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Kcrhav.Salish.
Thsgar~roiaes~inal system ata glirncdSalirh Kcrhrv.- 1st cd.
p. ; cm.
Includes index.
ISBNO-632-05472-7
I. Gaaroi~~artinalsyr~cm. 2. Gns~roiner~i~rnlsync~~~-Discsscr.
[DNLM. I. DigcrdueSyr~cm.2. DigcrlivcSysremDircarcr. W I 100
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2003004942

ISBN 0.632-05472-7

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Contents
Preface 7 24 Hepatic metabolic and synthetic function 58
Acknowlcdgcments 8 25 Hepatic detoxification andexcretion 60
List of abbreviarions 9
Introductionnnd overview 10 Part3 Disorders and diseases
26 Nnusc;t ;tnd vomiting 62
P a r l l Slruclure andlunclion 27 Diarrhoea 64
I Mouthand teeth 12 28 Constipation 66
2 Salivaryglands 14 29 Functional disordersand irritable bowel syndrome 68
3 Tongueand pharynx 16 30 Gastro-oesophagealreflux and hiatus hernia i O
4 Oesophagus I 8 31 Peptic ulcerand Helicobacrerpylon' 72
5 Stomach 20 32 Gastroenteritisand food poisoning 74
6 Duodenum 22 33 Gastmintestinalsysleminfections 76
7 Pancreas 24 34 Ulceralivecolitis and Crohn's disease 78
8 Liver 26 35 Coeliac disease 80
9 Biliarysystem 28 36 Obesity and malnutrition 82
LO Hepatic portalsystem 30 37 Colon and rectal cancer 84
ll Jejunumandileum 32 38 Gastrointestinal, pancreaticand liver tumours 86
12 Caecum and appendix 34 39 Haemorrhoidsand anorectaldisease 88
13 Colon 36 40 Gallstonesand pancreatitis 90
14 R e c t ~ ~andanus
lii 38 41 Heparitis and acute liverdisease 92
42 Cirrhosis and chronic liver disease 94
Pad2 lntegraled function
Entericmotility 40 Par14 Diagnosisandlrealment
Enlericendocrinesystem 42 43 Clinical assessment and bloodtesls 96
Enlcric iintl nuton<l~nic
nerves 44 44 Endascopy 98
Mucosal immunesystem 46 45 Radiology and imaging 100
Digcslio~land ;~bn,rp(ion 48 46 Functionel tests 102
Digestion ofcarbohydrates, proteins and fats 50 47 Pharmacothcrapy 104
Digestion of vitamins and minerals 52 48 Gaslrointestinalsurgery 106
Nutrition 54
Fluid and electrolyte balance 56 Index 109
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List of abbreviations
ACh acetylcholine HIV human immunodeficiency virus
AFP a.fetoprorein HNPCC hereditary non-polyposis colon cancer
AIDS acquired immuncdeficiency syndrome 5HT 5-hydroxylryptamint
ALP alkalinephosphalare IBD inflammatory boweldiseme
ALT alaninetranraminase IBS irritable bowelsyndrome
ANC A antineutrophil cytoplasmic antibodies IF intrinsic factor
SASA 5-ominosalicylicacid Ig immunoglobulin
ASC A antibodies toSacchammycescerevirioe IL interleufin
AST aspartate transaminare IMMC inlcrdigeslive migrating motor complex
lPSlD immunopmliferalive small inteslinaidiseasc
ATP . .
adenosine lriohosphale
K+ ionized potassium
ATPnse .ndcnorine
- triphosphatare
LPS lipopolysaccharide
BAT bileacid transponer
BEE basal energy expenditure MAD-CAIM mucosal addressin-cclladhesionmolecule
BMI body mass index MEN mullipleendocrineneoplaria
BMR basal metabolic rate ~g'+ ionized magnesium
BSE bovine rpongiform encephalapathy MHC major histocompatibility complex
Ca2* ionized calcium MOAT multispccific organicanion lransponer
CAMP cyclic adenosine S'J'-~yclic monophosphate MR A magneticreronanceangiography
CCK cholecyrtokinin MRCP magnetic resonance chalangiopancreatography
CD Crohn'sdiseare MRI magnelic reronancc imaging
CE A cnrcino-embryonic ailigen NA noradrenaline
CFT'R cyslicfibrosis tranrmcmbraneregulator Na* ionizedsodium
cGMP ~yclicgui~nosincmanopllosphate NAPQI N-acetyl-p-benroquinone-iminc
CGRP calcitonin gene-related peptide NO nitricoxide
CI- chloride ion NSAlDs non-steroidal anti-inkiammatorydmgs
carbondioxide OAT organic acid transpon
co, PBC orimarv biliarvcirrhorir
C oA coenzyme A
CRC colorectal cancer PET positmn emission tomography
CRP C-reactive protein PI~A polymeric immunoglobulinA
CT computerired!omography POMC pm-opiomclanoconin
CTI. chemoreceplorlriggerzone PSC primary sclerosing cholangilis
DA dopamine FT prorhmmbin lime
DMT divalent metal transponer PY peptide Y
DNA deoxyribonucleic acid RN A ribonucleic acid
entem-chmmaffin-like SBP spontaneous bacterial peritonitis
entemhaemorrllagic ficherichin coli SC secrelorycomponenl
EPEC entcmpathogenic Ercherichia coli SGLT sodium-glucose co-Wansponer
ERCP endoscopic rclrogradecholangiopancreatography sIgA secrelorydimericimmunoglobulinA
ESR erythmcyte sedimentation rate STa heat-stableenterntoxin
ETEC cnterotoxigenic Ercherichia o l i TECK lhymus andepithelialexprcrscdchemokine
PAP familial adenomatous polyposis TGFP Uansfoming growth f a c t 4
Pel+ ferrous imn npss Wansjugularinlrahcpaticponosystcmicshunt
Pel+ ferric iron TNFa tumour necrosis factora
GAB) y-amino bulyric acid TPN total parenteralnutrition
y-glulamyl transferase tTG tissue lransglutaminasc
yGT
H+ ionized hydrogen uc ulcerative colitis
water USS' ultraround scanning
H1O
H2R histamine receptor type2 VC vomiling centre
HCG humanchorionicgonadolrophin VIP vasoactive inreslinalpeptide
HCI hydmchloricacid VLDL very low-density lipoproteins
HDL high-density lipoproteins WHO World Health Organization
5-I-llA S-hy~l~~oxyind~rlc;~cctici~cid
Structure andlunction
n
hlegastrointestinal systemcomprises the hollow organs from mouth to
anus that form the eastrointeslinal tract, the Dancreas. which mainly
secretes digestivejuices intothermall intestine, and theliverand biliary
system, which perform vital metabolic functions inaddition lotheir con-
eibstion lodigestion and absorptionofnutrienls.
The intestinal tract
A hollow tubularstructure into which nutrient-rich food is coerced, and
from wtlich wanes arcexpelled, is found in the most primitive multicel-
lular organisms, from the hydra onwards. In humans, the tract is highly
specialized throughout, both slmcturally and functionally. The mouth
and teeth arc the fin1 structures i n this tract and areconnected by a pow-
erful morculartube. thcoesophanus,
. - to the stomach.The stomach stores
food aftcr meals and is the site where major digestive processes com-
mence.Thesmal1 intestineis thcmaindieestivcandabsomtive surface.
Thc large intestinc acts mainly as a reservoir for food waste and allows
reabsorption ofwnter from the mainly liquid material leaving the small
intestinc. I t is not essential for life and, paradoxically, is affected by a
numberof common, serious diseases, ruch as inflammatory bowel dir-
easeandcolorectalcancer.
T h e pancreas
Digestive rllzylllec are produced i n many pans of the gastroinrestinsl
tmct. inclurling lhe moalll (salivnry glands) and small intestine (envro.
cytcs). ; t l l l ~ a l ~the
g l ~cxoerine pancreas is the most prodigious
~-~ producer
of digcrlive enzymes. Pancreatic failure causes nralabsorption, which
can be reversedby anificialcnzymcsupplements.
Theliver and biliary system
Without the liver, survival is measured i n hours, and no anificial system
has yet bccn devised to substitute for hepatic funclion. The liver is the
largest
. solidoganinthe body and itsessential functions include rezala-
tion of protein, fat and carbohydrate metabolism, synthesis o f plasma
..
vmteins, ketonesand l i ~ o ~ r o l e i nanddetoxification
r, andexcretion. Via
the hepatic ponal circulation i t receives and filters the entire venous
drainage of the spleen, gastrointestinal tract and pancreas. Through the
production o f bile, i t is also essential for digestion and absorption, par-
ticularly ofdietary fats and lat-rolublevitaminr.
Inlegrated function
The gastrointertinal system is controlled by both intrinsic andextrinsic
ncuronal and endocrine mechanisms. Enteric nerves and endocrine
cells a% panicularly impomlant i n coordinatink motility, digestion and
absorption, and in regulating feeding and overall nutrition, including the
controlof body weight.
Theg;~stroinlestinalsystempresents a hugesurfacearea that has to be
protecred against injury, paniculaily from microbial pathogens that are
ingested with foodand from thelnrge populationofcommensal bacteria
that populate the intestine. The mucosal immune system is critically
imponant in regulating how the interline responds to thcsc challenges.
providing protection and not reacting inappropriately to normal compo-
nentsof thediet.
Diseases and disorders
Nausea, vomiting, diarrhoea and canslipation are common symptoms
and their basic pathophysjology illustrates imponant aspects of gas-
Iroinlestinal function.
Gastrointestinal symptoms are frequently not associated with any
discernible pathological abnormality. These medically unexplained
symptoms are often labelled functional disorders and, as our under-
standing of gastrointestinal physiology becomes more sophisticated,
we may discover new explanations and treatments that are more
effective.
Gastrointestinal system infections are common and an associated
with significant morbidity and monality worldwidc. They range fmm
self-limiting foodpoironingtolife-threateninglocalandsystcmicinfec-
lions. Evcnpepticulccrationirmort frequently causedby infcction,with
theHelicobocrerpylori bacterium.
Far some major diseases, ruch as inflammatory bowel disease. the
aaiological agent has not been identified, despite rapidly advancing
genetic and molecular rcsearch. Ccnvenely, coeliac j i r w e . another
serious andcommongastrointestinal inflammatorydisease,ircauredby
a well-characterized immune responsetowheat-derived mleins.
Coloncanceris amajorcauseofcancer-rclateddeathandourmolecu-
larand cellular understandingof its pathogenesis,and the pathophysiol-
ogy o f olher gastrointestinal, pancreatic and liver tumoun, is rapidly
increasing.
Livcr damage is often caused by infeclionsordrugs and maybe acute
orchronic.Acuteliverdiseasccanrapidlypropresstoliverfailu~,orcan
resolve, either spantaneously or with appropriate treatment. Chronic
liver disease may cause cirrhosis, which is characterizedby a variety o f
signs and symptoms and changes throughout the body, including the
effectsof hepatic ponal venous hypertension.
The gaslrointc~tinalsystem is kssentia~to nuuition, and disordered
- -
nutrition is a m.~jorissue worldwide both thmunh undcrnutrilion and
starvation and through ovcmuaition, which causes obesiiy, possibly the
single most imponanlmodem health problem i n the afRuent world.
Diagnosis a n d treatme~tt
Clinical assessment, including a focused history and examination,is the
foundation of diagnosis. I n addition, the gartroinleslinnl system can be
investigated by endoscopy, radiology and specific. fusctional tests.
Endoscopy and radiology may also be used therapeutically, and phar-
macotherapy and surgcry for gastrointestinal disorders u p l o i t many
unique fcatures of the structureand function ofthcsystem.
The nlouth and teeth admil food into the gastrointestinal tract. They cut
and break large pieces, chop, grind and moisten what can be chewed.
and prepare asmooth, round bolus lhat can beswallowed and passedon
to the rest of the system. Ofcourse. the lips and mouth also serve olher
functions.
Structure
Thesensitive. flexible, muscularlipsthal form the anlerior bordcrol'the
mnulh can aserr food by palpation, and their flexibility ennhles them
to se;d ol'l' the ol-al cavity and form variously a ft~nnel,suclion lt~hcor
shallow ladle to ingest fluids and food o f vnryingconsistency.Thc main
musclesofthelips areorbicularlsori.
The maxilla and mandible suppon the roof and floor of Ihe mouth.
respectively. The arch o f the mandible supports a sling o f musclcs that
formsthe floor, includingthe tongue.The maxillaiscontinuous with the
rest oflhe skull and forms the roof ofthe mouthanteriorly and, simulta-
neouslv. the floor of the nasal cavitv and oaranasal maxillary sinus.
Posleriorly. Ihe roof is formed by thesolt palate, composedofcanilage
andconnectivetissue.
The sides o f Ihe mouth comprise the cheek muscles, chiefly
bucclnalor, alld supponing connective tissue. Posteriorly. h e oral
cavitv . opens . .
. into the orooharvnx and the tonsils are situated between
Ihefauces laterally. markingtheposleriorlimitoflheoral cavity.
Thc cnlirc mouth, including the gingivae or gums, is lined with a
lough. not)-corniiied slrntilied squamousepilhelium, which changes
to skin (conlificd stratified squamous epithelium) at the vermillion
border o f lhe lips.
Teeth arise i n thealveolar bone o f h e mandibleand maxilla, infants
are born without external teeth and with precursors within the jaw. A
transient scl 0120 'milk' teelh erupts through the surface of the bone
-
between 6 months and 2 vaars o f aec. Thev arc shed between 6 and 13
yenrs of axe and perlnanent teeth take their p1ace.Therear.s 32 permn-
ncnt tccth and tile postarior molars, also known as wisdom teeth, may
only erupt in yoiingadulthoad.
Teetltn1.c Iivingstructureswitha vascularandncrvesupply(dcrived
-
from the triceminal. orIlIrd cranial, nerve) i n thccentre of each tooth.
which is termed the pulp. Surrounding h e pulp is a bony layer called
Aentineand surrounding this is anextremely hard,calcified laycrcalled
enamel. Teeth lie in sockets within the alveolar bone and the joint i s
filled with a layer of tough fibrous tissue (the periodontal membrane)
allowingasmall amount of flexibilily.The marginsof the loohjoint are
surrounded by gingivac, which areacontinualionof the mucosal lining
o f the nlouth.
mastication are the masselcr and temporalls, which powerfully bring
the lower jaw up against the upper jaw, and the plerygolds, which opcn
thejaws, keepthemaligned, and moves themsideways,and backwards.
and foiwards for grinding. The lrigeminal (Vth cranial) nerve contmls
themuscles of mastication.
. Teeth arespecialized fordifferent lasksas follows:
Inclsors hnve Ant, shnrp edges for cutting tough foods, such as meat
and hard fruits.
Cnnlnes hnve pointed. sharp ends for gripping food. panicularly
.
ment,nnd teari~tgnwaypieces.
Premolars and molars have flattened, complex surfaces that capture
tiny bits o f food, such as grains, and allow them to be crushed behvecn
thesurfaces oftwo opposed 1eeth.Aspeopleget older, thegrindingsur-
facesofthemolars aregradually womdowr,.
Cenain drugscanbe absorbedacross heoral mucosaandmay . beore-
.
scribedsublin&ally (underthetongua).ln thirway,thenecdto swallow
- ..
is avoided and the absorbed drue bvuasses the liver and avoids he~alic
first-pass metabolism. Glyceryl trlnitrate is one o f the most common
drugs administered in this way.
Common disorders
Herpes simplex infection of the mouth is very common, causing cold
sores, which oflen erupt on the lips when people have other illnesses.
Serinus oral infections, usually caused by a mixtureof anaerobic bacte-
ria, are lesscommon.
Thecornen of the mouth may be ulceratedor firsuredinpaticntr who
cannot rake care of lheir moulhs, for exampie after a ruoke. so careful
oral hygiene is imponan1i n these cases. Nutritional deficiency, pmico-
lady o f B comolex vitamins and iron, is also asrociated with firrurcr at
theedgeof the rnoulh, known asangular sldmatitk.
Shallow 'aplllous' ulcers i n the mouth are common and are usually
no1 asrociated with a more serious condition. Rarely
. rquamour
. cell car-
cinoma can develop. Risk factors includesmoking andchewing tobacco
or betel nut, whichis particularly commonon thelndiansubcontinent.
Dental caries is the commonest disorder of teeth, resulting in tooh
loss wilhadvancingagc.11is caused by chronic baclerialinfeclionofthe
gums and periodontal membrane, encouraged by carbuhydrate and
sugar-rich food residues left in the mouth. Bacteria qmw in the gap
between the loothcnamel andgums, forminga hard, impenelrablelayer
called plaque, within which hey multiply. Their meubolic products,
including organic acids, damage tooth enamel. Gradual erosion of
enamel and retraction o f h e gingivac weakens h e toothjoint. Infection
can penetrate h e pulp causing an abscess, and chronic infection can
destroy and devitalize the pulp.
Dcnlal hyglene, including brurhingandflossingand having fluoride .
in drinking wntcr, which slrcngthens tmth enamel. reduccs lhc
ineidcnccofcorie~.
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The ocsoph.~goscarries food and liquid from the mouth lo the ston~ach
and the rest of the intestinal tract and is an important site of common
gastrointestinal disorders.
Struclure
The oesophagus is a muscular tube, beginning at the pharynx and end-
-
ineat thestomach. Ittraversesthcneckand thorax. whcreit liesclose lo
the trachea, the great vessels and the leflalrium of the heart. The upper
opening of the oesophagus lies behind the opening of the larynx and
is repnr.~ted from it by the arytenoid folds. The eplglottls, auachcd to
the back of the tongue, can flap over the lavnx, pmtecting it during
swallowing and funnelling food towards the oesophagus. Just above
the gartro-nesophageal
. - junction. the oesophagus
~ ~ - traverses a natural
hintusor gapinthediaphragm, loenter the abdomen.
. - reflect the aeneral
The walls of the oesophaaus - organization
- of thc even swallow saliva and drools continuallv. Chronic obstruction may
intestinal w:~tl.Tl>ewallsareformedfromoutsidctoinside by:
udvct~tili;lorserora;
longirudinal muscle laycr;
.. circularmusclelayer;
submucoral layer;
musc~larismiccosae;
mucos.1 andcpithelium.
The muscle in the upper third is striated muscle and in the lower
~ ~
two-thirds, smooth muscle similar to the rest of the gut. The lower
oesophngeal muscle remains in tonic contraction and forms part of the
lower oesophageal sphincter. The angulatlon of the oesophagus as it
enters thcrtomach and thediaphragmatic muscle help lo keep thclowcr
-
~
The vagus nelve runs alongside the oesophagus and innervates
. - muscle directly and via intrinsic "elves in h e myenteric
ocso~haaeal
nerve plexus located between the longitudinal and circular muscle
layers, and thesubmucosal plexus.
.
The rubmueosa contains lobulatcd glands that secrete lubricating
~
material throughsmallducts that penetratethccpithelial surface.
-
Theoero~ha~eale~ilheliumisalough,non-comifiedstratifiedsqua-
mous epithelium, which changes abmpUy to a non-stratified columnar
epithelium at thegastro.oesophagealJunclion. known astheZ-line.
Importantly, venous drainageofthe oesaphagurformr asubmucosal
venous plexus chat drains directly into thesystemic venous circulation,
avoidin~thehcpaticportal
. ~
vcinandlivcr.Thirplexusanastomoseswith
veins in the stomach that drain into the hepatic portal system. In portal haematemesls. By contrast, oesophageal varlces formed in portal
..
hypertension, collateral veins divert Rastric blood lo the oesopha~eal
. .
veins. whichenlargeand form varices.
Function
Theoerophaguscunveyr food, drinkand saliva fromthepharynx lo the
stomach, by perlslalsis. PensfaIris comprises a coordinated wave of
contraction behind the bolus of food, with relaxation ahead of it, pro-
pell~ngthe food bolus forward. It is involuntary, resulting from intrinsic oesophagus, is becoming more common in the Westem world (see
neummuscular reflexes in the intestinal wall, independent of extrinsic
innervation. However, external stimuli modify the frequency and
strength ofperistalticactivity throughout the intestine.Verystrongpcri-
stalticconlractions can cause pain.
In vamlllng, peristaltic waves travel in the reverse di~ction,pro-
pelling food upward towardsthe mouth.
Common disorders
Dysphagla is difficulty in swallowing and odynophaela
. ~.is painful
swallowing. Sensations arising from the oesophagus are usually fell
retrosternally in the lowcr P M of the centre of the chert. Heartburn
describes a burning, unpleasant retmstemal sensation that may be
caused by acid reflux fromthestomachintotheoesophagus.
Obstrucllontoflowdown theoesophagus .. -
. . causesdys~hagiaandmay
be cnmplele, halting swallowing altogcthcr, so that the patient cannot
lcadloasplratlonoffood intothelarynx,causingpneurnonia.ReRuxed
stomach acid reaching the larynx can cause inflammation, causing
cough and a hoarsc voice.
Canccr of the oesophagus or trauma, caused, for example, by a fish-
. -
bone,cancreateafistula from theocsopharustothe mchea, whichhe
immediately anteriorly. This can lead to recurrent infeclion caused by
. -
bacteriaintheoeso~haaealfluid .
.(as~iratlonDneumonlal.
The lower oesophageal sphincter Is relatively wcalr; therefore.
acid reflux iscommon even in hcelth.but can beexcessive, whenit may
cause oesophagitis.
. . Chronic acid rcflux can induce the epithelium to
change from the normal squamous lining to a gastric or intestine-likc
columnar lining. This epithelial melaplasia is callcdBarrett'soesoph-
agus and it increases thc risk of developing adcnocarcinoma of the
oesoahaeus.
~
< ~~
-
The diaphragmatic hiatus through which the owophagus passes from
he thorax to the abdomen widens with age and it may allow the upper
part ofthestomach to herniate into thcrhorax.Thir is knownasasliding
hiatus hernia, whichincreases the riskofreflux wsophagitir.Thestid-
ing is aggravated by obesity and lying flat in bed (see ~ h a i l e r 3 0 ) .
Very powerful muscular contraction and peristalsis (d yrmotl1ity)can
caurc discomfort or pain. Progressive failure ofperistalsis and a chmni-
cally hypcrtonic lower oesophageal sphincter. leading to a dilalcd, non-
functioning oesophagus, is called achalasia.
Forceful retching or vomiting can causc a Mallory-Weiss tear in the
oesophageal mucosa, which may bleed, causing (usually) self-limiting
hypcnensioncan bleedcatartrophically (seechapter 10).
~ ~
Infections of the oesophagus are rare.The mostcommon is csndidls-
sir, occurring in immunocompmmised ~ a t i e n uand those with diabetcs
mellitur.
Squsmous cardnoma of the oesophagus is p h c u l a r l y common in
southern Africa and may relate to diet, smoking andcarcir.ogens in the
soil,as well togenetic facton. Adenocarcinoma, arisingfromBarrett's
Chapter38).
Oesophagus 19
The stameeh is the first wholly intra-abdominal intestinal organ. It is
adaotedformechanicalchurning,storareanddigestion
- . offoodandcon-
tribulcs lo neuro-endocrine coordination of inteslinal function. The
basic rhythni oftheintestine, thegaslricslow wave,originates here.
Structure
Tliestoniach is 'J'-shaped, wilh lesserandgreater curvatures, facing 10
the right. Thespleen lies lothc left and the pancreas lies inferiorly and
posteriorly. The liver lies to 1heright.Thestomach lies behind the left
Ihypouhontlri;!l region an tltesurfaceof theabdomen.
The stomachcomprises five distinct regions:
1 the cardla i~nmcdiatelyadjoiningtheocsophagus;
1 the dotne-shapedfundusexlending lothe left of thecardia;
3 lllc batly or corpus;
4 lheantrutn;
5 the pylorus, in which the circular muscle layer is rcinfareed,
and whiull h n n s a tight sphincter separating the stomach from the
duodenum.
- wall reflects the general
The structure of the aastric - -
organization of
hollow intestinal organs, with an additional oblique muscle layer that
.. -
SUDDOrlS its mechanicalchurninefunctionand allawsittoexeand. From
outside to insidethewallsarefomdfmm:
serasa:
longitudinal muscle layer;
. ci~~culnrmusclelayer;
obliquemusclelayer;
submucosa;
. muscularis mucasae;
mucosa comprising the lamina propria and columnar gastric epithe-
lium with its pits andgiands.
The coeliac artery supplies anerial blood to the stomach and venous
blood drains into the hepatic portal vein. The stomach receives
parasympathetic nerves via the vagus (Xth cranial) nerve and sympa-
thetic fibres fram thesplacchnicnerves.
Most of thegastric mucosa is thrown up incoanefoldscallcd rugae.
whilethe antral mucosa is much smoother. Alhickmucus layer ~.protects
against mechanical trauma. HCI and proteolytic enzymes.
-
Gastric its arenarrov, invaeinatians oftheepitheliuminlo the lam-
ins propria. Two orthree gastric glands areconnected lo each pit via a
-
narrow isthmus. leadine" tolheneckreeianafeachnland. -
- Garlric glands
are tubular stmelures with specialized cells for lhe production of
HCI (parietal o r oxyntie cells) and pepsin (chlef cells), as well as
mucus-producing goblet cells, undiffmntialed epilhelial 'cells.
entem-endocrinecellsand slem cells.
Parietal cells are found in glands throughout lhe fundus, corpus and
antrum. Thcy secrete HCI. theglycoprateins intrlnricCactor and gas-
Imferrin, which facilitate the absorption of vitamin B,, and imn,
respctlively.
Chief cells are found predominantly in the corpus. They secrete
pepsinogen and have an exlensive rough endoplasmic reliculum and
prominent apical secretory granules.
Themainentem-endocrinecellsofrhestomachareGcells.pmducing
gastrin, D cells, producing romatorlalin, and entem-chromaffin-likc
(ECL) cells, producing l~istamine(seechapter 16).
Function
Food is mlxed thoroughly by the churning aclion of gastric muscle
againsl aclosedpyloric sphinckr.The pylorusopens onlyto allowsuni-
lisuidmaterial(chyme) through intotheduodenum.~rcventinetheras-
area for morc cfficienl digestion and prevents damage to the dclicate
intestinal mucosafromlarge, hard,imegularfoodpanicles.
Rhythmicelectric activity in thestomach produccsregular peristaltic
waveslhreelimes ominute. known as thegartricslow wave.
Gastric secretlan is stimulated by the anticipation of f w d , the sa-
called cephallc phase, and by food reaching t i e stomach. the gactrfc
phase. Acetylcholine and histamlne, acting through MY.museadnlc
and ~~rece~torsstimulatethesecretionof~~~. - i
Parietal cells have an extensive intracellular eanalicular system.
numerous rnltochondria to generate energy, and a highly active K+M+
adenosine triphosphatase (ATPase) pump (proton pump) rhal secretes
H+ into the lumen. An apical chloride channel transports C P into the
iumcn.10 farm HCI. .
At the basolateral surface. HC0,-, formed intncellularly from CO,
and H,O, is exchanged far CI; so that circulating HCO,- levels rise
when the stomach secretes acid ('alkali tide'). The basolateral N a + W
ATParepurnp alsoreplenishes intracellular K+levels.
Differentiation and secretion of oarietal cells is also stimulate4 bv
gastr1n.Acid secretion is increasedbyexcesrgas~n, forexamplc,inthc
Zallinger-Ellisonsyndrome(seeChaptor 16),andisinhibited byvago-
tomy, which removes cholinergic stimulation, by HZ receptor antaga-
nists, such as ranitidine, and by proton pump inhibiton, such as
omeprazolc, which irreversibly bind totheK+M+ATPasc.
HClactivatcs pepsinogen, toproducepepsin, iniliatingproteindiges-
lion. Intrinsic factorbinds lo vitamin B,,,allowing illoescapedegra-
dation in Lhe stomach and inlestine and to be safely transported to the
rerminal ileum, where it isabsorbed. Gartraferrin binds toFe", facilitat-
ing absorption in theduodenurn (seeChapar21).
Common disorders
Symptoms relating to the aamach are extremely common, bur are
frequently not caused by discernableorganic dircasc(seeChapter 29).
Typical symptoms include nausea, epigastric pain and bloating.
Collectively these symptoms are lermed dyspepsia and paticnts may
refel to them as indigestion. With serious cnnditions of the stomach.
there may also bc vomiting, haematcmesis, melaena and lass of
weight.
