Medical and Nutritional Complications of Alcoholism: Mechanisms and Management

583 Pages·1992·72.91 MB·English

by  Charles S. Lieber (auth.)

Medical and Nutritional
Complications of
Alcoholism
Mechanisms and Management
With Contributions by
Siamak A. Adibi, M.D., Ph.D., Montefiore Hospital and University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania
Enrique Baraona, M.D., Mt. Sinai School of Medicine of the City University of New York
and Bronx Veterans Affairs Medical Center, New York, New York
Murray Epstein, M.D., F.A.C.P., University of Miami School of Medicine and Veterans
Affairs Medical Center, Miami, Florida
Lawrence Feinman, M.D., Mt. Sinai School of Medicine of the City University of New York
and Bronx Veterans Affairs Medical Center, New York, New York
Howard S. Friedman, M.D., Downstate Medical Center of the State University of New York,
The Brooklyn Hospital, New York, New York
Anthony J. Garro, Ph.D., University of Medicine and Dentistry of New Jersey, New Jersey
Medical School, Newark, New Jersey
Barbara H. J. Gordon, Ph.D., Hunter College of the City University of New York,
New York, New York
Gary G. Gordon, M.D., New York Medical College, Valhalla, New York
Mark A. Korsten, M.D., Mt. Sinai School of Medicine of the City University of New York,
and Bronx Veterans Affairs Medical Center, New York, New York
Maria A. Leo, M.D., Mt. Sinai School of Medicine of the City University of New York, New York,
New York
John Lindenbaum, M.D., Columbia University College of Physicians and Surgeons, New York,
New York
Finbarr C. Martin, M.D., Department of Medicine for the Elderly, St. Thomas' Hospital, London, England
Fiorenzo ParonettO, M.D., Mt. Sinai School of Medicine of the City University
of New York and Bronx Veterans Affairs Medical Center,
New York, New York
Timothy J; Peters, M.D., King's College School of Medicine and Dentistry University of London, King's College
Hospital, London, England
Romano C. Pirola, Department of Medicine, Prince Henry Hospital, Little Bay, Australia
Alan Rosman, M.D., Mt. Sinai School of Medicine of the City University of New York
and Bronx Veterans Affairs Medical Center, New York, New York
Maurice Victor, M.D., Veterans Affairs Medical and Regional Office Center, White River Junction,
Vermont, and Dartmouth Medical School, Hanover, New Hampshire
Medical and Nutritional
Complications of
Alcoholism
Mechanisms and Management
Charles S. Lieber
Bronx Veterans Affairs Medical Center and
Mount Sinai School of Medicine of the City University of New York
New York, New York
Springer Science+Business Media, LLC
Librar y of Congress Catalog1ng-1n-Publ1catIo n Data
Medical and nutritiona l complication s of alcoholis m : mechanismsa nd
managemte n/ [edite d by] Charles S. Lieber
p. cm.
Includes bibliographica l reference s and index.
ISBN 978-1-4613-6462-7 ISBN 978-1-4615-3320-7 (eBook)
