordered defecation and fecal impaction can occur as a result of injury to the pudendal nerve. The incidence of pudendal neuropathy is increased in elderly females [24]. Injury to the pudendal nerves can lead to abnormal perineal descent, which can impact rectal emptying by causing partial prolapse of the anterior rectal mucosa. Fecal impaction may lead to urinary retention, to intestinal obstruction or even colonic (stercoral) ulceration. Excessive straining at stool can affect cerebral, coronary and peripheral arterial circulation that may induce syncope or cardiac ischemia. Secondary constipation may be due to changes of diet and lifestyle. Dehydration, low caloric and low fiber diet are all risk factors for constipation and observed more frequently in the old age. Certain medications, such as calcium channel blockers, beta blockers, opioids , diuretics, antidepressants, anticonvulsants anticholinergics and antispasmodics, may cause constipation. Chronic illnesses are frequently associated with constipation. Congestive heart failure, chronic renal failure, diabetes mellitus, hypothyroidism, Parkinson's disease, autonomic neuropathy, cerebrovascular disease, depression and dementia are the most common chronic illnesses associated with constipation in old age.

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Diagnosis Most of these conditions can be identified by history, physical examination and selective diagnostic testing. A full medical history and physical examination remain the cornerstone of the diagnosis of constipation especially in the elderly where physiologic tests are frequently not possible to perform. The history may provide clues to the primary cause. The patient interview yields information about the frequency and consistency of stool, the need to strain or manually disimpact, the sense of incomplete evacuation, pain, bleeding, or prolapse. Risk factors for primary and secondary constipation to note during the interview include Low fiber diet, low fluid intake, lack of physical activity, endocrine and neuromuscular disorders, depression or anxiety, family history of cancer, and personal history of pelvic surgery. Medication lists should be reviewed and adjustment should be made if necessary before recommending laxatives or invasive testing. Alarm signs such as weight loss, hematochezia, changes in bowel habit and symptoms refractory to therapy may represent colon cancer and indicate the need for diagnostic testing. Physical examination should include perianal inspection, digital rectal examination, and a focused examination of the perineum. The inspection may reveal prolapsed hemorrhoids, a patulous anus (indicative of denervation), anal deformity or dermatitis resulting from frequent soiling (an indirect sign of fecal impaction). Excessive perineal descent (> 3cm) or rectal prolapse may be identified by asking the patient to strain as if to defecate. Perineal sensation is determined by lightly touching the perineal skin with a cotton-tipped stick. Induction of the anocutaneous reflex (a brief contraction of the external anal sphincter anal sphincter when the perineal skin is lightly stroked) indicates the presence of intact sensory and motor innervation. Digital rectal examination may reveal a contracted sphincter or a puborectalis muscle that contracts with the Valsalva maneuver, suggesting dysfunction. Digital rectal examination is useful to exclude structural abnormalities (e.g. mass, stricture or fecal impaction). Laboratory testing: If the history and physical examination suggest that constipation may be secondary, laboratory studies such as complete blood cell count, serum electrolyte levels, blood sugar level and thyroid function studies may help to rule out a metabolic, endocrine or organic cause. Plain abdominal radiographs are of value in defining fecal loading and megacolon and may provide the first hint of obstruction. There is scant evidence that routine colonoscopy is warranted in patients without evidence of secondary constipation and without alarm signs [25]. However, diagnostic studies are indicated in patients 50 years of age and older, if they did not have a previous screening colonoscopy. Alarm signs such as recent onset, hematochezia, anemia, a positive occult blood test, family history of colon cancer and unintentional loss of more than 5 kg are also an indication for colonoscopy. Due to its low cost and the infrequency of serious side effects, an initial trial of increased dietary or supplemental fiber remains a rational first step. Patients intolerant to fiber supplement may be treated with an osmotic laxative such as polyethylene glycol. Patients failing to respond to a trial of fiber or an osmotic laxative may benefit from additional physiologic testing. These tests require a certain degree of cooperation and are not suitable for patients with severe physical disability and for those with advanced dementia.

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Physiologic tests allow identification of patients with slow transit constipation and /or dyssynergic defecation. Symptoms alone do not adequately allow differentiation of these disorders. Balloon expulsion testing which can be performed bedside provides a simple, inexpensive screening test for dyssynergic defecation. In selected patients anorectal manometry and, possibly, defecation proctography may be considered. Anorectal manometry identifies the efficacy of propulsive forces, the presence of the rectoanal inhibitory response (it is absent not only in Hirschprung's disease but also in megarectum), and the presence of anal sphincter/puborectalis relaxation during strain. Radio-opaque marker transit tests will separate normal transit from slow transit constipation.

Management of Chronic Constipation in the Elderly

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The aims of treatment of chronic constipation are to relieve symptoms, restore normal bowel habit, i.e. the passage of a soft, formed stool at least three times a week without straining, and to improve quality of life with minimal adverse effects. Treatment should be individualized for each patient according to identified causes. Any elderly individual presenting with constipation should have a thorough review of their medications. Medications that can cause constipation should be replaced with an appropriate alternative medicine, when possible. It is often suggested to increase water intake, physical activity and a scheduled attempt at defecation when motor activity in the colon is highest, i.e., in the morning or after eating. Data on the efficacy of these recommendations are scarce and often contradictory. Nevertheless, many patients who comply with dietary and exercise recommendations have improvement in symptoms.

Bulk (Fiber) Laxatives Although patients with constipation have not been shown as a group to consume less fiber than individuals without constipation, an initial trial of fiber is a cost – effective, safe first therapeutic choice. Fiber laxatives increase the weight and water absorbent properties of the stool. A variety of options exist for supplementing fiber. The best fiber is the one that the patient is willing to try and continue. The best way to add fiber is by making subtle changes to the diet. The changes should be made gradually to avoid abdominal pain and bloating, which can occur with ingestion of fiber. Patients taking fiber and bulk forming laxatives are usually advised to drink plenty of fluid so as to avoid mechanical obstruction. Fecal impaction should be removed before initiation of fiber therapy. Food containing complex carbohydrates, such as prunes or melons, can also help normalize bowel movements. Insoluble fiber resists bacterial degradation in the colon and can retain more water than soluble fiber can. Bran 20 g/day increased the frequency of bowel movement by 55%, increased fecal weight by 157% and decreased intestinal transit time by 50% in women who had three or fewer bowel movements per week [26]. Elderly constipated patients who received 10 g of bran twice a day had significantly shorter transit times (89 hours vs 126

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hours) than did those who received 6 g of psyllium (a soluble fiber) twice daily. They also needed less additional laxative [27]. Soluble fiber, also affects the bowel habits of both healthy and constipated patients. Psyllium. In one study patients with chronic constipation were randomly assigned to receive either 5 g of psyllium twice daily or placebo for 8 weeks, followed by a 4-week washout phase in which placebo was given. Those who received psyllium reported significant improvement in stool consistency and pain with defecation , as well as significant increases in both stool frequency and stool weight. However, colonic transit times and anorectal manometric measurements did not differ significantly between the two groups [28]. Psyllium treatment was associated with increased stool frequency over a 16 week follow-up period, in a small group of patients with Parkinson's disease (mean age 66 years) [29]. Metylcellulose, is another non soluble semisynthetic fiber which found to be as effective as psyllium, at increasing stool frequency, fecal water weight, and fecal solids [30]. Side effects of bulk laxatives include the sensation of bloating and distention, excessive gas production, and abdominal cramping. Patients failing to respond to fiber or those who develop gaseous side effects may try laxatives as follows.

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Osmotic Laxatives These laxatives are composed of molecules that are either not absorbed or poorly absorbed. Hyperosmolality of these compounds results in a shift of water into the intestinal lumen to maintain isotonocity between the intestinal contents and the serum. Examples for osmotic laxatives are polyethylene glycol (PEG), poorly absorbed sugars (lactulose, sorbitol), salts (sodium phosphate, magnesium hydroxide, magnesium citrate) and glycerin. The most commonly prescribed osmotic laxatives are PEG (polyethylene glycol) and lactulose. Both are equally effective. PEG is generally better tolerated than lactulose and there is long-term data supporting chronic use [31]. PEG is not absorbed and lacks electrolytes, making it an attractive option in patients with underlying renal or cardiac dysfunction. Sorbitol (70%) may be a cost-effective alternative to lactulose in the elderly nursing home population [32]. Sugar laxatives, while effective, may have dose-limiting or uselimiting adverse effects such as abdominal bloating and flatulence. Although magnesium and sodium phosphate preparations are effective, there are multiple reports of clinically significant electrolyte abnormalities, renal failure, and congestive heart failure occurring with these preparations. Magnesium and phosphate toxicity were also reported. Magnesium interferes with the absorption of several medications, including digoxin , tetracyclines and chlorpromazine. Therefore the use of osmotic salts in the elderly is limited and requires caution and frequent monitoring.

Stimulant Laxatives Stimulant laxatives are usually reserved for use when bulking agents and osmotic laxatives fail. They include anthraquinones [senna, aloe, cascara, castor oil, diphenilmethane derivatives (bisacodyl, sodium picosulfate) and phenolphtalein (now withdrawn as shown to

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be carcinogenic)]. They act relatively quickly, often inducing a bowel movement 2-12 hours after they are taken, but frail elderly patients may have a slower response. Their mechanism of action involves increased intestinal motility and secretions by stimulating the colonic myenteric plexus and altering fluid and electrolyte flow. Their laxative effect is dose dependent since these agents inhibit the absorption of sodium and water at low doses and stimulate sodium and water influx into the colonic lumen at high doses. Stimulant laxatives may cause abdominal pain but not electrolyte disturbance when used in appropriate dosage [33, 34]. Tolerance may occur but it is uncommon in the majority of users. The potential for colon damage caused by chronic use of stimulant laxatives has been overstated and has led to a generation of physicians who are reluctant to use them on a long-term basis. Stimulant laxatives may be used on a regular basis when bulking or osmotic agents fail.