The main serious gastric conditions are peptic ulcer and gaslrltis. !
i
whicharemost frequently a s s o c i a I e d ~ ~ i t h H e l i c o b ~ c l e r p ~ ~ o ~ i n f ~ t i o n
and the use of non-steroidal anti-inflammatory drugs (NSAmr), and i
gastriccarcinoma (seeChapler31). i
Hiatus hernla occurs when part of h e stomach herniates though
the diaphragmatic hiatus through which the oesophagus parses (see
Chaptcrs30&38). Oartricoaletobstrucllon mayotcurin youngmale
iI
:
infanls.duetoacongenitally hyper(rophisdrphincter, causing projectile
vomiling. In adults. a more common cause is autonomic neuropathy. i
caused, forexample, by diabetes mellltus.
1
Stomach 21 i
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an!~saS!p ~o[ewaq1 ~IN!ISUOJ tuna!! pue wnunca[ a q .a3epns ~ lela s! qJ!qm 'esoJnmqns aql WOJj eSo3nm aql sale~edar' ~ s o ~ l l s!Jel lu
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p a r a l d w o ~Y1~elnlla38~1u!
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:ap!su!aqlol ap!srnoaql molj a s ! ~ d m o ~ L a q l ' l l cleu!lsalu!
m aql
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IBUIS
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a&!l&oSqe pUe a&!lsa8!p lo[ew l s ~ yaql s! UlnuJponp aqL
The pancreas is critically imponant for inlestinal digestion. 11is a large
exocrine gland. synthesizing and secreting lhc great majorily o f diges-
liveenzymes into the intestine. I t alsocontains imponant endocrinelis-
sue producing insulin and glucagons, thus also regulating nutrition and
gnstrointestinal function globally.
Structure
The pancreas lies transversely an the posterior abdominal wall and is
covered by . .~eritoneum.The head lies to the riehl,- adiacenl
. to the duo-
denum,andthe body andtailextendacmsstheepigasrriumtothespleen.
Thesplenieveinrunsalangthesuperiorbarderafthepancreasandloops
ofintestineare related to it anteriorly.
Branches of the coeliac and superior mesenteric aneries supply the
gland and venous blood drains into the hepatlc portal vein, supplying
the liver with hormone- and growth faclar-laden blood from the
pancrens.
The vagus nerve and splanchnic sympathetic nerves innervate the
pnncrens. Sensory nerves are routed through the coeliac ganglion and
pnncreatic palinmay be relieved by its surgical removalor deslruclion.
The main pnncreatic duct extends along the,lengrhof thegland and a
smaller accessory duct drains thesuperior panof the headandmay open
se~nrntelvinto the duodenum. The main duct ioins the common bile
duct hclonc o l > c ~ l i ~into
l p the duodenum through !he ampulla of Vdtcr.
S~,lnlle!. ~pitncre;llicducts drain into the main duct. forming n 'fishbone'
patlerl,. Exocrine pnncre.~lictissue is arranged in lobules composed of
the finnctio~lalunits, acini. which secrete pancreatic enzymes and fluid
into tlleducts.
Microscopically, pancreatic cells are arranged in spherical acini.
. . surFncetowardr lhecenlre and the b:bsolal-
will! theil-sccl-etorvol-n~ic;ti
era1 surface resting on a basement membrane. Ducruies drain each nci-
nus a~ldconlescelo form larger ducts lhat eventually drain into the main
pnncre;tlic duct, carrying digestive juices to the duodenum. Pancreatic
ocinar cells ;wr. highly specialized for prolein synthesis and secretion.
They have a .pyramidal crorr-section, with prominent basal rough
~
endoplosmic reliculurn, where prolein synthesis occurs, extensive
golgi apparntusandapical secretory (zymogen)granuler.
Over 10%~oocrinepancreaticislelsarescatreredthroughoulthepan-
creas and are supplied with a rich capillary network o f blood vessels.
They arc lnot connected by ducts lo the exocrine pancreas, but secllete
direclly into the bloodstream. The principle cells i n these islets arc P
cells, which secrere insulin, acells, that secrete glucagon, and D cells.
which synthesizesomatostatin.
Function
The pancreas is a powerful producer o f digestive enzymes. These ale
synthesized and stored as inactive precursors or pro-enzymes, to avoid
aurodigertion o f the enzyme-producing cells and the pancreatic ducts.
.
Pancreatic enzymes include:
trypsinagen;
chyniot~ypsinogen;
proca1,borypeptidasesAandB:
pro-elnstase;
phospl~alipareA:
pancreatic lipase (and colipase);
pancrentic amylase;
. ribonucleascs;
deoxyribonucleases.
Pancrealic secretion is stimulated by hormonal signals, particularly
cholecystoklnln, which is released when food enters h e duodenum.
Secrelln enhances the effect o f cholecystokinin.
The Dancrear ecreles about 2LJdav o f a blcarbonale-rich alksllne
fluid lhal helps to neutralize stomach acid and provides optimal condi-
lions for digeslion by pancreatic cnzymes. Centmacinar and duct cells
secrete most of the fluid and alkali, by exchanging HCO; for CI-ions.
using the cystic fibrosis transmembrane regulator (CFTR) protein.
Pancreatic insufficiency therefore occurs i n cystic fibrosis, where an
abnormal CRRgeneis inherited.
Pancreatic islets are the only source o f lnsulln and glueagon,
- - which
are produced by pancreatic P and acells, respectively. Insulin secretioti
- - -
is stimulaled mainly by increased blood glucose, while glucaaon sccre-
~ ~
lion is stimulaled by hypoglycaemia. Hormones, such 3s adrenaline.
have addilional modulatory effects on pencreatic islet secretion and
islels also pmduce hormones, such as somatostatin, which modifies
entem.endocrine function locally and throudhoul the gastrointeninal
lracl (seechapter 16).
Common disorders
Pancreaticdisearcsmayremainentirely. asymptomalicuntilheyarefar
~ .
advanccd.They may causeabdominal pain, felt i n theepigastriumand
radiating to lhc back. Damage to lhe common pancreatic and bileducls
may cause jaundiceand pancrealicerocrincinrufficiency may result in
malabrorption o f food, causing diarrhoea, steatorrhoea (fat-rich
stools), weight loss and nutritlonal deficiencies. Islet damage can
causediobeler mellilus.
-
Acute pancrealitis is a serious, potentially life-threatening illness.
The mas1common causes are excess alcohol ingestion and passage o f
galistoner rhrough the amuulla o f Valer (seeChanler40). Less freouent
causes include various drugs, abdominal traumaand viral infection.The
inflamed pancreas relenses enzymes into the circulation and acute pan-
creatitis is a systemic illness, nffecting the whole body. Pancreatic
lipases release fatty acids that interact with calcium lo fa-rm insoluble
calcium-fatty acyl salts, potentially lowering the concentralion o f cal-
cium in thecirculation todangerous levels. Adrnmatic risein lheserum
lip.~seorat~lylasclevcl ltelps lodiagnose ncule pancreatitis.
Chronic pancreatitis may follow repealed bouts o f acute pancreati-
tir. The main symptoms are abdominal pain and malabsorption due to
failure of the exocrine pancreas. Patients mav also develop endocrine
pancrcaticinsufficiency (see Chapter 40).
Pnncrearic adenocarcinomn is n leading cause of cancer-related
-
death and often becomes symptomatic only at an ndvanced stage. when
the lumour has become inoperable. Neuro.endocrine h m o u n , which
arise from enteric endocrine cells, are often located i n the oancreas.
althoughthey mayalroarisefr~mother~artsofth~gastrointesinaliract.
They arc gcnerally less aggressive than adenocarcinoma, but may cause
symptoms due lo their secretion o f gut hormones. Gastrin-producing -
turnours (gastrlnomas) cause excess gastric acid secretion'and peptic
ulceraLion (Zolllnger-Ellison syndrome). Tumours m'ay also secrelc
insulin, glucagon andother hormones (seechapters 16&38).
Theliver isthelargest solidorgan inlhe body, weighing 1.5 kgin a70-kg
-
adult. I t develoos from lhe embrvonic foreeut cndodem and is an inte-
gral part ofthe gastrointestinal system. I t performs vital metnbolic, syn-
thetic, secrelory and excretory roles, and life cannot be sustained for
morell~ann few hours without lhe liver. , .
Structure
The liver lie in the rich1 . upper quadrant
~~ . o f the abdomen, directly
under1herighthemidiaphragm,protected by thelowerribs. Itcmrscrthe
-
mid-line. where thc falciform ligament traverses it, se~aratinathe left - Hepatocytes are extremely metabolically active and contain many
lobe iron) the right. The liver can be divided into nine tunctional
segments thntcan beidentifiedsurgically, baredon vascularsupply and
bilinry drainage.
On the ihferior surface, i n the mid-line, the p o n d vein and hcpatic
artery enler and common bile d u a and lymphatic . . channels leave lhe
h i l u m or the liver. There structures divide into major right and left
branches within theliver.The inferiorvenacava lraverses theliverpor-
leriorly, where themain hepaticveinjoins it.
Thegallbladder lies under the liver to the right of the mid-lineand is
connected to thecommon bileduct by thecystic duct.The hepaticflex-
urenftl~ecnlonlies to the rightofthegallbladder.Theliverparenchyma
is enclnscrl in ;I tough fibrous capsule, which is mostly covered by peri-
loncutn, npxt rrom the barearea underthedomeofthediaphragm.
The hcpntic artery, arising from the coeliac trunk delivers alrcrial
blood 10 the liver, although 7590ofthehcpatic blood flow arrives via the
portal win, which drains the spleen, pancreas and interlines. Venous
dl-ain;lpc is via t l ~ e hepntlcvein.
Miumscnpic:nlly the liver parenchyma is homogeneous, with repeti-
tion of the same basic organization . throughour. Hepalocytes
~. form
three-dimensional cords and platesin the liver.These are separated by
sin~usaidsil~l.c~tgl> w h i c i ~1,lood flr~wsnlnwly.Tllcre arc lwn in;tin w;lys
c , l e c > ~ ~ c ~ . ~ , t ~the
; \ l itnicruscupic
~i~~g nrrangemest. I n the lobular model.
the hepatic venule is at thecentre, withponal vein branches at threecor-
nerr of a rix-sided lobule. I n the acinar model. the ponal vein and
hepmic nrterv branches nnd bile ducluler are at the centre in the vorlal
(riaads,with three zones (1. 2 and 3) defined by their dis1.1nce horn lhc
centre.
The walls of adjacent hepatocytes form bile canaliculi. Specialized
blliary epithelinl cells line small bile ductules, larger ducls aod the
.gallbladder.
Hepatic stellate cells, also known as 110 cells or fat cellr becallre they
colltain erorninenr droplets of fat and relinoicacid la vitamin Aderiva-
live), aresituated deep totherinusoidal endorhclium.They elaborate thc
connective tissue matrix of Lhe liver and respond to injury by causing
fibrosis.
Endothelial cells line the sinusoids.They rest on a looreconnective
r i x , as thesnaceofDise. andarediscontinuous.Thev
tissue ~ i ~ i ~ tknown
also contain gaps or tenestrae, which may allow molecules, parliclcr
and even cellr to easily penelratethe parenchyma from the sinusaids.
Withi,, rinomids, resident macrophages calledKupffercells interilct
with paniclesandcells.Numerouslymphoidcellsarepresent,including
. and dendrltlc cells. Their function is
special subsels o f lvm~hocvtes
. .
unknown, although they probably contribute to special immunalaeical
~ ~~
properties oftheliver(seeChapter 18).
. are large,
Hepatocvtes - cuboldal cells with a cenlral nucleus that is
occasionally tetraploid. They are functionally polarized. with slnll-
soidal and cansllcular poles. Tlghtjunclionsanddesmosomessealoff
(he canalicular membranes, across which hepatocytes secrete the con-
slituenlsofblle.Microvllli helplo increase thecellsurfacearea.
lnlracellular organelles. There is extensive smooth r n d o p l m i c
reticulum for lipid and cholesterol synthesis and rough e n d o p l m l c
reticulumforproteinsynthe~is.Therearemanymllochondrlainwhich
melabolicreactions, such as the Krebs cycle, occurand wherechemical
energy is generated. There are lysosomes, peroxlsomes and endocytid
vesicles rupponing digestive functions, and storage vacuoles, glyco-
gen granules and fat droplels.
Funclion
The liver's complex functions have not yet been reproduced artificially.
They include:
Regulating homeostasis of carbohydrate, lipid and-amino acid
metabolism.
- Storlngnutrien(ssuchasglycogen,fats andvilaminsBl,.AandK.
Producing and secreting plasma proteins and lipoproteins, including
clouingfactors andacutephasepmteins.
. Synlhesizingandsecrelingbllesallsforlipiddigestion.
Detoxifying and excreting bilirubin, other endogenous waste prod-
ucts and exogenous melal ions, dmgs and toxins (xenobiotics).
Clearing toxins and infective agents from the portal venous blood
whilst ~noinl:~iningsyrlcmic i~nm\~nctolerance tnantige~~sinthe portal
circulaliun.
I n addition. hepatocytes retain hecapacity to prolilersle, so h a t h e
livercan regeneratedramatically afterinjury.
Common disorders
Liver disorders can cause many symptoms and signs., ranging from
vague malaise lo fulminant liver failure, with disordered coagulation
and coma. Typical fenlures i<~cludeJaundice, tatlgue, loss olappelite
and pain in the right upper quadrant o f the abdomen. Because of h e
grcat reserve capacity of the liver, extensive damage may remain
asymptomalt.
Viral hepatitis is common throughout the world. Liver a b s c w m ,
causedby amoebae, bacteria and parasites, arecommonin somepartsof
h e world. Drugs and toxins, including med.cauons, also commonly
affect the liver and the most impomnl of there Is alcohul. Chmnicdam-
age may cause scarring and lead lo cirrhosls. Ovenvhelming liverdam-
-.
age,eilheraculely orchmnicall~,causesllverfallurr.Alhoueh~riman.
liver cancer is rare, metaslatic cancers are common (see Chapters 33.
38.41 &42).
Liver 27
Bile is formed by. hepatocyles
. . and modified by the specializcd biliary
epithelitlnl. It is an exocrine secretion necessaryfordigestion, anexcre-
tion oroduct far removal of toxins and metabolic waste and a van o f the
host defencesystem.
Structure
Macroscopically, the intrahepatic bile ducts, common hepatic duct.
cystic duct, gnllbladder and common bile duct constitute the biliary
system.
The gallbladder is a pouch-like structure with a thin fibromuscular
wall located under theanterioredgeofthe liver. Itsepithelium is thrown
up in complex fronds, increasing the surfacearea.Theneckof thegall-
bladder lerds to the cystic duct, which joins the common hepatic duct.
fornied frotnthe union oftheri~htandleft intrahepaticducts, lo form the
common bileduct, which leaves theliveratthehi1um.Thecommonbile
duct lies ndjncent to the hepatic anery andponal veinand joins the main
pancrcaticduct beforeentering theduodenum through the ampulla of
Vater. which is keptclosed by thesphinclerolOddl.
Thc hili:lwy cpill>eliamlining the major ducts and the gallbladder is
composed o f a single layer of columnar or euboldal cells resting on a
basemen1mcmbrone. ItcansecreteCI-and walerand in thegallbladder
the s:me cells nbsorb water, to concentrate bile.
The hilinry cnnalicutus is the primary site of bile production. I t is o
channel for~nedfrom apposed .. surfacer of adjacent hepatocyles. TighL
junctions sepnl.ate the canalicular membrane from the basolateral rur-
faceofthe hepalocyte, -
. . allowingtranrporl . proteins
. to create and maintain
concenlmtiongradients.As biliarycanaliculi convergeandenlarge,spe-
ciillizcd hili;lry epitheli;!l cellsreplace hepntncyles.
Functian
Each day, 6 0 0 m L of thick, mucoid, alkaline bile is produced. la main
constituents are:
.
a
primary bileac1ds:cholic and chenodeoxycholicacid;
secondarybi1eacids:deoxycholicandlithocholicacid;
phospla~lipids;
cholesterol;
bilirubin;
conjugated drugs andendogenouswasteproducts;
electrolytes: Na+.CI~,HCO,~andtracemetalr,ruch as copper;
secretory dimeric immunoglobulin A (sIgA) and other antibacterial
-
proteins;
mucinglycoproleins.
lkansporter proteins on the basolateral surface of the hepatocyte.
. .
such as the organic acid transport (OAT) protein, facilitate uptake o f
substances such as bilirubin and bile salts from the circulation. Trans-
pones in the canalicular membrane then secrete compounds from the
hepatocyte into bile. Imponant canalicular tranrponers include the bile
acid ifitnrpnl-ler (RAT) and the multispecific organic anion lrnnspnner
(MOA'I']. Spccilic transporters help lo exerele polenlini toxins; for
example, excess copper
.. is excreted by an adenosine triphosphale
. . (ATP)
-dependent copper transporter that is defective i n Wilson's disease.
causingaceumulationofcop~erinthe brainand liver.
Active secretion of bile acids, electrolytes and organic compounds
draws water with it and bile flow isencouraged bycwrdinatedconuac-
tionofcytoskeletal pmlelnsadjaeenltothecanalicu1armembrane.The
canaliculi secrete450 muday and bileducts add 150mUday.
About 60mLofbileis storedin thegallbladder.Cholestemlisamajor
insoluble constituent o f bile and it is stabilized by incoporation into
mixed micellcs, formed by bilesalts andphospholipids.
Abnormalbllemaybefonedifhepatocytesareoverloadedwithone .
or other component; forexample, haemolysisresults inovemroduclion
of bilirubin, which may crystallize to formgallstones.
Cholecystoklnln is released from theduodenum whenfwdarrivesin
it, stimulating contraction o f the gallbladder and relaxalion of the
sphincter o f Oddi, thus delivering bile to the duodenum just when it is
needed.
Bile promotes the dlgestlon and. absorption of fats and fat-soluble
vitamins in several wayr.The alkaline bile promotes emulsWeationof
-
fats, which allows greater access to digestive enzymes.
. . and bile acids.
cholestero! andphorpholipidsfommixedmlcelles,intowhichdigested
fauy acids and other lipids are incorporated. l h e alkaline p H is also
optimal for pancreatic lipases.
~ r l m a r bile
y acldsaie synlherired i n the liver from cholesterol and
95% o f the secreted bile acids are reabsorbed in theterininal ileum and
carried into the portal venous circulation. These secondary blle acids.
which have been metabolized by bacteriainthein!atiiline,arelakenupby
hepatocytes and resecreted into the bile. This constituta the entero-
hepatiecirculation(reeChapter24).
Bile isthemainpathway forexcretionofhydrophobicwastessuchas
bilirubin.
Camman disarders
Jaundice, caused by accumulation o f bilirubin, is theclassic symptom !
ofbiliary disease. Interrupting bile flow to theintestinecaurespalestool
and dark urine as bilirubin isexcreted via theurine. ltchingiscausedby
accumulation of pruritogenic substances that are normally excreted in
bile. Longstanding obslruction interferes with fat absorption and may
causc stealorrhoea, weight . loss and nutritional deficlencv. Obsmc-
tion and inflammation o f the biliary tract can cause pain. fever and i
malaise (seeChapten33gi40).
Damage to hepatocytes, for example by viral hepatitis, may inhibit
bile secretion, by decreasing ATP levels, interfering with Lranrprter
function and damagingcytoskeletal
-~~
proteins. This causes InIrahepatie
cholest~is,withnomacroscopicblockagetothe
dmas. can .produceasimilaieffect(seeCha~ter41).
biliarysystem.Cenain
Autoimmune damage lo inrrahepatic bile ducts, i n primary biliary
cirrhosis (PBC), causes progressivejaundice andliverdamage.
Gallstones are very common and may remain asymptomalic. l h e y
form when constituents, ruch as cholesteml or bile pigments, that are
parlizlly soluble, reach supersaturated concenlrations and tryrtallize
around a nidus, ruch as a stray bacterial cell.They can caurecholecysll-
tls i n the gallbladder and cholangltis or pancreatiiis when they lodge
i n the bile ducts, causing obstruction and superadded infection (see
Chapter40).
The liver receives 25% of the cardiac output, of which 75% arrives via metabolism removes the drug from the systemic circulation, reducing
the portal vein. which drains the spleen, pancreas and g'astrointestinal side-effects. The synthetic glucocorticoid budesonlde, which is used to
tract from stomach to colon. Thus, all the blood from these organs nor- treatinfla~nmatorjboweldiseasc,is anexample.
mally traverses the liver before it enlers the systemic circulation. This Microorganlams inevitably cross the inteslinalepitheliumandentcr
arrnngenlcnl serves many important functions. the bloodstnam(bacterlnl translocallon). Kup(Tercells inthe hepatic
sinusoids normally clear them effectively. Patients wjth chronic liver
Structure disease and portal hypertension are therefore at increased risk o f
The portalvein is formed from theconfluenceof thesplenlc veln, which bacterial infection.
drsins the stomach, pancreas and spleen, and the superlor mesenlcric The body recognizes that food antigens are usually harmless, and
vein. which drains the entire small intestine and most oflhe large intes- lhey generally do not elicit an immune response, a phenomenoncslled
tine. The Inferior mesenterie veln, which drains the rest of the large oral tolerance. The liver contributes to this, and antigens injected into
intestine. ioins the s ~ l e n i cvein. The ~ o r t avein
l enters the livcr at the the portal vein alsoinduce tolerance.
hilum, alongside the hepalicarteryandcommon bileduct.
Within the liver the portal vein divides, first into left and right main Porlal hyperlension
branches and then funher.so that small branches supply .. cnch acinus or
~
Liver cirrhosis is the commonest cause o f portal hypertension but i t
lobt~le.Theresmall branches lie in portal triads, with branches of the may also occur when the liver is congested inchronlc heart failurr or
lhee;!tic ;lrlcrv ;ad bile ducts, surrounded bv asmall amount o f connee- with portal vein thromborls. for example following trauma or infcc-
live tissue. PdtIai venous blood flows slowly through the hepatic sinu- tion. Portal hypertension causes splenomegaly and asclles. Ponosys-
soidsa\~dexits the liverthroughterminnl hcpaticvenules, which join to lemic shuntingcauscsvarices to formand, particularly ifthereisrevere
fc,ml the llcpnticveins, rejoining thesystemiccirculation at the inferinr underlying liverdiscare, itcausu hepatieencephalopathy.
vew cova (seechapter 8). Splenomegaly may cause hypenplenism and thrombocylopenia as
Impnrmntly, the venous drainage of the oesophagus and lower rcc- platelets ore trapped i n theenlarged spleen.
111n)CI>CI ~ l i ~ c c tintol y l l ~ esystemic circulation, bypdssing the pnrl;ll
Asclles is the uccumul.lion of fluid in the peritoneal space. Portal
venous system and theliver.Whenportalvenousflow is obstructed,col- hypertension increases hydrostatic pressurein intestinal and merenleric
l a t c r a l develop in these (and other) areas. joining portal and systemic
capillaricr, causing fluid leakage. The protein concentration of this
~i%!!litlitllls. ~ i l l l ~ i lpnrtnsyslemic
lg rhanting. Increased flow e;lurcs
nscilic fluid is low(transudnte)undillacksantibacterialfaetors,suchar
the collateral veins lo dilate and ealarge, forming varices, which can complement, so that it is prone lo becoming infected, rcsulling inspon-
blced. Furthermore, when bioodis diverted away from the portal circu- taneousbacterlalperito~itis.
lation, it enters the systemic circulation directly, wilhout first being Varices may form in the oesophagus and gaslric fundus, around the
detoxified by the liver. splenic hilum, at theumbilicus, in lhcrecrum and inscartissueandadhe-
lions created by abdominal surgery. They~. a n prone to damage
. and may
Function rupture. causing massive, life-threatening gastrointestinal haemor-
NutricnLs and hormones from the pancreasandintestineare carried by rhage.This usuallycnuses l~aematemesis.melaenaorhaematochala
the porn11vein to the liver, enabling itto regulate nutrition and metabo- (rectal bleeding).
. . c;lnnotrurvive without the oortal circulalion.even i f
lism. He~nlocvler Encephalopathy causes disturbances o f memory, a eharaeteristic
total bloodflow is ~naintainedfromthesystemicanerialcirculation.This flapping tremor of the hands (asterixis), clumsiness and an inability to
is probably due its need for growth factors, including insulin. derivcd draw r.mple shapes (mnslruclional apraxia). and drowsiness, wluch
from the intestines and pancreas. can progress to coma. Encephalopathy is caused by shunting of toxins
Theliver remover toxins that are ingested with food and produced by lotnc systemic circulalion and is worscuhen the capacity ofthe liverto
bncterial metabolism i n [he intestine. Toxic products o f bacterial
metabolism include amino acids that mimic neurotranrmitterr, such
-- -
tnacllvs!c 1or:ns i s red~ccdI t is also acnravated by- emtroinlrstlnal
haemorrhnge, as blood protein is digested, nlcaring excess amino
;IS glul:to>inu ;~ncl y-;,mind butyl-ic acid (GABA). ;~nd nrn~notli;t. ~lcitlatI1;1t arebrokeu d u w ~lol i-eleascnn~n~onla,
which contribulestothe
which inte~fere with mental function, contribucing to hepatic enccpholopathy.
. .
~ ~~

encephalopathy. Portal pressurecan be reduced by creatinganortificialportosystemie

Medicines absorbed from the intestine fintencounlcrthe liver, where
lhey can be efficiently metabolized. This 'Arst-pass metabolism' is so
efficient forsomedrugs that theoraldose has to be increasedor anaiter-
native mute of administration, for example, rublingual or parenteral.
subrtiated. Somedrugs aredesignedfor clearance by theliver,preserv-
ing the local therapeutic effect i n the inlaline, while the firrt-pass
shunt or with drum -
. such as O-blockers. Sureleal shunts can connect
the portal vein to the inferior vena cava, or a flexible metal slent
can be placed within the liver, via the jugular vein, under radiological
guidance This is called a transjugular intrahepatic portosystemic shunt
. (TIPSS). Shunts can reduce varices and ascitcs. and aggravate
encephalopati~y.
Thejejunum and ileum are themain absorptivesurfaces of the gnstroin-
testinal tmcl.Theynreessentialforlifeandinteslinalfailureoccurs when
stlrgery t~rdisc;~selenves
lers than a metreof functionnl small intestille.
Structure
Thcjej~~nun~begi~~satthejunclionwiththeduodenumat~heliganenlof
Treilr and measures about 3.5 m. The Ileum comoriscs the most distal
2.5 m o f small intesline,lerminating i n 1hecaecum.A loosc, redundant
foldofmucosaprotn~desintothecaecum, forming aflap. thellcocsecal
vnlve. which orevents reflux ofcaecalcontents into the terminal ileum.
a lotlg mesentery that allows free movement and rotation, so that the
~ o s i t i o n olooos
f - .variable.
of small intestineis hiehlv
The blood stlpply is derived from the superlor mesenteric arlery.
~ ~
Veno..s dlxnage is via the superior rnesentenc \em intothe portal vein
and lymp lnticsdrainintothe thoraclcduct ~iamercntcricl)nphnodes
nndnrcend. iglyn>phoidchnnncls
The microseo~irstructure of the .i . m i l e ~ mIS rimllar to
e i ~ n ~and
that of tile duodenum, except that Brunner'r glands are absent (see
Chap~er6). Jejunal villi are long, broadand leaf-shaped, whileileal villi
are shorter, rounder and more blunted. Jejunal crypts are deeper than
ileal crypts and contain fewer Panethcells. Plicae circulare. which are
submucosal folds, increase surface area and are most prominent i n the
jejunum. The rizc of the lumen gradually reduces distally. Peyer's
patcltes are most prominent in the distal ileum.
Function
Mucoral cnzymes, pnnicularly disaccharidases and peptidnscs coin-
plete the digestive processes initiated by yprncrcalic enzymes in ille
lumen (see Chapter 20).
I n addition, jejunal epithelial cells express specialized enzymatic
. .
pathways to orocess and absorb dietav folic acid. The tcrminal ileal
epithelium is specialized for thedigestion of vitamin B, which i s dis-
assaciatd fro~nintrinsic factor in theterminal ileum (seeChaoter20.
~ ~
Bile salts are released from mixed miceller as f a l l are digcsled and
absorbed proximally and are reabsorbed i n the terminal iieum through
specific transpon proteins. The liver then recycles bilcsalts through the
entero-hepatic circulntian. Specialized ileal function is therefore
essential for healthy nutrition (seechapter 24).
Appmxilnnlely l m o f functioning small intestine musl remain to
allow adequate absorption o f nutrienll. Surgery or disease that leaves
less than this causesshort-bowel syndrome and intestinal failure.
