Table Of ContentThe Hepatobiliary System
Fundamental and Pathological Mechanisms
NATO ADVANCED STUDY INSTITUTES SERIES
A series of edited volumes comprising multifaceted studies of contemporary
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Volume 2 - Nematode Vectors of Plant Viruses
edited by F. Lamberti, C.E. Taylor, and J.W. Seinhorst
Volume 3 - Genetic Manipulations with Plant Material
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Volume 6 - Metabolic Compartmentation and Neurotransmission:
Relation to Brain Structure and Function
edited by Soli Berl, D.D. Clarke, and Diana Schneider
Volume 7 - The Hepatobiliary System: Fundamental and Pathological Mechanisms
edited by W. Taylor
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The Hepatobiliary System
Fundamental and Pathological Mechanisms
Edited by
w.
Taylor
The Medical School
The University
Newcastle upon Tyne, England
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
NATO Advanced Study Institute on the Biliary System, 2d, Aalborg, Denmark,
1975.
The hepatobiliary system.
(NATO advanced study institutes series: Series A, Life sciences; v. 7)
Includes bibliographical references and indexes.
1. Biliary tract-Congresses. 2. Biliary tract-Diseases-Congresses. 3. Liver-Con-
gresses. 4. Liver-Diseases-Congresses. I. Taylor, William, 1922- II. Title. III.
Series. [DNLM: 1. Biliary tract-Congresses. W3 N136 1975h/W1700 N108 1975h)
RC849.N37 1975 612'.35 76-2486
Proceedings of the Second NATO Advanced Study Institute on the Biliary System,
held in Aalborg, Denmark, August 24-30, 1975
© 1976 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1976
Softcover reprint of the hardcover Ist edition 1976
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, mechanica1, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
ISBN 978-1-4615-8902-0 ISBN 978-1-4615-8900-6 (eBook)
DOI 10.1007/978-1-4615-8900-6
Foreword
A volume on the biliary system appeared in 1965, based on a
symposium of the NATO Advanced Institute held in September, 1963,
in Newcastle upon Tyne in England. It soon became an authorita
tive text on the problems of the biliary tract and, for instance,
the discussion on the biliary secretion of organic anions, organic
cations and inorganic ions were classic references. The worn
pages of the volume in many libraries, including my own, bespeak
its usefulness over ten long years. The initiative and energy of
the Director of the first Institute have to be admired, even more
so since he was able to assemble a Second Institute in Aalborg,
Denmark, in 1975. His wisdom is reflected in the selection of the
subjects discussed. The comparison between the two volumes tells
something about the advancement in the time interval in knowledge
about liver and biliary tract diseases, about the turnover of
researchers interested in the liver and its diseases, and also
about the present philosophy in biologic science. For this com
parison, this volume is particularly suited because, in contrast
to many other recent conferences, the more leisurely pace of the
NATO Institutes permits more comprehensive but still scholarly
reviews of the problems.
The foreword of the first volume, written by my colleague,
the late Harry Sobotka, expresses his, now dated, astonishment
about the progress of knowledge of biology of the bile, so much
less accessible to study than urine. He states his satisfaction
that the study of morphological observations was being supple
mented by graphic presentation of functional data. Ten years
later we almost forget that such developments were still sur
prising.
v
vi FOREWORD
Taylor, in the opening address to this Second Institute, in a
way on which I cannot improve, points out the progress made in
these ten years and gives the reason why he selected the topics
presented.
Interesting is an account of the degree to which the scholarly
predictions of the excellent summaries in the first volume came
true. Almost prophetically, Sherlock raised the ethical problem
of transferring animal experimental procedures to man. Her state
ment that the mechanism of cholestasis is mysterious is as true
today as it was then. But when she considered gallstones "a
dreadful subject to work on," we can look with satisfaction at the
past ten years, when the putative mechanism was moved from mechani
cal processes in the biliary tract to alterations of hepatocytic
function. Her question of whether the biliary tract is a simple
conduit or contributes to the constitution of the bile, as the
renal tubule does, has been resolved in favor of the latter. Her
emphasis on genetics in both gallstone formation and in adverse
drug reactions has been justified.
Brauer, as a physiologist, emphasized two problems: the mech
anism of bile formation, and the hepatocytic injury and its rela
tion to recovery. The first problem has since been clarified to
a measure anybody scarcely hoped for, but the pathogenesis of liver
cell injury and particularly of the death of the hepatocyte is a
greater problem today than it was ten years ago. The initial in
jury caused by biliary retention can be explained by detergent
action of bile acids on hepatocellular organelles and possibly by
some effects of bilirubin. By contrast, the mechanism of liver
cell death has become more of a riddle in biliary retention as
well as in chemical or immunologic or virus induced liver injury.
The common terminal event is cell membrane injury, but how it
comes about is not established. This lack of information inter
feres with attempts to favor hepatocytic regeneration and to pro
vide a rational therapy for the sick liver cell beyond the removal
of the offender.
Andrews emphasized the importance of the blood, biliary, and
tissue fluid flow, as well as intracellular transport. His analy
sis of the situation sounds almost up-to-date because here the
development followed the prediction more clearly than in any other
area.