Stool Softeners Stool softeners include docusate sodium, docusate calcium and liquid paraffin. Docusate is of questionable efficacy, has been associated with the development of fecal soiling in the elderly and is therefore, not recommended for use in this age group. Liquid paraffin is only rarely recommended and only for a short period of time. It can cause inhibition of fat soluble vitamin absorption and in rare cases lipoid pneumonia if aspirated [35].

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Enemas and Suppositories Rectal disimpaction and colon cleansing with large –volume warm-water enemas combined with oral polyethylene glycol is used in elderly patients with fecal impaction to provide immediate relief. Enemas and suppositories play an important role in the management and prevention of fecal impaction. Suppositories can help to initiate or facilitate evacuation. Elderly patients require an ongoing program to prevent recurrence of fecal impaction and overflow incontinence. Such programs involve regularly scheduled defecation with the assistance of laxatives such as lactulose or PEG with a glycerin suppository and a tap water enema once weekly [36]. Combination of a laxative and a suppository was used successfully in stroke patients [37].

Biofeedback Biofeedback is the preferred treatment for dyssynergic defecation. Patients are trained to relax their pelvic floor muscles during straining and to correlate relaxation and pushing to achieve defecation. Two randomized controlled studies have provided convincing evidence of efficacy for biofeedback in patients with dyssynergic defecation [38, 39]. Studies show that the benefits of biofeedback are long-lasting. Biofeedback treatment in the elderly may be limited in some patients because of the inability to cooperate fully with the biofeedback programme.

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New Therapies for Chronic Constipation Chloride Channel Activators Lubiprostone is an agonist of the chloride channel subtype 2, found on the apical membrane of intestinal epithelial cells. It causes increased chloride secretion into the intestinal lumen, enhancing intestinal fluid secretion into the intestinal lumen, enhancing intestinal fluid secretion. It has been shown to be effective in chronic constipation by improving stool consistency and increasing the motility of the small intestine and colon. It is approved for treating chronic constipation in adults [40]. At a dose of 24 mcg twice a day, lubiprostone was more effective than placebo over the four week period of the study [41]. The drug is well tolerated, but its adverse effects include nausea, diarrhea and headache. The drug appears to be well tolerated by older people (over 65), in whom adverse effects occur less often than in younger users [42]. Lubiprostone appears to be an appropriate alternative for patients failing less cost – effective agents.

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Serotonergic Prokinetic Agents Serotonin is involved in regulating gut motility, visceral sensitivity, and intestinal secretion through serotonin 5-HT4 receptors, which are expressed mainly by enteric nervous system interneurones. The motility enhancing effects of many of the newer classes of prokinetics are mediated by stimulation of 5 - HT4 receptors on these enteric nervous system interneurones to enhance the peristaltic reflex. Cisapride, a 5HT3 receptor antagonist and 5HT4 receptor agonist was effective in relieving symptoms associated with chronic constipation. However, safety issues (cardiac arrhythmias) necessitated withdrawal of cisapride from the US market in 2000. Tegaserod, a serotonin (5 - HT4) agonist, was used in women with constipation predominant irritable bowel syndrome and in men and women with chronic constipation. However, in the US, tegaserod has not been approved for use in patients aged >65 years. Furthermore, it was suspended from the market in the US in 2007 owing to concern about a high risk of adverse cardiovascular effects compared with placebo. Prucalopride is a highly selective 5-HT4 receptor agonist. Prucalopride has been shown in several studies to improve spontaneous complete bowel movements [43]. However, high quality data supporting its use in the elderly are unavailable. Renzapride, A mixed 5-HT4 agonist and 5-HT3 antagonist, that has shown promising results in early studies on patients with constipation – predominant irritable bowel syndrome [44].

Guanylate Cyclase C Activators Linaclotide, a pro secretory agent, stimulates the luminal receptor guanilate cyclase-C on enterocytes, increasing cGMP and activating anion channels. This leads to increased chloride and bicarbonate secretion into the intestinal lumen. Phase 2 studies shows that linaclotide

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accelerate ascending colon transit and improve stool pattern and consistency in women with constipation predominant irritable bowel syndrome [45].

Peripheral Opioid Antagonists The recent approval by the FDA of 2 medications – methylnaltrexone and alvimopan – introduced a new class of therapeutic agents to clinicians. These peripherally acting mu opioid receptor antagonists selectively reverse opioid actions mediated y receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone , administered subcutaneously, is indicated for the treatment of opioid induced constipation in patients with advanced illness (eg, cancer,AIDS).who are receiving palliative care , when response to laxative therapy has not been sufficient. Alvimopan , an orally administered medication , has been used to facilitate recovery of gastrointestinal function after bowel resection.

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Conclusion Careful history taking, physical examination and blood tests, often reveal the cause of constipation in the elderly. Further testing is warranted only when there is diagnostic uncertainty, or if the patient fails to respond to treatment. The management of constipation requires an understanding of the patient's main symptoms and should be tailored to each individual's needs and expectations. Special attention has to be focused to those at risk for fecal impaction. Prophylactic measures may well be indicated in those at risk for impaction. Iatrogenic factors have to be searched for. Medications that can cause constipation should be replaced with an appropriate alternative medicine, where possible. The first line of treatment includes non pharmacologic approaches such as increasing fiber in the diet or taking fiber supplements. Additionally lifestyle changes such as increased physical activity when possible and dietary modifications may relieve symptoms in a subset of patientsOsmotic laxatives are the next step. Stimulant laxatives can be used intermittently in the more refractory cases. Newer drugs may play a role in the future.

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[25] Brandt LJ, Prather CM, Quigley EMM. Systemic review on the management of chronic constipation in North America. Am. J. Gastroenterol. 2005;100 Suppl1:S5-22. [26] Graham DY, Moser SE, Estes MK, The effect of bran on bowel function in constipation. Am. J. Gastroenterol. 1982; 77:599-603 [27] Anderson H, Basaeus I, Falkheden ,T Melkerson M. Transit time in constipated geriatric patients during treatment with bulk laxative and bran: a comparison. Scand. J. Gastroenterol. 1979; 14:821-826. [28] Ashraf W, Park F, Lof J, Quigley EM. Effects of psyllium therapy on stool characteristics, colon transitand anorectal function in chronic idiopathic constipation. Aliment. Pharmaceol. Ther. 1995;9:639-647. [29] Ashraf W, Pfeiffer RF, Park F. Constipation in Parkinson's disease objective assessment and response to psyllium. Mov. Disord. 1997;12:946-51. [30] Hamilton JW, Wagner J, Burdick BB, Bass P. Clinical evaluation of methylcellulose as a bulk laxative. Dig. Dis. Sci. 1988; 33:993-998. [31] DiPalmaJA, Cleveland MV, McGowan J, Herrera JL. A randomized, multicenter, placebo controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am. J. Gastroenterol. 2007; 102:1436-1441 [32] Volicer L, Lane P, Panke J, Lyman P. Management of constipation in residents with dementia sorbitol effectiveness and cost. J. Am. Med. Dir. Assoc. 2004; 5:239-241 [33] Kienzle-Hom S,Vix JM, Schuijt C. Comparison of bisacodyl and sodium picosulfate in the treatment of chronic constioation. Curr. Med. Res. Opin. 2007; 23:691 -699 [34] Muller – Lissner SA, Kam MA, Scarpignato C. Myths and misconception about chronic constipation. Am. J. Gastroenterol. 2005;100:232-242 [35] Bosshard W,Dreher R Schnegg J, et al. The treatment of chronic constipation in the elderly people: an update. Drugs Aging. 2004;21:911-930 [36] Chassagne P,Jego A, Gloc P et al. Does treatment of constipation improve fecal incontinence in institutionalized elderly patients? Age Aging. 2000; 29:159-64 [37] Harari D, Norton C, Lockwood L et al. Treatment of constipation and fecal incontinence in stroke patients: randomized controlled trial. Stroke. 2004;35:2549-2555 [38] Chiaroni G, Whitehead WE, Pezza V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology. 2006; 130: 657-64 [39] Rao SS, Seaton K, Milller M, et al. randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin. Gastroentrol. Hepatol. 2007;5:331-4 [40] Camilleri M, Barucha AE, Ueno R. Effect of the selective chloride channel activator, lubiprostone , on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am. J. Physiol. Gastrointest. Liver Physiol. 2006; 290:G942 – G947 [41] Johanson JF, Morton D, Geenen J et al. Multicenter 4 week , double – blind, randomized, placebo – controlled trial of lubiprostone, a locally – acting type-2 chloride channel activator, in patients with chronic constioation. Am. J. Gastroenterol. 2008; 103:170-177. [42] Ueno R, Panas R, Whale A, Zhu Y, Holland P. Long – term safety and efficacy of lubiprostone for the treatment of chronic constipation the elderly (abstract). Gastroenterology. 2006;130 (suppl 2):A188

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[43] Camilleri M, Kerstens R, Ryks A et al. A placebo - controlled trial of prucalopride for severe chronic constipation. N. Engl. J. Med. 2008; 358:2344 – 2354 [44] Tack J, Middleton SJ, Home MC et al. Pilot study on the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol. Ther. 2006;23:1655 – 1665 [45] AndersonV, Camilleri M, Busciglio IA, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation predominant irritable bowel syndrome. Gastroenterology. 2007;33:61-68

Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter VI

Diseases of the Stomach in the Aged Huy Nguyen, Raziuddin Ali, Joshua Barocas and Marie L. Borum* Division of Gastroenterology and Liver Diseases Department of Medicine George Washington University Washington, D.C., U.S.

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Introduction Advances in technology have resulted in improved diagnosis, treatment, and prevention of gastric disorders. Identification of Helicobacter pylori (H. pylori), development of proton pump inhibitors (PPIs), and refined endoscopic technique are principal means by which physicians better understand and treat gastric disorders. Elderly individuals endure a disproportionate share of gastritis, peptic ulcer disease, and gastric related morbidity and mortality. It is estimated that 35-40% of elderly patients experience gastrointestinal symptoms over the span of one year [1]. Risk factors that predispose to gastric conditions include presence of comorbidities, increased use of nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, antiplatelet agents, and changes in gastric physiology. As the world’s population ages, it is important to optimize methods to prevent, identify, and treat gastric disorders. The elderly population presents unique difficulties in medical management and access to care. Polypharmacy is common and is associated with increased cost and potential drug-drug interactions. There is often limited data on adverse drug effects in elderly patients [1]. Additionally, elderly individuals may have difficulty adhering to complex medication regimens. Regimens with numerous medications per day, varying frequencies, and

*

Corresponding Author: Marie L. Borum, MD, EdD, MPH; Professor of Medicine; Director, Division of Gastroenterology and Liver Diseases; George Washington University; Washington, D.C. 20037; U.S.A.; (ph) 202-741-2160; (fax) 202-741-2169; (e-mail) [email protected];

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instructions to avoid or take with food are more common in older patients and may be more difficult to manage.