. -.
Thercis ~norelvm~hoidtissueinthedistalileumthaniheieiunumand
, and Y'rsinia ertferocolifica infection can appear clinically identical to
proximal intestine. This reAecls a higher bacterial load and, as the
terminal ileum is also panicularly prone to Crohn's disease, intestinal
rubemulosis and Yer.rinia infection, it may serve a more fundamental
immunological function(seeChapters 18-338 ~ 3 4 ) .
Commondisorders
Abdominal pain. diarrhoea. flatulence, welghl loss and nutritional
deficiencies ate [he main symptoms o f small intestinal disorders.
Obstruclion of thes~iinllintenline nrsy becausedby disease wilhinlhe
intestine, or by external compression, or twisting, as i n a strangulated
hernia.Typical symptonls are pain, nnorexla and vomiting.
Chronic Infection with Gindio lornblia, and with various round-
worms, hookworms and tapeworms, is a common causeof malabsorp-
tioninendemicareas. Microsporidiaandcryptosporidiaareparlicularly
troublesome i n immunocompromised individuals, causing intractable
diarrhoea.
Saimoneila ~yphi,the cause o f typhoid fever, gains enlry into the
body throughpcyer's patches, which may becomeacutcly inflamedand
can perforate
Commensal bacteria thalarrnomallyfoundonlyinthelargeintatine
mav , ovcr~row
" and accumulate i n the small intestine in oatiem with
anatomical abnormalities, such as congeniul pouches and diverticulae.
or surgically created blind loops, or with motility disorders. Bac-
terial overgrowth causes flatulence, abdominal pain, diarrhoea and
malabsorption.
Tropical sprue is associated with chronic bacterial infection of the
intestine, panicularly i n visitors Lo tropical regions, and caucs malab-
somtion due to damage . to thesmall intestinal mucosa. Its incidcncc has
declined dramatically.
Neoplasia is rare and the most frequcnt tumoun are benign or
maligant neuro-endocrine turnours. lymphomas and smooth muscle
tumourr. Inareasofhigh endemicgastrointestinal infection,such as the
FarEast, a form of smnll intestinal lymphoma
.
~
knownns immunoprolif-
erative small intestinal disease(lPS1D) is relatively frequent.
Meckel'sdiVerlic~luminthdsmallintestine.atthesiteofinachmcnt
to the embryonic yolk sac, may contain wtopic, acid-secreting gastric
mucora that can develop peptic ulceration, causing pain and bleeding.
I t is thc most common malformation of thesmall intestine, but is rarely
rympromatic.
Cmhn's disease can affect any pan of he intestine, but i n about
60% of cases it preferentially affects the terminal ileum, causing
mucoral ulceration and transmural granulomataus inflammation.
An inflammatory mass and fistulae between the small intestine and
adjacent structures, such as the bladder, may occur. Crohn's disease
of the terminal iieum has beenshown to beassociated with mutalions i n
theNOD2 gene, whlch may determine how monocytes and Panethcells
interact with esleric bacteria (see Chapter 34). Ileocaecal tuberculosis
ilealCrohn'sdisease.
Loops of small inlestine are extremely mobile and may be caught i n
hernlal sacs or i n adhesions. This can cause tntestlnul obstructlon.
whichmay need to berelievedsurgically.
The caecum is the most proximal pan o f the large intestine, into which
theileumopens.The appendix is a blind-endedtubepmtrudingfrom the
caecum.
Structure
The caecum and appendix lie in the right iliac fossa. The lleocnecal
valve, protruding into the lumen oflhe large intestine, marks the upper
borderofthecaecum, whichextendsdowntoformabawl-shapedcavity.
Theappendix lies in thedistal ponion of thecaecunland is connecled l o
it by nslit-likeopening.
The blood supply is derived from branches of the superior mesen-
terlc nrlery anddrains viarhesuperlormesenterlcveln inlothe portal
vein. Lymphatics drain into the thoracic duct via mesenreric lymph
.
-.
nodes .and nsccndinelvm~hoid channels.
The caecum and appendix are connected to lhc posterior abdominal
wall on ;I vnrinhle length of mesentery, which generally fixes thc csc-
cum l o t l ~ c~~nrlcric,r;~hdominnl
wrll and 1e;lves thesppendix lnorelreely
mobile.
The c;>col walls are relalively thin and lhe lan~itudinalmusclc layer
isg;!thend in~oihreecords,orlaeniae,whichmeetaltheapexofthccac-
- -
cum. forminealriradiatefold thatcan bcsccn durinecolonoscopy. ..
The micmscopic structure of the eaecvm is typical of the large intes-
tinal epithelium, wilh no vllli and deep crypls (see Chapter 13). The
epithelii cells aremainly matureenlerocylesandgobletcellswithscat-
tered cntc\o-endocrineand Pancth cells.
The epithelium of thc appendix may be disrupted and ulcerated.
~ ~
exposing theextensivelymphoid tissue i n the mucosa and submucora.
Entero-endocrine cellsarercattered through the epithelium.
Function
The caecum and appendix apparently have no spccisl function in
humans, although in other specics they are well developed, conlaining
commensal bacterla that metabolizecomplexplantcarbohydrater,par-
licularly cellulose, lhalcannotbedigested by mammalisnenzymcr.
Lymphoid tissue i n the appendix may somehow contribute 10
Immune regulation; for example, thcincidence ofulcerallve colitls is
reducedi n people who have had an appendlcectomy.
Common disorders
Appendicltls results from obstruction of the appendiceal lumen, caus-
ing infection and inflammation. An obstructing faecallth is often seen
when surgery is performed for appendicitis. Initially, appendicitis
causes perl~umbllical paln, nausea and vomiting. This is because *Is-
ceral nerves from mid-gut stluctures refer pain to lhe peri-umbilical
area and stimulate the vamlting centre. As inflammation progresses.
reaching theoutside ofthcappendix, from the parietalperitoneum nerve
fibres carry precise spatial information ro the somatosensory cortex
and pain is locali7td to the right lliae fossa, overlying the inflamed
appendix. Umreated, appendicitis may progress to form an appendiceal
abscessorruptureintotheperitoncalcavity,causing perltonills.
Bacterial translocation into the veins draining the appendix may
travel in theponal vein totheliver, wherethey maycauseliver abscess
(seechapler 33).
Carelnoid lumoursoccur frequently i n lheappendix.whcre h e y may
remain asymplomalic.
The lhin-walled caecum is prone to parlorstion, forexample, dueto
inteainal obstruction or i n severe colitis (toxic dilatation) (see Chapter
34).
Caecal volvulus occurs when the caecum twists on its own mesen-
tuy. obstructing h e lumen and the blood supply. ultimately causing
necrosis and perforation.
lhberculosis andCrohn'sdiseasecanaffec~lhecaewm,ascancolo-
rectal cancer. Unfortunately, caecal tumours can remain asymptomatic
foralong timeandsomay only bedetected at alatestage.
Caecum nrtd appendix 35
 ~ ,480
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arllolanp LnuanbaJjaJe u!edpu!mopqe puee~oqus!p'uo!1ed!1suo3 -aql!d??ql s ~ e o a ~ e q l s n ~ n m ~ o s ~ u n o w s s n o ! d o ~ a ~ n p o ~ d s ~ ~ a a ~ a ~ q o ~
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'Su!leaq le!laql!da Bu!le!nm!rs
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 proximitlly in the sigmoid colon and to relax the internal analsphlnc-
The rcculm ;and anus comprise the ,nos1dirlnl part ofthc gi~stroi~~testit~:~l
tclCl. ter. Parasvmvathetlc nerves from the sacral olexus amolifvlhisinrrin-

Structure and ifilrelaxes whenthe internal anal sphincterrelaxes,defecationcom-

The rectum is 1Zcm long and extends from the sigmoid colon to the
anur. I t lics in front of the sacrum and is retroperiloneal, except proxi-
mally m d anteriorly. I t lics behind the prostate gland and seminal
vesicles in men and behind thcpouchotDouglns, uterusandvagina i n
women.
The wnli ofthe rectum is similar to thecolon, except that the longim-
dinal muscle layer is continuous.The mucorair thrown into threesemi-
lunar transverse folds, known as the valves of Houston, which sep-
arate flaws from faeces and prevents them entering the distal recmm
spr,ntoncously.
Distally, the mucora forms longitudinal ridges, called rectal
cnluntns, itnd the intervening furrows terminale in rmnll folds at the
.LO~~IU:I.~~~,
1:tion. termed anal $aives The line through the anill v ; n l v o
is a l w the squamucolumnar junction between the rectal and anal
rnAcu\.#e a i d .rtermcd tnc dentaleline
-
Tilree c~shlonsof.oose conncclivc lirruc arc arranged circumfcrcn~
tialiy above the dentate line. They contain a venous plexus (haemor-
-
mences. Puboreclalis and levator an1 relax, allow in^ the anorectal
angle to straighten, and abdominal muscles conlract, to increaselnlrn-
abdominal pressure and help expel faeces. Conversely,iftheexlemal
anal rphinclerdocs not relax, the urge todefecale passes.
Althoughthe rectum does not normally absorb nuhienls, medications
canbeadministered by asupposiloryoranenemasndnr~absorbcdinto
thesystemiccirculation.This isparticularly usefulinbabiesandpatientr
whocannolswallow.
Common disorders
Anoreclal disorders typically caujc pain, itching ( p r u r l l k snl) find
bleeding (haematochesia). Pain can inhibit defecation, resulting i n
hardening of the stool and a self-perpetuating cycle ofconstlpalion.
-
lnflanlmation causer dlarrhoca and the .passage of mucus. Chmnic -
inflammation can reduce the ability o f the rectum to dilate, causing
- .
uraencvofdefecalion. Tenesmus i a the sense ofincom~lete
Incontinenceisadistressingsymp~om,whichmayresultfromlocaldis-
defecation.

rhoidal plexus) and contribute to anal sphincter function. The veins ease, severe diarrhoea or neuromusculardisorders.
enlarze
. with time. forming ..pilerorhaemorrhoidr. Bright red rcctal bleeding occurringat the end ofdefecation is usually
Thc anus is 2.5-4.0cm long and its lumen is dirccted posteriorly. caused by hacmorrhoids. Blood mixed with stool indicates bleeding
- -
formin. " a709annlewith the reclal lumen.Thir ancuialion assists anal
sphincter function.Thecircular smooth muscle layer, which is continu-
fromamoreproximal source.
The anus can be examined externally to reveal prolapsed haem-
our with the rcclsl muscular layer, forms the powcriul internal anal orrhoids, skin tags and anal fissure. To complete clinical examination
sphincter. A n external layer o f voluntary (striated) muscle constitutcr o f the anorectum, a gloved finger is inserted into the anus (digital
thcexlernalanalsphincter.Musclefibresafthelevatoraniandpubo- rectal examination) and this can bc followed by a pmctoscopy or a
rectalis muscles, which form pan o f the pelvic floor, encircle theanur; slgmoidoscopy (seeChapters43 & 44).
the levator ani lift the anus while the puborectalis pulls it forward and Cancer and Inflammation affect the rectum as frequently .. as the
upw;lrd, making the nnoreclnl angle moreacute, funher strengthening remainder of the large intestine. I n ulcerative colilis, pmclills (inflam-
thesphincler. mationoftherectum) is almostinvariably .
. oresent. Crohn'sdiseasedaer
The anus is lined by a non-cornificd stratified squamous epithe- not always affect thc recmm; however, anorectal Crohn's disease caus-
liumtha~iscontinuouswiththcperi-analskin.Submu~salanaleiandr " ingabscerrer andfirtulacaccursin30%ofcases(seeChapterr34&37).
situated deep to the sphincter communicate with thc surface through Haemorrholds are caused by engorgement o f veins i n the soh con-
narrowductsand theirsecretionslubricaleandprotectthcanal canal. nective tissue cushions around the anoreetal junction. First degree
Autonomic and somatic nerves from the sacral scgmenlr of the haemorrhoids remain within the rectum, second degree haemorrhoids
spinal cord inncrvatc the rectum and anur. Internalanal sphincter lone is reversibly prolapse out o f the anus, and third degree haemorrhoids are
maintained by parssympatheticsignals and the external anal sphincter permanently prolapsed.
is controlled by sacral motor neurons. The anur is innervated by Passage of hard stool against a tight anal sphincter can tear the anal
somatic sensory nerveendings and is, therefore, assensitive as the skin rkin,causing ananal fissure.
to pain and touch. Abscesses and fistulae i n theroft tissuemound theanus arecausedby
infection of the peri-anal glands. They are treated with antibiotics and
Function surgical incision anddrainage. . , ..
The rectum acts asa reservoir for faeces and the anur is a powertul Sexually transmitbd diseases, including peri-anal wails caused by
sphinctercantrollingdefecalion.Thcrectumiswidcrthantherer1ofthe the human papilloma virus, genital herpes and syphilis-my affect Ue
large inlerl.wand canbe funherdirtcndcd anorectum.
Defecation .s i n : l i ~ c dby dirtencionoflhc recl~m,ca~r.nz -
.ncrc~red Pain i n the anus, without any disccmable organic cause is pmctalgla
pressure, which rtimulales intrinsic nerves to increase peristalsis fugax(seeChapter29).
Smooth muscle in the inlertinal tract powers the disruption, mixing and
propulsion of food from moulh toanus.It also dischargesglandularcon-
tenls and allows sphincters lo separate inlestinal companmenls.
Structure
Apart from the moulh, tongue, pharynx and external anal sphincter,
which hnve striated muscle under voluntary control. the gaslroinleslinal
system contains non-strialed smooth muscle undcr enteric and auto-
na~nicncrvou control. Unusually. the upper oesophagus has s~riated
musclc th;\t i s notundcrvoluntaryconlrol.
The al;\in masclebulk is arrnnged inan outer longitudinal layer and
an lnnercirculariayer,allowinl:rhaneningandconstrictionofthe
low luhe. In lhe cnceum and colon. the longitudinal layer is bundled in
Iln~.rr sr~l;,l.:blr cords or Inenita. AII i ~ ~ n c r ~.
o l ~ l l t ~ t t ~ l i ~IIICSC
1;tycl.s i n lhc slonrnch and thecircular layer is thickened uruund sphinc
-
ters, incre~sincthe constrictive force. Themain sphincters arerhe lower
oesopl~agealsphincter.the pyloms, the sphinclerofOddi. the ileocaecal
valve and the anal sphincter.
Arhin layerofmuscle,themuscularis mucosae,separatesthelamina
propria from thesubmucosa.
Smooth muscle cells are spindle-shaped and lack striations crealcd
by organized bundles ofactinand myosin.
Function
Commction is mediated by cross-linking of aclin and myosin, as
in striated muscle. Contraction is initialed by increased imracel-
lular Cal+ concentration, which is regulated by hormonal and neural
signals.
Intrinsic clectric pacemaker cells are interspersed among the
muscle eclls and there provide a characteristic. low frequency wave o f
elccll-ic:cl clup<rlnricatinnand repolariznlion, known as the slow walvc.
Ihnl lritvcls down Ihe intestine. Pacemaker cells communicate via gap
- -
junctions. with lhc signal travelline: faster circumferentially than
tlnnsvcrscly, so that a synchronous wave is propagated along the
intestine. Dirtinet pacemaker frequencies characterizeeach organ: for
exnml>le. the gastric slow wave frequency is three contractions per
minute. which can be measured throueh
wall (electmgastrography).
,
,
-
'
electrodes on the abdominal
Toniceontractions
These are mainly sustained, low-pressure contractions that occur i n
-
oreans with a mnior storage . function, such as the allb bladder and rec-
turn. High-pressuretonic activity characlerizessphineterr.
Phasiccontractions
These short-lived. rhythmic contractions predominate in the intestine.
They are controlled by intrinsic pacemakers, autonomic newer and
.coordinnted reflex enteric nerve activity, and include:
Peristalsis: whichis acomelexmovementwhereby a waveofmurcu-
larrelax.ntion. followed by a waveof conlraction,passes dawn the intes-
tinal iract proximally to distally. The wave forces intestinal contents
bcforc it nnd is mast prominent i n the oesophagus, stomach and small
inlestine. In vomiting, peristaltic contractions move rctrogradcly
-
(distally tup~~oximally).
Gastric churn in^: . which is the result o f tonic cootraction of the
pylorur and vigorous peristalsis i n the stomach, repeatedly squeezing
-
and nlixinc- solid food. tumine: it into a semi-liquid chyme that is
relcase<linto tl>cduodenum.
Segmenting movements: which are randomly spaced, non-
propagating circular musclecontractions that mix intestinal contents.
Colonlcmassmovement: whichisapowerful.sweepingconmclion .
that occurs a few limes a day, forcing faeces into the reclum and rlimu-
latingdefecation.
Interdigestlve migraling motor complex (IMMC): which com-
prises three stages lasling about an houreach, occurring between meals.
In rtagel, movement is absent. StageII,compriringofrandomregmer,t-
ina
. movements. is followed by -
. stage 111. which com~riswa forceful
wave o f contraction that migrates from lower oesophagus la terminal
ileum. This wave, sweeping the stomach and lntwtine clean of food
hol- debris, is lermed the 'intestinal housekeeper'.
y ~ r i t ~ Regulation
~g~~~~~~ls
Pcrislalsir is intrinsic lo the intestine, occurring even i n surgically ira-
lated scamenls,
. and is mediated by reflex enteric nerve activiw. Nitrlc
oxlde (NO) is the main mediatorofrelaxation i n the advancing f m t o f a
peristaltic wave, while acetylcholine (ACh) and other neumuansmil-
terr mediateeontraction.
Enlem-endocrine and neural pathways mediate reflex molllily
involvingspatially separatedp~rofthegasuointestindsystem, suchas
thechalecystokinin-inducedcontraction o f the gallbladder i n response
to food in the duodenum. the garlrocolic reRex (urge lo defecate ahcr
eating) and the ileal brake (reduced ilwl perisklsir whcn food reaches
the distalsmall intestine).
Serotonin (5-hydraxytryptaminc. SHT), releared by emera-
~ ~~~
endocrine cells, is a critical regulator o f intestinal motility lhraugh its
. .
effects on enteric neurons. 5HT. reccDlors mediateincreased intestinal
motilily,while5HT4receplorrmediatctheapposileeffect,andselective
inhibiton could prove to be useful therapeutically.
Common disorders
Dys~notility may manifertaspain,discomfort,earlysaliety.vomiling.
diarrhoea or eonslipation. I t is associated with same rare but serious
conditions andrame morecommonconditianr.
Ocsophagealdysmotil~tycancaurepain(odynophagia)anddifficulty
i n swallowing (dysphagia). Powerful, uncoordinated spasms (nul-
crncker oesophagus) can cause severe pain. I n achalasia, Ionic hyper-
activity of the lower oesophageal sphincter, and absent peristalsis
proximally, causesdysphagiaanddilatationafthedirtalaesophagur.
lnfantsmay deve~o~gastricoutletobstluction with penistent projcc-
tilevomilingduelocongenitalhypertrophyafthepylorlcsphlncter.
Followingsurgery or severeillness, generalizedparalysis oftheinles-
tine, known as paralytic lleur, may develop. This is aggravated by
hypokalaemia, hypocnlcaemia and the use o f opiate.$, which inhibi!
intestinal motility. 11usually resolvcssponlaneously, althaughtheinter-
tine may dilate to such an extent that the wall becomes irchaemic and
emergency surgery is necessary.
Less well-defined abnormalitiw o f motility may contribute to slow-
transit constipation, functional bowel disorders and lrrltable bowel
syndrome (IBS).
Muscular spasm may be treated medically with ~elaxentssuch as
mebeverine and hyorcine. Sphincter spasm may be mechanically
dilated or botulinum toxin injections may induce temporary paralysis.
Bolh lechniquesareused lotreat achalasia.
Metoclopramide may stimulaleforegutmotility, as may erythromy-
cin, acting on motilin receptors, and neostigmlne, aclingon murcarinic
acetylcholinereceptors.
The first lhormone ever discovered was the enteric hormone secretin.
Subsequently, over30enteric(orgut) hormones havebeendescribed, all
secreted by specialized entero-endocrine (also called ncuro-endocrine)
cells distributed throughout the gastrointestinal system. They mainly
control g:~rtrointcrtinnl motilily and secretion, and they mediate
camrnonicntion fromonepnrt of the intestine to another and outside the
intestine. iorexan~ple,tothecensalnervoussystem.
Structure
Entero-endocrinecells
The entero-endocrine system is diffusely distributed. Mort entero-
endoel.ine cells a1.e found i n theepithelium of the intestine. They vilry
in sh;~pe,although most arc pyramidal with the base of the pyramid on
~ ~
the basement membrane, where prominent secretory granules are
located. Somecellsspan theepilhclium, with theapex incontact with the
lumen, whilc athers do not. Entero-chromafin-like cells (ECL) are
similar in structure but are located i n the submucosa or in the ~ancreatic
islets.
Many entera-endocrine cells contain more than one hormone, and
hormones are preferentially distributed i n cells i n different parts of the
system. Entcric hormones are alro found i n neurons i n thcenteric and
centrnl nervous systems and are, ihercfore, often called aul-brain
- however. this is hard to pmveand rcmainr swculative.
peplldes. Endocrineand neura-endocrineeffects i n thegartraintestinnl
system therefore often overlap.
Enteric hormones
Alnlort ail cntero-endocrine cells contain serotonin (5-hydroxytrypla-
mine. SHT), in addition to peptide hormones, while E C L cells
contain histamine. Most enteric hormones are short peptides that are
synthesized as larger 'prepropeptides and modified by. for example,
cleavage. amidillion and sulphntian. They fall intostructural familit-
and liss~tcdistl-ibulion :~ndfunction vary widely (see table in ligure
opporile).
Function
Enteric hormones perform a great range o f functions and work i n differ-
ent ways. Some are relatively well understood and others are only now
beginning to beunderrtaod.The functions ofsomepeptidehormones are
shown in the tableapposite.
..
Enteric hornlones may act locally (paracrinc action) i n [he im-
'
mediate vicinity of where they are secreted: forexam~le,somatostatin
produced by D cells i n pancreatic islets inhibit insulin and glucagon
recrctian. They may alro first enter the circulation and then be trans-
poned to targets i n other parts of the intestine (endocrine acrion). All
exnnlpic is cl~olecysrokinin(CCK) released by cells i n thc d~adcnum reduced efficiency of digestive enzymes i n an acid milieu. Gasbinomas
and then inh.b~t!ng- gas1r.c
- gar1r.n pmduct~anand rttmulat~ng gal.blad-
- -
dercontraction.They may alsa betransponedtootherargansand, in par-
-
liculnr, to the central nervoussystem. Lentin and e l l n l i n are recently
discovered exsmples, which signal satiety, and arc involved in the
canlrolof nutrition.
Indlndual l~onnonermay also have different effeca an different tar-
gcts,somel mcsmed vted by separate receptors Examples .nciudegns-
tun u~~~~hb~nd~toCCK-AandCCK-Breecptors,and5IIT,wh~chh~r~r
least five different receptors (SHTI-, receptors), sometimes mediating
oppasiteeffects.
Some enteric hormones and their receptors have very jpccific effects
thal have been successfully largeled therapeutically. Hlstamlne re-
ceptor LypeZ(H2R)
~ .~ antagonists, such ar cimetidineandranitidine.Ihat
reduce gastric acid secretion. are amollg the mast successful agents of
this type.
Similarly, octreollde. a modified octapeptidc (8 amino acid) homo-
logue of somatostatin, is widely used to inhibit the secretion of other
enteric hormones, inhibit intestinal exocrine secretian and reduce
splanchnic blood flow.
There are now also new agents aimed at inhibiting different 5HT
receprors.totreal aspectsofthe irritable bowel syndrome0BS). '
Attempts to use leptin to decrease appetite and induce weight loss
have been aenerally unsuccessful; however, now that the role ofenteric
hormones i n regulating body mass has been appreciated, this is e chal-
lengingand promising areaofclinical rescarch.
Common disorders
Subtle enlera-endocrine dysfunction may be rermnsiblc far very
common conditions ruch as the irritable bowel syndrome and obesity;
Most serious cntero-endocrine diseases are rare, although clinically
silent carcinoid tumours are frequently noted alautapsy.
Symptoms caused by disorders of the enter-endocrine system are
protean, reflecting the many effects of enteric hormones. To diagnose
-
entero-endocrinedysfunction.cireulatine:enterichormonelevclsmav
be mcasured (in the fasting slate, as feeding alters the levels of mast
hormones) and excess 5HTsecretion may bedetermined by measuring
urinaryexcretionofS-hydroxyindoleaceticacid(S.HIAA),-
~ ~
Carcinoid tumours arise from entern-endocrine cells, and are rela-
tivelycommon.They maysecrelcavarietyofhormoncs andgrawthfac-
tors and 5HTsecretion is usually prominent. Carcinoids urnally wisein
theappendix,butmavoccurinother~Msot~he
.. inlestine.Thcoorialcir-
culation delivers 5HTfrom intestinal carcinoidr to theliver, which effi-
ciently clears it, so thal patients remain asymptomatic. However. when
the tumours metastasize to the liver nnd deliver their hormonesd i i c t l y
intothe syslc~~~~ccirculal on. lhcy glvc rare lo the carcinoid syndrome.
character zed by~. -
cp.rodcs of Rushina caused bv release of SKT and
fibrosis of !he heart and peripheral tissues, caused by gmwth facton.
such as transforminggmwth factor P (TGFp)released by the tumour.
G-cell tumours (gartrinomas) secrete excess gastrin, causing the
Zollinger-Ellison syndrome, which is characterized by severe gastric
hyperacidity, mcurrenl peptic ulceration and malabsomrion due to the
may occur sporadically, or in association with otherendocrine tumours
i n a syndrome known as multiple endocrine neoplasla I, or MEN-I.
The syndromeis caused by an inherited abnormality i n therumoursup-
pressor gcneMEN1.
There are many other rare entcro-endocrine tumour syndmmes, ruch
as glucagonomas and vasoactive intestinal peptide (VIP)-secreting
tumours that cause the syndrome of watery diarrhoea and hypokalaemia
(Werner-Morrison syndrome) (see Chapter38).
17 Enteric and autonomic nerves

44 Integraled function
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The gast~~ointerrinal system presents a large exposed surface ilren tho1
must be maintained and defended. Furthermore, prions, viruses, bacle-
. .
ria.. oarasites. inert articles and toxins areconstantly. innested
.. and there
is a large resident microbial flora, particularly i n the large inresrine.Tlie
mucosal immunesystem regulates how the body responds to thesechal-
lcnges.
Structure
Many structures contribute lo gaslrointestinal defences, Innate defence
mechanisms include:
The constant movement o f intestinal contents, and their periodic
expulsion.
The p H andchemicalcomposition ofintcslinalsecrclions; forexam.
.
ole.corrosivestomach
. -
acid and delereen1bile salls.
Anlibnclerial enzymes and peptides, ruch as lysozyme in saliva and
-
otherexocl-incrcererianr.
Mucins form atough, slippery mucous gel.prolcctingepithelialcellr
from ~echanicaldamage.
Int~.insicecllt~lnrdcfcncer in epithelial cells. which can rcsist and
-
limit invasion by pathogens.
Specialized inleslinal epilhciiai cellr, such as Paneth cellr, which
recrcle mimy ;~nlibacrerialenzymcsandpcplider.such
. . as dcfenrinr.
M n s l cells, corinophils, neutrophils, macrophages and dendritic
. .
cells i n lhc lamina ~ r o n r i aconstitute a first line o f defence against
- aurncl subsets o f lymphocytes to different pans of Ute intesline; for
~pe!l,ogco.; ~II;II Ih~~cnch
the cpitl~fli:~ll:tyer and also process and present
nnli~et,riocelisol'tl~eadilplive immunesyrlem.
- Adnplivc im~nun~edefences include:
1,sminn 1,ropria lyntpl~oeylec:thcsc B nndTcells ;,re distinct <n>m
.
those round in the bloodand arespccifically targetedtotheinlestine.
Intra-epithelial lymphocytes: T lymphocytes are found belween
ei,ill~clii~lrells.p;~rliculn~~ly
i~~Ihcsm:tllinlcrtine.Theynrcnotmigrating
through. but o~.cresidemin this position. Many ofthcsecells erprerry6
T-cell receptors, with a rcrtricted repertoire, rather lhan [he regular ap
T-cell receptors foundelsewhere.Thcy react lolipidantigcnsprcsented
o n C D I cell surfacemolecules rather lhan pcptidcr prerented onclassic
major histocompatibility complex (MHC) class I or 11molecules, and
may have a special role responding lo protcolipid antigens i n bacterial
ccll membranes.
