Bile Acids in Health and Disease: Update on Cholesterol Gallstones and Bile Acid Diarrhoea

316 Pages·1988·4.64 MB·English

by  A. F. Hofmann (auth.)

BILE ACIDS
IN HEALTH
AND DISEASE
BILE ACIDS
IN HEALTH
AND DISEASE
Update on Cholesterol Gallstones and
Bile Acid Diarrhoea
Editors
Tim Northfield, Riadh Jazrawi and
Patrick Zentler-Munro
Department ofMedicine, St. GeorgesHospital Medical School
London, UK
KLUWER ACADEMIC PUBLISHERS
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BritishLibraryCataloguinginPublicationData
Bileacidsinhealthanddisease.
1. Man. Bileacids
I. Northfield,Tim II.Jazrawi,Riadh
III. Zentler-Munro,Patrick
612'.35
ISBN-13:978-94-010-7054-6 e-ISBN-13:978-94-009-1249-6
DOl: 10.1007/978-94-009-1249-6
Copyright
© 1988byKluwerAcademicPublishers
Softcoverreprintofthehardcover Istedition 1988
Allrightsreserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,
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Contents
Preface YIn
Listofinvitedspeakers x
1 Overview: the enterohepaticcirculationofbileacids-a topic
inmolecularphysiology
A.F.Hofmann 1
SECTIONA BILIARYCHEMISTRYANDPHYSIOLOGY
2 Hepaticbile acid transportandsecretion
S. Erlinger 21
3 Hepaticbiliarylipidsynthesisand transport
1. Graham, H.Ahmedand T.e. N01thfield 27
4 Biliarylipidsecretionand itscontrol
R. Coleman, K Rahman, M.E. Bel/ringerandM. Carrel/a 43
5 Lipidsolubilisationinbile
M.e. Carey 61
6 Gallbladdermotorfunction
A. LanziniandT.e. Northfield 83
SECTIONB PATHOGENESISOFCHOLESTEROL
GALLSTONEDISEASE
7 Thesecretorydefect
K EinarssonandB.Angelin 99
8 Thephysico-chemical defect
R.T. Holzbach, R.L. BarnhartandI.M. Nader 117
9 The motilitydefect
I.e. Forgacs 135
v
BILEACIDSINHEALTHANDDISEASE
SECTIONC GALLSTONEPREVENTION
10 Cluesfromepidemiology
K. Heaton 157
11 Post-dissolutiontrials
K.A. Hood 171
SECTIOND NON-SURGICALTREATMENTOFGALLSTONES
12 Cheno-versusursodeoxycholicacid
L. Barbara, F. BazzoUandE. Roda 183
13 Cheno-plusursodeoxycholicacid
M. Podda, M. ZuinandP.M. Battezzati 187
14 Methyl tert-butylether
J.L. Thistle 195
15 Lithotripsy
G. Paumgartner, M. Sackman, J. Holland T. Sauerbruch 201
16 Overallstrategy
T.e. NorthfieldandR.P.Jazrawi 205
SECTIONE LIPIDDIGESTIONANDBILEACID
ABSORPTION
17 Fatdigestionandsolubilisation
B. Borgstrom 217
18 Bileacidabsorption
A. Stiehl 229
SECTIONF LIPIDMALDIGESTIONANDBILEACID
MAlABSORPTION
19 Fatdigestionandsolubilisationindisease
P.L. ZentIer-Munro, D. FineandT.e. Northfield 239
20 Bileacid malabsorption,diarrhoeaandsteatorrhoea
H.V.Ammon 253
21 Bileacids inirritablebowelsyndrome
M. EastwoodandM. Merrick 267
vi
CONrENTS
SECTIONG DIAGNOSISOFBILEACIDMAlABSORPTION- ROLE
7S
OF SeHCAT
22 75SeHCAT: anoverviewofitsphysiologicalpropertiesand
clinicalvalue
R.P.Jazrawi, R. Fe"arisandT.e. Northfield 277
23 Wholebodyand abdominal retentionof75SeHCAT
G. Sci~etta, G. Faglioli,A.Furno, G. ViciniandP. Malaguti 291
24 Gallbladderretentionof75SeHCAT
R. Fe"aris 301
Index 307
vii
Preface
Bileacidsoccupyacentralpositioninintheabsorption,excretionandmetab
olismoflipidswithinthebody.Ourunderstandingoftheiruniqueproperties
hasilluminated manybiochemicalandbiophysicalprocesses. Animals have
evolved a unique system of preserving these important detergent-like
moleculeswithinthebodyand reusingthemmanytimes- theenterohepatic
circulation.
Disorders ofthe enterohepatic circulation contribute to a correspondingly
wide range ofdiseases, and recentdevelopments have centred inparticular
oncholesterolgallstonediseaseandbileaciddiarrhoea.Successfulmanage
ment of these diseases is increasingly based on an understanding of the
physicochemical and biochemical properties of bile acids, and of their
pathophysiological role indisease.
Professor Alan Hofmann starts this book with an overview of the
enterohepaticcirculationofbileacids.Thefirstsectionthendiscussesbiliary
lipidsynthesis, transport and secretionby the liverand the solubilisation of
cholesterol in the bile. The next section applies this knowledge to the
pathogenesisofcholesterolgallstones.Separatechaptersfocusondefectsin
biliary lipid secretion, in cholesterol solubilisation and in gallbladder
motility. The succeeding sections then review posssible approaches to
gallstoneprevention, and assess recentdevelopments in non-surgicalforms
oftreatment.Twoexcitingnewtherapiesthatreceiveparticularattentionare
contact dissolution therapywith methyl tert-butyl ether and extracorporeal
shockwave lithotripsy. Further sections turn to the absorptive functions of
bile acids in health. These relate to the absorption offat and electrolytes,
and to the subsequent reabsorptionofthe bile acids themselves.Therefol
lowsadiscussionofthecontributionofbileacidstothepathogenesisofdiar