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Gastric Anatomy and Physiology in the Elderly Knowledge of changes in gastric anatomy and physiology in the elderly is vital to manage gastric disorders in the elderly. The stomach functions as a reservoir that mixes and grinds gastric contents and controls its rate of delivery to the duodenum. Anatomically, the stomach is divided into the cardia, fundus, and antrum [2]. Macroscopically, rugae dominate the landscape of the stomach. Microscopically, these folds contain pits which house deep gastric glands. These glands are most shallow in the cardia, intermediate in the antrum, and deepest in the fundus. The vast majority of gastrointestinal epithelium is columnar, which begins in the cardia. Gastrointestinal mucosa has a remarkable ability to renew and regenerate itself. While these processes slow with age, studies show that proliferation of new precursor cells occurs throughout life [3, 4]. Repair occurs by mechanisms of restitution, a process by which healthy cells migrate to adjacent areas of injury to serve as a temporary plug. Within 24 hours of injury, new gastric mucosa will generate by cell division [5]. Damaged cells then slough off. The epithelium of the cardia protects the gastric lining from caustic agents (such as gastric acid, pepsin, and NSAIDs) by secreting mucus and bicarbonate. Aging reduces this production and secretion [6]. Decreases in prostaglandins and glutathione reduce mucosal defenses, mucosal integrity, and the quantity of gastric mucous production. Decreased perfusion to the gastric mucosa may also partially explain the reduction of mucus and bicarbonate [6, 7]. The primary function of the fundus is to secrete hydrochloric acid and pepsin. Hydrochloric acid is produced by parietal cells in response to histamine (via H2 receptors), acetylcholine (via M3 receptors), and gastrin (at CCK-B receptors) presumably as a defense mechanism against bacteria in ingested food [2]. In most elderly individuals, gastric acid production changes little with age. However, patients with chronic atrophic gastritis have a decline in the secretion of hydrocholoric acid. Pepsin production from chief cells, which are predominantly located in the fundus, decreases with age. Investigators have shown that a decline in chief cell mass and function associated with aging reduces basal and stimulated pepsin secretion [8]. The antrum is responsible for mixing and grinding gastric contents into small particles. It propels these particles into the intestines and facilitates gastric emptying. Both gastric motility and emptying appear to decrease with age, especially with solid meals compared to liquid meals [9]. A potential reason for this is autonomic nervous system dysfunction, which has a higher prevalence in older populations [10]. Slow gastric motility and delayed emptying can produce feelings of increased fullness and early satiety that may lead to weight loss, anorexia, nausea, and vomiting. An important feature of gastric motility is receptive relaxation. As the walls of the stomach are stretched during filling, the gastric musculature relaxes to accommodate the food bolus. This response ensures food is not forced back into the esophagus and helps induce

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satiety. Several hormones are associated with this mechanism and are being studied for changes related to aging. Cholecystokinin (CCK) has been proposed as a link between food intake, gastric motor function, and satiety because of its release with nutrient intake, its interaction with gastric sensory receptors, its effects on the central nervous system, and its proposed effects on gastric motility [10]. Elderly individuals retain their sensitivity to the satiating effects of exogenous CCK. One study demonstrated that exogenous CCK administration resulted in decreased oral intake which was more pronounced in elderly individuals compared to younger individuals [11]. Endogenous plasma CCK concentrations are higher in older individuals and may contribute to anorexia in the elderly [11]. Leptin may also be involved in an early CCK-mediated response to food intake and is thought to have an important influence on long-term energy balance. It may have a role in sensing meal intake [10]. Leptin levels have been demonstrated to be low in frail elderly persons and thought to contribute to cachexia [12]. Ghrelin, a 28-amino-acid acetylated peptide, is a hormone secreted predominantly in the stomach which stimulates appetite and food intake and is believed to be an endogenous ligand for the GH secretagogue receptor [13]. Some studies have noted a decrease in ghrelin levels or receptor expression with aging [14, 15, 16] while other studies have not [17]. Decreased ghrelin activity may contribute to malnourishment and cachexia in the elderly, but further studies are needed to determine its role.

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Helicobacter Pylori Gastric pathology in the elderly results from numerous etiologies but bacterial infection plays a prominent role. Helicobacter pylori is the most common bacterial infection in the world, affecting approximately 60% of the world’s population and is a major cause of gastric disease in the elderly [18]. It is a motile, gram-negative, spiral bacterium that is linked to peptic ulcer disease, atrophic gastritis, and gastric cancer [19, 20]. It is usually acquired in childhood and has higher prevalence in lower socioeconomic conditions [20, 21]. Transmission is person to person or water borne and genetic susceptibility has been confirmed [20]. Virulence factors promote gastric colonization and induce tissue injury. H. pylori’s flagella, urease production, and adherence factors enable it to persist in the gastric lining [20]. Lipopolysaccharide, leukocyte recruitment, and vacuolating cytotoxin induce tissue injury and promote mucosal thinning [20]. The association of H. pylori with cytokine upregulation and achlorhydria leads to increases in gastrin levels by 35-45% [22]. Gastrin is a growth factor for gastric mucosa and sustained elevations may contribute to abnormal growth, polyp formation, and increased risk of cancer. The risk of gastric cancer in individuals with H. pylori infection is increased threefold and the risk of developing mucosal associated lymphoid type (MALT) lymphoma is increased two to six-fold [23]. Testing for H. pylori should be considered in a variety of clinical scenarios. Active peptic ulcer disease and prior history of ulcer disease without treatment of H. pylori are situations where testing for H. pylori is warranted [24]. Screening asymptomatic first degree relatives of patients with gastric cancer (particularly those of Korean, Japanese, Chinese, or Russian

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descent) or peptic ulcer disease or individuals beginning therapy with NSAIDs or aspirin remains controversial. Diagnostic testing for H. pylori can be invasive or noninvasive. Tissue biopsy usually occurs through upper endoscopy although biopsy with nasogastric tube and fluoroscopy is possible [25]. Rapid urease testing and H&E/silver stains are used to detect H. pylori on biopsy specimens [26]. Sensitivity and specificity are over 90%. Several noninvasive tests are available for detecting H. pylori. A urease breath test using 13 C or 14C-labeled urea is commercially available [24]. In this test, H. pylori, which is a urease-producing organism, breaks down urea into ammonia and 13CO2 or 14CO2. The radiolabeled 13CO2 or 14CO2 then diffuses into the blood, travels to the lungs, and is exhaled. Breath samples are collected and the radiolabeled CO2 level is measured. Sensitivity and specificity are greater than 90% [24]. A stool antigen test for H. pylori, which requires an acorn-sized aliquot of stool, is often used for diagnosis of H. pylori [27, 28]. It is an enzyme immunoassay that has a sensitivity and specificity greater than 90%. Both the stool antigen and the urease breath test have a lower sensitivity if acid reducing agents are used prior to testing [29]. It is recommended that PPIs be held for 1 week prior to testing [29]. False positive stool antigen tests have been described in patients with acute upper gastrointestinal bleeding [30]. Serum ELISA testing for H. pylori IgG identifies prior infection but does not necessarily indicate current infection. In patient populations with a low prevalence of H. pylori, the positive predictive value of a positive serum ELISA IgG is poor and urease breath testing or stool antigen testing should be performed [31]. In patient populations where the prevalence of H. pylori is greater than 20%, serum ELISA IgG may be helpful. Serum ELISA testing for H. pylori IgA or IgM is less reliable and not commonly used [32]. H. pylori treatment is most often with triple agent therapy with two antibiotics and a proton pump inhibitor. [33] Antibiotics effective against H. pylori include amoxicillin, clarithromycin, tetracycline, and metronidazole [34]. Treatment length is 10-14 days. Shorter treatment courses have resulted in substantially lower cure rates [34]. Resistance to clarithromycin and metronidazole is becoming more common [35, 36]. Cure rates with triple agent therapy range from 60-90% [34, 37]. Sequential treatment of H. pylori shows promise as a future treatment regimen. Treatment with a PPI and amoxicillin for five days followed by PPI, clarithromycin, and metronidazole for 5 days has been shown to have a cure rate greater than 90% [38]. Further studies in diverse patient populations to confirm these findings are needed before sequential therapy can be globally recommended. Clearance of H. pylori can be determined by repeat endoscopic biopsy, urease breath testing, or stool antigen testing. Serum ELISA testing is not helpful in documenting clearance [24]. Testing to determine eradication of H. pylori should be done at least four weeks after completion of H. pylori treatment [24]. Approximately 20% of individuals initially treated for H. pylori will fail [21]. Quadruple therapy with a PPI, bismuth, metronidazole, and tetracycline for 10 days show cure rates of 80% [24]. Salvage regimens for H. pylori treatment have also been used. Addition of rifabutin 300mg daily or levofloxacin 250mg twice daily with amoxicillin and pantoprazole have shown eradication rates ranging from 60-87% [39].