Peycr'r patches: there are distinctive ruucturer wilh a specialized
epitheliitl lining,conlainingBandTlymphoeyterandantigenprcrenling
cells. They arc [noit numerous in [he terminal ileum. The spccializcd
dome epithelit~mleckr villi andcrypls and the glycocalyx ~. formed by
micravill~nnd membrane glycoprolelnr is dcfi:ienr. It conlntns rpccial-
izcd ewnc. al cells called micmfold or M cells. wh.ch lack microv~lln
and contain membranous folds enclosing lymphocytes, macrophages
and dcl~d~.itic -
cells. Thev. t r .a ~anliaenr and transoon them across the
cl~ilheii~l~ll.1K1 inlerialwith immunecells.
UndcrlhcdomeepiBelium, lymphocyter,macrophagesanddendritic
cells form a loose T-cell-rich cortical reglon and compact B-ccli-rich
follicles, resemblingtheorganizationoflymphnodes.
Tonsils are lymphoid aggregates surrounding the opening o f the
hypopharynx, with a broadly similar structure and function to Peycr'r
~p:~lcllcs.iancl in 11,~: s l o r l ~ n ~CI~IIIII
l ~ . l ~ appcndlx,
d Peycr's pillch~slnlity
be substituted by less well-defined lymphoid aggregates in lhe lamina
proprin.
While host defences murl prevent infection and damage to the absorp-
tive epithelium o f thc gaslrointestinal tract. the commeiual flora ofthe
intestine is essenlial for health and thesystem musl distinguish between
beneficial and harmful bacteria. Furthermore, while the intestine musl
mounl irnnit~ne responses l o pathogens, it must also preventreaclivily to
food antigens l o avoid allergits and hypersensltlvlty. The mucosal
immunesyrlem fulfils these functions in wayrlhalaresrill poorly under-
stood. Thus while pathogens are generally repelled, om1 tolerance
develops lowards lo harmless inlestinal conlenu.
M cells. These Vansport intact peplides, viruses and bacteria amss
the epilhclium and pass them on to antigen processing and presenting
cells. The surface molecules involved i n this transpon are presently
.
unknown.
Mucosal homing. Anligenr taken orally are Vansported lo regional
lymph noderwherethey causcprolifera1ionnflymphocyler.Theserpe-
cific T lymphocytes and antibody-producing B lymphocyles leave the
lymphnodes and returntomucosalrurfaces.
Homing to the mucora is mediated by cell surface molecules h a t
inaract with receplors on blood vessels i n the gastrointestinal tract
(sddrtslns). ~ymphocyteshoming I"the intestine express h e a4p7
integrin molecule that inleracu w i h the mucoral addrersin-cell adhe-
sion molecule (MAD-CAM). Specific cytokines (chcmokiner) also
cx;tmplc, thymus ;~ndcpilhelirl expressed chemokins (TECK) attracts
cells lolhesmail inlcslinc.
Secretory dimcric immunoglobulin A (slgA). Mort B cellr at
mucor;al rurfaccs produce IgA, which is the most abundanl
immunoglobulin in bronchial, rcproduclivc =ct and intestinal recre-
lions. Two IgA molecules, joined together lo form polymeric IgA
(plph), hind lo a receptor callcd sccmlory compuncnt (SC) on the
basolaleral surfaces of epithelia. The complex is transparted across
the ccll cylopiasm (transcytosed) and slgA is released at the luminal
surface, by proteolylic cleavage of SC.
Common disorders
Thc intestinal epithelium is no1 impervious lo proteins, virurer and
bacteria, as war previously assumed. Prions, such as h e bovine
spongiform encephalopalhy (BSE) agent, viruses, such as human
immunodeficiency virus (HIV), nnd pathogenic bacteria, ruch as
Skigella, are taken up by M cells, allowing systemi- spread and
infection.
Selective I g A deficiency affectr; about 1: 500 people, wilhout much
eifecl on cntcric immunity.
Chronic immuncstimulation, for example, by Helicobocrerpylorior
bycoelikdisease,canlcad loerc~sproliferalionofimmunecellr,neo-
plaslicchangeand inlestinallymphoma.
Truefood allergies are rare, although they may be becoming mprc
frequent; particularly thosecaurcd by nut antigens.
Dysregulated immune responses are implicated i n coellac diseare,
where here is hypersensitivity to peptides derived from wheal and
other cercals and in Inflammatory bowel disease (IBD). Inflam-
~nsliul\o!ily nunn;tlly he ttctively prevcntcd by subscls of T lympho-
cytes, which might have regulatory functions that are defective i n
IBD.
The main function ofthe intatine is todigestandabsorbnutriena, and it
is variously adapled for this. Taste provides a guide lo thc nutritional
valueor potential toxicity offwd,and while thecolon is nolesscnlialfor
nutrition it helps to conscrve water and mlts. Details o f digestion und
absorptioll are considered in Chapters 20 and 21 and here general
principles oreemphasized.
Coordinalion
Hunting. gathering and nupermarket shopping all requirc exquisite
neuromuscular eaardination, as do biting, chewing ands\vallowing.
-
Thus. ~atienlswhoace weakorwho haveneurolanicaldisease. suchar a
stroke, c.an rapidly become malnourished. Once food passcs from the
mouth to the oesophagus. the involuntary enterlcnnd autonomic nerv-
ous s y s t ~ t ~itt~d
~ stlormanes produced hy the entcro-endocrine system
cnol-<linntccligestio~tnnd;~bsorption.
Molilily
Food moves progressively through the intestine aided by peristalsis.
which is nlodificd by neuronal and endocrine signals. Anlegrade move-
ment is complemented by churning in the stomach, which mixes and
~ulvcrizesfood into chvme, and the action of sohincten, which seua-
~.;lle i'<v><linto ;~pproprinteeomp;~nments. For example. the pyioric
sphinctcrkeepsfood i n the stomach until il is thcconectconsistency for
dipestion in Iheduodenum.
Mechanical disruption
Many R~ods;Ire ih;,rd nnd irreg~~iainnd could damage the delicate intes-
1in;d iit~iug.TIC 1011g11oral epill,elium and leelh break and grind b o d
into snlnll picccs, wllilesaliva moistens and lubricates it. Panicle riles
are h~rtherreducedin thestomach, wherepowerful muscular churning
converts food intoa thick suspension called chyme. Reducing thesizeof
food particles increams thesurfacearea tovolume ratio,enhnncin%the
action o f digestive cnzymcr. Chyme remains liquid until i t reacher the
large intestine. where waste is convened into semi-solid faeces by wnter
Solubilizalion
Food must bedissolved in an aqueous medium focdigesriveenz.ymes to
act ilnd \vI?iIc r ~ l l i i efluid is ingested, most ufthe liquid in the intestinal
lumen is nctively secreted by theintestineandexccrineglands. Itissub-
sequently reabsorbed, to maintain fluid balance.
Emulsification and micellelormation
Mnsl dictnl.y fill is too hydrophobic lo dissolve in wdter, so mixing in
tile alkaline intestinal lumen emulsifies it, creating tiny panicles
and inc~.ensinpthe surface area available for lipid-digesting enzymes.
A ~ n p l ~ i l ~ l tbilcsalts,phospholipidr
ilie nndcholcrlero1,esterssecreted in
bile form micellcr, which are microscopic particles withn hydrophobic
ctrrc ;tnrl the Ihy~lropllilicp:ms o f the molecules on theoutside. nigesled ,
lipi~ls.suvl~ ;Is I'atly acids, pal-titioointo ti~ehyd~ophobiccore;~nde:~nbc nppropr.ittccell mctnl, anc lransportersandchannels lnaddilion,rcc-
absorbed from ~teintertinallumen.
Acidification and alkalization
Optimal digustion in thestomach requires an acid environment, created
by HCI, secreted by gastricparietalcells. Conversely, optimal digestion
by pancreatic enzymes requires an alkaline medium, provided by
HCO;,secrcted i n the bileand pancreaticjuice.
Enzymes
Enzymes arethemoslcriticalelementofdigestion,enablingchemieslly
complex, polymeric focils to be processed to absorbablemonomers at
physiological temperaturesand i n a reasonable timescale.
~ ~
Enzymatic digestion starts in the mouth with sallvary amylare.
-
whichbreaks downstarch toformsunars.Stomachacidinhibi~~amvlase
aaivity and activates gastric pcprinogen lo form. pepsin,
. thus initiating
protein digestion. Mort enzymatic digestion takes place i n the duc-
denum and.jejunum,
. where pancreatic and small Intestinal enrvmes
act in an aikalinc milieu. The pancreas produces a prorligiour amount
and variety o f digestive enzymes, including protelnases, amylaer.
l i p a s s and nuclears, and pancreatic failure invariably causes malab-
sorption and malnutrition.
Enzymes can potentially digcstcomponents o f thecells that pmduce
them (autndige~tion);therefore, many are synthesizedas inactivepro-
enzymes. Other enzymes activate them by proteolytic cleavage; for
example, pancreatic trypsinogen (procnzyme) is cleaved to q p s i n by
entemkinase secretedby duodenal enterocytes.
Enterocyter contribute a critical final stage of enzyme digestion.
whereby brush-border disaccharldases and peptldases attachcd to
theirapical sutfaces break down panially digestedsugarsand peptidesto
absorbable monomersandoligornea.
Within enterocyler, enzymes continue the digestive process; for
example, fatty acids are reconslltuled inlotri~lyceridesandasrembled
. ~
into chyiomicrnnsbeforeexportat the basolateral membidneand trans-
pon lothecirculation vialymphaticchannels.
Special laclors
Intrinsic factor isaglycoprolein prcduccd by the stomach,whichbindr
vllamin D,,,
.. protcct.ng :t from breakdoan i n the proximal intestine. I n
Ihe terminal ileum, vitamin B,, is released and absorbed. Similar ryr-
tsms operate for other essential minerals and vitamins. Some nutrients.
for example, vitamin K, may be synthesized i n the intestine by com-
mensal bacteria.
Surlace area
Abroqtion o f digested food depcndr critically on a well-adaotsd and
ample surface area.The small lnleslineis the main absorptive surface,
-
n l l h o u ~ l ~ s o m e s ~ ~ b s l ; ~beabrorbedthmuehtheoralmu~saand
~~c~~c.~n
others i n the stomaclt (e.g. alcohol, which notoriourly 'goes straight to
the hcad').
Pllcae circulare nrctransvene folds, which increase the surface area
threefold, and villi are finger-like projections inlo the lumen, which
increase inte7tinal surface area 10-foid. Micmvilli, which are micro-
scopic, linger-like projections on thc apical surface o f enterocyter.
increase theabsorptive sutface area 20-fold. so that overall the surface
area is increased 600xover thatofasimplchoilow tube.
. .
specialized absorptivesurlaces
Entemcyte~arc crq! lritcly adapted lor abcorption by capresing the
1.0"s of the intestine arc specialized for absorbing panicularnutricrts:
--
for exarnplc, folic acid is mostly abscrbcd in the leiunum and vitamin
n,,and blle.~cldsarc mostly ahsorbzd in lhetermlnal Ileum
Enterocytes can regulate the extent o f absorption; forexample, Iron
transportis inhibited when there aresufficientbody stores and, ingenetic
haemochromatosls, regulation malfunctions and paticntr accumulate
iron.
Digesrion ondabsorprion 49
Chylomicron Chylomimn Fat n- . Fez
sccrnion synthesis cstcrification diqcscion
 'uon&osqe(em lelaual sosne3 lunl u! qqqm 'saiLo~alu:,u! agl aialdwos .tap.!oq qsnlq aqi u! sasa~!idad p a ~ ! ~ a p - n 6 ~ o l a i u a
uo!is~nmnsseplle K~ua!~yap p!dy rasne3 ' s u o ~ ~ ! w o ~ Lluauodwos
q~~o '(s!sKle$eaoIns)
Ie!iuasn us s! q~!$n u!alo~dod!lods j o Bu=!3yap 3!1au=~.sp!=e
'a u ~ a o u ! s d h ~salnlalom
o ~
laqio alChp38 U E uaql u!rd& 'ualou!sdL~l
ou!ws sy!sads JO sapuapyap asnw s ~ a ~ ~ o d ~s yu! ~ s a~ jd~osra!l!lcm ~ a l n n ! l ~leql
e ascp!idadopua pahllap-aiL~0.1al~~ LIE s! as~.t~!>lwalua
-1ouqs Jllauaf) '$l!~aluao~lnsaSnO!lJaju! j o lnoq e lu!molloj dolahap -sap!ldadol!(o voqs l u ! ~ e a ['leu!uual [Lxoqles ; r q ~modJ rppe ou!me
Lwm Lllua!suaJI a m pus ' s d n o ~ s!uql
l :, swos u! iuanbalj L J ~ pus A allu!s ahom= ieql nsep!ldadoxa ale a pue y sasep!)dadbxoq
pwpuolap Llpsgaua8 s! qs!qm'L~ua!syap aselselanllmlasloj i d a ~ x a -1es aql altqm 'u!qs apndad aqi u! sanp!sal 3g!sads IF an~a13leql
ew
' a m Llaans1;u.?~suo!!&osqe ~ u a p ~ n u a ~JO~ sa!l!leslouqe JaqlO nsep!1dadopuaare~se)selaordpueua8ou!sdKrlowLq~'uaaou~sdL~
am uo!~&osqepm ruaynuolsew JO sasnes snollas isauomwos a q ~
'111550
osp ([OOIS uapeklej lu!ssed) eaoquoleals pue Zu!]aolq 'saoqlretp
'uopd~osqejawp w uo!~sa@pa~a[dmoau! ~ n 'qelu!pa~npulou
q s! asnos
aql J! 'Tahamoq :uo!lsalels u! uaas oqe ale sa8ueqs a s q L 'a~nl!ej
usaJo!l!nw moll a!p slua!rcd pue pau!clu!rLu aq louues e!laql!d:, pue
ueaq 'uys se qsns sanss!] le!luass= Lllcnluana .ICJ p w epsnm j o 8u!
-IssAt 4 spear Llp!dcl sluaulnumsetu qlosqe p a t 1sa9!poi Ll!l!qeu! aqL
sJapJos!p uowmo3 ~~?!~~m'uo!lnlosuo!~e~pLqa~ ~ e ~ ouj oo! ~ ! s o d u ~ oUL~III!J!II!IJ
~a~i pasn
s! s~~!!Bnspuc suo! +rNj o vodsuc~i-03s ! q ~.s~auodsue~~ paldllo?-+"~
lualan!p lu!sn w s e l d o ~ haqi oru! riles ol!q pue sppe ou!mw 's~pueqs
-Jesouow uodsue~r01pasn r! ased~y,x,+e~aql Lq palcl:ual)ua!pera
+EN owso so pue ~ ! u a l o ~ i ~ aa l q a [la3
~ a91 u!ql!m le!iualod =-!disala
an!ia%oullems e su!elu!sw osle (ascdLv) aseieqdsoqd!~~ au!souape s ! q ~
' ( d ~ v )areqddsoqd!~~ ;ru!souape j o r!rLlmpLq aqi m o l j panpap L&aua
8u!m 'suo! +eN a v q l l o j a8ueq3x:, u! [la3 aql oiu! ruo! +xom1 sdiund
l e q ~dmnd +X/+WNpaleni!s Llle~aleloseqaq1 Lq mn!pos j o pa~aldap
aql olu! auelqwaw llas aql ssoloe paqlosqe ale sp!d!l pa~rol!pasaqL I[ruelsuo~s! wseldolh p h o l a l u a aqL .mseldoiB aql olu! Sap!J
~lola~saloq~puesp!d!loqd -aqsscsouow l ~ o d s u e'salL=olalua ~l j o asejlns les!du aql u! ' ( I - ~ ~ 1 3 ~ )
:soqdosLl '!oJa$p IL>BOUO~'sp!se L I I ~ 01 sp!d!l LJDIO!~ UMOP ~ I ? J J ~ _I>]J<~~SUFJI-UJ2~03"la-UlnJp~S?gl SE LlJllS ' ~ 1 ~ l l 0 d ~ l l~!I!JJ*S l:ll
'r-uedaq~ Lq pazcsaq~uLsam q3!qmju luel~odm!ISOW a q 'sasnaisa ~ .sappeq=sesouom 01sop!lcqssss!~lpuu ssp!n:qml:ss!p
~ m l s l o qpue~ sassd!loqdsoqd 'sassd!? .r~alsaloralsaloqs pus JO uo!lsal!p leuy aql uuopad pue JapJOq q s n q aqr o! luasa~dale
'alnxlow s!~!qdolpLq e Lq pa=slda~s! u ! s q ~163e Lllsj auo q q m
u! 'spld![oqdsoqd 'auoqpsq 101asLll e 01 payull L ~ I U ~ B ASOU !~E ~ J
~ L s ~ X l l Su!sudwo~'sapl.'aLll!~la~s
q q sp!d![ h e l a p u!em aqL :saqJuelq uoqs ql!m suulxap l!m!! pue 'aso!nol!ew puc [asorleu) sap!l
'asepns albsola~uaaqloi sp!d!l p a ~ s a l ! p h e ~ ' a ~ c j l n s -eqmes!p'(asosn[l) sapueqmesouom osnpo~dsasalLmy -as~ldmu s!le
palnqz '3!1!qdolpLq wow e pue ~ J O J ~ ! q o q d o ~ p Lsqaleam sluau - a ~ s u e dLq pswroyad s! uo!lsal!p isow 'spuul8 L ~ e ~ ! l e Lqs pasnpo~d
-odsoss!q~ed!qdweq~!qmu!'saxa~dwo~~elns~~owo~scm~s~q~'sp!d!~ s! oselLmeamos qlnoqllV'nselLme Lq palsal!p ale sap!~eq3scsLlod
h a ! p pay!rpma q!m sal[a~!wpax!w m l o j 01dlaq 'slq)ed!qdwe ale .aaeqlnor l o aJqy L~e~a!psl! amouq
qJ!qm'walsalmalaloqJpuesp~d!loqdsoqd'qles al!q'aJomlaqund on[" s! q ~ ! q f i'sllnm 1125 lucid u[ ap!~eqm~!sLlod~opcu aql 'JSUIIIIIJJ <I!
'uolslnmausjauo!lem~ojaqlsalowo~d sa8exu!l ~!p!soaL~%$-~d~saa!plouuv~ rucwnH .asu)s~.~uY put! asu~nl3
p!ny leu!lnlu! JO ~d ou!pyle aqr pue lu!r!w pus lu!mnq3 .luau j o pasoduos r! 'yl!w U! Jeans ~ o l e m aql 'asope? 'aso)snq puu asosnla
pus sa~e~pLqoqls:,o?!lun
-vaql PUB alqnlos i a e m am q q m 'su!a~o~d 'xaldmos e s! q3lals )uE!d ~sap!leqsJesouomj o slaloblod .lal.toqs
sp!d!i l o ~ a l u oal e qyqm 's~sanspue saqaaels re palsalu! aim salolpLqoql\r3
sale1phqoqle3
'UO!leln5J!J
aql 01 payes am pus 'auelqmow lelaleloseq aql u! SlauucqD an!lsalas 'la!p2ql WOlJ SlU9!JlnLlOJ3l!~qlOSqU PllU 15UIY9
s!h UO!I~I~JII!~ aql Jalua rp!3e ou!me 'wrsldo~Lsaql w o ~ .rp!se
d ou!we L l l ~ a ! ~ y jsms!ueqmu
a ~snqoa'sanss!t Lpoq 10, papaau rlu!laicw
paanqs 4a~!re%aupus paareqs Lla~!~!sod 'ou!w! 's!lowo~e'lellnau !elnlsnllsaqljo isow pue LUaua hcio!p aql Ile ap!~oddsua!llnuomew
203 aa!l~alas 1wq1 w a ~ l o d s u e ~ ~ -lualagp
oa a r y lu!sn 'suo! +aN 'sa!i!~ue~ibm c ~ l o ~ ~JO! wme~8!ll!m u! papaau Llao ale qs!qm ' s u p
qt!m Buols s a g m a l r n Jalua sp!~sou!wy .paqmsqe ;us 1eq1 sap!rdad -sl!n se qsns'slualr)nuors!w 01l s e ~ ~ u!'s)ua~r~nuwselu
uo~ EL! UA!OU)(
-ypus -!p pus sp!se ou!we ollu!s Bu!snpoJd 'sap!~dadj o uo!lsal!p aJc pul!la!paql~oucdlo~ewaql u l ~ osp!d!l
j puusu!a]old's~11!~pL~oq~~3
 urns sasneahuapyap ~ u ! ~ ' b ~ ! u n m w
u! !a101e sbeld I!leql lu!lsaZlns -qlal-A) UO!lE3y!pOUJ leuo!~elsue~~-~sod aql l o j pal!nbaJ s! )( u!mel!A
'sqysuaqseil 01 a~uss!salpooqp[!q3 sanoldu! uopsluaua]ddns pue ~paleZpsanu!%u!aqs!alOllJexasl!pue luep!xo!lue ues! ~ u ! u l e l ! ~
i!
1 YOI~EJ uo!~du~susqpue sawbzua duem u! 1olaejo3 le!luassa ue r! a u ! ~ 'nay311pue e!ae[awoaJsosasne~ iJua!=yaa .uo!~ew
i 3u!z - r o j auoq bqlleaq pue s!selsoamoq mnplelJoj [a!~uassas! u!wel!A a
I 'r!l!leuuap
puesnupu!lq-~q~!usasne~i~ua!~yaa.uo!s!nloj luenodiu! LIP~!I!J~s!
pue suo!13unj lelnllaa ~ U e ~ Jle!luassa
oj s! (p!Je a ! o u l i ~ ~v)l l ! m e l ! ~
'aseas!px!(auJ
se qms 'iiloloqled leupnaru~llews ql!m pue P~usl=y~nsu! ~ l i e ~ ~ ~ u e d
o! palauxa s! ssa=xa PUB lS~!alo~d
Zu!pu!qladdo~ 01 punoq 'I?n![ aql u! pue a3!pune!'an!1~~~lsqu'ast?s!p J J A ~ U! J ~ J Oalojalaql sa!sua!J
puols s! I1'sambzua aApep!uo buew l o j ~013ej03IB!IU~ES~ ue P! laddo3 -yaa .esomwleu!lsas! llews l>ea!ue pue uo!lallasllesal!q=lenbape
laddog uo spuadap a pue 3 'a '\r s u l w q *alqnlas-1ej aql j o un!l&osqy
I
sp!ee h l ~ ele!iuassa
l puesu!mel!n alqnlos-lej
'naql!l pue e p
'Ells5
p m ~ l l s e l q o l s l a u'paZ~eluaq~!m'elwasus bllensn s! I q j a [eJ!u!ll
-warn [ e u ~ ~ s i u ! a qlu!pn[m!
l 'salb~ola~ua u! su!nold l u ! u o d s u e ~pue
~ panlasqo ]sly 141 qlnoqlle 'sl3aga peaJdsap!m snq blua!~y=p puc
Zmpu!q wn!Jle3jo s!saq~ubs~ I O salelnm!ls q ~ ! q m'a u!wq!n i q PJI~I suo!Iwa uo!lelLqlam l o j paqnbaJ ale " 8 u!mel!n pue p p u 3!10.~
-nSai s! pus auqsa~u!![ems aw ~ n o q l n o ~sln330 q ~ uo!l&osqe mn!qea 'sa~olueinlZouom
mn!qeg 01sa~emc~n!Zb[a'daqlaneapsa~i~o~a~u??~aqm~wnun[a(aql u! paqlosqe
ale salemernl%b~odlbol?~d pue p p e x j o d .e!lalaeq leu!lss~u!b q paz!saqr
.bqredobmo!ple~pue
sm!llaw nlqe!p 's!soqm!3 J ~ ! I J S ~ ~UJ E pue ~ sanss!] laqlo pue ueaq
'ssamued'Ja~!l aq) u! saelnmnme qaqm 'uo!l&osqe uol! pallosuomn
asnea slsolemcuq~owaeqb~oi!paraqu! suo!~qnug f l .uo!~dlosqe ~
u o l ! l ~ u ! l s a l u ! s a a n p ~ ~ o ~ ~ e ~ u ! p ~ a d a ~ ' a ~ ! ~ d. ~dp~~~~~~-~a~~~Zu~~~~n~~~~e
p u e ' ~ o ! ~ s a ~ d x a ~ a % ~ ! ~Un OI! ~ unse
u ' ~ ~~ase~b ae m
s ' s ~leu!lsalu!
~al
asnunu! u! passaldxa 'u!a)ord = f l ~aqL .uo!ssaldxa J , W ~paseanlp
qsnanll b e d uo!l&osqe u o ~ !m n p u s?lols uol! bpoq s s m r g ~ b ~ u s ! ~ y a p j le
o qilreln~!ped
s~ ajojaJaql ale suela* 'spooj ucpe~aSan
' u ! ~ ~ a l s uZu!~elnm!>o~
e~i spu!q u! alll!l q~!m' Y I ! ~ pue sPZa ' r a m m o g pan!>ap b[u!em s! " 8 u!mel!A
.T~.A![aq1 u! PJJOIS bllensn s! z ' g u ! m e ~ ! ~ janlasal
o sqluoul ~ l s c aly
l
~~ - .u!meleqo~sue~)'u!a~old laqloue 01punoq p a l ~ u d s u cs!i ~''a
.io!lhosqe>oj il!l!qe u!mel!n psqlosqe'uo!nln>J!Jaql u['paq~osqeaqus~u!me~!naq~ lcqios
i -l!ene nl %u!u!elu!em pus suo!ue or Bu!pu!q S!I Zu!~uanad'+=ad SPIJ!~ 'elt!2oss!p 01xaldluo~aqlsmo!!c q~!qm'r3lb2o.!alu~ I!:JI! 110 1p"ss9.1~lx?
' s l l ~l q a p d ~ u l s e iLq
l pa~uaaso!aio~do3bl%e ' u l r r a j o r ) s e ~.mnu ~ o l d a s JE 01 spu!q pue au!lsalu! aql u! uo!lepe~3apmall "(1 u ! l u e ! ~
sroalold lojaej I!EU!IIUI.S~~~J le)a!red je!laq~!da J!JISU% bq paz!saqlubs
~!110~dO3b[Z e'(g~)J013ejl!sU!JIUI 01 SpU!qUaqlzlg U!~UBI!A 'LI3JUIOIS
J~II(I! papc~3apJln lcql su!alo~dql!m pDxaldlu03 s! o!ll~l:~!n
Llals!~
~
. ( u ! ~ e l e q o e o x o l p h q ) ~u!rnel!A
~a
'uuoja[qs~!ene-o!qrrow aql s!puemnuaponp 9q1
u! pxpsqn4p!de1 s! (leaw %u!~eamo~j pan!lap blu!em) waeq u! u o q
.uond~osae
malqold lnleaq ap!mp110m e s! L u a l l u a p u o r ~'su!alo~d Bu!u!eluo~ aql u! u o d s u t ah!lle
~ ~ ~uapuadap-+e~ l o uo!snjj!p a+s!.sod b q pJqJosqe
-waeq iaqlo pus u!qolZowaeq j o iuauoduoa le!juassa ue s! u o q u e au!10q3 pue lol!sou! 'p!~e l!uaqlo)ued 'u!]o!q 'au!xop!>Ld 'u!le!u
UOll 'u!neyoq!l ' ( l a u!ma!n) au!me!ql 'p!m ~ ! q l o l s y.su!wsl!r xaldluoa-a
aql pue (p!3e J!qIolse) 3 u!wei!A ale su!mel!n a[qn[or-lalem u!clu aq,L
'(p!383!uop!q~ele) s!saq~uis su!ee~!na~qnlos-rale~
u!puel%e~so~d
pue anss!laNau u! u!labmjos!sqlubsaqlloj pa~!nbaJale
. ..
paqwsald aq plnoqs sruamalddns pue sa!r!~wnbs!xol u! alulnlun33e ado alllos 'sluaplnuorllw se u m o q am puu sa!l!)uerh [II!LYS blan!lnla~
us2 baql 0s ' p a l a ~ x a4lua!3yja IOU alr b a q sa)6~olodl1l
~ u! palols I!! ~pal!nbalsllllcql sluamalahela!p !c!luasraalcspau!ul1pu1!S"U!LL~CI!A
Assimililling nutrients is the central function of thegastrointestinal sys-
-
tem. whichnlsorenulates -
theirdistribution,stora~eanddisoosal. Conse-
quenrly, gastrointestinal dysfunction causes disordered nutrition and
disordered ntlllilion has profoundeffects on thegartrointertinolsyrtem.