DOI 10.1007/978-1-4615-3320-7
1. Alcohol—Physiologica le ffect . 2. Alcoholism—Pathophysiology .
I. Lieber , Charles S., 1931-
[DNLM: 1. Alcohol , Ethyl—advers e effects . 2. Alcoholism -
-complicat1ons. 3. Nutrition—dru g effects . 4. Nutritio n
Disorders—etiology . 5. Nutritio n Disorders—therapy . WM2 74
M487]2
QP801.A3M5 31992
616.86'1 —dc20
DNLM/DCL
for Librar y of Congress 92-49893
CIP
This limited facsimeil edition has been issued
for the purpose of keeping this title availabel
to the scientifci communit.y
10 98765432
ISBN 978-1-4613-6462-7
© 1992 Springer Science+Busines sMedia New York
Originally published by Plenum Publishing Corporation in 1992
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, mechanica,l photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
To my children
Colette, Daniel, Leab, Samuel, and Sarab
in appreciation for their patience and understanding
during the writing of this book and the ones that preceded it
Preface
In the Western world, alcohol is the most abused drug. recognized that a majority of patients with cirrhosis do
For all the attention being directed toward heroin, co admit to excessive alcohol consumption. Other tissues
caine, and marijuana, the favorite mood-altering drug in can also be severely affected, including brain, gut,
the United States, as in almost every human society, is heart, endocrine systems, bone, blood, and muscle. A
alcohol. In nature, the fermentation of sugars is the question often raised is, "In what way does an alcoholic
major source of ethanol, but how humans first encoun differ from a nonalcoholic?" Inquiries have focused on
tered it is unclear. It most likely occurred in either psychological make-up, behavioral differences, and socio
fermented fruit juices (wine), fermented grain (beer), or economic factors. More recently, however, physical dif
fermented honey (mead). Whether the Paleolithic Stone ferences have been delineated. Prior to the development
Age man knew of ethanol is undetermined, but it is of various disease entities, chronic ethanol exposure
abundantly clear that his Neolithic descendants were results in profound biochemical and morphological
familiar with the product of fermentation. With the changes. Consequently, an alcoholic does not respond
exception of the original inhabitants of Tierra del Fuego, normally to alcohol, other drugs, or even other toxic
the Australian aborigines, and some polar tribes, all agents. Some of these persistent changes are conse
known human groups (even among the surviving Stone quences of the injurious effects of ethanol and associ
Age cultures) are familfar with alcoholic beverages. The ated nutritional disorders, whereas others may represent
purpose of this volume is not to discuss the effects of adaptive responses to the profound changes in inter
ethanol on mood and behavior that have led to its mediary metabolism that are a direct and immediate
widespread use but, rather, to focus on the conse consequence of the oxidation of ethanol itself.
quences, sometimes disastrous, of the metabolism of In this volume we describe these general effects of
ethanol in the body and how, as a result, alcoholics differ alcohol. More specifically, we summarize the symp
from nonalcoholics biochemically and pathologically. tomatology, pathogenesis, and available treatment for
A few decades ago, the medical issues relating to various medical complications of alcoholism. These
the disease of chronic alcoholism were not widely stud complications involve virtually the entire field of inter
ied, because the intrinsic toxicity of alcohol was not nal medicine, much of pathology and biochemistry, and
fully appreciated and alcoholism was considered pri some pharmacology. Because of its wide impact, syph
marily a social or behavioral problem. However, the ilis was called "the great imitator"; this can now be
prevalence of just one medical problem, cirrhosis of the said of alcoholism, since its complications can mimic a
liver, has now reached a magnitude such that this com great many other diseases. Indeed, there is hardly any
plication of alcoholism represents, in and of itself, a tissue in the body that is spared by alcohol. To know the
major public health problem. We now recognize that pathophysiology of alcohol-induced lesions is to under
75% of all medical deaths attributable to alcoholism are stand the pathological responses of most organs.
the result of cirrhosis of the liver; in large urban areas, Because of their wide impact, the medical disor
it has become the fourth leading cause of death in the ders associated with alcoholism represent one of the
active age group of 25 to 65 years. Although not all most important public health problems confronting our
cirrhotic subjects are alcoholics, it is now generally society. The significant progress made in developing
vii
viii Preface
tools for diagnosis and elucidating concepts of patho early stages; and (3) recognition of preexisting enzyme
genesis may open up new avenues for prevention. In defects or other preexisting abnormalities, such as pre
deed, the significant progress made in our understand cirrhotic lesions, or the detection of contributory genetic
ing of the metabolism of ethanol and its effects on the factors, may permit screening for alcoholics predis
body allows for some cautious optimism. Although we posed to the development of major complications of
may not understand why alcoholism develops in only alcoholism such as cirrhosis. A concentrated therapeu
some ethanol consumers and why major complications tic effort on this more manageable subgroup might
such as liver disease occur in only a minority of heavy arrest the disease at a potentially reversible stage, prior
drinkers, we may nevertheless be able to intervene to the social and medical disintegration of the individ
successfully once we acquire a better understanding of ual. At our present state of knowledge, full implementa
how ethanol affects the chemistry and structure of the tion of such a public health approach is not yet possible,
body. A public health approach at three levels of inter but I hope that this volume, by summarizing the ad
vention can now be conceptualized: (1) biological vances made to date, may kindle the start of such an
markers of alcoholism are being developed that, when approach and bring closer the day when full implemen
perfected, may allow for early detection of heavy drink tation will be feasible.