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Gastritis Gastritis is a common gastrointestinal disorder in the elderly. It is a term with varied meaning that has been used since the 19th century and represents different entities to clinicians, pathologists, and endoscopists. It may refer to symptoms or endoscopic/histologic appearance of the stomach. In this chapter, gastritis will refer to microscopic inflammation. There is no single accepted classification for gastritis. In 1996, the updated Sydney system was proposed to unify classification schemes and terminology [40]. However, the complexity of the system prevented widespread acceptance. Currently, most classification systems use etiology, histology, anatomy, and endoscopic appearance in varying degrees to classify gastritis. H. pylori and NSAID use are the most common etiologies for gastritis in the elderly. Other etiologies include infectious, granulomatous, eosinophilic, lymphocytic, collagenous, alcohol-induced, portal, ischemic, and radiation-induced gastritis. Zollinger-Ellison syndrome or Menetrier’s disease may also cause gastritis. Chronic gastritis is more common in the elderly population and is most often secondary to H. pylori infection. H. pylori’s virulence factors enable it to persist and injure gastric mucosa leading to inflammation. Increased release of interleukin-8, generation of oxygen metabolites, and induction of CD11b/CD18 on neutrophils lead to neutrophil binding that ultimately increases microvascular permeability and mast cell degranulation [10, 41]. Chronic inflammation then superficially spreads through unclear mechanisms and destroys epithelial cell lineages causing atrophy [2]. Atrophic gastritis is identified by gland loss, achlorhydria, and potential metaplasia [42]. Active H. pylori infection can produce different patterns of gastritis with different natural histories. Diffuse antral-predominant gastritis (DAG) is caused by infection with H. pylori in the antrum and is not associated with increased risk of cancer. Multifocal atrophic gastritis (MAG) results in antral and body mucosal atrophy and potentially intestinal metaplasia that may lead to dysplasia and adenocarcinoma. It is multi-factorial in etiology with H. pylori, genetic, and environmental factors all having a role. Diffuse corporal atrophic gastritis (DCAG) is an autoimmune destruction of fundic glands that may relate to H. pylori infection. It may lead to incomplete metaplasia and patients with DCAG are at higher risk for dysplasia and adenocarcinoma [42].

Gastric Polyps Gastric polyps can be incidentally found on upper endoscopy or barium examination in the elderly. Often polyps are asymptomatic but may present with occult upper gastrointestinal bleeding or rarely with gastric outlet obstruction. H. pylori infection, chronic atrophic gastritis, and autoimmune gastritis all contribute to gastric polyp formation. There are four main types of polyps: hyperplastic, fundic gland, adenomatous, or carcinoid. In general, simple polypectomy is therapeutic unless invasive carcinoma is present in which case surgical resection is often necessary. The most common gastric polyps are fundic gland polyps, which comprised 47% of all polyps in a large series of 4852 patients [43]. However, in the elderly population, hyperplastic

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polyps are more prevalent and make up more than half of gastric polyps in patients over the age of 70 [43]. The average age of patients with malignant polyps such as adenocarcinoma ranged from 64 to 70 years of age [43]. Hyperplastic polyps account at least 30% of gastric polyps and are related to chronic inflammatory conditions including pernicious anemia, atrophic gastritis, and postgastrectomy gastritis [43, 44]. These polyps result from unchecked, hyperregenerative epithelium in response to a chronic inflammatory stimulus. It has been reported that 0.5-2.1% of hyperplastic polyps have malignant potential, usually when polyps are greater than 1.5cm in size [44, 45]. Fundic gland polyps are small (< 1cm) hyperemic, sessile, flat, nodular lesions with a smooth surface that occur in the gastric corpus. These may occur sporadically but are also associated with familial adenomatous polyposis (FAP) or attenuated FAP. While these polyps have little neoplastic potential, dysplasia can occur in individuals with FAP or attenuated FAP. Concerns about an association with PPI use and fundic gland polyps were raised after a report was published where three patients developed fundic gland polyps while on omeprazole [46]. Several case reports and case series associating fundic gland polyps and PPI use followed. One large retrospective study examining gastric biopsies in 2,251 patients receiving PPI therapy for at least four weeks compared to 28,096 control patients not on PPIs showed no difference in fundic gland polyp frequency (5.2% PPI vs. 5.0% control) [47]. A smaller retrospective study of 599 patients suggested that duration of PPI therapy may play a role in fundic gland polyp development. Patients in the study who were on PPIs for less than one year were not found to be at higher risk for fundic gland polyps compared to controls, but patients on PPIs for more than one year were found to be at higher risk [48]. The clinical significance of increased fundic gland polyp frequency is probably minimal as fundic gland polyps in patients without FAP do not appear to have neoplastic potential [48]. Adenomatous polyps account for 6-10% of gastric polyps [44]. They can be flat or polypoid and may range from a few millimeters to centimeters in size. Gastric adenomas have a significant risk of malignant transformation, ranging from 10-17% in large series [49, 50]. The risk of invasive cancer is increased with increased size, degree of dysplasia, and presence of villous contour. Surveillance endoscopy following polypectomy should occur though there are no formal recommendations for surveillance intervals. Carcinoid polyps are sessile, broad based, polypoid lesions with a smooth surface contour. They are endocrine cancers arising from nonfunctioning enterochromaffin-like cells [51]. These are rare polyps, representing less than 0.5% of gastric cancers [51]. There are three types of carcinoid polyps. Type 1 polyps account for 70-80% of carcinoid polyps and occur in setting of chronic atrophic gastritis. Type 2 polyps occur with Zollinger-Ellison syndrome or multiple endocrine neoplasia type 1 and occurs secondary to hypergastrinemia. Type 3 polyps are sporadic carcinoids. Management may range from polypectomy to surgical resection and is determined by the size of the polyp, invasiveness, and histologic features [51].

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Peptic Ulcer Disease Peptic ulcer disease is more common in the elderly and is associated with a disproportionate increase in morbidity and mortality [52]. 10% of all adult patients note a history of peptic ulcer disease [53]. Mortality rates for complicated peptic ulcer disease increase rapidly with age, with nonagenarians having an upper GI bleed mortality rate of over 30% [54]. One study evaluating hospitalized British patients estimated mortality from peptic ulcer disease in patients over the age of 65 to be 20 times greater than in patients aged 35-64 [55]. Risk factors for increased peptic ulcer disease include age, H. pylori infection, NSAIDs, corticosteroids, blood thinners, and history of gastrointestinal bleeding. Gastric ulcers tend to be larger, more proximally located, and heal more slowly in the elderly.

Presentation Peptic ulcer disease typically presents with epigastric pain. However, in the elderly atypical symptoms that are vague, poorly defined, and localized often occur. Dyspepsia can be a common complaint. Early satiety and weight loss are also symptoms that can rarely occur in the elderly with uncomplicated peptic ulcer disease. Additionally, one third of elderly individuals can present without pain [56].

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Etiology H. pylori is a major risk factor for peptic ulcer disease [20] and has already been discussed above. NSAIDs are commonly prescribed medications that cause 15-40% of elderly patients to experience gastrointestinal symptoms. Endoscopic studies have shown that gastric and duodenal ulcers develop in 10-45% of patients taking NSAIDs [57]. The pathophysiology of NSAID induced ulcers includes both topical and systemic effects. Topically, NSAIDs have a tendency to denude the surface epithelium and increase mucosal permeability via uncoupling of oxidative phosphorylation [58]. Inhibition of cyclooxygenase and increased expression of intracellular adhesion molecules are systemic effects that decrease gastric mucosal bicarbonate, reduce blood flow, prevent increased cellular replication, and delay mucosal repair [58].

Treatment Treatment of active ulceration is with discontinuance of NSAIDs and short term use of a PPI. Individuals infected with H. pylori should have the infection treated. Maintenance therapy with a PPI or an H2 receptor antagonist (H2RA) should be continued until clearance of infection. Individuals that have failed H. pylori treatment or that have H. pylori negative ulcers should be kept on maintenance acid suppression, especially if they have risk factors that put them at high risk for recurrent peptic ulcer disease [59]. Elderly individuals with giant

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ulcers (>3cm), who have had complications from ulcer disease, or experienced more than one episode of ulceration should also be kept on maintenance acid reduction therapy. Patients with refractory or poorly healing ulcers should undergo a repeat upper endoscopy to assess the ulcer to determine if it represents a malignant lesion. Patients who have persistent dyspepsia with alarm symptoms such as weight loss, recurrent vomiting, anemia, dysphagia, odynophagia, or gastrointestinal bleeding should also undergo repeat upper endoscopy. It is recommended that elderly individuals taking NSAIDs also take a PPI or misoprostol to decrease ulcer risk [59]. Studies have shown that physicians often do not prescribe appropriate ulcer prophylaxis for high-risk patients taking NSAIDs [60, 61, 62]. Cost, concerns about polypharmacy, and adverse reactions may affect prescription.

Complications

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Complications of peptic ulcer disease may occur in 50% of patients over the age of 70 [63]. Hemorrhage Hemorrhage is the most common complication of peptic ulcer disease. Elderly individuals are four to seven times more likely to die from gastric bleeding than younger individuals. Risk factors for increased mortality include the presence of comorbid conditions, NSAID or antiplatelet agent use, and requirement of more than five units of blood. Anemia, melena, and hematochezia are characteristic signs of upper gastrointestinal bleeding. Elderly individuals present with fewer antecedent symptoms of abdominal pain, dyspepsia, and heartburn than younger patients [64]. Treatment is multidisciplinary with medical and surgical teams working in concert. Management is aggressive and geared toward volume resuscitation (intravenous fluids and blood products) and use of vasopressors if needed to maintain hemodynamic stability. Monitoring of pulmonary status and use of high dose PPI should also occur. Once hemodynamically stable, the patient may undergo endoscopy to diagnose and potentially treat sources of bleeding. The safety and efficacy of endoscopy is the same as in younger individuals. The likelihood of ulcers to rebleed is based upon characteristic endoscopic appearances [65]. Use of electrocautery, hemoclips, or injection of alcohol or epinephrine may control bleeding. If endoscopy is unable to stop the bleeding, surgery may be indicated, although it confers a high mortality rate in the elderly. Perforation A less common complication of peptic ulcer disease is perforation. Perforation of gastric ulcers in the elderly can be catastrophic and confers a high mortality rate. Mortality from perforated ulcer in patients over the age of 50 is over three times that of patients under age 50 [66]. Risk factors for perforation include smoking, NSAID use, and possibly H. pylori [67]. Up to 25% of individuals with perforated peptic ulcer have no prior history of ulcer disease [10]. Management involves early surgical consultation, nasogastric aspiration, parenteral antibiotics, and intravenous fluids. The surgical approach is often simple closure as opposed to definitive surgery. Eradication of H. pylori may reduce relapse of ulceration.