-
The sloean: 'what we eat. what we are and what wcdo' encaorulales
nutrition. An adequate supply of nutrients must be available, the recipi-
~ ~
en1 must be in a slate to metabolize nulrienls to build and repair tissues
andutilizechemicalenere~.and -.. whatultimateuseirmadcofnutrientsis
determined by what the recipient doer.
Thus. :Isedentary office worker user food diflercntly lo an Olympic
athlete or n critically ill patient on a mechanical ventilator. In each case
what they do is potentially enhancedor limited by nutrition.
Basic nutritional concepts
.
The main foods.. orotein. corbahvdrilte and fat. are maeronulrlenls
required i n llelntivcly large quantities to provide energy and organic
building m.aterinls. Micronulrienls are required in milligram ormicro-
gramqt~antiliesforrpcciolbioshemicalfunctions;thesearemainlyvita-
mims. ~nincl.illsand csscnlial fatty acids. Non-digestible plant material.
- - is needed foroplimal intestinal function.
called libreor rouahaec.
Energy intake must at least equal output. Even in a slate of total rest.
energy is requircd for metabolism-the basal energy expenditure
(BEE). Basal energy expeiditure varies with age and sex and most
people must consume 1.3-1.5xtheir BEE to remain in equilibrium.
although l h i ~may increaseto2xBEEwilh severemetabolicstress.
Metabolic energy is stored in the chemical bonds in organic com-
pounds, with fats being the most energy dense, with the highest number
of calories per g n m weight, followed by carbohydrates and then
proteins.
Glucose isessential forenergy supply to thebrainand red bloodcellr.
It is usually derived from ingested polyraccharider, and the liver can
mainlain blood glucose levels from stored glycogen (glycogenolpsis)
and by converting aminoacids toglucore(glueoneogenesis).
. and wasting of muscle and fat. while cholesratic liver disease reducer
Although fats cannot beconverted into glucose, metabolic adaptation
in starvation means that the brain can use fatty acids and ketones for
someof its energy requirements.
Amino acids are required to produce proteins, which are constantly
renewed and replaced. even in adulthood when growth has ceased.
Amino acid flux is measured in terms of nitrogen balance, as dietary
nitrogen is almostentirely containcdin aminoacidsand nitrogen - excre.
lion, via ores. is mainly due to amino acid breakdown. Thedietary pro-
tein resuirement to remain in nilroeen
. balance varies with nee. sex and
metnboliestate.
Assessing nutrition
In children, growth ehsrls help todetect potential nutritional problems.
Other simple clinical measurer include the body mass Index (BM1)
(weighfieighl'), measured in kilograms and metres, giving a global
fold thlcknesr,refleeling bbdy fat.
-
measure. mld-arm circumfemnce. reflectine muscle mass. and skln-
S.mple blood tests can tdcntify deficiencies in iron, calci~m.n n c .
copgcr,
.. v~taminrA. D , K. B,,,- and folste. and nitrogcn
. balance can be
csti~n;\ledby oiensuring urinary urea excretion.
Control of body mass
Maintaining healthy body weight and proportion lhmugh life is acorn-
plex featofneuralandendocrlnecontml. thedetails ofwhich anonly
now being discovered.
Food and calorie intake is regulated behavlourally and neumnal
control involves the conex and centres in the hypothalamus and
brainstem. Many n e u r o t r a ~ m l l t e r s including
, peptide Y (PY), pro-
opiomelanocortin (POMC), noradrenaline (NA) and serotonin (5-
hydroxylryptamine, SHT), are involved in the control of aowtite. ..
POMC- and PY-containing hypothalamic neurons integrate signals and
-
communicate with the brainstem. which in tumssienalstothehvwthal-
amur using NA.
.
,
Leplin is a critically important peplide hormone rrlearcd by
adipocytes and lntesllnzil cells lo signal that adequate calories have
been consumed and stored as fat. Ghrelin, released fmm the intestine.
mediates long-ten control ofeating andbody mass.
Body masscan also becontrolled by regulatingenergyexpendllure.
In rodents, the basal metabolic rate (DMR) is increased by adaplive
thermogcncsis. whereby energy expenditure is increased in brown fat.
generating heat. Humans havelittle brown fat, althoughBMRrimwith
regular exercise, which may explain how regulai exercise impmves
weight control. However, BMR falls as body weight decreases, counter-
actingslimmers'effortr toloseweight.
Gastrointestinal disease and nutrition
Gastrointestinal disease inevitably interferes with nutrition. Rcduced
intake may be due lo nausea andvomiling, poordcntition,or dysphagia
secondary to oesooha~eal
. . disease. Pancreatic. biliarv and intcslinal
diseases cause malabsorption. Coeliac disease and Cmhn's disease in
particular are associated with multiple deficiencies, including calcium
and vitamin D deficiency leading lo orteo~orosis.
Chronic liver disease is characterized by nutritional abnormalities
absorption offatnandfat-rolublevilamins.
Gastrointestinaldiseasescanalsocausespecificnutrientdeficiencier.
~. -
ruchar atrophicgaslriliscausingvitamin ..
B,,deficiency.
Metabolic derangemen1 caused by systemic disease is aggravated
when the intestine, livcroroancreas is involved. as theoatient'rahililvto
~ ~
assimilate nutrients is compromised.
Enteral and parenteral nutrition
High caloric Itquid dicts that can be administered by inmavenour infu-
sion have made tolal pamntcral nulrilion rrPM. oosrBle.
. Total oar-
enteral nutrition is used when patienls cannot be fed enterally, for
example, because of intestinal failure, orsurgery.
WithTPN, homeostaticmechanisms regulatingdigestion andabsorp
tion arebypasred; therefore, nutientlevels mustbecarehrlly monitored
and the feed modified accordingly. This, and therisk ofinfection asso-
ciated with infusing nutrient-rich solutions, make TPN demanding and
potentially dangerous.
Furthermore, the lack of enteral feeding atrophies the intestinal
epithelium and may increase bacterial translocation and the risk cf
sepsis.Thus,enteral or panialentcral nutrition is preferred.
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~suo!a~!~~uL~~c~!~ornso
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snql puu )no ruo! +EN? ? J ~ I~ oaaucq~ra
j u! llaa aql olu! suo! +xom1
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I ! a q u! sdwnd uo! pue slauueq3 'sa~odpaz!!e!=ads qBnorq~rarny
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L l p a y w re qJns Ylloljxuup pue ~ z a ~ o u u e ~ oa!do?d q m u! pau!elu!em
pue palen!eAa Qlyare3 aq ?loj?laq plnoqs uo!leJpLH 'p?qs!u?ld
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o s l e Xlpv
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Xrs!l!q pue SBWJUQ~'au!IsaIu! llems 'spue1B Xle~qesaql u! suo!~ au!moxa sa 'JaBml q ~ n male saxny p!ny ~ " 1 '~U!IS~IU!
2 ~ J ~ U!
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u )seal IC 01lunowo
'(dN33)
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pa1eln8aiamslal;uaqa-l3laq1oal!qm'n~3joBu!uadoaq1alelnaaJ
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rtorcs before a competition by eating a carbohydrate-rich meal
(cnrbo-Innding).
The livcralsoproducesglucosefromamlnoacldsby gluconeogene-
sls. whereby transaminares removethe amine -eraup . and feed the prod-
uctr into the Krebs cycle. Fatty acid metabolism also producer the
two-carbon-containing acetyl coenzyme A (acetyl-CoA) molecule that
-
fceds into the Krebscycle; however, new six-carbonruearr.ruchar elu-
cost, cannnt be synthesized from fatty acidr via the Krebs cycle. Thus
rugarcon be laiddown as fat, but fat cannot beconvened tosugar.
Hormones such as insulin, glueagons, growth hormone. corlica-
steroids and catecholamines, acting via cell-surface and inlracellular
receptors in the hepatocyte, determine the balance of glycogcn synthe-
sis, glycogenalyrir and glucaneogenesir.
Lipids
Dlclary lipidscarried, far example, i n chylomicmns, are laken upfmm
the circulillion bv the liver and broken down into comooncnt parts
including fatty acids, phospholipids and cholesterol.
~~~
The liver then repackages there lipids as lipoproteins, for expon to
the rest o f the body via the bloodstream. Li~apmleinr .. arc macromo-
lecular conlplexer formed from lipids and rpccific proteins called
apolipoprateinr.lhey allow hydrophobiclipids to bctranrponcdinthe
blood, and specific receptors that bind to different apolipoproteins allow
targeting to thedifferent tissues that express the necessary receptarr.The
main lipoproteins exported from the hepatocyte are very low-density
lii,oproleins ( v L D L ) ~ hi ~ g~h-densit y lipoproteins (HDL).
The liver also takes up and recycler lipoproteins
. . and free fany acidr
from thecirculation, funller regulating the dinrihutian of lipidr arodnd
the body.
Thc liver is themajorriteafcholesteralsynthesisand most circulat-
ing cl~olcsterolis derived fmm hepatic synthesis rather than directly
froln the rlia. The rtatin drugs, which are the most effective treatment
for hypercholerterolaemin. act pr.rnar.1~an the liver, by inhlbattng ihc
r;~ie.ltoul ~.z c n.~ y r nincho.e;reralsyniner~r.
e HMC-CoA reductarc
Cholesleml is urcd to synthesis bilesalts, which are then conjugated
with taurine andelveine
-. .[amino acids) andseereled i n bile.
Ketones are synthesized from acetyl-CaA, derived from the oxida-
tion offatry acids andprovidcarourceofcirculatingmetabolicfuel dur-
ingfarlingandrtarvation.Cellssucharncuronr,whichnormallyrequire
glucorc, can adapt theirmetabolirmtourc kaoncr
Amino aclds and prolelns
Essenlialamlnoacidscannolber)n~hesizedinsufficientamoun~sfmm
precunon and must be derived f i m the diet. The L i v c p d u c e s a 611
com~lemenlofaminoacidsbv lranramlnallonsnd other modifications ~~~
of dietary amino acids and expons these for use i n protein synthesis
thmughout the body.
- Excess amino acids are metabolized by removal o f lheaminogmups.
releasingammonla, whichis potentially toxicand is convenedintourea
in the livcr, via the urea cycle, and excreted in the urine. Tbe eerbon
rkelelans are used for ellergy prod~~ction or convened into glucme for
storage or expon. Thus, during fasting, stmation or savereillnerr;,thc
liver can conven muscle protein and other tissues into essentialenergy.
The liver synthesizes many proteins, includinz
~ ~ .enzymes
. ior in own
metabolic processes, and plasma proteins l o r export. Tbe liver pro-
duces albumin, which conslilutes 50% of plasma protein, caagulallan
factors (including 11, VII. I X and X, which arepost-translationally mod-
ified by vitamin K-dependent?-carboxylatlon) complement pmleinr.
circulating protease inhibitors, apolipopralelns
~ ~ . . . and carrier omlelns
that bind hormones and othersmall molecules i n thecirculation.
Inflammation causes the release o f circulating pcptide mcdiatarr
called eylokines, of which interleukin 6(IL-6), is particularly
. impnanl
.
i n stimulating the hepatic acute phase response, whereby the liver
rapidly increaser its synthesis o f host defence proteins and reducer
albumin synthesis. Acute phase proteins include C-reactive protein
.
(CRP),semm am~loidA,recreto~y~hos~holi~areA?andcoanulation
.. .
and complementproteinr.
Metabolic and synthetic failure
A l l hepatocytes can pcrfotm basic metabolic and synthetic functions.
so thereis a vast reserveolpacil~.Dis~~tedcar~hvdrate.oratein
. ~ . .. and
lipid metabolism results in laligue, wasting o f body muscle and fat
resewer, and biochemical abnomalitics including hjpglyeaemia.
hypoalbuminaemlnandreducrd coagulation lactors.
Hypoalbuminaemia can cause oedema, due lo reduced plarma
oncotic pressure allowing extravasntion offluid Fromcapillaries intotir-
sues. Reduced clotting factors cause a coagulopathy, with a prolonged
pmlhrombintime(PT).
Coagulation factors have a half-lifeof few hours i n thecirculation and
rapidly disappear when the liver fails suddenly.Albumin has a half-life
ofabout21 days, so i t taker longer far levels t i fall.Tblhus. the PTis the
most sensitiveclinical teslofrapidly deterioratingliverfunction.
Hepatic merobolic andsynfhericfuncrion 59
 u!qm!l!q paleanruo3 amoS -alqnlos-mic~~.nou~ are q>!qn\ 'ap!uoln>
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-erlxa aql u! uo!laIuIsqo 3!do~so~aeu ou I! 31aql SB '(ampune[~!~edaq)
qmsa[oqa ;~ledaqer~ulpallea s! s ! q ~.uo!lJunj u!aiold u o d s u c ~ ~ j o 1ulwuedruo3 leuosom!u lo 'runln>!lal ~!mseldopuaq ~ o o ~ uaq~.
s
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d pue sasepjxo
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aqpune(leleuoauuanas sasnea'aua8 awes ar(, u! IJajap lemiaruise Lq u! laqi!a paiajaxa ;UP PUB alqnlos-~alm~ aJom Lllc~aua8am s l m p o ~ d
PamW S! U~WM'~ULUPULS . I ~ m ~ - . I a l % 8 ~'lSBIlU03
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laqloou pup iauolpuLss.paqll3) aa!punel8~!1en13ny'pl!ru asnn uea 'sa!la!oru alqnlos-laiem qi!m simpo~dalrcm puc su!xol 'sanlp q u ! ~
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~ aql u! slolmjoa ~ ! a pus
q ~ sawi[zua Bu!1118111uug
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parsam! Lq pame3 q Lsm e!maou!qn~!l!q~adLqpaiean!uo3u" !I
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' u o l ) a ~ a s ~ e l n ~ l l s u e ~ L q a l !palamxa
qo~u! L~n!1!q1ola~!ljo1a~~erupa~nouoq-au!ius! uo!lal3xau!q1u!!!ql,a~!udru!
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-n!umun 10lunome lallerus q m m e pus 'p1e8n[uoa amos Llleuuou al!q u! uo!laJaxa l o j mar(, %u!~sdaldpue 'sass3 isom u! ruaq~%U!IEA
s! i u a q 'miU..aa!ln aql u! paiamxa s! pue meanspoolq aql oiu! sasn#!p -!I~cu! .salnaapmo!q ar![oqelam 01 LI!JC~CJ asuaum! uu s ~ lan!l q aqL
Forcefully expelling luminal contents from the stomach and inlestine is
an imporlnnt defence against noxious agents that could be swallowed
with food, nnd the process is tightly controlled. Vomiting is coordinated
by
. risnnlr
. fmm the intestine, body and brain. reaching nerve centres i n
the brainstem, which control voluntary and involuntary muscles in the
-
nbdomen.chest and eastmintestinal andres~iratorytracts.
Nausea is the dysphoric desire to vomit, often accompanied by dis-
taste for food and loss of appetite (anorexia). Although nausca usually
orecedes vomit in^,
. either may occur in isolation.
Retching is the rhythmic reverse peristaltic activity of the stomach
. - . accomoaniedbv conuaction ofabdominal muscles and
and oesoohaeus.
deep,sighingrespiratorymovemenlsthat oftenprecedeactualvomiting.
. - ~ ~
Retching is 'dry', i.e. whileitfeelsasthoughoneis abouttovomit,there
is naefflilx of vomilus.Duringretchina.
. . -
. theoesopha~usdilaresand may
accull~olatevomitus that is subsequently expelled.
Vomiting is the forceful expulsion of loud out ofthe mouth, usually
accompallied by increased salivation, sweating . and tachycardia.
Vomiting is different from passive regurgitation, where acid stomach
contents and partly digested food reflux into the mouth.
Muscular coordination
Intrinsic muscles o f the stomach and oesophagus relax the gastro-
oesophngenlsphinctcrandforcegastriccontentsoutofthcstomach and
ocn<ll~ltspas by reverse perislalsis. Vomitus rarely cont.linr material
fmln beyond the ileocaecal valve, although reverse peristalsis can con-
vey intestinal contentsall theway from the ileum.
Abdominal muscles, including the diaphragm, contract, greatly
increasing intrc-abdominal and intrathoracic pressure, thus helping lo
empty theupper gnstrointesliml tract.
Simollaneously, the epiglattir shuts off the larynx, which is
dmwn forwa~.dand upwards by muscles i n the jaw and neck. The
sofl p:!l;tlc i s dwwn upwards, closing off the nasopharynx. These
cnorclin:~lcd il~oscutitrmovements protect the airway as vomitus is
expelled. In unconscious or inebriated individuals these protective
mecllanislns are disrupted and vomitus may be aspirated into the
airway.
Neural control
Thevomitingcenlre(VC),inthed~nalparlofthereticularformationo~ auentionshould befocusedon treatingtheunderlylngcaure,whilesup-
the medulla oblongata, is the main site o f neural control o f vomiting.
The VC is essential for vomiting, whatever the primary stimulus, as it
receives and coordinates signals fmm a number of other centres and
coordinates theoutout.
The chemoreceplor trlgger zone ( a ) i n the floor of the fourth
ventricle lies outside the blood-brain barrler and therefore senses
blood-bolne chetuical stimuli that induce vomitxng, such as dmgs like
morphine and d~goxin.The.CI2 i n turn stimulates the VC to lnduce
vomline. -
Motion sickness and diseases ofthe inner earcause vomitingby send-
-
ine newe sienals from the nucleus o f the vestibulocoehlear (VIIIth
cranial) neweto theVC, possibly via t h e m .
Other areas of the brain, suchas thecortex, thalnmus andhypolhal-
amus, also signnl to the VC, mediating vomiting associated with, for
example, pain. emotional upset, feverand serious physical illness. Veri-
abllity in the way that these stimuli are pmcessed may aecountforwhy
somepcople vomit more readily thanothers.
Sensory inputs from the gastminteslinal met and other viscera. car
ried by the ";gal and splanchnic autonomic ncrves, also stimulate the
VC, so that -aastrointestinal distension, infection and inflammation can
all inducevomiting.
The autonomic centres regulating sweating, lacrimation, salivation
and head rate all lie close to the VC and these autonomic ohenomena
are all stimulated in thc surge of neuronal activity that accompanies
vomiling.
Commoncauses
Common causes are detailed i n the figure. Neumgenlc or psychic
stimuli, chemlcnls end mechanlcal or chemical irritation of ihe
lnlcsllnal lract itself may stimulate vomiting. I n many instances the
exactpathway remains unknown.
Eflectsand consenuences
Physiologically, vomiting expels noxious material fmm the gasuoin-
testinal tract. Normally, neuromuscular reflexes pmtect the respiratory
tract, but i n inebriated or unconscious individuals ~rotectivemecha'
nisms may fail, allowing espiralion o f vomitus, which can cause
asphyxiation or chemical inflammation and bacterial infection of the
iungs(pneumonla).
Thc strongproplstbe forces generated dunngrelch~ngandvorml.ng
cancause a tear in the oesophageal
. . mucora(Mallory-Welsstear).nts
typically causes haematemesis (vomiting blood). Generally the tear is
superficial and heals rapidly.
Chmnic vomiting, as in bulimia,cancauseacid damagelothe teeth
and gums. Furlhermore, prolonged or profuse vomiting can deplete
fluid and electrolytes, leading to dehydration and altered blood chem-
istry. Vomiting o f gastric conlenLr typically causes hypokalaemia,
hyponatraemla and melabolicalkalarir, whileloss o f HC03-in inles-
tinal contents can cause metabolic acidosls.
Treatment
Vomiting should generally be viewed as a protective mechanism and
porlive measures for the patient should aim to replace fluidand elec-
trolytelossas. ?
Inothercases, however,nauseaandvomitingarertimulatedby minor
events, or by an essential treatment, such as chemotherapy for cancer. .
and must be treated even while the inducing agent is present F o m - !
nately, powerful drugs that intempt vomiling in. different ways are
available. These include ecelylcholine (ACh) receptor antagonis& and
i
I
histamine I11 reccpar antngorusts, which arc panicularly useful for
I
motion s~ckncrsand vcrtibulocochlear dvsfuncl~on, d o ~ a m i n eDl i
receptor antagonists, such as phenothiazines and metoclopramide, that
block stimuli from the CTZ serotonin (5-hydroxytryplamine. SHT)
1
:
SHT,receptor antagonists, such as ondansctron, that block the VC and
afferenls from the gastrointestinal lract; and cannablnoids, whose 1
mechanismof action is still unknown. f
Nosseo and vomiting 63
Inl'cctiot~sditurhoea is not only a nuisance to travellers-it also causes
major ~norbidityand monality in pans o f the world where sanitation.
cletin drinking water and nutrition areinadequate.Diarrhoeacan nlsobe
symptomatic of serious underlying gastrointestinal diseases, such as
inflammatory boweldisease (IBD) and colorectalcancer
B y delinition, diarrhoea implies that an e x c w volume o f stool is
passed, and this is usually accompanied by lncresscd frequency . . of
defecation and increased liquidity o f the stool. Normal stool volume
varies betweell individuals and is about 200-300 mlidav.
Diarrhoea m.ay be accompanied by abdominal and rectal pain.
urgency to defecate and incontinence o f faeccs. Whcn diarrhoea is
caused by f~od'~oisoning.theremay bcconcurrcnlvomlting.
Diarrhoea1 stool is usually more liquid. I t may also contain more fat
when c.aused by malabsorption (ateatorrhoea) and i t may contain pus
and blood when caused bv intestinal inflammation (see Chapters 34 &
Diarrhoea is usually acute; that is, sudden i n onset and shon-lived.
-
although it can be chronlc.The causes, mechanisms and treatment are
genernlly different in acute and chronic diarrhoea.
Mechanisms
Although the mechanisms are considered separately, for any onc cause
ofdiarrhoea m u l r i ~ l mechanisms
e may .
. operate. Forexample, ulcerative
colitis causer inflammation and also increased secretion and motility
recandnry to thestimulationafenteric neuro-endocrine pathways.
Secretory diarrhoea
Whcn increased secretion into the intestine exceeds the capacity of the
sm;,ll and large intestine to mbsorb fluid, stool volume increases.
Incl-c;tscd rccrclian by entemeytes is often aggravated by a concurrent
abao~ptivedefect.
Cholcra is n common, serious and well-characterimd example.
where hypersecretion is mediated by the bacterial exotoxin of Wbrio
cholcrrrc. Cholera toxinA irreversibly nctivates adcnyl cyclase 10 pro-
duce cyclic adenosine 3'5'-cyclic monophosphnte
. . (eAMP), which
stimulates runained chloride secretion into the intestinal lumen by the
-
cvslic fibrosis transmembrane reeulator (CFTRI. Nat nnd wmer are
secl.eted wilh CI-, maintaining eleclronculrality and osmotic balance
Cholera can kill i n a few houn by causing profound dehydration. The
stool may bevirtually clear electrolyte-rich fluid, known as 'rice-water
stool'(s;e~ha~ter%).
Cholera is spread via the faecal-oral route, so diarrhoea enhancer
infectivity and aids the organism's survival. Conversely, diarrhoea
clears bacteria from the intestine and is pan of the body's defence
system.
Otherbncterialtoxina, hormoneselaboratedby hormone-producing
lumours, particularly earcinolds and vasoactive intestinal peptide
(VIP).amar, and tubulovillaua colonic adenomas that secrete fluid
and i?keus fmm the abnormal epithelium can also cause secretory
di;t~.rl~oca.Excess bilesalts thaturenotrcabsorbed intheterminal ileum.
as n result of terminal ileal disease or rcscction, can induce colonic
hypersecretinn.
Osmotic diarrhoea
Anon-alraorbable ormotlc load i n the intestinecon overload the intes-
tillc's c:q>;!city ibr renbrarbing wilter "guinsl theosmotic gradient.Thus
more fiuid remains in the intestinal lumen and is excreted, causing
diarrhoen. An example is inherited or acquired lactase deficlency.
Lactare is the enzyme that normally splits lactose, the predominant
disaccharide in milk, into the absorbable monosaccharides glucose and
galactose. Without lactase, ingested lacloseremains In theinlestim.cre-
ating an osmotic load. Hereditary lactase deficiency is more freqwnt i n
populations wheremilkisaminorpanofthetraditionaldiet,andcanalso
beacquired as aresult ofdamage to the intestinalepithelium,caused by.
for example, gastroenterills.
Other causes o f osmotic diarrhoea include the useof "on-absorbable
food sweeteners, such as sorbitol, and laxallves, such ar IacNloseand
magnesiumsulphate.
Malabsorption of other dietarycomponents can alsocause dianhoea.
although generalized malabsorption, such as i n pancreatic failure.
predominantly causes steatorrhoea, which is increased faecal fat
content, causing large, pale stools that float on water and have an
unpleasant odour, panly due to metabolism o f fatty acids by colonic
bacteria.
Inflammation
Damageto the intestinal lining, caused by bacterialor viral infection, or
immune-mediated processes, causes infiltrationof fluid and inflamma-
tory cells into the intestinal wall and exousion ofthis inflammatoryem-
dateinto theinlcrtinal lumen. Excess mucus may also besecretedbylhe
damaged epithelium. ~nfiammationalso increases fluid secretion and
inhibitsreabsorption (seeChapters32&34).
Pain and urgency oftcn accompany inflammatory dianhoea and leu-
cocylesand blood are foundmixed inwith thestool.
Common caurcr include bacterial and amoebic dysentery and IBD.
Dysmotility
Increased motility can incrcasc the frequency ofdefecation, andwheni t
isseveretheremay bcinsulficicnttimefor nomalreabsorpllonoffluid
from the stool, resulting i n increased stool volumes. Dysmotility may
occur with aulonornlc neumpalhy, for example, in diabetes melliNs.
Other causes include thyrotoxicosls and motility-stimulating drugs.
such as acetylcholineste~seinhibitors used l o m a t myasthenia gravis
(see Ch;~ptersI 5 & 17).
Treatmenl
Most acute diarrhoea is c.aured by short.liyed and selt-limiting bacter-
ial or viral infection and, as the diarrhoea is a defenk mechankm
against infection, antidiarrhoealr should be used with caution. Treat-
ment should be rflainly supponivc, to prevent dehydration and elec-
trolytedepletion.
Hydration can be maintained using a slightly hypotoni~and alkaline
oralrebydrationsolutioncontainingglucoseandsodiuminthecorrect
ratio to exploit active absorption via the apical Na+-glucose m
vansponer on enterocytes, which draws water into the cells along the
osmotic gradient(see Chapter23).The WHOrehydrationformulationis
3.5gNaCI. I.SgKC1, 2.9gNa citrate and 2.0g glucose per litre. ?his
provides 90muNat. 20mM Kt, 8 0 m ~ C I - . I O m cilrate and l l l m ~
glucose. In more severely ill patients Intravenous hydration may be
required.
Spccllic causescan also betreated, for example, antiblollcs for bac-
terial or amoebic dysentery and rtemlds and 5.amlnosalicylates for
IBD. Malabsorption caused by pancreatic insufficiency can be treated
with oral pancreatic enzyme supplemenls, while secretory dianhoea
caused by hormone-secreting tumoun can be convolled using somato-
slotln, which reduces hormonc secretion.
The most frequently used anlldiarrhoeals an the opiates codeine
and loperamide, which inhibit intcstinal motility and increase the time
available for intestinal fiuid reabsorption.
Diarrhoea 65
Constipation is one of the commonest gastrointestinal complaints. I n
addition, people often auribute symptoms such as tiredness. lethargy.
nausea and headache to what they,perceive as constipation. Often no
medical explanation is found and there is no proven link between infre-
quentdefeearion and general illhealth.
Causesand mechanisms
Irregular bowel habit can exacerbate constipation, as the colon and
-
rectum continue to remove water from stool. hardening it and making - straining at stool contributes to the development of haemorrhoids and
passlge more difficult. Thus, constipation can be self-perpetuating.
I n severe chronic constipation, parlicularly i n the elderly, faeces may
becomeso hard, dry andimmovable (Isecal impacllon) that they cannot
be passed without medical or surgical assistance, leading lo intcslinal
obstruction
Reducedmotility
Reduced colonic motility . may becongenital as i n Hirschsprun~'sdir-
~ ~.
ease, where myenteric nerves are absent from the distal colon, causing
chronic obstmction and a massivelv dilated, faeces-filled ~ r o x i m a l
colon (megacolon).
Paralytic ileus occurs after abdominal surgery, or with electmlyle
abnormalilles, such as hypakalaemia.
