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Thsgar~roiaes~inal system ata glirncdSalirh Kcrhrv.- 1st cd.
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Includes index.
ISBNO-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 ingested with foodand from thelnrge populationofcommensal bacteria
n
hlegastrointestinal systemcomprises the hollow organs from mouth to that populate the intestine. The mucosal immune system is critically
anus that form the eastrointeslinal tract, the Dancreas. which mainly imponant in regulating how the interline responds to thcsc challenges.
secretes digestivejuices intothermall intestine, and theliverand biliary providing protection and not reacting inappropriately to normal compo-
system, which perform vital metabolic functions inaddition lotheir con- nentsof thediet.
eibstion lodigestion and absorptionofnutrienls.
Diseases and disorders
The intestinal tract Nausea, vomiting, diarrhoea and canslipation are common symptoms
A hollow tubularstructure into which nutrient-rich food is coerced, and and their basic pathophysjology illustrates imponant aspects of gas-
from wtlich wanes arcexpelled, is found in the most primitive multicel- Iroinlestinal function.
lular organisms, from the hydra onwards. In humans, the tract is highly Gastrointestinal symptoms are frequently not associated with any
specialized throughout, both slmcturally and functionally. The mouth discernible pathological abnormality. These medically unexplained
and teeth arc the fin1 structures i n this tract and areconnected by a pow- symptoms are often labelled functional disorders and, as our under-
erful morculartube. thcoesophanus,
. - to the stomach.The stomach stores standing of gastrointestinal physiology becomes more sophisticated,
food aftcr meals and is the site where major digestive processes com- we may discover new explanations and treatments that are more
mence.Thesmal1 intestineis thcmaindieestivcandabsomtive surface. effective.
Thc large intestinc acts mainly as a reservoir for food waste and allows Gastrointestinal system infections are common and an associated
reabsorption ofwnter from the mainly liquid material leaving the small with significant morbidity and monality worldwidc. They range fmm
intestinc. I t is not essential for life and, paradoxically, is affected by a self-limiting foodpoironingtolife-threateninglocalandsystcmicinfec-
numberof common, serious diseases, ruch as inflammatory bowel dir- lions. Evcnpepticulccrationirmort frequently causedby infcction,with
easeandcolorectalcancer. theHelicobocrerpylori bacterium.
Far some major diseases, ruch as inflammatory bowel disease. the
T h e pancreas aaiological agent has not been identified, despite rapidly advancing
Digestive rllzylllec are produced i n many pans of the gastroinrestinsl genetic and molecular rcsearch. Ccnvenely, coeliac j i r w e . another
tmct. inclurling lhe moalll (salivnry glands) and small intestine (envro. serious andcommongastrointestinal inflammatorydisease,ircauredby
cytcs). ; t l l l ~ a l ~the
g l ~cxoerine pancreas is the most prodigious
~-~ producer a well-characterized immune responsetowheat-derived mleins.
of digcrlive enzymes. Pancreatic failure causes nralabsorption, which Coloncanceris amajorcauseofcancer-rclateddeathandourmolecu-
can be reversedby anificialcnzymcsupplements. larand cellular understandingof its pathogenesis,and the pathophysiol-
ogy o f olher gastrointestinal, pancreatic and liver tumoun, is rapidly
Theliver and biliary system increasing.
Without the liver, survival is measured i n hours, and no anificial system Livcr damage is often caused by infeclionsordrugs and maybe acute
has yet bccn devised to substitute for hepatic funclion. The liver is the orchronic.Acuteliverdiseasccanrapidlypropresstoliverfailu~,orcan
largest
. solidoganinthe body and itsessential functions include rezala- resolve, either spantaneously or with appropriate treatment. Chronic
tion of protein, fat and carbohydrate metabolism, synthesis o f plasma liver disease may cause cirrhosis, which is characterizedby a variety o f
..
vmteins, ketonesand l i ~ o ~ r o l e i nanddetoxification
r, andexcretion. Via signs and symptoms and changes throughout the body, including the
the hepatic ponal circulation i t receives and filters the entire venous effectsof hepatic ponal venous hypertension.
drainage of the spleen, gastrointestinal tract and pancreas. Through the The gaslrointc~tinalsystem is kssentia~to nuuition, and disordered
production o f bile, i t is also essential for digestion and absorption, par- - -
nutrition is a m.~jorissue worldwide both thmunh undcrnutrilion and
ticularly ofdietary fats and lat-rolublevitaminr. starvation and through ovcmuaition, which causes obesiiy, possibly the
single most imponanlmodem health problem i n the afRuent world.
Inlegrated function
The gastrointertinal system is controlled by both intrinsic andextrinsic Diagnosis a n d treatme~tt
ncuronal and endocrine mechanisms. Enteric nerves and endocrine Clinical assessment, including a focused history and examination,is the
cells a% panicularly impomlant i n coordinatink motility, digestion and foundation of diagnosis. I n addition, the gartroinleslinnl system can be
absorption, and in regulating feeding and overall nutrition, including the investigated by endoscopy, radiology and specific. fusctional tests.
controlof body weight. Endoscopy and radiology may also be used therapeutically, and phar-
Theg;~stroinlestinalsystempresents a hugesurfacearea that has to be macotherapy and surgcry for gastrointestinal disorders u p l o i t many
protecred against injury, paniculaily from microbial pathogens that are unique fcatures of the structureand function ofthcsystem.
The nlouth and teeth admil food into the gastrointestinal tract. They cut mastication are the masselcr and temporalls, which powerfully bring
and break large pieces, chop, grind and moisten what can be chewed. the lower jaw up against the upper jaw, and the plerygolds, which opcn
and prepare asmooth, round bolus lhat can beswallowed and passedon thejaws, keepthemaligned, and moves themsideways,and backwards.
to the rest of the system. Ofcourse. the lips and mouth also serve olher and foiwards for grinding. The lrigeminal (Vth cranial) nerve contmls
functions. themuscles of mastication.