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Gastric Outlet Obstruction Peptic ulceration of the antrum, pylorus, or duodenum can result in inflammation, edema, or scarring that leads to gastric outlet obstruction. Patients may present with nausea, vomiting, epigastric pain, early satiety, and weight loss. Diagnosis can occur through endoscopy, barium contrast examination, or gastric emptying study. Medical therapy is with nasogastric suctioning, intravenous fluids, acid suppression with a PPI, discontinuance of NSAIDs, and treatment of H. pylori. Endoscopic balloon dilatation may be an option for strictures [68]. Surgery is uncommon and reserved for refractory obstruction. Penetration Penetration occurs when peptic ulcers bore into an adjacent organ. Gastric ulcers can penetrate and involve the left lobe of the liver, the pancreas or result in the development of a gastrocolic fistula. Literature detailing penetrating ulcers is sparse. Symptoms are usually typical symptoms of peptic ulcer disease. However, a change in the pattern of pain may relate to penetration. Clinicians rarely have confirmation of penetration until computed tomography or surgery is performed.

Malabsorption

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While most nutrients are absorbed in the small intestine, certain nutrients require a normal stomach environment to be absorbed, including vitamin B12, iron, and calcium [69]. Changes in gastric motility secondary to changes in physiology and use of anticholinergic medication can affect the absorption of hematinics, vitamins, and medications in the elderly [70].

Vitamin B12 Pernicious anemia presents predominantly in the elderly population [71]. Vitamin B12 absorption is dependent upon the presence of intrinsic factor, which is produced by parietal cells and, to a lesser extent, chief cells in the stomach. Intrinsic factor is a glycoprotein that binds vitamin B12 to facilitate its absorption. Intrinsic factor-vitamin B12 complexes bind to receptors in the ileum to absorb vitamin B12. If intrinsic factor is not produced, vitamin B12 cannot be absorbed in the ileum effectively. In pernicious anemia, autoantibodies against parietal cells develop, decreasing the production of intrinsic factor. Decreased mucosal cell mass and decreased parietal cell mass also contribute to decreased intrinsic factor production in elderly people, increasing the risk of vitamin B12 deficiency. Severe deficiency in intrinsic factor is required before vitamin B12 absorption in the small intestine is impaired. Presentations for pernicious anemia are diverse and may include anemia, glossitis, pancytopenia, peripheral neuropathy, limb weakness, and spasticity [71]. Laboratory assessment begins with measurement of serum levels of vitamin B12, methylmalonic acid, and homocysteine [72]. The Schilling test, historically the confirmatory test for pernicious anemia, is now infrequently performed as it often does not change clinical management [73]. Confirmation can be attained through measurement of anti-parietal cell antibodies or anti-

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intrinsic factor antibodies [73]. Treatment is with intramuscular vitamin B12 injections or high dose oral vitamin B12 [72].

Iron Iron solubility is affected by the acidity of the stomach. Decreased acid production (from PPI therapy or H. pylori infection) results in decreased solubility of iron with subsequent decrease in iron absorption in the duodenum [69, 74]. In elderly individuals who are on chronic PPI therapy, iron deficiency can be exacerbated by decreased solubility. Iron supplementation and iron rich food should be recommended. Heme iron from food sources are absorbed more efficiently. Notably, iron supplementation in high doses can predispose to constipation and stool softeners may be necessary [75]. Additionally, vitamin C can be taken with iron because it acidifies chyme and aids in absorption of iron supplements.

Calcium

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Decreased gastric acid production reduces calcium solubility and conversion to its ionic form. Decreased conversion to the ionic form decreases ionic calcium absorption in the duodenum and jejunum. This is an issue with insoluble calcium supplements such as calcium carbonate but can be counteracted by passive absorption of calcium in the distal intestine if large amounts of calcium carbonate are ingested [76]. In addition, soluble calcium supplements such as calcium citrate and milk calcium are absorbed effectively in the absence of gastric acid [77].

Feeding Tubes and Nutritional Support Provision of enteral nutrition, whether by mouth or by feeding tube, is often encountered in hospitalized elderly patients. Percutaneous, radiologic, or surgical feeding tube placement is often requested in situations where patients are unable to take food by mouth for an extended period of time. Many feeding tubes are placed in elderly patients because of poor oral intake secondary to dementia. The patient is either not aware enough or unable to coordinate chewing and swallowing a food bolus. There is significant data to suggest that dementia severe enough to prevent a patient from eating is indicative of end-stage dementia. More than half of demented patients that receive gastrostomy tubes will not live past one year [78] and, unfortunately, gastrostomy tubes have not been shown to decrease aspiration pneumonia, heal decubitus ulcers, or extend lifespan in patients with dementia [79, 80]. Furthermore, demented patients with feeding tubes may need to be restrained to prevent manipulation of the feeding tubes and many studies have shown increased morbidity and mortality with restraint use [81]. However, there is evidence that feeding tubes placed in nondemented elderly patients may be beneficial in liver disease, perioperative states, and in critical care settings [82].

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Given the lack of data for gastrostomy tubes showing benefit in demented patients, initial discussions with caregivers regarding feeding tubes in a demented patient should center upon expectations of the caregivers and whether they are realistic. It is important to discuss with the caregivers the risks, benefits, alternatives, and, most importantly, intended goals of feeding tube placement so that an informed decision can be made [83]. This discussion also provides an opportunity to discuss the long-term prognosis of the patient as well. Minor complications of feeding tubes occur in 5-13% of patients and major complications occur in 1.3-3.0% of patients, with mortality from the procedure estimated at 0.2-1.0% [84]. Minor complications include tube clogging, peristomal wound infection, pneumoperitoneum, granuloma tissue, peristomal leakage, ulceration, vomiting, abdominal pain, and tube dislodgement [84, 85]. More severe complications may include peritonitis, a buried bumper syndrome, necrotizing fasciitis, intestinal ischemia, and tumor implantation [84]. It is critical that staff and caregivers are trained to use the tube and recognize problems with the tube early. Removal of the tube can usually be done at the bedside when it is no longer needed. Occlusion of the tract occurs as early as four hours later if the tube is not replaced.

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Gastric Bypass The prevalence of morbid obesity is increasing in the elderly. The number of gastric bypass surgeries being performed is increasing as well [86, 87] and as more gastric bypass surgeries are being performed in older patients, studies will be needed to evaluate the safety and efficacy of bariatric surgeries in this age group. One recent study demonstrated survival benefit at 11 months after surgery in patients greater than 65 years of age when compared to a matched nonsurgical cohort [86]. Another retrospective study using a large inpatient database suggested similar in-hospital mortality and morbidity in elderly patients compared to younger patients receiving gastric bypass surgery [88]. Case volumes may be a major factor in perioperative morbidity and mortality. A retrospective study showed 30-day mortality rates in elderly patients following gastric bypass of 4.8% but mortality rates were only 1.1% in patients treated by the most experienced surgeons [87]. Patient selection is important in elderly patients undergoing gastric bypass as one study showed that patients with heart disease, liver disease, and kidney disease had the highest inhospital mortality [89]. Significant improvements in diabetes, hypertension, sleep apnea, hyperlipidemia, and coronary artery disease were observed in those elderly patients who had undergone bariatric surgery [86]. Another study evaluated laparoscopic adjustable gastric banding in patients older than 60 years of age and showed a mean weight loss of 54% over a 2 year period [90]. These studies show promise in geriatric bariatric surgery. However, further prospective, large scale studies need to occur to fully elucidate risks and benefits in this population.

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Medications Medication use among elderly adults is, perhaps, the most salient issue in geriatric medicine. The prevalence of gastric diseases in the elderly results in a large number of prescriptions of medications. Awareness of drug side effects and drug interactions will minimize the risk for iatrogenic injury. The classes of medications that will be discussed in this section include proton pump inhibitors, H2 receptor antagonists, prostaglandin E analogs and medications used to treat H. pylori. The potential effects of iron and potassium supplementation are also discussed.

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Proton Pump Inhibitors Proton pump inhibitors block H+/K+ ATPase which is the final site of gastric acid production. PPIs can decrease acid production in the stomach by over 90% [91]. These agents are best taken before meals, as they bind to proton pumps that are actively secreting acid, as during a meal [92]. Taking the medications when the patient will not be eating for several hours leads to fewer actively secreting proton pumps for the medication to bind. PPIs have been associated with thrombocytopenia [93]. One retrospective study suggested PPIs as a risk factor for increased hip fractures [94]. In this study, the increase in incidence of hip fractures was more pronounced with higher doses of PPI. The study investigators recommended that elderly patients on a PPI be offered the lowest effective dose and calcium supplementation should be given with meals [94]. A case-control study suggested an increased risk of community acquired pneumonia in patients using PPIs [95]. Omeprazole and esomeprazole have been shown to reduce the clearance of phenytoin and diazepam though the clinical relevance of these interactions is controversial [96, 97]. PPIs decrease absorption of ketoconazole, itraconazole, atazanavir, and vitamin B12 [98, 99, 100]. PPIs also increase absorption of digoxin [101].

H2 Receptor Antagonists The H2 receptor antagonists cimetidine, ranitidine, famotidine, and nizatidine are commonly used acid suppressing agents. H2 receptor antagonists block histamine receptors on parietal cells, which leads to decreased acid production by H+/K+ ATPase. Cimetidine is the most extensively studied H2-blocker and has the most drug-drug interactions as it inhibits several cytochrome oxidases, including CYP1A2, CYP2D6, and CYP3A [102]. This inhibition leads to higher drug levels of many medications. If a patient is taking cimetidine with medications with narrow therapeutic windows such as warfarin, phenytoin, or theophylline, an alternative acid reducing agent should be prescribed [102]. Ranitidine is also metabolized in the liver but has a much lower affinity for CYP isozymes. Famotidine has little effect on the activity of CYP isozymes [102] and nizatidine does not inhibit the cytochrome P450 pathway [103]. All currently available H2RAs have significant renal excretion and dosing needs to be adjusted in renal insufficiency.