.. Intestinal motility may be
~ ~
reduced acutely by stress,due to sympathetic autonomic nerveactivily,
and .ueoule
. who are severely. iniured
. or otherwise unwell may become
constipated for severaldays.
Ncurnnriueular dysfunction caused by hypercalcaemia directly
reduces intestinal motility.
Reduced colonic motility may also be constitutive, i.e, normal for
thal penon(slow transit constipation).
Drugs.
Drugs such as opiates, antidepressants and others with anlicholinergic
effects reduce intestinal motililv. Similareffccls are seen with oral iron
supplements and aluminium-containing antacids.
Excessive, chronic use of stimulant laxatives, such as senna, can
reducc motility, presumably by damaging ordcpletingenteric neurons.
causingcolonicatonia.
SHT, mccplor antagonisls that have been used lo treat diarrhoea in
irritablebowel syndrome (IBS) can also cause severe constipation.
Stool b u l k
Stool volu~ucandthefrcquencyofdefecationvary withdiet. fluidintake
and iotcntinal secrclion. Dietnry Ahrc. which mainly comprises nnn-
diecnii~lopti~ntpolysacchnrides, draws water around itself. incrctaing
stool volume. Thus,chronic constipation is often caused by lack o f
dieta~yiibre andlor Inadequate fluid Intake, which is required to
t~ydr:~te(lietnrvAhreand tosoften thestnol.
Will, lasting, the frequency o f defecslion deciines, panly becuuseof
reduced reflex colonic activitv and also because of reduced stool vol-
ume, although a large proporlion o f the solid material in stool actually
cam~xiscscnlcl-icbacteriarnthcr than food residue.
Neuro.psychological dysfunction
Defecation is imbued with social and psychosexual constraints
that influence bowel habit, and it can be inhibited volunprily via the
externnl anal sphincter and by cortical signals acting on autonomic
"ewes.
Neurological damage to the braln a n d splnsl cord, for example.
i n mulllple sdemsk and pedpheral neumpathy can lead 16chmnic
constipation as well as incontinence. . . , :,:.
Local causesand obstruction
Local obstn~ction,for example, by a tumour, may cause pain anddiffi-
cully i n defecation. Painful local lesions, such as pmlapsed haemor-
rhoids and anal fissure, inhibit the urge l o defecate. Constipation and
. . . ..:
fissure.
Clinical features
The normal frequency of defecation (bowel movement, bowel open-
ing)variesinthepopulationfromaroundthreetimesaday toonceevery
3days,althoughmany peoplelieou&idethisrange. . . . L::. ,,,: '
-
True constipation implies reduced defecation frequency or stool vol-
ume, although patients also complain o f slralning during defecation.
pain on defecation and hard, dark stool.'lhe wnreof incomplef.ieyi&;
ation is called tenesmus. : . .: ,,:: ?t::p;?!,:c,:agt:
Paradoxically, chronic constipation and faecal impaction:pacticu-
larlyin thcelderly, may cause incontinknceandpassageoffluidprre;-
tum, so-called overflow incontinence.
Diagnosis
Perceived and actual problems mustbedistinguished.Amrefulhktory
ofdietary habits and any dmgs that might cause constipation should be
taken. !,<;
Faecal impaction alid local lesions, including anal and rectal cancer.
can be detected by digital rectal examination. Faecal loading o f the
colon may be seen on plain abdominal X-ray. Timing the passage of
radio-opaque markers through the intestine (shape lest) is used todiag-
nose slow transit constipation. , . :. ,
Treatment
Stopplng drugs that cause constipation and ensuring thal sufficient
fibreand fluid are ingested areessential. Increasing dietary fibre forms
the basis of laxatives that rely on increasing stool bulk, althoughenccss
fibrecanexacerbatecnnslipation. : ,.. ,:,~'.;.
Where psychological or social factors are implicated, itis important
thattheyareidentified.
Comcting cleclrnlylc abnormalities and allowine the bowel time to
. - r
cally, Painful or obslmctive pri-anal and rectal condition; may also
requiresurgery. . . .. . ..: ., ~,,.:.::
'
,
. :. : ,;:
Where constipation does not respond to simple d i e m i o r lifestyle
measures, and is nut caused by identifiable pathology, laxatives may be
used. They work in a number o f different ways, including increasing - .
stool bulk, increasing osmotlc fluid secretion, soiteningstool, stlmu-
laling secretion and motility viaenteric neuro-endocrinepathways'and
directly stimulating neuro-endocrineresponses by receptor-targellng.
Thesearedetailed in the table within the figurebpposite. ,: : :
29 Functional disorders and irritable bowel syndrome
-

PoychologlcalfacCoro

Limbic systcm Sornsro-eensory

, Classlficatlon
. .. . . ..

... - . . i l.r.r..
~ ..,,.. . ..

. Behevioural

. Olctaltcrarlon
C o r r ~libre
~ t IhCAkc

Corrccc fluid intake

.Antispasmodics
c.g. Mcbcvcdnc

- -
. Xcawurancc

: : :),::I:

Garlrointatinal symploms without direernable organicPalhology are uealment remains unsatisfactory, but i n some patients a1 laasr, symp-
common; occurring i n a quaner of the population and accounting for tomscanbcparlially relieved.
halfafallconsultationrw~~hgnr~roenterolog~r~s Allr~oughmany peop:e
. -
have r.v m ~ t o m sthat are conrtslent w t ~ nn c . ~ n ~ c adla~norls
I afa f ~ n c Oelinition
tional boweldisorder,only aminorily reekmedical allenlion. The basic fealureoflhesedisarders is pain or discomfort refirred to lhc
Althoughlhesymplomrcanbedis~resring,theredisordeisdonolpre~ gaslroinleslinal lract, wilh somc allered bowel funclion, such as diia-
dispose l o moreserious illness, so patients can be reassured onceserious rhoea or conslipalion. The diagnosis is clinical, based on patienls in
pathology has beenexcluded. the right demographic group prcscnting with typical synlptoms in the
The pathogenesisof funclional bowel disorders is unknownand lheir abscnccof anyevident patllalogy. Symplomsaremorelikely to bedue
68 Disorders and diseases
 .,.. ..,..
. .. . . 'Ll~eay!~ads
uo!iedpsuo:, pus u a o q e ! p ~ a % s
01 pld0laha~8~!aq am qS!UOanUe ~ o r d a a aYHSPUB [LHS .Bupco~q
p m mmds ql!m panposse u!ed aql a m l a Leu [!o lu!uuaddad pvs au!
sahpeml y l ! ~uogsd!~surn'sjwoqm!pgue q l ! ~parean aq Leu uaoql leumu jo SauaIIxa 13aua1 L l d u ! ~sa!I!ICuIouqe pa1[ea-o~'ianamoq
.m!p s n ~ ~ a l e u d o ~ s!d ~
d su a m n lea!%olo~euusqda!leruo1duL~
a~~ 'uarjo 'samo~puLsiaplon!p pmoq leuo!lsunj aqr jo amos 103 lunoa3e
'Ldelaq~oqaKsdsaoprs'nua!lsdawos rdpq plno:, leql paq!lasap uaaq ahsq suo!lelalle lea!aolo!rLqd snolamnN
peqpmjo!q pus s!soudLq .uo!~sxela~ Sulpnlx! Ad~laq~ pna!nsqag A60l0!sh~dO~led
.uopedpsuoa a!uo~qao ~ ~ l n q p ~ uu wo a~ I I IOOI
! I al!qn\ .8u!lealq
pus p!ed leulmopqe a l e ~ e S 8 uaa s a q y ssama 'aqelu! p!ny pun aJqy '(lus
L&!1a!p Su!~olnilupus 'woldwLs ?r~!d!aaid leql spooj pue 1oq031e s!l!ln~d) Bu!q31! ~sue-!lada1 peal Lcm Bu!lvams pus uo!sual~a13u!qds
ssasra ilu!p!ohs Llle!aadn'dlaq uaijo n8usqa alQsaJ!l pun Llmala lvue ah!ssaaxa x s a n j s @ [ m ~ o l dss u m o q s! LBoloqled a!ueBlo
'lej osiuam~ea~joLs~su!em aqr aic nua!lnd Bu!~nssea~ a1qc.11suowapou ql!m leuc? I U U sqr
~ u! u!cd lu=lln?aX .uo!!!n?lal> ql!m
pue Moloyled a!uealo snouan Su!pnl~xa's!sou%c!puuy e 3u!qs!lqejsg pale!3osre u!cd l o 'lools Bu!rscd B[n~yJ!pJO u!eldma3 Lucu slua!led
lualulearl sawo~puLsle~~a~ouv
'Llleluamuadra pareB!lna~u!Bupq lie
a18 ~ l o lamoq
u U! SUO!IBIal)IIPpue Ll!l!lom leu!lsaru! '.ll!n!l!suas leIaas!n
q8noqrp 'uab~os!ppmoq 1suo!r3unjloj s s a l ay!a~dsou ale a l a u
. a ~ l n pols
a pue 'Ldoasomolo~~o Ldoasop!ou8!n Udo3sapua
lesLqdosw-onre8 'aseas!p >e![aoa JOJ nsal le3!ilololas 'uo!reu!u .8u!1uolqpu!uopqs
:mmwjoaBesscd ..
!(~0!1en3ena
araldua3u! '%u!u!egs Yausa~n a ) aacssed ,001s palalie .
!BU~IE!EUOJ 1001sp533!ls
:Lauanbxj loois pa~allu
..
:8u!mo1lo3aqljoaom l o om1 pue 'uo!leaa)apLq
- 'UO!lUalle pa~a!la~L~~a!dB'po~moau s ! p~l leu!mopqejosqluolu
od g lsval rv
.
[cxpau qaas 01 qdoad asods!pxd Leu Laql 'suorduLs annw IOU :lo sas!ldmoa ( ~ 9 1aw0lpuLS
)
op uolaej pa!So~oqaLrd J! u a q -=Isredas 01 preq am uo!re!~osss pmaq alqer!u!lsqmjoasuas e s a q 8 so861 aql u! paqs!lqcisa e!la)!l> leur
aldu!s pm1~i)~a'asne3qSnoqlle 'sa~!euuo!gsanb uo!ssaldap pusba!
-xus uoiaq8y uoas Lllelauail SI:PJOS!P IaMoq leuu!~aunjq1!m Ylu?!led
u o j a e j [sa!SoloqaLsd Lcw uo!rcd!~suoal o caoquc!a .uo!launj lou!lsalu! palarll: puu 3u!luolq
'u!ed leu!mopqe q~!m 'dno~aa!~nauae!p s!ql olu! l l ~ slua!lad
j Lucx
L ! y ~ e l ~ ~ ! s~! qs ~a u~oed J n s o ~ a ~ e p l e ~ u s u amolpuLslaMoq alqe1!1~1
-uadxa pue sa!pnls a!lemalsLs lnq 'uo!launj lamoq uo naaga rueay!ua!r
a~eq,L1qeqoldeualasq leu!)salu! luap!sa aql pus la!p uaamlaq suo!~
- a u q l l ~~ p c mlnqued
o ~ or h!n!~!suas pasealau! u o d a qua!lrd Luew
eloy lamoq paJaqls pue uo!)~aju!')a!a
'Ll!~!l!suasladLqlwaas!h puo Ll!l!low pala1lr:ioj 1uno33o .s~sdadsL;).l~y~l-llou
Leu '(ms'au!undXllLxo~pLq-s) uluololas b ! s n aroql L~ielna!ued s! auoipuLr lnuommoa aq& -LBoloqled luap!t.a Lou ]llalll!s 's~aplos!p
tSUWnaU aualua s!sUyu! jo Q!A!I~Bp a s s a a u ~.stua!red jo slaqmnu sno!las laqlo pus s!lp~seB'?seas!p laqn a!ld?d =!u!m rwold~uLsalaH
lleus u! pa1,Msuomap uaaq ssq uo!launjsLp a!)aq~sdruLspus l d s ~ slaplos!pleuaponpollseg
; . -: uo!jaLny ma?sLssnoNaua!~a~ua p u e almouolne palallv
.,, .1eo~qrsqr u! dmnl e asuas s]ua!led alaqm
u! pawnsuomapuaaq seqlappslq Xleuun pus dun1 aql ss qms
.,,:-,:~a 'sn3!la]sLq snqol8 ss qans 'samolpuLs 9 ~pus s ~'uo!~el!B~nhlp!3e lue3
'smao leu!~n~u!-enrau! alamm qloous jo U O ! I ~ U
palarlv
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sraplos!p l e I e q d o s a 0
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's!souBc!p rs!sss 01 yauyap LIICUIJOJ
uaaq aneq ' p a l a a ~ ~uca ~ s h sleu
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-naualu! pu!ds o ~ u onm!do snoua8opua asualal saluaa ~ s a ! u omag
~
sumnau Xlo]!q!qu! Lqaaqm '!lnm!:s lnju!cd JO Ou!re8 ~cu!dsqanaq]
L p d 'uo!ld?alad u!ed n a g s uolaej 1~3!%010qaLsdPUU 1~11111113
30 Gastro-oesophageal refluxand hiatus hernia

Acid In conrect with

aquamous cpithctlvm
/ o(OC50phse"5 Cllnical f e a t u r e s

heartburn and poselbly

-- A ngu1stion of
ga4t~0-0~50ph~g~IJ~n~tlon
Diaphragm
-- ~0"ZTlb"c.zS
Heartburn and
cplgsscric pain

. +z ,.~,
P,. ...
'DJephtigrnatl.~
:..-..-.; h ..i a .t u s. h e. r n i a
i.
Barrett'e oesophagus
Columnar cplrhcllum
(gasrrtc or InKestlnal type)

II II I/ lining lowcro~sophagua

Die m I conLra ti n

. .
k:..".. .'
p;i!~sg. fils:;
, -ecnla;(ra-re) ..:.
womcncd b ~ . , . : . ., r...

.
1ncn;ascdsbdomlnal pwssvrc
obcslty

.
..lyrng sup1nc
.. catlng meel* bdon; bcd

.. ,,,.. , , . . . .. .
Symptomsindicslingpossiblegastrodesophagealrefluxarecommonin Pathogenesis
Ihe general population. They vary greatly i n severily and the actual Tonic contraction o f thickened inuinsic circular s n ~ o o t lmuscle
~
underlying damage is also variable, so thai careful and thorough diag- closes off the gasuo-oesophageal junction, separating the gasuic
nosticevalualio~~
is needed toguidcireat~nent. and cesophageal luntens. Diaphragmatic musclc Bbres reinforce this

70 Disordersand diseases
sphincter function and the oesophagus enters the gastric fundus at an
angle; which also tends to seal the junction. Funhennore, while the
lower oesophagus and gastro-oesophageal junction remain i n the
abdominal cavity, . any . increase i n lntrs-abdominal pressure, which
lends lasqueezegarlriccontentsoutofthestomach,alsoimpingesonthe
iunction and counteracts thiseffect.
Stomach contcntsdo regularly reflux through thegartro-oesophageal
sphincter. even i n normal individuals. wheh the lower oesophageal
sphincter relaxes to allow food, drink and swallowed saliva to enter the
stomael~.Thisphysiological reflux is probably notharmful.
However, whenoesophagealanddiaphragmaticmuscletonedeclines
nnd intra-nbdominal pressure is chronically increased, for example, by
nhesity. 1p;ll-ticul;!rly i n older individunls, reflux may bccotne mnre frc.
qucol iandscvcre.
Rcll!$r o l g;lstric cnnvnts stimulates nerve endings in thc lower
nemph:\gus, which can cause pain and discamfort. Chronic stimulation
m;ny allso inulaase the sensitivity of nerve endings, causing - pain even
~
i n tile absence o f concurrent reflux. Severe and prolonged reflux can
damnze and emde the lower oesophageal . . epithelium
. and provoke
inflammation (oesophagitis).
Citronic rcflux can also induce metaplastic chanae . in the epithelial
lining of the lower oesophagus, which is normally a non-cornified
-
stratified rtlunmous e~ithelium.and can chanae to a simple columnar
epithelium, with gastric or small intestinal features. This gastric o r
intestinal metaplasia is known as Barrett's oesophagus, which may
undergo dysplssia and can go on tadevelop into adenocarcinoma (see
Chaptel.s4 & 381.
Themost likely causeofdamageduetorefluxisgastrichydrochloric
acid (HCI), although other gastric contents, such as enzymes, and bile
acids from the duodenum, may also contribute. Bile acids, chemically
altered by acid, may be particularly imponant in inducing metaplasia.
dyrplasia and cancer.
Helicobaclerpylori infection tends to reduce gastric acid secretion.
particularly whenitcauseschronie gastritis,so that, theoretically, eradi-
cation o f hi. 10'lori infection, which reduces the risk o f gastritis, peptic
ulcer and onslric cancer, may actually exacerbate acid reflux (see
chapter31)
--
Reflux can be further aecravated bv thedevelo~mentof a hiatus h e r
nia, which forms when part o f thestomach herniates through the hiatus
(or gap) in the diaphragm through which the oesophagus enters the
aWamen.Araresult,thehemiatedponionofthestomachcamerroliein
thc thnr:tx. Ilsunlly the gastm-oe5ophngealjunction and gastric cnrdia
- -
slidc opwards. cl.eating a slldinc hiatus hernia, which compromiser
sphincter function by straightening out the angle of the gastm-
aesaphngeal junction and removing the diaphragmatic contribution
to sphincter function. Furthermore, as thejunction now lies within the
thorax, which has a law pressure, increased inlra-abdominal pressure.
transmitted through the stomach, tends to force gastric contents
through the rphincrer.
Asliding hiatus hemiaeanrpontaneously reduce, for example, when
.-
lying flat, and by reducing inlra-abdontinal pressurc. which encourages
the stomach toreium to the abdomen.
Less frequently, a fold of gastric cardia may herniate through the
diaphragmatic hiatus alongside the mophagus, creating a mlllog
hiatus hernia, whichcan becomestrangulated.
Clinical lealures
Heartburn is described by patients as an acid, buminp sensationin the
.-
e~izaslrium or lower chest, often localized to iusl behind the ncmum
(relrosternnlly). I t is the typical symptom of gaslro-oesophagealrcflux.
Patients may also complain of eplgastrlc paln and dyspepsia aggra-
vated by meals, alcohol and lying flatin bed.
Stnmach conkntn may reflux into the mouth and occasionally be
aspirated into the larynx, cauringeough and hoarseness. Reflur may
also be completely asymptnmatlc and, paradoxically, the development
of Barrett's oesophagus, which is relatively resistant to acid damage,
may improverymptoms.
Diagnosis
Upper gastrointestinal endoscopy is the main diagnostic test. Bioprics
are fakentodistinguish oesophapitir and Bamtt'roesophagus hlriolog-
lcally. A barium swallow can demonslrate hiaNr hernia and reflm o f
stomach contents into the oesophagus, as well as revere d e w o f
oerophagitis.
Oesophagcaland gasl~icp H can be measured directly visa nasogas-
trically placcd sensor Episodes ofreduce pHcan then becorrelated with
symptoms and in the Bernstein test, acid is infused into the lower
oesophagus, i n an attempt to reproduce the symptoms and confirm the
diagnosis (seeChapter46).
Oesophageal manometry helps to distinguirhdysmotilityfmm reflux
(seeChapter46).
Treatmenl
Lifestyle changes such as having smaller meals, giving up smoking.
reducingalcohol intake, losing weight and sleeping withthe headofthe
bed raised can effectively reduce symptoms. Simple antacids arr also
effective, althoughselective histamine HZ receptor antagonists, such
as ranitidine, and the proton pump inhibilors, such hs omcprazole;
which irreversibly block acid producti~nby parietal cells, an the most
effectivelreatment.
Hiatus hernia usually does not require specific !xeatmenr, such ar
nurzery, although it cnn be repaired by fundopliestlon, whereby the
gastric fu'ndus is partially wrapped around the lower oesophagus.
strengthening the sphincter and preventing migration Wough the
diaphragmatic hiatus. Fundoplicaiion can also be used to weat
intractable refluxin the absenceofahiatur hernia.
Baneu's oesophagus is premalignant and, therefore, regulru.
endoscopic surveillance with biopsies to detect. dyrplaria is'
advocated. If dysplasia i s detected, the patient may undergo
oesophagectomy.
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Pathogenesis
~ ~ i d ~ n r t r i c a c i d ( ~ ~ l ) ~ m d u c t i a n i s s tby
i mgastrinsecrsted
ultd
.
by O cells in the antrum.. acetylcholine -
released by the vaaus nerve and
histamine released by entem-chmmaffin-like (ECL) cells. ail of which
stimulate reeepton on acid-pmducingparlelalcells.
-
Duodenal ulcers areexceedinely- rare in .people . who do not produce
gastric acid and multiple, recurrent ulcers occur when acid production
is greatly increased, for cxample, by gastrin-secreting tumours (see
Chapters 16 & 38). However, gastric acid production is usually low in
peoplewith gastric oiccrs and this may betheresuitofchronicgastritis.
- ..
Prortaelandinr.Thc riskof oeoticulceris increased in vatients who
usenon-steroidal anti-inflammatorydrugs (NSAIDs), inciudingarpirin.
which mhibil prostaglandin production by epithelial cells. Furlhermore
the r sk cf .peptic
. ulcer is reduced by an arlificial .prorlag'andin
- EZ ngo-
~nist,~n~isol~rostil.
Smoklna, -
. slcohol. nenetlcs and s t r s s . Other risk factors include
smoking tobacco and drinking alcohol, although the mechanisms by
which these act areunknown. Inaddition. thereisasmall genetic - vredir-
position. There is little evidence that stress or lifestyle factors play any
.
role.
Helicoboeterpyiori. Spiral bacteria in the stomach had been noted for
over a hundred years, yet thcir significance only became apparent in
1982 whenWarrenandMarshallculturcd&pylon'from I I patientrwith
garaitis and Dr Marshall then dcmonshated that it caused gastritis by
intestine
. .n test dare himself. He was subsequently . . curcd by antibiotic
treatment.
H. pylori infection is present in the majority of paticntr with peptic
ulcer, although only about 15% of infected people dcvclop ulcers.
Eradicating H. pylori infection permanently cures peptic ulcer in the
majority of carer.
H. pylori infection of the gastric antrum, which stimulates gastrin
production, causer the greatest hyperacidity and duodenal ulceration,
while infcction ofthe gastriceorpus, wheremart parietal cellsare pres-
ent, tends to rcducertomach acid production and is associated with gas-
tritis, gastric ulcer, gastric cancer and gastric lymphoma.
~ ~
Strains of Kbyloylori vary in pathogenicity and virulence, determined
- clusters.Thur both host factors and thebacler-
by various bacterial gene
iai strain determine theoutcomeof infection.
Peptic ulceration results fmm an imbalanee between gaslroprotec-
live fnctors, such as the mttcur layer and prostaglandins. nnd aggresrivc
factors, such us stomach ucid and the effecls of smoking, alcohol
and NSAIDr. H. pyiori infection dramatically tips the balance against
protection.
Clinical features
Epigastric pain, often aggravatedby hunger or by meals and relieved
by antacids, suggests peptic ulceration or gastritis. There may be
nausca, vomiting and anorexia. Anaemia may develop from chronic
haemorrhage.
Peptic ulcer may cause major acute bleeding, leadingto haemateme-
sb andlor melaena, which is a msdical emergency. Similarly, peptic
ulcers may perforate the stomach or duodenum, causing perltonlllr.
Peptic ulcer may penelrate into the pancreas and cause pancroatills.
Scarring of the duodenum by chronic ulceration may cause intestinal
obstruction.
Diagnosis
Uppergasfrointestinal endoscopy is the bestdiagnorticest. Ulcencan
also be dctccted by barlum contrast X-rays.
H. pylori infcction can be diagnosed serologlcally, orby the urease
breath t a t , in which I1C-labelled urea is taken orally and themulling
"CO, released by the urease enzyme is measured on the b m h (see
Chapter 46). H. pylori organisms
~ ~ . can be demonstrated hislolonlcall~
" .
and the urwse enzyme can bedeteclul using a simplecolorimellictest
(CLOtest,forCompylobocfer-likeorganism) inmucosal biopsicstaken
duringendoscopy (seeChapter46).
Gastric ulcers may be caused by carcinoma or lymphoma, io they
must always be blopsied locheck that they arenol malignant Duodenal
ulcers are very rarely malignant.
Treatment
Surgery. Exccpt ioremergencies, surgical Malmentir now obsolete.
Partial gastreclomy to remove pan of the gastrin-producing. G-cell-
rich antrum was once routinely performed. ~ n o t h eapproach
i was to
selectively section branches of the vagus nerve (selective vagotomy)
that stimulated acid secretion, sparing fibres that controlled th.ipyloric
sphincter.
Simpleantacidsandanticholinergirrarereiativeiyineffecti~e~ha~e
.
tobe taken frequently and produceside-effccts. . .. . ,
The first effective medical Malment for peptic ulcer emerged when
rclcctive histamineH2receptorantagonisls weredeveloped.Forsome
time drugs such as cimetidine and ranitidine were the mbst widely pre-
-
scribed medications worldwide. . .
Proton pump inhibitors, which irreversibly block acid production
by parietal cells, have ovcnaken the HZ receptor antagonists, and
omeprazole, the first proton pump inhibitor, accounts for the greatest
worldwideexpenditureon a single dmn. .
Helicoboeterpylori eradlcatlon provides a permanent cure for most
cases a i peptic ulcer. Successiul eradication requires combined ther-
apy with an acid suppressor and two or three antibiotics. Most standard
renimcs
. -
are succcslful in ur, to 90%ofcases. althoueh antibiotic resist-
ante is cmcrging.
Emergency treatment. Bleeding or perforation may q u i r e emer-
gency surgical or endoscopic therapy, such as injection of adrenaline
around an exposed vessel, to arrest haemorrhage.
Peptic ulcer andHeiicoboererpylon' 7 3
 4 m u m
~g gss a" 9%0 i a9S S o g P %m :-+
%F-=
,3,rf; $erst g ~ x$%$
$ z z 2 : :SB 3cs ;
--c
z ol . es =$ qg = ; 8~ :;; z z K a
C > Z g = Eli; $2; !: H5: q " " e g O X s ,
r --kr. ;?, L1=
-2 = r = p - =. r ; . mjg 2% a3 i
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r.0 l 0o ;$ - 2 5 g
9
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(ETEC) secrete heal-sensitive or heal-stable entemloxins that drive Gastroenteritis can also cause prolonged lactose intolemna and
excessive intestinal secretion. Staphphylococcus aureus and Bocillus post-InfecUouslrrfLable bowelsyndmme.
ceratrr produce emetogenic toxins that are absorbsd systemically and
stimulate the vomiting centre. Some toxins cause intestinal inflamma- Food polsonlng
tion: forexamplc.Lecytotoxin secretedby Closrridiumdificiie. This is the commonsyndromeofgas~oenteritiscausedby contaminated
~ d h e s i o 'nd
n persistenceinlheintestine.~heflowofluminalcon- food. Usually spores or organlsms that multiply i n the intestine are
-
tents throueh the intestine limits harmful microbial effects and some
orpnnisms overcome this defence mechanism by producing adhesive
ingested. I n cases where preformed toxlns are ingesled, symptoms
occursooner, within houn (see table within the figure),
nrue1o1.c~ ( ~ ~ d l ~ c s ithal
n s )intcmct with proteins on the hart cell mrfacc.
Multiceliulnr uarasites. such as worms, may use mechanical hooks and Traveller's diarrhoea

-
suckers to resist being swept away.
InvsslonofenlthelialcellsandmucosaldamaCe.Enrempatho~enic
-
E. coli (BPEC).Co,npylobuererjejuni. Salmonella and Shigella species.
. -
loboerer. Shigella. Solmanello and E. coli are the commonest cause,
..
Wiwio parniraerr~olyricz,.r,viruses such as cytomegalovirus, and amoc- followed by vlruses and protozoa (Giardia lambiia and Entamoeba
b:be [Crtrrsrto~i~a itirfoiyticd), invade the epithelium, cnusing u1cer;ition hisrolyficu).
and inflammation. I n bacterial, viral and amoebic dysentery, the stools
contain blood and leucocytes and there is a systemic inflammatory Endemic and epldemlc diarrhoea
response. resemblinginflammatory boweldisease. Oulbrcaks ofgastmenlerilis occur i n nurseries, schools, camps andhos-
Invnsion tlvough the Intestine. The dysentery-causing bacteria. E. -
uitals where overcrowdinp. and communal facilities allow raoid roread.