Doisy referred, as would be expected, to the field of bile
acids, in which he pioneered, and predicted significant results
from Haslewood's comparative studies and hoped, with more justifi
cation than one would have then expected, that BergstrBm's school
at the Karolinska would open up the field. Supported by the Mayo
Clinic's additional contributions, this is probably the area in
FOREWORD
which greatest progress has been made in biliary tract disease in
these ten years. We marvel at his wisdom when he regrets the
neglect of lithocholic acid, which is at present a limiting factor
in the chemotherapy of gallstone disease.
The turnover of scientists reflected in speakers and partici
pants is an interesting comment on the sociology of science. Be
sides the unfatigab1e Director, only two scientists spoke at both
Institutes and one then only in the discussion. Otherwise, only
four of the speakers and participants of the first conference were
also present at the second although four of the key speakers of
the first were invited but regretfully could not attend.
The years between 1963 and 1975 saw a dramatic change in the
intellectual climate of biomedicine in the entire world. A socio
logic revolution altered the values and standards of society as a
whole and the governments' as its arm. The aspirations of the
youth shifted emphasis from biologic to sociologic problems in
medicine, often with antagonism toward science as a potential
source of environmental disaster. A revolution in university
governance in many parts of the Western but also of the Eastern
world thus may have caused the fear in many that in this time of
turmoil or crisis, many of the values might be destroyed that had
brought biomedicine to its peak. It is reassuring that the aca
demic standards of this conference and the intellectual climate of
the assembly remained as solid as they were at the first. It is
even more reassuring that an essentially political body, as NATO
is, considered it important to assemble biologic scientists by
giving this conference its support when one might have assumed
that NATO would be preoccupied with more mundane problems. Let us
hope that a Third Institute wi 11 be assembled in a similar spirit
of peaceful endeavor. Besides Dr. Taylor and the splendid hosts
in Aa1borg, symbolized by Dr. E.H. Thayson, the NATO organization
deserves the appreciation of the scientific community.
Hans Popper
Preface
This volume contains the Lectures, Commentaries and Discussions
of the Second NATO Advanced Study Institute on 'The Bil iary System'
held in Aalborg, Denmark in August, 1975. In selecting the topics
for presentation at the Institute, which took two years to plan, I
did not attempt to cover all aspects of the hepatobil iary system.
Indeed, so vast is the information on this system, and so rapid
the progress, that it would be difficult to present a comprehensive
survey of the subject at a single Institute.
The purpose of the Institute was to bring together workers
from as many discipl ines of the biomedical sciences as possible,
so that fundamental aspects of membrane structure and transport
mechanisms could be seen in relation to the indirect methods which
are of necessity appl ied to structure and function in normal and
experimentally disturbed hepatobil iary systems, and finally to
attempt to relate these to problems facing the cl inical hepatologist.
I hope it is obvious that multidiscipl inary interchanges of ideas,
concepts and problems in different fields of research were a sal ient
feature of the discussion sessions.
It is also apparent from the papers and discussions that
although a vast amount of data about the hepatobil iary system has
been accumulated in the past few years, our real understanding of
the normal and abnormal processes in the bile secretory apparatus
has been furthered only a I ittle. Mysteries remain, and many of
these have been highl ighted by the work of the Institute.
Differ~
ences of opinion about many processes, methods of approach, etc.
have been freely discussed, but not necessarily resolved.
ix
x PREFACE
It is my hope and expectation that the free interchange of
ideas during the formal and informal meetings of the participants
will encourage new outlooks, result in greater collaboration and,
above all, to stimulate workers in one area to consider their
results in the I ight of results obtained by others using different
approaches to the problems.
I am grateful to the members of the Advisory Committee,
particularly Drs. Popper and Thaysen, who provided invaluable
advice and a great deal of encouragement in my efforts to
organise the programme.
The meeting could not have been held without the financial
support of the Scientific Affairs Division of NATO, and I am sure
that all who attended the Institute would wish me to express their
thanks to NATO. I am particularly indebted to Dr. T. Kester of
NATO for his advice and help during the planning of the Institute.
Generous financial support was also provided by Dr. H. Falk
and by Drs. R. Preisig and G. Paumgartner.
We are greatly indebted to Dr. Hess Thaysen for his unflagging
efforts to assist with the local organisation of the Institute,
which created such a pleasant atmosphere at the Institute. Also
we express our thanks to the Civic Authorities of the City of
Aalborg, and also to the citizens of Aalborg whose kind and
friendly natures made our stay in the city so pleasant.
Most of the material in the discussion sessions is presented
without editing by the participants themselves. Many will regret,
and, perhaps justifiably, criticise the lack of references to back
up the statements made in these discussions. However, I feel
that the rapid publ ication of this volume will compensate for the
lack of references. Also, it may be felt that the volume lacks
comprehensive coverage and a balanced appraisal of all current
problems related to the hepatobil iary system. Although the
Advisory Committee were generous with their suggestions and
comments about the programme, the ultimate decisions about the
selection of speakers, the form of the programme and the rapid
production of this volume are mine. Therefore, any failure in
the wisdom of these decisions is my responsibil ity alone.
Whatever success the Institute may have had, and the value
of this volume, are due to the enthusiastic support of the