ing; (2) in these individuals at risk, improved blood tests
may eventually permit detection of alcohol-induced Charles S. Lieber
liver injury and other medical disorders at reversible, Bronx, New York
Acknowledgments
No single individual's expertise could be sufficient to extremely helpful in proofreading and contributing
span the vast area of medicine involved in the medical many constructive criticisms concerning several of the
disorders associated with alcoholism. I was fortunate in chapters. I am grateful to my office staff, Ms. Renee
the writing of this book to benefit from considerable Cabell and Ms. Patricia Walker, who very skillfully
help from a large number of colleagues. Those specifi typed a large part of this monograph. Furthermore, I
cally involved in the preparation of some segments of wish to thank Ms. Gloria Spivacek and her staff at the
the book are identified in the appropriate chapters. Medical Media Department of the Bronx VA Medical
Others have helped in more general ways. I am partic Center for much of the skillfully executed artwork and
ularly indebted to Ms. Leonore DeCarli, my long photography, and Ms. Margaret Kinney and her staff at
standing associate, whose unceasing dedication to our the medical library of the Bronx VA Medical Center for
research projects has allowed me to collect many of the their assistance in collecting the bibliographic citations
data reported in this book. Dr. C. Kim has also been in this volume.
ix
Contents
Chapter 1. Metabolism of Ethanol
Charles S. Lieber
1.1. Pathways of Ethanol Oxidation .............................................. . 1
1.2. Alteration in the Metabolism of Ethanol after Chronic Ethanol Consumption ........ . 14
1.3. Effects of Liver Disease, Blood Flow, Circadian Rhythm, Gender, and Other Factors on
Hepatic Alcohol Metabolism ........................................... . 19
1.4. Effects of Other Drugs on Ethanol Metabolism .................... ' ............ . 20
1.5. Ethnic and Genetic Factors in Ethanol Metabolism ............................. . 21
1.6. Extrahepatic Ethanol Metabolism ............................................ . 22
1.7. Summary ............................................................... . 24
References .............................................................. . 24
Chapter 2. Acetaldehyde and Acetate
Charles S. Lieber
2.l. Pathways of Acetaldehyde and Acetate Metabolism ............................. . 37
2.2. Effect of Chronic Ethanol Consumption on Acetaldehyde and Acetate Metabolism ... . 39
2.3. Effect of Liver Injury on Acetaldehyde Metabolism ............................ . 43
2.4. Effects Attributable to Acetaldehyde and Acetate after Acute and Chronic Ethanol
Consumption ........................................................ . 44
2.5. Summary ............................................................... . 47
References .............................................................. . 48
Chapter 3. Alcohol, Hormones, and Metabolism
Gary G. Gordon and Charles S. Lieber
3.1. Hypothalamic-Pituitary-Thyroidal Axis ...................................... . 55
3.2. Parathormone and Calcitonin ............................................... . 57
3.3. Adrenocortical Function: Glucocorticoid Secretion ............................. . 58
3.4. Adrenocortical Function: Mineralocorticoid Secretion ........................... . 62
3.5. Adrenal Medullary Function ................................................ . 62
3.6~ Growth Hormone ......................................................... . 63
xi