Virusessuch astherotavirusandtheNorwalkagentarethecomon~l
hisrolylico and Solmonelb typhi. the cause o f typhoid fever. may cross
. .
cause. Wan. floodsand earthquakes can cmleconditions foroulbrraks
theepithelium and causelocal anddistant disease.S. ryphiinilially mul-
o f cholera and typhoid. These outbreaks, aggravated by rcarciiy o f
tiplies in intestinal lymphoid tissue; however, the most seriouseffectsof
lypl~oidresullfromryrtemicbacteraemia.lnvarionisanessentialstepin clean drinking water and basicmedical care,cancausegmtsuKeering.
the lifecycle ofsome parasites and worms. ~.
lmmunocompromised patients
Clinical features Diarrhoea is common and often chronic in oatientr with actluired
Typically
~. ~
infection rapidly follows ingestion of contaminated food or
~ ~
immunedeficiencysyndrome(AIDS)andinthoscwhoareimunosup-
drink and is short-lived andseif-limiting. pressed. Organisms thal are normally non-pathogenic, such as Cryp-
Vomitlnc-may. be induced directly , - by- ernetocenic
. enterotoxins and losparidin and microsporidia, can caureopporlunirtlediseare.
is also medialed by efferent nerves stimulated by intestinal distension
and mucoral damage. Serotonin (5-hydroxylryptamine. 5HT)released Antibiotic-associated diarrhoea
fro~nneuro-endocrine cells may stimulate the chemoreceptor trigger Antibiotics alter the normal balancc of enleric commensal bacteria
zone (CTZ)(see Chapter26). and may cause diarrhoea. This is frequently caused by overgrowlh o f
Diarrhoea is caused by numerous facton: toxins stimulating secre- toxin-producing Closhidirtm discile, which can cause severe inflam-
tion; neuro-endocrine reflexes stimulating motility and secretion; mauon(pseudomembmnouscolitis).
inflammntion causioa " exudation o f fluid and cells into the intestine;
and aceduced digestiveandabsorptivecapacity forrugan (particularly Diagnosis
lactose), creating an osmotic load (see Chapler27). Blood and leucocyles instooldistinguish inflammatorydiarrhocafmm
Abdominal pain is caused by distension o f the intestine, muscle othercauses.
spasmsresullingfrom hypermotility, and inflammatorydamage to the hlicrobiological diagnor:~may bc netcssaq for public health rea-
mucosa. sons, or lo d:agnosc lhe caurc of persistent dimhoea. Rotavirus is
Fever and other systemic symploms are unusual with simple gas- detcclcd i n the stool by clcctron microscopy end amocbae can be
troenteritis or food poisoning, although they are frcquent i n bacterial or detcclcd by light microscopy. Bacterial pathogens q u i r e stool culmre.
amoebicdysentery.They suggest invasiveinfection. while giardiasis rcqu:res jejunal aspiration and microscopy to make
Deltydrnlion may causc hypolenslonand renalfailure. thediagnosis
Hearnolytic-uraemic syndrome i s a life-threatening syndrome
causcd by enterohaemorrhagic E. coli (EHEC) serotype 0157: H7. Treatment
which is endemic among cattle. Outbreaks have often been traced to The mainstay o f treatment is to malnfain hydration, either with oral
inadequatcly cookedground beef. Vomitinganddiarrhoeaarefollowed rehydration solutions orlntravenous fluids (seechapten 23 Br27).
by high feverand damagelo bloodvessels,andthekidneys may bedam- AnUbioticslikcclprofloxacincanreducethedurationand severilyof
aged
. by . theEHEC cyloloxin. Antibiotics may aggravate
~-~ thesyndrome. bacterial gastroenteritis but are usually unnecessary. Giardiasis ~ n d
Reiter'ssyndrome andother reactive arlhritis syndromes, character- amoebiasis areeffectively treated with metronldazole.
ized bv combinations o f arthritis. urethritis. coniunctivits. uveitis and -
Because diarrhoea is a host defcnce mechanism aeainst infection.
variousmucocutaneouslesionsmay followbaclerialdysentery. antidiarrhocals likeioperamide should generally be avoided.
Guillain-Barrd syndrome, caused by immune-mediated demyeli-
nationofperipheralnerver, may follow Compylabacrerinfection.

75
Ga.~rroenteririrandjoodpoi.~~ning
I n addition to gastroenteritis and food poisoning, microorganisms cause
various othergastrointeslinal system-relatedillness. Furthermore, there
-
is a laree resident or commensal .population
h e ~ l t and
h disease remains unknown.
. o f bacteria, whose role in
Commensal llora
Bacteria colonire the entire intestinal tracl, with the greotest number.
10'2/g,in the lnrgeinlestine.They apparenlly causenoharm andpoten-
tinlly benefit thc host, possibly by excluding pathogenic species. There
;we nvcrSt10 llillcrenl spcclcs and the dominvnl specics and gcncr;! arc
,Tsclrericl,in coli. U$dobocferio andLocrobocillus.
E, coli. Enremcoccus, Srreprocohus, Closlridio and others retain the
ability to cause disease. either by -
. acquiring
. virulence faclors, which are
usually plasmid or phagc DNA-cncoding toxins, adhesins, etc.. or by
exploiting reduced host defence. Closfridium dificile, for example.
causes diarrhoea when antibiotic ueatmenl upscts thc normal microbial
populalion, allowing it to produce its cytotoxin.
Bacterial overgrowth
The small intestine normally contains very few bacteria because o f thc
constant movement o f foodand theeffectof antimicrobial proteins pro-
duced by Paneth cells, for example. Bacteria overgrow, however, when
the normal anatomy is disrupted, for example surgically, or where dis-
eases like sysfcmicsclerosiscausedysmotilityand stasis.
Thebacleriamerabolizenulrients, thusdepriving thepatient.andpro-
duce excess intestinal gas, damage the mucosa and cause malabsorp-
lion.Symptomsincludeabdaminalpainandflatulence.Brealhtestscan
be used to establish the diagnosis. Antibiolics and corrective surgery
may benecessary.
Worms and parasites
Mulricellular worms and parasites commonly infest the intestine.
particularly where sanitation is poor. Hookworms. (apeworms and
round!vorms can remair: i n the intestine for many yean, causing
chronic dianhoea, malabsorption and anaemia. Roundworms invade
the intestine and migrate through the lungs
- as part
. of their life cycle.
causing systcmic disease. The pork tape-worm, Toenia solium, leaves
encysted eggs throughout the body, causing cyslicercosir. Treatment
requires helminthicides such as albendazole.
Candidiasis
Co~zdidnololbicn~zs,
theonly major fungal pathogen of the intestinal trilcl.
. .
is a commensal i n most oeoole. Reduced immunilv. .
.. as i n neulrooenia..
diabetes mellitur, stetoid usc or acquired immune deficiency syn-
drome(A1DS) allows Condido to invadethe superficial epithelial layers
of the tongue, mouth, pharynx and oesophagus, causing inflammation
and pain. Diagnosis is confirmed by detecting fungal hyphaein cytolog-
ical specimens, or by cullure. Topical or systemic antifungals such as
nystatin orfluconazoleareeffectivetherapy.
Whipple'sdisease
This rare, chronic, intestinal infection caused by Zhpherymo whippelii
typically affects middle-aged Caucasian males, resulting i n diarrhoea.
~labsorptionandfevcr.Duodenalbiopsyshowrmacmphagesconlain-
ing mnlly bnc1eri.a and thetreatment isa prolongedcourseofnnlibiolics.
Tropical sprue
Chronic diarrhoea and malabsorplian, associated with enteric infection,
which used lo be common in long-term rcsidents of the tropics is now
disappearing.Duodenal biopsy demonstralcsblunt villiand hyperplas-
liccrypts. resembling cocliacdiscnsc, and antibiotics mcurativc.
Systemlc Inlecllon, abscesses and masses
Intestinal bacteria can migrate into the portal veln and f o m llver
abscesses, while some entcric organisms, especially. slreotococcifrom.
the mouth and gut, can cause infective endocardllls. Therefore, p p l c
..
with valvular heart disease have .proohvlactic antibiotics before dental
and same endoscopic procedures. Salmonella ryphi causes syslemic
inleclion and in immunocomprnmised patienu. less virulent, non.lyphi
Solmanella species can alsocauseosteomyellUs. bralnabscw,endo-
cnrdilis.etc.
Enlamoeba hirrolyfica causes liver a b s w s and abdomind wall
masses (ameoboma) as well as acutedysentery. . .
Echinococcus species (hydatld worm), acquired from shecp and
dogs,invadetheinlestinalwall,spreadsystemicallyandformlarge,egg-
filledcysts i n theliver, lungsandotherorgans. ...
Liver abscesses typically cause abdominal pain, fever and abnormal
blood tests, although they may be asymptomatic. Ultrasound and com-
puarizedtomography (~~scanning&usedtomakethedia~nosisand
- - . are used l o &Ibacterial
antibiotics, with or without sur~icaidrainage.
and amoebic abrcesses. Hydatid dise~erequirrssurgicaltreatment.~
Perl-anal abscesses, arising from anaerobic infeclion o f the deep
anal glands, are relatively common and are mated by incision and
drainage and antibiotics. Recurrent peri-anal sepsis may indicate
. .
anorectal Crohn's disease.
Inflammatory bowel disease
-
I B D is notcaused by a discreteintestinal infection,although bothulcer-
alive colitis (UC) and Crohn's are lriggered by cnvirontnental factors
lhat arc almosl certainly enteric microbes or their ~ m d u c kAntibiotics
.
aregenerally ineffective in UC, but do improvcsomcforms of Crohn'r
disease,andadministering pmbiolics,whicharclivccomensalbacte-
ria, ameliorates some forms of lBD.
Intestinal infection with Mycobocrerium fuberculosir and Yerrinia
species can slrikingly
- . resemble ileoc~ecal Crohn's disease. Similarlv.. .
bacterial and amoebic dysenlery, cytomegalovirus and herpes simpler;
virus infection can cwse bloody diarrhoea. abdominal pain and intes-
tinal ulceration that can be confused withUC.
Clinical presentation anddiagnosis
Chronic inteslinaliniectionscancauseabdominalpain,dimhoea.flatu-
lence, weight loss, malabsorption andior anaemia.
Stool culture can detect bacterial pathogens and micmscopy can
detect ova, cysts and parasites. Radiological imaging, endoscopy with
biopsy and culture, blood culture and serological tesk detect deep-
seatedabrcerreranddislanlinfwtion. ; . ' ,' j .~~~ !'':,;:!>': ':; . ,;
Treatment
The potential role of enleric commensals i n health and disease is
a reminder that anliblotics should be used cautiously. Conversely,
live bacteria or probiollcs may be used therapeutically i n certain
circumstances.
Selecllve entcric decon(aminaUon, with non-absorbedantibiotics.
such as neomycin and norfloxacin, cen be used before IntesUnnl
surgery and i n chronic liver disease, l o e a t hepatic encephalopalhy
and lo prevent spontaneous bacterial peritonltb. The intestine is not
sterilized butthe balanceofspeciesir altered.
Gosrminlesrinal rprem infections 77
Two diseases constitute idiopathic inflammatory bowel disease (IUD):
.
ulceralivecolitis(UC)and. . . .
Crohn'sdisease~CD).Thevaredistinct but
similar, and both are chronic, relapsing and remitting conditions.
Together they affect about 150/100000 o f the population i n Western
counlrics.
Aetiology
The intestine is constantly i n contact with the harsh digestive environ-
ment and-may be regarded as being in a state o f chronic low-grade
inflammation. Challenges to the intestine include p H extremes.
mechanical trauma, ingested bacterialand viralpathogensand toxlns.
and the microorganisms that comprise the resident commensal
microflora o f the bowel. Immunological reactivity may, therefore.
develop tocomponents o f thedietor themicroflora.
The aetiology o f 1BD remains unknown and it probably results from
one or more envlronmental trlggers acting against a background of
inherited gcnclicpredisposllion.
Recently. C D of the terminal ileum has been genetically linked to
-
mutations i n theNOD2eene. which is ~robablvanintracellularrecerrtor
for bacterial cell wall components, expressed i n monocytes and Paneth
cells.
Furthermore, experimentally disrupting the immune system i n
laboratory animals often leads to intestinal inflammation, which only
develops when enteric bacteria are present.
Uicertnive colitis and C D may have a number o f differem primary
c;n!ser.a l l rcntlting in ri~nil;~rclinicnl
and pathological outcomes.
Macroscopic pathology
Ulcernlivc colitis only nffcctr the 1.1rge intestine and does not extend a,
thesm;~llintestine.Furthermore,therectumisslmostinvariablyaffeeled
and infln~n~nntion extends proximaliy la avariableexlent.
Crohn'a discnse can nifect nny part of the intestinal trael, aiti~oclgl~
thrcc p i ~ t t ~ ~ ~) ~ocs~ l ~ ~ n terminal
i n x l c : ileal inflammntinn, otlilis ;xnd
nnnrect:~li~~fl;~mm;ttinn. An individual patient could have one, two or
three ol'lhcse ;wens niiected, in any combination. Furthermore, while
infl.nm~n;ttion in U C is contiguous, extending for a variable distance
from the rectum. in CDthere mav benormal areas inters~ersed between
inflsn~cdsegmenls:'skip lesions'.
Microscopic pathology
The mucasd is ulcerated and there is an inflammatory reaction in the
laminnpropl.ia.
I n UC. there are reduced numbers nfgoblet cells (gohlet ccll dcplc-
tion) and increased numbers of Paneth eells. Furthermore, while nor-
mal colonic cryptsareshort andstraight, inUCthey aredistorted and
branched. Another typical feature is a collection of neutrophils within
..
thecryrrtlumen, formingcryptabscwes.
. ~.
Within the lamina propria there are increased numben of inflamma-
tory cells.Tl~cirillammato~reaction in UCdoes not extend deeeer than
the lamina propria. I n contrast, in CD, inflammilion typically extends
tmnmmurnlly through the wall of the intestine. I n addition. there
itre gr:~nlulatnas in CD, consisting of activated lymphrlcyles ilnd
macrophnges.
Clinical features
Colitis (UC ar Crohn's colitis) causes diarrhoea, which usually con-
tains blond i l n d p ~ ~ s o r m u cIn
~ snddilian.theremay
. benhdonlinnl pain
and n~nlaiscduclo thesystemicrespanaela inflammation.
I n CD, terminal ileitis may cause diarrhoea or constipation, abdomi-
nal pain and a palpable Inflammatory m a u i n $e right iliac fms8.
Chronic terminal ileitis may interfere with absorption o f dtamln
B,t and bile salts, causing anaemla and predisposing to gallstones.
Inflammation may also cause strictures, resulting i n inteslinal
obstuction.
I n CD, because the inflammation extends mnsmurally, intestinaliis-
tulaeanddcep-seated abscessesoccur.
Thesystemic inflammatory responsechdracterired by fever,malabe
and welghl loss tends lo be milder i n U C and more pronounced in
CD.
Extra-intestinal features o f I B D include skin rsshcs. such as
pyoderma gangrenosum and erythema nodosum, srthralgia and
arthritis (in up to 15% of patients), and inflammation o f thc eyes
(Irllls and uveilis). Apthous ulcem i n the mouth are pMicularly
common.
Longstanding UCpredisposes tocolmcancerandprimary sclerosing
chalangitis (PSC) occurs i n a b u t s % ofpatiena with UC.
Diagnosis
The mainstay of diagnosing colitis is to perform sigmoidoscopy and
colonoscopy, with mucosal biopsies10 histologically confirm thediag-
naris. A barlum meal and rollow-thwugh examination visualizer 6 c
terminal ileum, demonstrating inflammation, fistulae and stricmw.
TherearenospecificbloodlestsforUCorCD, butanaenia,vitaminBII
JeficienCy, and raised inflammatory marken, such as the C-readlve
protein, are common. 11 a proportion of U C patiena, antineutmphil
cytoplasmic antibodies (ANCA) are found, while i n CD, antibodies to
Soechrrmmyce.~ccrevi.~ioe (ASCA) may bedetected.
Treatment
- 5-Aminasalicylic acid (SASA, mesalarine). This camp?und hw a
lrrcal anti-inflammatory action, particularly in the colon, and can be
administered rectally or orally. Slow release formulations (pentara or
asacal) dissolve in the colon, while conjugated farms o f SASA (rul-
phasalarine, alaalazine and balsalaride) are enzymatically released i n
thecolon by bacterin.
Corticnslemids. Steroid treatment is usually effective at inducing
remission and is used pnnicul.~rlyto treat acute exacerbations. It may be
administered parcnlcrally, orally or rectally. Prolonged systemic steroid
treatment has many advcrsc cffects, including worsening osteopomsis.
Uudeso~~ideisasynthelicstcroidthatisnpidly metabolized by theliver,
resulting in low systcmic levcls, and it may bcpillticularly effective far
terminal ileal CD.
In~munosupprersives. Dmgs such as azathioprine, bmercapto-
purine and methotrexaa are used, parricularly when freo!~ent relapses
necessitate repeated steroid use. Antibodies to the eyiokine Nmour
necrosis factor a (TNFa) are dramatically effective in a proportion o f
.
people wilhCD.
Antibiotics. Metronidazolc may induct remission i n some cases of
CD but is not effecliveinUC.
Probiotics. Live bacteria, to restore the normal balance of enteric
flora, are used with somesuccess.
Surgery. Panprnctocolectomy (removal o f thecolon and rectum) is
cur;tlive lor UC und is used is a lasl resort for Severe disease or where
dysplaaia develops.CD almost invariably recunafieraurgery; therefore
the use o f surgcry is largely liniited to, for example, relieving aympto-
maticstrictures ordrainingabscessses.
Ulcerurive coliris and Crohn'sdiseme 79
Coeliac disease is also known as glulen enteropathy because it is
caused by immune reactivity triggered by glulamine- and proline-rich
glulenproteins,found mainly inwlleat,rye, barleyandoa(s.Theillness
may become apparent at any age, from infancy to old age. may remain
asymplomalic.and may be detected incidentally.
Aetiology and pathogenesls
The healthv small inlestinal eoithelium is maintained bv constant cell
turnover, nnd the balance between normal shedding a f old epithelial
cells at lhe lips o f villi and the formation of new cells from stem
cells i n the crypts maintains a 2: 1 ratio between villus height and
crypl deplh. The lamina propria contains a small number of lym-
phocytes. m.ncrophages, fibroblasls, capillary endathelial cells and
other cells. The epithelium itself contains a population of resident
intrnepilhclinl lymphocytes that maintain surveillance against
potenlinl pnthogens.
In genetically susceptible individuals, immunological reaction lo
gluten-derived gliadin peptides develops upon dietary exposure. The
exncl genes cm~singcoeliacdisease have not been identified but cenain
r n ; ! j ~ r ~ h i s t ~ , c o t ~ ~ ~complex
n ~ b i l i t ~(MHC) class I1 gene alleles arc
strongly~- associated with the condition. Early dietary . exposure
. to gluten.
panicularly after weaning from milk, may increase the risk of dcvelop-
ing thedi.;e:trc.
The ilhifluitaus cellular enz.yme tissue lransglulaminase (CCG).
wllicll mw~n:tllycrr,s.;-linksglulsn~ineresidueswithlysineincon.ective
tissueprolein.i,plnyr an essential ralein the pathogenesis, byconvening
glutnmineresidues in nativcgliadinpeptides lo glutamate,creating more
imm~~nogenicpeptides. Howevernodisease-associaledpolymorphisnis
in thcf7%gc~~el~nvc been irlentilied.
Lymphocytes
. . . - ..
react with the modifiedaliadinoe~tides an the surface
o f nntigcn-presenling cells and proliferate, increasing the number o f
intrnepithelial and lamina propria lymphocytes. Activated lymphocytes
secrete inflammalor] mediators, including the cytokines, y-interferon
and tumour necrosis faclor u(TNFa), recruiting and aclivaling mare
inflammatarycellr.alteringtheproliferativcrsteofinteslinalepiihelial
stem cells, and increasing the rateofprogrammedcell death (apoptasis)
i n mature enterocytes. This creates an aedematous, swollen intestinal
mucosa, wilh short, thick, blunt villi and deeper than normal crypts
(subtotal villus atrophy), and the reduced epithelial surface area
and compromised epithelial digestive and absorptive capacity leads to
mnlabsorptian.
Theconcentration of dietarygluten is highestpmximally in the intes-
tine and therefore caeliak disease affects the duodenum and proximal
jejunum mast severely.
Clinical features
Coeliac disease can become apparent at any age, allhough most
cases are diagnosed i n enrly childhood or in middle age. Coeliac
<lisc;~scrimy rc~nsincli~~ic;\lly
silent and people with circu1.1ting inpti-
hodies to ITG, hut no avert palholagy, may be considered l o have lnlenl
disc:lsc.
Malabsorption causes diarrhoea and weight loss. Inability lo
absorb fats rcsults i n steatarrhaea, wilh bulky, pale, foul-smelling
stools that float in water, because of their high fat content. Anaemia.
caused by iron deficiency is frequent. Malabsorplion of calcium and
vitamin Dincreaseslheriskofdevelopingosleopomsls.
Nutrients that are mainly absorbed i n the proximal small intwlinc.
such as i r o n and calclum, are most affected by coeliac disease, while
nulrienlspredominanlly absarbedinthejejunumandilel;m,suchasfollc
disease.
.-
acid, vllamln C and vilamin B,, are affected onlv i n more advarced
Patients may complain o f abdominal pain and U R d n e v and, for
- -
unknown reasons, neurological com~lalnts,ranging from mild.perioh- .
era1 neuropalhy to more severe central nervous syslem disfurtmce,
occurinuoto IO9oof oatients.
Asmall number of peopledevelop a blistering rashcalled dematitls
herpetitormis,associatedwithantibodiesto~TGreactingwihafamof
thisenzyme indermalcells.
Possibly as the result o f chronic inflammation, people with uncon-
trolled coeliac disease are at increasedriskofdeveloping intestinal neo-
plasms, panicularly intestinal lymphoma. This risk is substantially
reduced by slricl adherenccloagliadin-freediet(seeChapter38).
All thesesigns and syrnptamsdisaoDear
. .
Ihediet and reappear i l i t is reintroducrd.
-
.. when eliadinis omilted from
Diagnosis
Uncxplatned ~nnemi;landvagueabdominal andncuralogicalsymploms
shobld prompt the physiclan to check for cocliac disease, as it is often
missed and is parliculrrly common in some pap~~latians, such as people
originating from western Ireland. Conversely, i t remains rare among
Africans.
Circulating antibodies lo tTC otFer an excellent ser~logicalmarker
of coeliac disease, with sensilivity and specificity approaching 100%.
Thetest wasfir~tdescribedasdetectinganunknownanti~kinthelining
.
of oesophageal smooth muscle (endomysium), hence lhe term anti-
endomysial antibody. This test replaces the anligliadin anti-body lest
lhathaslowersensilivily and specificity. Serological tesls rely on dcrecl-
ingimmunoglabulin A(1gA) intibodies andkunreliable in theI : 500
individuals with selective IgA deficiency..(seechapter 18).
Upper gastrointestinal endoscopy and duodenal mucasal blopsy, to
confirm subtolal vlllus atrophy and lymphocytic infilmtion, is per-
formed before treatment, after initiating a gliadin-free
~ - diet, and azain-
afterreinlroduclionofagliadinchallengediel,andislhegoldstandardof
-
diagnosis. With the advent o f reliable serological testinn,
-. it is now used
lersliequently.
Rare forms o f small intestinal disease, such as Whipple's disease.
Crohn's disease o f the small intestine and troplcal sprue may mimic
coeliacdiseaseand hereaduodenalorjejunal biopsy may @panicularly
hclpful i n thc diagnosis.
Treatment
The mainstay o f trealment is for patients to follow a gluten-free diet.
Wheat, rye and barley proteins are present in many ready-made meals
andsnacks, sothe helpaf s professional dietician ahd a oatients'asraci-
ation,such as !he c o c ~ i a c s h c ~ien~t yh e ~ ~ , s h o ube~nlisledto
ld main-
tain vigilance. I n severe, uncontrolled coeliac disease. acute intestinal
inflammation can be treated with conicostemids, but this is hazardpus
and rarely indicated.
Coeliac disease 81
m
N

: Basel mcUlbollc re* (BMR)

0
CL
9s
L
P
I

BMI
Obesity
Obesity is arguably the most prevalent health problem i n the Western
-
world and ils incidence is increasing worldwide. Body -
. weight is tighlly
- .
regulated so thatst~ategiesto gain or lose weight muslovercomestrong
homeostatic mechanisms (reeChapterZ2).
Measuringobesity
Obesity implies anabnormal ratioofadiposetissuetoleanmarr(mainly
bone and muscle). The body mars index (BMI) (weighl in kg/(height in
m)>) is a practical guide to healthy body weight. The normal B M I is
between 18and25; over25isoverweight,over30isobeseandover40is
morbidly obese. Skin-fold thickness also measures body fat stores, as
does totnl body impedance to a low frequency electrical current, and
total body density, whichcan bedetermined in rescarchseltings.
Obesity is nssocialed with excessive rates o f illness, particularly
hypcrtcnrion, diabetes mellitus, stroke, vascular thrombosis and
henrl discnse. A simple measure of overweight that correlates with the
risk of c;s~liovasculardisease is the waist: hlp ratio, with the normal
rario being less than one.
Treatingobesity
Body~. weight lends to increase with age, und preventing obesily is as
-
inqx~rlnntas redktcingweight.
Diet. Rerrricting calorie intake reduces body weight. lniliai weight
loss tends to be followed by rebound weight gain after a few months.
Sornc~lialsrcstrict fluid intoke and dehvdration causer ranid b u t s ~ u r i -
our weight iorr.To maintain weightcontml, diets must besustainable
and nutritionally adequate and not lack essential vitamins, minerals or
macmnutrients. Very low calorie diets, carry the risk o f undernutrition
and should be supervised by a physician, while law calorie diets, for
examole. thoreadvocated bv -
. WeightWalchersm, aresafer.
Large portions and a preponderance of caloric-dcnrc foods, that is.
fats, lend to increase calorie intake. Ideally the proportion of calories
consumed as fat should be between20and 309oofthetolal.
Excrcirc. Regularexercise helps tolimit body weight, panly by eon-
suming calories to provide energy to muscle and alsb by suppressing
appetiteand raising thc basalmetabolicrate(BMR) (seeChapler22).
Pharmacolherapy. The medical consequences of obesity are being
increasingly recognizedandeffectiveLreatmentsactively sought, paRly
slimulated by-!he discovery o f leptin and other endogenous appetile-
suppressants, and the results ofresearch into neuro-endocrinecontrol o f
body~. weight.
The most effective appetite suppressants were the amphetamine
derivatives dexfenfluramine and phenteramine, which unfortunately
caused major cardiac side-effects and were withdrawn from use. Sibu-
..
trnmine is another effective appetite rupprersanl
.. - -
acting through sero-
toninerglc pathways. Orlistat is aspecific pancreatic liparelnhibltor
-
thnt -?uses fat malabsomtion and weiehtlorr. Side-effects. ruch as oilv
stool and fat-soluble vilamin deficiencies, limit its use.
Oe~asianally,obesity is caused by endocrine dysfuncljon, ruch as
and treat in^
-hqpolhqroidisrn,
.. . .the underlying
. .condition is effective.
Surgery. Surgical removal of fat, for example, by liposuction and
gastrointestinal surgery to limit food intake and absorption are the main
options. Cosmetic surgery has only short-term knehts and risks
scarring and infeclion. GasMinteslinal surgery is raerved for mating
morbid obesity. Jejuno-Ileal bypass is no longer performed, kcsuse i t
caused severe liver disease (steatohepalllls). Jaw-wlrlng, whiehlimits
food intake, and gastroplicatlon, whereby a ponion o f h e stomach is
slilched or enclosed with a rubber band, rzducing the sizeof the gastric
reservoir, ore the most frequent operations for obesity (se~Chapter48).
Starvation, malnutritionandanorexia
Malnutrition has many causes, of which economic deprivation is the
commonest. However, even i n wealthy societies, ill health, gaswin-
tertinal diseases, such as oesophageal cancer, and anorexia nervosq as
well as voluntaryfasting,canallcausemalnutritionandstarvation.
Measurlng malnutrition
The B M I is abnormally low and other measures, such as skin.fold
lhickness and muscle strength and mars, are low. Listlessness and
lethargy occur and with severe starvation, mulllple organ failure may
occur. I n women, menst~atlonceases.Theremay also besigns ofspe-
cific vitamin and mineral deficiencies.