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In the elderly, H2RAs can have central nervous system side effects, including confusion, disorientation, and somnolence [104]. H2RAs have been associated with cytopenias, particularly thrombocytopenia [105, 106]. H2RAs also decrease the absorption of ketoconazole, itraconazole, and atazanavir [98, 99]. A retrospective study associated H2RA use with an increased risk of pneumonia [107].

Prostglandin E1 Analogs Activation of prostaglandin E receptors on parietal cells decreases acid production and has a mucosal protective effect. The prostaglandin E1 analog misoprostol acts on prostaglandin E receptors and produces similar levels of acid reduction as H2RAs [10]. The most common side effect of misoprostol is diarrhea, with up to 40% of patients having this side effect [108]. This in addition to the frequency of administration (up to four times daily) can make misoprostol difficult for elderly patients to tolerate. It should be noted that misoprostol has significant fetal side effects, and women of childbearing age who live with elderly individuals on misoprostol should be informed.

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Helicobacter Pylori Treatment All antibiotics used in the treatment of H. pylori can potentially cause elevations in prothrombin time in patients taking warfarin. Clarithromycin inhibits CYP3A4 and can elevate serum levels of theophylline and carbamazepine [102]. Metronidazole has a disulfiram-like effect and patients should not take alcohol when taking metronidazole. Case reports have described lithium toxicity in patients who took both lithium and metronidazole [102]. Leukopenia is seen in 25% of patients taking rifabutin [34]. The number of pills that are taken per day in a H. pylori treatment regimen range from five to fourteen, with varying levels of complexity for the patient. Prepackaged regimens of triple therapy for Helicobacter pylori, where one opens presealed packs twice daily and ingests the contents, are convenient, but the cost of these regimens may be prohibitive for patients. Discussing the advantages and disadvantages of these regimens with patients and mutually deciding on an appropriate regimen will help ensure adherence.

Iron and Potassium Supplementation Iron and potassium supplementation have been associated with gastritis [109, 110] and supplementation is best taken with meals. As mentioned above, iron can cause constipation as well. Bisphosphonates, more commonly associated with pill esophagitis, have also been associated with gastritis [111].

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Conclusion The aging of the world’s population has led to an increase in many gastric conditions in the elderly. New therapies, new discoveries, and improved screening have no doubt improved outcomes for elderly patients with gastric disease. However, the challenges of treating an elderly population, with regards to access to health care, polypharmacy, comorbid conditions, and medication adherence have not changed. It is imperative that we adapt to the needs of our elderly patients so that we as practitioners can prevent and treat as much gastric disease as possible.

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[89] Varela JE, Wilson SE, Nguyen NT. Outcomes of bariatric surgery in the elderly. Am. Surg. 2006;72:865-9. [90] Taylor CJ, Layani L. Laparoscopic adjustable gastric banding in patients > 60 years old: is it worthwhile? Obes. Surg. 2006;16:1579-83. [91] Howden CW, Forrest JA, Reid JL. Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man. Gut. 1984;25(7):707-10. [92] Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118:S9-S31. [93] Watson TD, Stark JE, Vesta KS. Pantoprazole-induced thrombocytopenia. Ann. Pharmacother. 2006;40:758-61. [94] Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-53. [95] Gulmez SE, Holm A, Frederiksen H, et al. Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch. Intern. Med. 2007;167:950-5. [96] Meyer UA. Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole, and pantoprazole with other drugs. Eur. J. Gastroenterol. Hepatol. 1996;8(S1):S21-S25. [97] Labenz J, Petersen KU, Rosch W. A summary of food and drug administration-reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole, and pantoprazole. Aliment Pharmacol. Ther. 2003;17:1015-9. [98] Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. New Engl. J. Med. 1994;330:263-72. [99] Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur. J. Clin. Pharmaol. 2008;64:935-51. [100] Reyataz™ (atazanavir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2008 Sep. [101] Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin. Pharmacokinet. 1988;15(4):227-44. [102] Humphries TJ, Merritt GJ. Review article: drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol. Ther. 1999;13(S3):18-26. [103] Axid® (nizatidine) package insert. Liberty Corner, NJ: Reliant Pharmaceuticals, Inc; 2004 May. [104] Dua KS, Shaker R, Koch TR, et al. Gastroenterologic disorders. In: Duthie EH, Katz PR, Malone ML, eds. Practice of Geriatrics. 4th ed. Philadelphia, PA: Saunders; 2007:577-604. [105] Wade EE, Rebuck JA, Healey MA, et al. H2 antagonist-induced thrombocytopenia: is this a real phenomenon? Intensive Care Med. 2002;28:459-65. [106] Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H2receptor antagonists. Med. Toxicol. 1988;3:430-48. [107] Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955-60. [108] Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhoea. Drug Saf. 2000;22:5372.

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[109] Laine LA, Bentley E, Chandrasoma P, et al. Effect of oral iron therapy on the upper gastrointestinal tract: a prospective evaluation. Dig. Dis. Sci. 1988;33:172-7. [110] Moore JG, Alsop WR, Freston JW, et al. The effect of oral potassium chloride on upper gastrointestinal mucosa in healthy subjects: healing of lesions despite continuing treatment. Gastrointest. Endosc. 1986;32:210-2. [111] Graham DY. What the gastroenterologist should know about the gastrointestinal safety profiles of bisphosphonates. Dig. Dis. Sci. 2002;47:1665-78.

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In: Gastrointestinal Tract in the Aged Editors: S. Malnick, E. Melzer and S. Tal

ISBN: 978-1-61122-519-8 © 2011 Nova Science Publishers, Inc.

Chapter VII

Small Bowel Diseases in the Elderly Bernd Lemos and Jörg C. Hoffmann

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Medical Clinic I St.Marienkrankenhaus Rheinland-Pfalz Rhineland-Palatinate, Deutschland Germany Small bowel diseases in the elderly patient usually present with diarrhea and/or malabsorption. According to the WHO-statistics in 2008 2.2 million people worldwide died from acute infectious diarrhoea. In the developing countries particularly, children are the victims of this disease. The situation is different in industrialized countries, where 85 % of diarrheaassociated mortality strikes elderly people. Diarrhea often becomes life threatening because of the morbidity of these patients rather than diarrhea itself. Dehydration leads to hypotension, which is often followed by organ failure. Regional statistics show an increasing number of antibiotic-associated diarrhea as well as virus-induced enteritis. The severity of these common disorders and also the heterogeneity of the underlying etiologies requires a rational and cost-effective diagnostic work-up. Therefore both a successful therapeutic and hygienic management of diarrhea is needed in order to avoid complicated courses and spreading of the disease. Little and inconsistent data is available concerning the epidemiology of malabsorption in the elderly. Statements range from being an “uncommon problem” to a “major health problem” in the geriatric population. Information about the etiology of malabsorption in aged people discloses that half of the cases are related to small bowel disturbances. In the individual patient other causes of diarrhoea not involving the intestine must be considered, particularly pancreatic insufficiency, colon cancer, or biliary tract disease. Rarely intestinal parasites or obstruction of the intestinal lymphatic system turn out to be cause of diarrhea.

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(1.) Biological Basics – Age-Related Changes (1.1) Histological Changes Investigations concerning histological changes in the elderly have focused on the mucosa and myenteric plexus. Most studies report, that there is no significant difference with regard to the structure and the composition of the mucosa when comparing elderly and younger people [1]. Crypt depth, villous height, crypt-to-villous ratio, enterocytes, brush border and Brünner glands are more or less equal during different periods of life. Immunohistochemical investigations revealed a significant increase in both, enterocyte apoptosis and proliferation, resulting in cellular immaturity in aged people [2] . This might explain the impairment of absorptive function observed in stress conditions within the elderly population. When looking at the plexus of Auerbach a reduction of neurons was found in the small as well as in the large intestine. This seems to be of little importance as far as bowel motility is concerned. Extra intestinal problems, for instance thyroid disturbance or diabetes related autonomic neuropathy have a greater influence on motility.

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(1.2.) Physiological Changes Testing of elderly subjects revealed a progressive reduction in absorptive capacity with advancing age [3]. This is due to a decreased number of sugar transporters/mg of bowel. Similar effects were seen when looking at the amino acid transport. Moreover the metabolism of disaccharides such as galactokinase, lactase and sucrase is impaired in aged people, which might bring about chronic diarrhoea due to malabsorbtion of lactose. Another point is the unmetabolized absorption of galactose which entails increased numbers of cataract formation. Unlike the sugar and amino acid transport, fat absorption seems to be maintained with increasing age. As far as vitamins are concerned, studies have shown that intestinal absorption is unaltered in the elderly population. This applies to water based and fat soluble substrates. Deficiency symptoms often occur due to disease not directly related to the small or large bowel, e.g. vitamin B12 deficiency caused by atrophic gastritis [4, 5]. Another example facing this problem is calcium metabolism. Although the intestinal ability to absorb calcium and even 25-hydroxyvitamin D is unchanged in the elderly, vitamin D deficiency may occur because of renal failure resulting in decreased synthesis of 1,25-hydroxyvitamin D. This consequently reduces calcium absorbing transporters in the upper jejunal mucosal surface. As noted above, neurons in the myenteric plexus are reduced. Nevertheless normal aging does not affect gastric and small intestinal motility, whereas the propulsive capacity of the colon seems to be reduced [6]. With regard to epithelial barrier functions, small-intestinal leakiness does not increase with age as measured by the lactulose/mannitol absorption test [7]. Increased prevalence of lactose malabsorbtion in the elderly is mostly due to clinically non-apparent small intestinal bacterial overgrowth, rather than mucosal factors [8].

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(1.3.) Immunological Changes Not every step in intestinal immune function and its special relation to the elderly is completely understood [9, 10]. In terms of leukocyte subsets, some evidence exists that intraepithelial lymphocytes are reduced and IgA-producing plasma cells are slightly increased. Little is known about antigen uptake by M cells and antigen presentation by dentritic cells and lymphocytes. Immunohistochemical analyses showed that - after antigen presentation - the migration of the IgA immunoblasts from the Peyer's patches to the “usage site” is compromised in the elderly. The production of the mature IgA antibody in the intestinal mucosa and also the secretion by the intestinal lamina propria seems to be equally high in young and older individuals (rodents and primates). There does not appear to be any age related differences with regard to IgM- and IgG producing plasma cells or with regard to eosinophils and mast cells. Overall only minor differences between young and elderly subjects regarding the intestinal immune system have been reported.