Structure
Thesensitive. flexible, muscularlipsthal form the anlerior bordcrol'the
. Teeth arespecialized fordifferent lasksas follows:
Inclsors hnve Ant, shnrp edges for cutting tough foods, such as meat
and hard fruits.
mnulh can aserr food by palpation, and their flexibility ennhles them Cnnlnes hnve pointed. sharp ends for gripping food. panicularly
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.
.
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
The maxilla and mandible suppon the roof and floor of Ihe mouth. thesurfaces oftwo opposed 1eeth.Aspeopleget older, thegrindingsur-
respectively. The arch o f the mandible supports a sling o f musclcs that facesofthemolars aregradually womdowr,.
formsthe floor, includingthe tongue.The maxillaiscontinuous with the Cenain drugscanbe absorbedacross heoral mucosaandmay . beore-
.
rest oflhe skull and forms the roof ofthe mouthanteriorly and, simulta- scribedsublin&ally (underthetongua).ln thirway,thenecdto swallow
neouslv. the floor of the nasal cavitv and oaranasal maxillary sinus.
Posleriorly. Ihe roof is formed by thesolt palate, composedofcanilage
- ..
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
andconnectivetissue. drugs administered in this way.
The sides o f Ihe mouth comprise the cheek muscles, chiefly
bucclnalor, alld supponing connective tissue. Posteriorly. h e oral Common disorders
cavitv . opens . .
. into the orooharvnx and the tonsils are situated between Herpes simplex infection of the mouth is very common, causing cold
Ihefauces laterally. markingtheposleriorlimitoflheoral cavity. sores, which oflen erupt on the lips when people have other illnesses.
Thc cnlirc mouth, including the gingivae or gums, is lined with a Serinus oral infections, usually caused by a mixtureof anaerobic bacte-
lough. not)-corniiied slrntilied squamousepilhelium, which changes ria, are lesscommon.
to skin (conlificd stratified squamous epithelium) at the vermillion Thecornen of the mouth may be ulceratedor firsuredinpaticntr who
border o f lhe lips. cannot rake care of lheir moulhs, for exampie after a ruoke. so careful
Teeth arise i n thealveolar bone o f h e mandibleand maxilla, infants oral hygiene is imponan1i n these cases. Nutritional deficiency, pmico-
are born without external teeth and with precursors within the jaw. A lady o f B comolex vitamins and iron, is also asrociated with firrurcr at
transient scl 0120 'milk' teelh erupts through the surface of the bone theedgeof the rnoulh, known asangular sldmatitk.
-
between 6 months and 2 vaars o f aec. Thev arc shed between 6 and 13 Shallow 'aplllous' ulcers i n the mouth are common and are usually
no1 asrociated with a more serious condition. Rarely
yenrs of axe and perlnanent teeth take their p1ace.Therear.s 32 permn- . rquamour
. cell car-
ncnt tccth and tile postarior molars, also known as wisdom teeth, may cinoma can develop. Risk factors includesmoking andchewing tobacco
only erupt in yoiingadulthoad. or betel nut, whichis particularly commonon thelndiansubcontinent.
Teetltn1.c Iivingstructureswitha vascularandncrvesupply(dcrived Dental caries is the commonest disorder of teeth, resulting in tooh
-
from the triceminal. orIlIrd cranial, nerve) i n thccentre of each tooth. loss wilhadvancingagc.11is caused by chronic baclerialinfeclionofthe
which is termed the pulp. Surrounding h e pulp is a bony layer called gums and periodontal membrane, encouraged by carbuhydrate and
Aentineand surrounding this is anextremely hard,calcified laycrcalled sugar-rich food residues left in the mouth. Bacteria qmw in the gap
enamel. Teeth lie in sockets within the alveolar bone and the joint i s between the loothcnamel andgums, forminga hard, impenelrablelayer
filled with a layer of tough fibrous tissue (the periodontal membrane) called plaque, within which hey multiply. Their meubolic products,
allowingasmall amount of flexibilily.The marginsof the loohjoint are including organic acids, damage tooth enamel. Gradual erosion of
surrounded by gingivac, which areacontinualionof the mucosal lining enamel and retraction o f h e gingivac weakens h e toothjoint. Infection
o f the nlouth. 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~.