Melnutrilion cuuser widespread abnormalities, including changer i n
the. -
gastminteslinal tract. Villi are shorter. less digestive enzvmcs me
synlhesized and the intestinal barrier lo the entry of pathogens is
reduced. This atrophy occurs whenever the intestine is not used, so
palientr whoarefedparenterally arealsoatrisk.Malnourishedchildren
havestunled growthand, due to mucosalalrophy andageneralreduclion
i n immune competence, are paRicularly susceptible to infections.
such as gastroenteritis, which aggravates the malnutrition and may be
fatal.
Metabolic adaptation, which reducer dependence on glucose and
lowers the BMR, allows the organism to survive for longer at a lower
energy .~ -
intake, An imponant consequence is that rapid refeedine:after a
periodofstarvationcaninduceseriousmetabolicabnormalities(rrIe~d-
lngsyndrome).
Kwashiorkor, or protein-energy malnutrition, occurs when protein
deficiency is greater than overall calorie deficiency. lissue and blood
pmleins areinadequately renewed,causingrkin, hair andserum pmtein
abnormalities and, characterirlica:ly, peripheral aedema. Mararmus.
i n contrast. is global malnbtrition, withautoedema.
Specific micronutrient deficicncier also occur i n malnutrition and.
paradoxically, global malnutrition may mask specific vilamin dehcien-
. .
c i a . For example, malnourished alcohol-dependent oeoole. who
neglect nutrition i n favour o f alcohol, may be lhlamlne (vitamin B,)
deficient The dehcieney may not be clinically apparent while they con-
sumea diet laclang carbohydrales.However, ifthey areadmined to hos-
pital and given lntravenuur glucose or a good meal, acute thiamine
deficiency occurs, becausethiamineis an essential cofaclorforthe .pym-
~
vale dehydrogenaseenzyme, which metabolizes glucose i n cells. Acute
thiamine deficiency is a nicdical emergency
- . and can cause wmanenl
neurological damage (Wernicke's encephalopathy) ifthiamine is not
administered immedintely.
. .. .--T.-l-
*.a .-.lI.,..---I.,-,II...,.--.... I....A. . . ~ . * , . .. .. ...,,,.,..? ~
./..#,.. ', ' . -.. . . . .. ..... , -
Gastrointestinal cancers impose a major health burden: colon and rectal
cancer (colorectal cancer. CRC) is the second commonest cause of
cnncer-rcl;!tcd death in the Western world. while gastric, oesophageal.
p;tncrc:ttic ttl~dIivercnncerilrealsorelatively frequent.
Pathology
The development ofcalareclal cancer follows a characteristic pnuerni n
most cases. with the earliest lesion being a microscopic focus o f aber-
rant epithelial cells. With time these form a small dysplastic polyp.
which enlarges, comprising epithelial cells with increasing numbers
of mutations i n cancer-related genes and a progressively dysplaslic
phenotype.
Some cells may became malignant, forming a focus ofcarcinoma in
silt,, which is confined to the epithelium of thepolyp.These malignant
cells may penetrate the basement membrane and invade first the inles-
tin;bl w,dl snd then lymphatics via which they are carried to regional
ly~npllno<les.Finallythey may invade blood vessels and r o melaslaslze
todistant organs such as the livcr and lungs.
Thc D t ~ b c s s t n ~isi n~iscd
~ lo determine prognosis nnll op1im;i 1rc;tl-
mcnt (sce ligure).
Aetiology and pathogenesis
Environmental factors including diet influence the incidence of CRC.
Western dietsthat are high i n fat and red meat and low i n fibre predis-
pose In CRC, while vegetables, vitamins, trace elements, such as sele-
nium, and non-steroidal anti-inflammatoly drugs (NSAlCs:, such as
sulindac, seem to bcprotective. Smokingtobacco also increases the risk
of CRC. High-fat diets induce the production o f carcinogens, while
reduced dietaly flbrecauses canstipationsothatthecarcinogenr remain
incantact with theepithelium for longer.
Chronic intestinal inflammation. as i n ulcerative colilis, also
increaser the risk. possibly by increasing epithelial cell turnover, and
thus increasing thechance ofgenetic mutations.
There is a strong genetic element and the risk o f CRC is increased in
people who haveoneor moreaffected firstdegree relatives.Thesludy of
familial forms o f CRC, panicularly aulosomal dominant familial ade-
nomatous polyposis (FAP) and hereditary non-polyposls colon a n -
cer (HNPCC), have helped to elucidate the molecular pathogenesis of
CRC, bnscd on the 'two-hil' and multiple gene theory o f how tumour
suppressor genes function.
Colonic epithelial cells undergo p r o g r w l v e change from normal.
through increasing dyrplaria. to carcinoma. These cellular changes are
causedby genetic changes: Someaf which may be inherited and others
acquired through the effect ofcarcinagens. Mutation o f a single allele
is usunlly insufficient to alter cellular function, so, for each gene, both
alleles must bcmulated.
I n genetic CRC syndromes, one mutant allelc is inherited, so only a
single sccond mutation i n that gene is required. To produce cancer,
numerous genes mustbc mutated; therefore, ittakes many years to accu-
mulatesr~fficienlmutations. Forcxample.FAPir caused by mutations i11
the adenornatous polyposis coli (APC) gene, which is frequently
mutated even i n sporadic, non-familial CRC. Patients with FAPdevelop
many hllndredsaf polyps and thencanccr i n their early 20s i n almost all
cases.This occurs becauseeachcolonoeytealready camesonemutared
APCgene, so that environmental carcinogens only have to mutate and
inactivate the sinxleremnining copy to produceopolyp, whichcnn then
goon todevelopintoncancer.
HNPCC doer not involve a polyp-forming stage and is asswiated
with mutations in the genes rerpocsible far ensuring that rnist&es i n
copying D N A during mitosis are repaired (mlsmalch repair genes).
Patients lose the ability to correct genelic mistakes and thus armmulate
mutations i n neoplasia-inducinggenes,including ACP, pS3 and Am.
Clinlcalfealures
Exceptinfamilialsyndmmcr.CRCisrarebeforetheagcofSOyeanand
it increases i n incidcnce thereafter. Early cancers and'adertomar in the
colon may remain entirely Bsymplomatic. Larger adenomas and can-
cers may bleed micmrcopically over time, causing nnneda. Larger
lumoursmay causeoven rectal bleedingandaltered bowelhabil(con-
slipation and/or diarrhoea). Intestinal abrtmction, abdominal pain and
weight loss occur when thediseaseis funheradvanced.
Diagnosis
Barium enema and colonoscopy are the main diagnosticfests. H i t o l -
o n ofcolonic polyp biopsies can demonstrate dysplasia and neoplasia
(see Chapters 44& 45).
Stool examination may demonstrate occult bleeding. Faecal occult
blood testing is bared on the guiaic chemical reaction with haem, and
false positives may be caused by dietary haem, far example, frommeal
(seeChapter43).
Blood tests may show iron deficiency or anaemia. Increaredcirculat-
ing levels o f an embryonic protein, carcino<mblyonic antigen (CEA),
are associated with CRC and can be used io manitorNmaurrecurrence
after rurgely and chemotherapy. . ,
Removal o f adenomatouspolyps before they become malignant dra-
matically reduces the risk ofdeveloping CRC. Therefore, because CRC
is so common, some nuthbritier advocate population screening, using
barium enema. colonorcopy or faecal occult blood testing for people
overtheageof50 years.
I n FAP, the panproctocolectomy (surgical removal of the whale
colon and rectum) i n early adulthood prevents CRC.
Trealment
Surgery. simple adenomas may be removed during colanoscopy by
snaringandexcision (polypectomy), whileCRC has toberemavedsur-
aicallytoaether withs m a r ~ i nofnormal tirrueto ensure taralresection.
f f CRC isdetected early, particularly if it has not extended beyond the
intestinal wall. theoveration mavbecurative. MetastaticCRC cannotbe
cured, although surgely may palliate symptoms, such as bleeding.
obslruction and pain.
Chemotherapy and radiotherapy: adjuvant chemotherapy may
lncreasesurvrval after rurgely and radiotherapy may be used to reduce
tumourbolk.
Prevention: adletthat is low in fat and red meat andhighincarbahy-
drate and fibre is recommended, and the use o f N S A D s is being
invwegated.
Colon andrecfolconcer 85
Tumourrofthecolon,oesophagus,stomach,pancreasandlivcrarccom-
mon worldwide. Colon cancer is the most common (see Chapter 37).
There is marked geographlcal and raclal varlatlon in the incidence of
~ ~
gastric, oesophageal, pancreatic and liver cancer In cirrhosis, primary
livercanceris eommonandtheliverisalsoafrequentsiteformetaslasls
from many othercancers.
Gastric cancer
Gastric cancer is particularly prevalent in Japan, but the incidence Is
-
decreasinc worldwide. Environmental factors, such as smoked foods.
.play a role and chronlc gastritis, causcd by autolmmune disease, or
~
more commonly by Helicobnelerpylon' infection, predisposes Lo both
adenncn~.cinnmaandgastric lymphoma (sceChnpter3 I).
Synlpla!ns includenbdotninnl pain, dyspepsia.anaemia and occullor
theepignrtri~~ni
-
ovcrl intcstin:tl hlee~lin~.Advnncedcnncermavc.~usearralrrahlem;~ssin
. .
andlymphaticsprelid may ereatcapalpable lymph nodc
in theneck-'Virchow's node'.
Endoscopy !nay revenl a gastric ulcer. All gastric ulcers should be
biopsied and a rccond endoscopy performed after2 months oftreatment
toarsess henling: "on-hcalinggastriculcen may bemalignant.
Oesophageal cancer
Squamous cell carcinoma of the oesophagus is the commonest farm
and is particularly prevalent in parts ofsouthern Africa. In the Western
world, however. the incidence of oesophageal sdenocsrcinoma is
increasing.
Squatnous cell carcinoma is related tosmoking anddrinkinCalcohol.
. boiizes SHT However, when carcinoids metastasize to . h e Liver,
while chronic gartro-oesophageal reflux and Barrell's oesophagus
. .
~redirooseto adenocarcinoma. Chronic reflux can cause mctaolaria
of the oesophageal epithelium, from stratified squamous to simple
columnar, intestinal-lype epithelium. This change is termed Barrett's
oerophaeus,
. - ..
which carrier ariskofdvsplasia -
and subsequent maliananl
transformation (seechapters 4&30).
Dysphagia (food sticking) and odynophagia (pain on swallowing)
signify oesophagcal disease and may be accompanied by weigh1 loss.
Malignant trachco-oesophageal fiselae may cause recurrent aspiration
pneumonia. Barium swallow, endoscopy, biopsy and brush cytology
confirm thediagnosis.
Very early disease may becured by oesophagectomy but usually the
cancer is non-resectable and patients receive palliative trealmcnt by
dilatation ofrtrictures,placementofmcchanieaistentsorlasertreatment
tored\~cetumourbulk.
S~r~~~c;~~~thorilies:alvncntereg~~lnrcndoscnpicsurvclllance todctect and clrrhnrir, pnrlicularly when theliverdiscaseis eaused by hepatitis B
. .
dysplasin in Barrett's oesophagus so adenocarcinoma can bc detected
and trintedearly
Gastrointestinal lymphoma
Gastric and intestinal lymphomas are rare and are usually causcd by
chronic inflammation and activation of the local immune systcm, as
with H. pylon' infection, coeliac diseasc and immunnproliferative
s~nz~li intcsti~lnldisease (IPSID), which occlirs with chronic intestinal tumour obstructs bile flow, jaundice. Serum levels of liver enzymes
infection (secChapters \ 8 , 3 1 &35).
Symptoms include weiglit loss, diarrhoea, malabsorplion and
abdominnl pain. Diagnosis is hampered by the difficulty in reaching
parts of thesmallintestineby endoscopy (seeChapter44). Bariummeal
and follow-through examination,computcrizedtomography(CT), mag-
netic rest>ll2lnceimaging (MRI) scanning and exploratory laprrotomy
with intcslinal biopsy are often used to makerhc diagnosis (see Chapter
45).
Eradicating H. pylori infection. or prolonged antibiotic treatment of
IPSID, may cure earlv cases. In coeliac disease. strict adherence to a
~ ~~ ~~
gluten-free diet removes the antigenic stimulus to lymphocylu and
reduces the riskof lymphoma.
Pancreatlccancer
Pancreatic adenocarcinomas may present with abdominal pain or,
when they occur in the head of the pancreas, may obslruct hecommon
bile duct, causinglaundice. Very early cancers may be m l e d bywide
excision of the pancreas, duodenum and related slruciures (W3lpple's
operailon). . .,,,.% ..
Neuro-endocrine tumours and carclnolds
Tumoun arising from entero-endocrine tissue may be benign or malig-
n.ant, and may occur spnradically or as part of inherited multiple
endocrineneoplasia(MEN)syndmmes.Theymay
. ~ . . bearvm~tomalicfor
. .
many years, or mayproducesymptoms by virtueofaberrant hormone
secretion.cvcnwhilethetumouritselfisextremelvsmalland~hvaicallv .. .
inapparent; for example, lumoun of G-cell origin pmduce gastrin.
resulting in excess stomach acid production and peptic ulceration
(Zollinger-Elllson syndromc). Other tumours may produce insulin;
glucagon or vasoactive intestinal peptide (VIP), causing diarrhoea a i d
hypokaiaemia (Verner-Morrlson syndrome) ( a. e. r 16. .' .';'
~
Carclnoids are typically slow-growing Nmoun h a t pmduce an
excess of serotonin (5-hydroxytryptaminc. SHT) and peptide p w h
facton. They usually remain asymptomatic, as the liver npidiy maa-
5HTis released directly intothesystcmiccirculation,causingsymptoms
such as flushing and diarrhoea, which constitute thecarelnoid
syndrome.
Hormonal effects are oflen the fin1 sign of neuro-endocrine tumours.
Anatomical localizationcan be difficult and relieson CTandMRI imag-
ing and radionuclide-based scans to localile tumour cells expressing
surfacc somatostatin receptors, which are present on most neuro-
endocrine tumours (octreotide scan). Excess urinary excretion of 5-
hydroxy-indoic acetic acid (5-HIAA), a metaboliteof5HT, can beused
to diagnosccarcinoid syndrome.
Octreotidc or somatostatin injections may alleviatesymptoms by s u p
pressing hormone secretion, and surgery is potentially curative.
Liver cancer and masses
Primarylivercancer (hepatoma) is nre,exccpt inchronieliverdisease
virus infection. People with primary sclerosing cholangitis (PSCj are
particularly prone to develop cancer of the biliary epithelium, cholan-
giocsrcinoma.Non-malignanthepatlcadenomaissssociatedwihhe
use of the oral contraceptive
. .pill. n ~ mostcommonlv
e -
m u r r i n e can-
ccrr in the liver are melastatic deposlts from cancer of h e stomach.
colon,pancreasand breast
Typical symptoms ~ncludenghl upper
~ .~ quadrant pain and, if h e
~
and bilirubin may bc raised. In heontoma, elevated circulatine
levels of the embryonic protein, a-fetoprotein (AFF) may be
-
detected.
Ultrasound. CT and MRI scans and a liver biopsy may be needed
lo confirm the diagnosis and lo distinguish cancer from benign cysts.
~ ~
haemungiomas. abscesses and benign lumours (seechapten 33 & 45).
Treatment remains unsatisfactory. '
Ganminres!inal, pancreoficand liver rumours 87
Theperi-anal regioni~afrequentsourceofpain,discomfonanddislress. between the internal and external sphincters and may b m e
Fonunately, many conditions affecting this region are benign and
treatable.
Haemorrhoids
Heamorrhoids are commonly known as piles. They may cause rectal
paln and bleeding and may interfere withdefecation.
Externel piles are actually dilated superficial veins in the peri-anal
skin. which become thrombosed and exquisitely painful. Occasionally.
thethrombosedpilemay blced.Whenthey heal,anexternal skin tag may
remain.
Internal haemorrholdsarisefromsuperficial veins in themucosaof
the lower rectum, which become engorged through chronically raised
intra-abdominalprerrureandstralningduringdefecation.Theveinsare
supponed by cushionsof soft connective tissue, which hypertrophy and
contribute to the swelling (see Chapter 14). Chronic straining is the
commonest cause of haemorrhoidal vein enlargement and contributing
factors include pregnancy,obesity and weightlifting.
First-degree internal haemorrhoids comprise hypenrophied cush-
ions, wilh enlarged veins that may bleed but do not protrude out of the
rectum intotheanus.
Second-degree haemorrhoids prolapse through theanus, but reduce
sponlnneously.
Third-degree haemorrhoids require manual reduction of the pro-
lapse and lnurth-dcgrce haemorrhoids cannot be reduced manually.
Internal haemorrhoids generally do not cause pain unless they pro-
~ ~
lapse and ulcerate. They may cause a sense ofrectal fullness, diseomfon
and intomplete evacuation (tenesmus). m e most common symptoms . .
include bleeding, typically at the end of defecation, and the effects of
prol.apre, which includechronic leakageof mucus and subsequentperi-
anal itching (prurllisani) andexcoriation.
The diagnosis is confirmed by careful examination of the peri-anal
region and anal canal using a proctoscope. Barium enema and
colonorcopy may beneeded toexcludeother causes of rectal bleeding.
Medical treatment includes altering diet to avoid constipation.
using stool softeners and changing behaviour toavoid straining during
defecation.
Suxically,
. . haemorrhoids can betreated by elastic band ligatlon,sele-
- mucus dischargecaused by haemorrhoids.
rolherapy or excision. External piles do not usually requirelrealment,
sp;w li-wnincision ;~ndev;~cu;~tionolanacutely pninlut thrnmbur.
Anal fissure
Asplit in the skin of the anal canal causer acute tearing paln, panieu-
larly ondefecation.Theremay also besomebleeding.Thecause iscon-
~ L i p i l lnlld
i ~ ~hnrd stool.
On examination, there is a linear tear in the skin. Ninety percent of
tears are porlerior and 10% anterior. m e r e may be a skin tag, called a
sentinel pile,al theedgc of achronic tear.
Stool softeners and alleviating constipation are the main treatments
and, in the acute state. local application
.. of glyceryl
.~ trinllrateoinlment.
~
whichrclaxesthcanalsphincter,mayallow thefisruretoheal.Inchronic
cases, surgical division of the internal anal sphincter (splrlncterotomy)
may be performed
Anorectal abscess and fistula
The deep anal glands, which secrete mucus into the anal canal, extend
obstmcled and Infected. m i s causes deep-sealed peri-anal absnsses
that manifest with anal paln, fever and usually a palpable peri.anal
mass. When the abscess ruptures onto the surface, a m c t or M u l a
may persist and can become chronically infected. dlscharglng mucus
and pus. Anorectal fistulae may also occur after surgical incision and
drainageofabscesses.
Abscesses and fistulae may be deeper than clinically apparent and
computerized tomography (CT) and magnetic resonance imaging
(MRI)scannlngofthepeivis may be helpful beforesurgical matment.
Surgical lnclslon a n d dralnage are usually required and bmad-
speclrumantlbloties, including melronidazole lo trealanaembic infec-
tion. are used.
Chronic and recurrent anorectal sepsis may be caused by anoreclal
Cmhn's disease, in which case additional anti-inflammatory treabnenl
is also required (see Chapter34).
Proctitis
Superficial inflammation of the rectal mucosa, causing bleedine. -. diar-
rhbea, urgency of defecation and mucus discharge, may be caused by
ulcerative colitis or Crohn's disease. In many cases..~inflammation
remains confined to the recmm and never extends proximally. Recral
steroids and 5-aminosalicylic acid (SASA, mesalazine) are usually
effective and long-term treatment with oral SASA may h
initiated.
Radiation proctltis. Pelvic irradiation, for example, to treat cervical
cancer in women,orprosualecancerinmen, may causechronic varcular
damage and mucoral fibrosis, with the formation of friable, abnormal
blood vessels that bleed spontaneously. 'The symptoms of diarrhoea.
rectal .bleeding and discharge may develop years after the initial
radiotherapy.
Pruritis ani
Poorperinealhygeine may cause imtationofhperi-analskin and,con-
versely, overzealous cleaning with soaps may dry the skin,also causing
.
irritation. Infestation with pinworms (Enlembiw vermiculnrisl.. which
crawl onto theperi-anal skin, may albo cause prurltis, as might chronic
Proclalgia fugax
Proetalgna fugax is a stabbing pain in *herectum, oftenafter defecation,
and usually has no direemable organzc cause and is hard to Mat (see
Chapter29).
Anal wartsandsexually transmitted infections
Infection with human papillomavirus may cause pen-anal w a s that are
treated m rhesame way as genilal wans. Syphilis may alsocause w m -
like papules, as well as pen-anal ulcers. Other sexually transmined
~ ~
diseases, such as herpes simplex virus infection and gonorrhoea, may
cause pen-analinflammationandulceration.
Peri-anal tumours
Squamous cellcarcinomais the most common anal Nmour and may be
associated with infection by human papillomavirus 16 and 18. Chronic
hypertrophic ulcers with rolled edges are the typical manifslation and
they may caurebleeding,itchingandpain. , .. ,...
 40 Gallstones and pancreatitis

Cllnlcal features
. , ,....~ 2

Excceebllc
plgmcna

+ Pancreatic IosuKiclcncy
Wncreatlc Islets- Dlabckb mdlitus
Lung demsgc ' T I S ~ Udamage
C :

: :,;:, , " .

. ~

.:*_..i _ P i ' . . .
I !. ' ., , . i.. , '!
' .Gallstones affectup.to 20% ofthe population in the Western world and Gallstones i
Formation -2. L
h e incidence i~rcreaseswith age. They may remain asymplomatic or I
they may causeseriousillners. Bile is stored in the gallbladder, where it is concenlratcd by epithelial 1
Pancrealitis is often caused by passage of gallstones. It can be "cry cells reabsorbing water. This causes supersaturnlion of bile con- *i
severe, may becomecluonic and can impair pancreatic func~ion.
. . .
stiluenrs, particularly cholesterol, which form stable mired micelles . ,I
''
i
90 Disorders a n d diseases

iI
withphospholipidsand bilesalls.However, thesupersaturatedsolution
is unstable and cholesterol may cryslallize amund a micmscopic pani-
cle or nidus. such as a bacterial cell. Initially crystals are very small.
forming sludge or biliary sand, but they grow by accretion over time.
Eighty-five percent of gallstones are cholesterol stones, formed in this
way.
Less frequently,
. . bile withexcessively. hiahconcenlrationsofbilepig-
. ~ -
ments is secreted, for example, in haemolytlc diseases, such as sickle
- .-
cell anaemia. causine the formation of ~lementstoner.
Ileal disease that interrupts the enlero.hepatic circulation of bile
snla.lncreases the riskof gallstone formation.
Pathogenesis
Most gallstones remain in the gallbladdcr and are asymptomatic.
although
. there is a slightly
. . increased risk of gallbladder cancer, which
itselfis very rare.Gallstonesejectedfromthegallbladder,however, may
. .
obstruct the bile ducts and are the main causeofsvmotomatic -
eallstone
disease. A stone i n the cystic duct can obstruct the gallbladder, which
may then become infected, causing cholecystitis. Impacted stones in
the common bile duct cause intrahepatic and extrahepatic biliary
obstruction and, if theobstructed bileductsbecomeinfected, ascending
eholaneitis results. Stones in the common bile duct or the a m ~ u l l aof
Vatermay causepancreaticobstruction,resultinginpancreatitisaswell
as cholnngitis.
Clinical presentation
Biliary disease often causes nausea and anorexia. Symptoms may be
aggravated by falty meals, which stimulate cholecyslokinin release.
whichi~~tl~rnstimulatesgallbladdercontraction.Abdominal pain,local-
ized to the right upper quadrant, is caused by distension of the gall-
bladder and bile ducts, and a tender, inflamed gallbladder may be
palpnble.Thepain islypically colicky, orepisodic,aggravated by waver
of ineffective peristalsis. Pancreatitis and bacterial infection cause
severt.~crrirtent~ain, whichmav bea=companied by teverandrieors. -
Biliary obstruction causes jaundice, pale stools, due to abscnt bile
-
.viemena in the intestine. and dark urine. due la urinarv excretion of
conjuguled bilirubin. Inadequate excretion ofpruritogenic substances.
which have not been well characterized. causes itchinc. - Persistent
biliary obstruction results in malabsorption of fats and fat-soluble
vitamins due to thelackofbilesaltsin theintestine.
Symptoms may be transient, as stones can be spontaneously ejected
through thesphincter ofOddi.
Diagnosls
Blood tests show raised biliary enzymes, conjugated bilirubin and
inflnmmnrory markers, ruchasC-reacllveproteln(seeChapter41).
Ultritsotand scanning of [he nbdomen sensitively dctects gnllstones
and also shows if they are causing obsuuction. Computerized tomogra-
phy (CT)and magneticresonanceimaging(MR1)seanningmay alsobe
used (see Chapter45).
Endoscopic relragrade cholangiopancrealography(ERCP) provides
-
contrast-enhaneedimaaesofthe . . -
biliarvlract,demonstratinaobstruction
and slones in clear detail. In addition, stones can be removed endoscopi-
cally,or thesphincterof Oddi cut (sphlncterotomy), allowingstoner lo
pass sponlnneously.
Treatment
Cl~oleqslitis,cl~olnngilisnnd pnncreatitis are serious multisystem
inflammatory disorders. Treatment includes supportive c ~ eanalgesia
,
andantlblotls.
Gallstonesareonly removed whenthey causeclinicslproblerns.Dur-
ing an episode of acute obstrucllon, infection or pancreatitis, they may
be removed urgently by ERCPor surgery. More usually. the gallbladder
and stones are removed surgically (cholecystectomy). when theacute
episode has settled (seeChapter48).
Pancreatitis
Pathogenesis
Obstruction and damage to pancreatic ducls by stoner, hlmours o r
- duct tissue. inid-
trauma releases pancreatic enzymes that auto-dieest
sting aself-perpetuatingcycleoftissuedamageand enzyme relearethat
can rapidly destroy large pads ofthe pancreas. Bacterial lnfectlon and
leakage of enzymes into the bloodstream often accomvanv. . this tissue
damage, causing severe tissue damage at distant sites, particularly the
lungs.~usacutepancreatitisisaseveremultisystemdirorderthatcan
berapidly talal.
The same mcchanismr can be initiated by chemical damage to thc
pancreas caused by drugs, panicularly excess alcohol, which is thesec-
ond commonest cause of acute pnncreatitis. Pancmtitis may also bc
caused by trauma, for example following ERCP, and by Infection, for
example with themumps virus.
Clinical presentation
Abdominal paln,anorexia,vomllingandfeverarethemainsymptamr.
Multisystem failure, with hypotension, hypoxia and widespread
inlravascular haemorrhage, occurs in severecases.
Diagnosis
Blood lesu show greatly elevated circulating levels of pancreatic
enzymcs, panicularly
. amylase
. and lbase. Inflammatorv marken such
as C-reactive pmlein areraiscd. Hypoxia and hypoealeapmia indicate
severe ~ancrealilis.Abdominal ultrasound and CT or MRI scannine
may demonstrate an enlarged. oedemalaus pancreas.
Treatment
To minimize pancreatic enzyme production, the patient is kept nil-by-
mouth and thc stomach is empllcd by nasogartrlcsuction. Antiblotis
for presumcd lnfcct~onand supponlte measures are the mainstay of
treatment S~cclficlnhibltorrof~ancma~csec~tion.andof~anmatic
enzymcs, have notyct provedclinically useful.
Chronicpancreatitis
Repeatedpassageofstonesandchmnic alcoholexcessmay causerecur-
(CFTR),
-
rent pancreatitis. Inherited abnormalltier in the cystic Rbmsls eene
which regulates CI-secretion in duct cells, also predisposes to
chmnic pancreatitis. Repealeddamaae - affects exocrlneand endocrine
pancreatic function, causing malabsorption due to p&cmtic enzyme
, In addition.
deficiency and diabeler mellitus due to insulin deficiencv.
damageta sensory ncrves and scarring and obsuuction ofthepancreatic
duct cause abdominal pain, which can be enlreme.
The s c m d pancreas may develop calcified areas that are visible on
plain abdominal X-ray.
Treatment involves replacing pancreatic enzymes wilh oral rupple-
menls, treating diabetes wilh Insulin injections and relieving pain.
which may bedifficult. . .