(2.) Symptoms and Signs

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(2.1.) Abdominal Pain Abdominal pain is the most important symptom in small bowel disease. In elderly patients severe disease only results in minor abdominal discomfort rather than pain. All the more it is important to inquire about related symptoms such as nausea, vomiting, stool frequency and medication in order to reach a realistic assessment. The quality of pain provides a hint to the underlying cause: Excruciating pain with a sense of doom, followed by an interval without pain should lead to the working diagnosis of mesenteric ischemia. Colic like periumbilical pain should focus on movement disorders of the small intestine. Permanent pain together with abdominal tenderness is the typical pain in peritonitis. To narrow down the possible cause of pain, a careful work-up containing history, examination, laboratory tests (e.g. blood count, liver enzymes, renal function test, CRP, bilirubin, lipase, urinanalysis …) and medical imaging, such as ultrasound examination is necessary. Often enough the results of these diagnostic tests are sufficient to make a definite diagnosis.

(2.2.) Diarrhoea (2.2,1.) Definition Diarrhoea is defined as loose bowel movements (water content more than 85%), more than three times a day with stool weight more than 200 g/day. Pseudodiarrhoea, by contrast, may occur with frequent and urgent defecation, but the stool weight is less than 200 g/day. Patient with these complaints may also have normal gut transit times. They are said to suffer from irritable bowel syndrome.

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(2.2.1.1.) Predisposing Factors to Acute, Infectious Diarrhoea Concerning Elder Patients Epidemiological data reveal infections to be the most common reason for diarrhea in the geriatric population. Several factors contribute to the susceptibility to acute infectious diarrhoea: • • • • • •

hypo-/achlorhydria proton pump inhibitors immunodeficiency (for instance by chemotherapy) co-morbidity (for instance intestinal ischemia) antibiotic therapy voyages

(2.2.1.2.) Differential Diagnosis It is important to keep in mind, that diarrhea is not always due to small bowel diseases. The following causes need to be considered:

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Common causes: • • • • • • •

infections drug-induced diarrhea [11] malabsorption (for instance bacterial overgrowth) constipation paradoxical diarrhea by colon carcinoma diabetic diarrhea (diabetic autonomic neuropathy) irritable bowel syndrome

Less common causes: • • • • • • • •

celiac disease inflammatory bowel disease thyrotoxicosis Pancreatic insufficiency Gastrointestinal manifestations of systemic sclerosis Whipple`s disease Small bowel manifestation of amyloidosis Small bowel tumors

(2.2.2.) Classification

(2.2.2.1.) by Duration Acute diarrhea lasts for no more than 14 days. Chronic diarrhea continues for more than 30 days. If disorders stop in the meantime, we are talking about persistent diarrhoea.

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(2.2.2.2.) by Pathogenic Mechanism (2.2.2.2.1.) Osmotic Diarrhoea Osmotic diarrhoea is characterized by cessation upon fasting. The reason for this clinical feature is that osmotic substances - either because of ingestion of non-absorbable agents or because of endogenous reasons - increase the intestinal concentration of ingested osmotic active substances. Intraluminal water is combined which leads to rapid intestinal transit. In elderly people non-absorbable solutes occur in the diet containing sugar substitutes i.e. sorbitol or in drugs, e.g. laxatives. Most common endogenous causes are celiac disease and bacterial overgrowth. In old age a fasting test should be done under controlled conditions because of the risk of exacerbation of an ongoing secretory diarrhoea. Differential diagnosis of osmotic diarrhoea in the elderly: Common exogenous causes • • •

Drugs containing poorly absorbed di- and polysaccharides, ethandiol or sodium sulphate/magnesium salts (laxatives, i.e. lactulose, PEG, Glauber’s salt, antacids) Dietary nourishments (sweets containing artificial sweetener)

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Common endogenous causes • Exocrine pancreatic insufficiency • Bacterial overgrowth • Celiac disease • Lactose intolerance Less common exogenous causes • Drugs ( cholestyramine, colchicine, neomycin, NSAID) Less common endogenous causes • Infections (i.e. Rotavirus, parasitic diseases as Gardia lamblia or coccidiosis, Thropheryma whippelii, tropical sprue) • Eosinophilic gastroenteritis • Metabolic diseases (adrenal insufficiency, thyrotoxicosis) • Short bowel syndrome • Jejunoileal bypass • Bile obstruction/bile acid diarrhoea

(2.2.2.2.2.) Secretory Diarrhoea In secretory diarrhea, loose stools persist in spite of fasting. Persistent diarrhea is caused by toxic agents such as bacterial toxins, laxatives or drugs whereby intramucosal cAMP concentration increases resulting in stimulated luminal chloride channels. Consecutively the

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active secretion of chloride and bicarbonate as well as passive efflux of sodium, potassium and water result in hypovolemia, electrolyte disturbance and metabolic acidosis. Differential diagnosis of secretory diarrhea in the elderly: Common causes: • Infections by enterotoxines producing bacteria (Clostridium difficile, E. coli, Staphylococcus aureus, Vibrio cholerae) • Drugs (laxatives as bisacodyl, misoprostol) • Food toxins (mushrooms, shellfish) • Alcoholic diarrhea • Diabetic diarrhea

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Less common causes: • Food allergy • Thyrotoxicosis • Villous adenoma • Neuroendocrine tumors (i.e. carcinoid syndromes, VIPoma) For a better differentiation between osmotic and secretory diarrhoea, the stool osmotic gap should be calculated [12]. In order to calculate the stool osmotic gap the stool sodium and potassium concentrations need to be determined and entered into the following equation: 290 mosml/kg H2O - 2 (Na+K) mmol/l. A sodium concentration of more than 90 mmol/l and a stool osmatic gap of lower than 50 mosml/kg H2O provides a clue to the diagnosis of secretory diarrhea (osmotic diarrhea: sodium concentration less than 60 mmol/l, stool osmotic gap more than 100 mosml/kg H2O). Some authors caution that correct measurement of stool electrolytes is technically difficult making the stool osmotic gap a difficult test to perform in clinical practice [13]. Further difficulties arise from the fact of overlapping pathogenesis, so that there might be poor resolution between results from patients with secretory diarrhea and those with osmotic diarrhea [14]. To sum up, calculation of the stool gap requires an accurate collection of specimen and the results at best give a hint of the underlying aetiology and pathology. (2.2.3.) Inflammation Inflammatory diarrhoea can be elicited by several noxious stimuli: • Infection by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica) and non-invasive cytotoxin-producing bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile) [15, 16]. Invasive organisms get into the intestinal mucosa, cytotoxin-producing bacteria adhere to the mucosa. Both of them produce inflammation by activation of cytokines and inflammatory mediators. • Inflammatory bowel disease • Crohn’s disease and ulcerative colitis represent the most common intestinal inflammations resulting in diarrhea in elder patients [17]. • Exposure to radiation

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•

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In addition, chronic radiation enterocolitis needs to be considered, although this mainly affects the cecum and the rectum rather than the small intestine. To prevent enterocolitis caused by adjuvant radiation of a rectal carcinoma it is usefulif previous surgical therapy provides placement of an omental pedicle graft in the pelvic hollow. By this way, the small intestine is kept off the irradiated area. Finally, several autoimmune diseases may elicit inflammatory diarrhea (in particular different forms of vasculitis) [18].

(2.2.4) Practical Approach Treatment of diarrhea is an important issue for health care worldwide. Focused on the fact, that diarrhea is the most common reason for worldwide mortality in children, most guidelines and recommendations concentrate on the practical approach in younger patients. For instance in 2003 the WHO modified the ORS formula, which now provides reduced osmolarity. Additionally, the intake of zinc tablets is advised. The new formula is supposed to be more efficient for treatment of children with acute diarrhoea. By contrast literature research leads at best to regional guidelines dealing with this problem in elderly patients. Whereas in the developing countries secretory diarrhea caused by infection (rota virus, shigellosis) is most common, the most common causes for diarrhea in the “Western world” are fecal impaction and food-poisoning (mediated by toxins) [19]. The latter typically lasts for no longer than 24 hours. If looseness persists and dehydration is imminent, ORS should be offered to theses patients, too. In case of not being able to swallow because of vomiting, intravenous fluids must be prescribed. The intention is to avoid hypotension and consecutive organ failure. Accurate history taking and physical examination results in appropriately defining and classifying diarrhoea. Furthermore they are required for the subsequent diagnostic work up (figure 1). In case of acute diarrhea and a clinical suggestion of infection, stool cultures should be considered. The course of action is different in outpatients from hospitalized patients. If stools are sent for culture from an in-patient later than three days after admission, a low yield (50%. Non-infectious causes include diverticulitis and its variant of segmental colitis, ischemia, radiation, microscopic colitis and drug induced colitis. The incidence of diverticular disease rises with age and thus elderly patients are at increased risk. Diverticulitis can be confused with IBD clinically (presence of fever, abdominal pain, abdominal mass, leukocytosis, elevated ESR, obstruction and fistula formation) and radiographically. Endoscopic evaluation is usually indicative of one over the other. Confusion happens when there is a skipped area of segmental colitis approximate to the diverticula that macroscopically and at times microscopically resembles CD, but does not respond to standard medical treatment of CD [71, 72]. Ischemic colitis is more prevalent in the older population with co morbidities, especially atherosclerotic disease. Patients usually present with abdominal pain, diarrhea and passage of blood per rectum. The disease is most common in the "watershed" areas (splenic flexure and sigmoid colon) and can be diffuse or segmental. The rectum is often spared and complications such as stricture formation may occur. The medical history of the patient as well as histology, help differentiate it from IBD