rhoea and steatorrhoea.The most noteworthy clinical advance has been in
the diagnosis of bile acid malabsorption and bile acid diarrhoea using the
gammaemitting75SeradiolabelledbileacidSeHCAT,whichhasprovideda
diagnostic tool available for the first time in any hospital with a gamma
camera.
This book is addressed primarily to gastrointestinal physicians and
physiologists. However, anyonewhoshares ourinterestinthesefascinating
moleculeswillgleannewinsightsfomthiscompendium.Theinvitedauthors
Vlll
BILEACIDSINHEALTIIANDDISEASE
are drawnfrom those international centreswhich have contributed most to
ourunderstanding.Theircontributions have beenheavilyedited to achieve
acohesivevolumeofuniformstyleandformat.Aseditors,weacceptrespon
sibilityfor anydeficienciesin thefinal result.
DepartmentofMedicine TimNorthfield
St. George'sHospitalMedicalSchool RiadhJazrawi
London PatrickZentler-Munro
Acknowledgements
The preparation ofthis bookwas stimulated by the enthusiasm ofthe con
tributorsatameetingentitled"BileAcidsinHealthandDisease"heldatthe
Royal Society ofMedicine, London in September, 1987. This meetingwas
generouslysponsoredbyDr.HerbertFalkthroughtheFalkFoundation,and
byhis UKcollaborators,ThamesLaboratories.Wewouldalsoliketo thank
MissMarionAmosand Mr. MartinListerfortheirvaluableassistanceinthe
productionofthebook.
IX
List ofInvited Contributors
ProfessorHelmutAmmon, HenryFordHospital, Detroit,USA
ProfessorLuigiBarbara, Universitadi Bologna,Italy
ProfessorBengtBorgstrom, UniversityofLund, Sweden
ProfessorMartinCarey,Harvard Medical School,Boston, USA
Dr.RogerColeman, UniversityofBirmingham, UK
Dr. MartinEastwood, WesternGeneralHospital, Edinburgh, UK
Dr.Kurt Einarsson,Huddinge UniversityHospital, Sweden
ProfessorSergeErlinger,HopitalBeaujon,Clichy,France
Dr.Roberto Ferraris, Ospedale Mauriziano,Turin, Italy
Dr.IanForgacs,King's CollegeHospital,London, UK
Dr.JohnGraham, S1. George'sHospital MedicalSchool, London, UK
Dr.KenHeaton, BristolRoyal Infirmary, UK
ProfessorAlan Hofmann, UniversityofCalifornia,SanDiego,USA
Dr.ThomasHolzbach,Cleveland Clinic, USA
Dr.KathrynHood,Guy's HospitalMedical School,London, UK
Dr.RiadhJazrawi, St.George'sHospital MedicalSchool,London, UK
Dr.AlbertoLanzini, Ospedale Civili, Brescia,Italy
Dr. PatrickZentler-Munro,Raigmore Hospital,UK
Dr.TimNorthfield, S1. George'sHospital MedicalSchool, London, UK
ProfessorGustavPaumgartner,KlinikumGrosshadern, Munich,FRG
ProfessorMauroPodda, Istitutodi MedicinaInterna, Milan,Italy
Dr.GiuseppeSciarretta, OspedaleMaggiore,Bologna,Italy
ProfessorAdolfSteihl,UniversityofHeidelberg,FRG
ProfessorJohnThistle, Mayo Medical School, USA
x
1
Overview: Enterohepatic Circulation
ofBile Acids - a Topic in Molecular
Physiology
A.F. Hofmann
DivisionofGastroenterology, UniversityofCalifornia, San Diego
LaJolla, California 92093, USA
INTRODUCTION
In principle, the scope of physiology should begin where cell biology ends.
Physiology deals with the orchestrationoffunctions ofmultiple cells in dif
ferentorgans,theendresultsofwhichareco-ordinatedphysiologicalproces
sessuch as digestion and absorption orglucose homoeostasis. A triumphof
cell biology has been the elucidation ofcellular regulatory circuits, and the
limitingcaseisthatinwhichcellsregulatetheirownactivitiessoreliablythat
there is no needfor regulatorycircuitsinvolvingmanyorgans. Ina sense, by
analogy, thegovernanceofauniversityfacultyusuallyuses atinyproportion
oftotal energy expenditure at the university because most facilities govern
themselveseffectively, at least mostofthe time.
For the enterohepatic circulation of bile acids, the major regulatory
circuits are at a molecular and cell biological level, rather than at a higher
level of integration. The one obvious exception to this generalisation is
gastrointestinal motility, which is co-ordinated both enterally and centrally.
Inthis briefessay, Iwish tosummarisemyownviews ofthefour subcircula
tions of bile acids encompassed in the inclusive term 'enterohepatic
circulation'.Itis probably useful to include the cholehepaticor biliohepatic
circulation within the term enterohepatic, since the Greek word 'entero' is
not very specific and could well include the biliary tract. Indeed, the tradi
tion has beenfor gastroenterology to include considerations ofhepatic and
biliaryfunction, physiology,andpathology,sothisviewhasampleprecedent.
In this article, four subcirculations of the enterohepatic circulation
willbedistinguished- bytheir location, mechanismoftransport,and conse
quenceoftransport.Sincetheseenterohepaticcirculationsinvolvemanyor
gans, the appropriate discipline is physiology. Yet any consideration ofthe