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Table 4. Differential Diagnosis of IBD in the Elderly Infectious Etiologies Bacterial: Salmonella, Shigella, E Coli, Campylobacter, Yersinia, Clostridium Difficile Non infectious Etiologies Inflammatory: Diverticulitis, Appendicitis, Diversion colitis, Microscopic colitis, Ischemic colitis, Radiation colitis, Solitary rectal ulcer syndrome, Eosinophilic gastroenteritis, Neutropenic colitis, Bechet's syndrome, Graft versus host disease

Viral: CMV, Herpes Simplex, HIV Parasitic: Amebiasis, Isospora, Hookworm, Strongyloides Neoplastic: Lymphoma, Metastatic carcinoma, Carcinoma of the Ileum, Carcinoid, Familial Polyposis

Fungal: Histoplasmosis, Candida, Aspergillus Mycobacteria: TB, MAC

Drugs: NSAIDS, Gold, Chemotherapy

Radiation colitis can manifest as early as a few weeks after radiation treatment or can develop many years later. Colonic involvement manifests as bloody diarrhea and tenesmus Tal, Sari. Gastrointestinal Tract in the Aged, edited by Stephen Dh Malnick, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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while small bowel involvement is associated with watery diarrhea. Later complications include stricture formation, bacterial overgrowth and malabsorption. Endoscopic appearance is suggestive with multiple telangectasias, mucosal granularity and occasional ulcerations and histology confirm the diagnosis. Microscopic colitis including collagenous colitis and lymphocytic colitis are diseases of the elderly with peak incidence in the sixth and seventh decades. They usually present with chronic watery diarrhea and can readily be differentiated from IBD by the normal appearing mucosa on endoscopy. Additional etiologies in the differential diagnosis of IBD which can usually be easily distinguished endoscopically include solitary rectal ulcer syndrome, diversion colitis, irritable bowel syndrome and colonic neoplasia. Drug history, especially NSAIDS, should always be thoroughly investigated and considered especially in the elderly patient who is often treated with multiple medications

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Treatment There are no controlled trials comparing medical management of elderly patients with IBD to younger patients. Furthermore, there are no controlled trials comparing different medications in this age group. It is generally accepted that medical treatment of elderly IBD patients, does not differ from what is known and accepted in the younger population of IBD patients [14-17]. Several observational studies, in CD, revealed minimal differences in the outcome of medical management between young and older patients [14, 15, 73]. Data on medical treatment of elderly patients with UC is limited and inconclusive. Two studies found that elderly patients with UC received more systemic corticosteroids, had a more severe, protracted first attack and shorter remissions. However, the total number of admissions and final outcome did not differ between the two groups [38, 74].

5-Aminosalicilic Acid (5ASA) Representatives of this class of drugs include Sulfasalazine and Mesalamine. Different coatings or assemblies are used to release the drug in an either PH dependent manner (Asacol® – delayed release or Pentasa® - controlled release) or via bacterial cleavage (Olsalazine®). The therapeutic mechanism of this class of drugs, include inhibition of T cell proliferation and antigen production by B cells, inhibition of macrophage adhesion, decreased production of IL-1, TNF-α, Prostaglandin E2, Leukotriene B4 and Platelet activating factor among others. Many of these effects seem to be mediated through down regulation of TGFβ [75]. Earlier trials demonstrated that sulfasalazine in doses of 4-6 grams per day is better than placebo for the induction of remission in patients with mild to moderate Crohn's colitis [7680]. Results of trials with mesalamine are inconclusive. Earlier studies suggested a benefit over placebo in the treatment of mild to moderate Ileal CD, however subsequent studies failed

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to show a benefit over placebo and the role of mesalamine in the treatment of CD remains uncertain [76, 77, 81]. Oral 5ASA agents including sulfasalazine and mesalamine have been proven to be effective in inducing remissions in mild to moderate UC [76-78, 82-86]. Sulfasalazine is effective in doses of 4-6 grams per day, while 5-ASA derivatives are effective in doses of 2-4 grams per day. Once remission is achieved, these agents are effective in maintaining remission. The same dose that induced remission is recommended as the maintenance dose. Topical 5ASA agents are used for mild to moderate distal UC. They can be administered as enemas (distribution to the level of the splenic flexure), suppositories (disease limited to 20 centimeters from the anal verge), or foam which has a more uniform distribution and longer persistence in the distal colon. Topical 5ASA preparations have similar efficacy and fewer adverse effects as the oral agents for treatment of left sided colitis. A combination of oral and topical preparations seems to be more effective than oral treatment alone [87-89]. Common adverse effects of this class of drugs include fever, rash, nausea, vomiting, diarrhea and headaches. Less common, but potentially serious adverse effects include hypersensitivity reactions and impairment in folate absorption and renal function [86]. Disturbances in folate absorption are attributed to the sulfa component of sulfasalazine and patients who are treated with sulfasalazine should receive folate supplementation. Up to 90% of the patients who cannot tolerate sulfasalazine will tolerate mesalamine [86]. Elderly patients are more susceptible to the potential nephrotoxicity of these drugs, mainly interstitial nephritis, due to decreased GFR. These drugs can also potentiate the effect of warfarin and prolong the INR [76].

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Glucocorticosteroids Glucocorticosteroids have numerous anti-inflammatory and immunosuppressive effects including inhibition of pro-inflammatory cytokines, adhesion molecules, MHC class 2 molecules, leukotrienes, elastase and coagulase. These agents penetrate the cellular membrane, bind to soluble glucocorticoid receptors which enter the cell nucleus and bind to elements on the DNA that activate different transcription factors which in turn induce a large variety of physiological effects [90]. Direct interaction with cytoplasmatic proteins, interaction with membrane bound glucocorticoid receptors and regulation of cytoplasmic transcription factors occurs as well. Glucocorticosteroids are indicated for inducing remission in moderate to severe CD. Doses can be as high as 1 mg/kg/day. High response rates of up to 80-92% by one month can be expected [76-78, 91, 92]. Glucocorticosteroids however are not effective as long term therapy and have failed in maintaining remissions in CD patients [76-78, 93]. Up to 20% of the patients fail to respond to these agents within the first month of treatment i.e. steroid resistant. Up to 45% of patient, who are initially responsive, will not be able to taper off the treatment and become steroid dependent [91]. Clinical factors associated with steroid dependence and bad prognosis, include smoking, colonic disease and young age at diagnosis. Furthermore, initial treatment with steroids, age below 40 and penetrating disease were shown to be clinical predictors of severe disease [94]. Budesonide is a novel glucocorticosteroid which has an increased first pass metabolism that limits its systemic exposure. Various studies have shown that budesonide at a dose of 9

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mg/day is more effective than mesalamine and nearly as effective as prednisone in achieving remissions with fewer adverse effects [95, 96]. Budesonide is considered first line therapy for patients with mild-moderate active ileal, ileocecal or right colonic disease. However, similar to prednisone, budesonide does not decrease the relapse rate at 1 year and is therefore ineffective and not recommended for maintenance therapy [95-97]. Glucocorticosteroids in doses equivalent to 40-60 mg of prednisone per day, are effective in inducing remission in moderate to severe flares of UC [76-78, 82, 98, 99]. Having no role in the maintenance therapy, steroids should be tapered down within 12 weeks. Patients who are unable to be tapered off the steroids or experience disease flares, should be managed with the addition of steroid sparing agents. Topical steroids in the form of liquid or foam have been shown to be efficacious in the short term treatment of distal UC [98, 99]. They are however less effective than topical mesalamine in inducing remission. The combination of topical 5ASA and topical steroids appears to be more effective than either treatment alone [100]. Budesonide enemas are as effective as prednisone enemas and slightly less effective than mesalamine enemas [101, 102]. Glucocorticosteroids have frequent and often severe adverse affects. The more common adverse effect includes neuropsychiatric symptoms such as mood changes and sleep disturbances, cosmetic effect including acne, male pattern hair distribution and cushingoid features. The potentially serious adverse effects include adrenocortical suppression, glucose intolerance, myopathy, bone loss and increasing risk of serious infections. All patients on continuous steroid treatment should be evaluated for osteopenia and treated appropriately [103, 104].

Adapted with permission from Silverberg MS, Steinhart AH: Bone density in inflammatory bowel disease. Clin Perspect Gastroenterol 3:117, 2000. Figure 5 - Management of metabolic bone disease in Crohn's disease. (T, T score; DEXA, dual-

energy x-ray absorptiometry).

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Azathioprine (AZA) and 6-Mercaptopurine (6-MP) Both drugs produce metabolites which inhibit de-novo synthesis of purine ribonucleotides and thereby cell proliferation. In addition, both drugs possess immunosuppressive properties including inhibition of cell mediated immunity by causing a reduction in number of circulating natural killer cells, by apoptosis induction in proliferating T lymphocytes [105] and by depletion of antigen-specific clones following repeated antigenic exposure. Both these drugs have a delayed onset of action of up to 8-12 weeks that may be explained by their mechanism of action [106]. In CD, AZA and 6-MP have been proven to be effective in inducing remission, maintenance of remission, healing of fistulas and as steroid sparing agents [76-78, 107-110]. AZA is used in doses of 2-3 mg per kg per day and 6-MP in doses of 1-1.5 mg per kg per day. These agents should be considered for patients with CD who have failed to respond to first line therapy or who cannot be tapered off steroids or as first line for patients with bad prognostic signs. They are also indicated for patients with fistulous complications who are intolerant to or unresponsive to antibiotic treatment. There is no information to date on the recommended duration of treatment and decision to stop the medication should be individualized and after discussion of the potential risks and benefits with the patient. Several controlled trials have demonstrated the efficacy of AZA and 6-MP in the treatment of active UC [76-78, 81, 110-112]. There is also evidence to their effectiveness in maintaining remissions and as steroid sparing agents [113, 114]. Adverse effects severe enough to cause discontinuation of the treatment occur in up to 9% of patients [107]. Nausea is common in the first few weeks of treatment and gradually subsides. Allergic reactions such as fever, rash and arthralgias are seen in up to 2% of the patients. Pancreatitis is an idiosyncratic reaction observed in up to 4% of patients and resolves upon discontinuation of the medication. Elevated aminotransferase levels occur in approximately 9% of the patients but cholestatic hepatitis is rare (