Mourh ond leer11 13

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The ocsoph.~goscarries food and liquid from the mouth lo the ston~ach innervation. However, external stimuli modify the frequency and
and the rest of the intestinal tract and is an important site of common strength ofperistalticactivity throughout the intestine.Verystrongpcri-
gastrointestinal disorders. stalticconlractions can cause pain.
In vamlllng, peristaltic waves travel in the reverse di~ction,pro-
Struclure pelling food upward towardsthe mouth.
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
Common disorders
Dysphagla is difficulty in swallowing and odynophaela
. ~.is painful
opening of the oesophagus lies behind the opening of the larynx and swallowing. Sensations arising from the oesophagus are usually fell
is repnr.~ted from it by the arytenoid folds. The eplglottls, auachcd to retrosternally in the lowcr P M of the centre of the chert. Heartburn
the back of the tongue, can flap over the lavnx, pmtecting it during describes a burning, unpleasant retmstemal sensation that may be
swallowing and funnelling food towards the oesophagus. Just above caused by acid reflux fromthestomachintotheoesophagus.
the gartro-nesophageal
. - junction. the oesophagus
~ ~ - traverses a natural Obstrucllontoflowdown theoesophagus .. -
. . causesdys~hagiaandmay
hintusor gapinthediaphragm, loenter the abdomen. be cnmplele, halting swallowing altogcthcr, so that the patient cannot
. - 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: lcadloasplratlonoffood intothelarynx,causingpneurnonia.ReRuxed
udvct~tili;lorserora; stomach acid reaching the larynx can cause inflammation, causing
longirudinal muscle laycr; cough and a hoarsc voice.

.. circularmusclelayer;
submucoral layer;
musc~larismiccosae;
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
mucos.1 andcpithelium. . -
bacteriaintheoeso~haaealfluid .
.(as~iratlonDneumonlal.
The muscle in the upper third is striated muscle and in the lower
~ ~
The lower oesophageal sphincter Is relatively wcalr; therefore.
two-thirds, smooth muscle similar to the rest of the gut. The lower acid reflux iscommon even in hcelth.but can beexcessive, whenit may
oesophngeal muscle remains in tonic contraction and forms part of the cause oesophagitis.
. . Chronic acid rcflux can induce the epithelium to
lower oesophageal sphincter. The angulatlon of the oesophagus as it change from the normal squamous lining to a gastric or intestine-likc
enters thcrtomach and thediaphragmatic muscle help lo keep thclowcr columnar lining. This epithelial melaplasia is callcdBarrett'soesoph-
agus and it increases thc risk of developing adcnocarcinoma of the
-
~

The vagus nelve runs alongside the oesophagus and innervates

. - muscle directly and via intrinsic "elves in h e myenteric
ocso~haaeal
oesoahaeus.
~

< ~~

-
The diaphragmatic hiatus through which the owophagus passes from
nerve plexus located between the longitudinal and circular muscle he thorax to the abdomen widens with age and it may allow the upper
layers, and thesubmucosal plexus. part ofthestomach to herniate into thcrhorax.Thir is knownasasliding
.
The rubmueosa contains lobulatcd glands that secrete lubricating
~

material throughsmallducts that penetratethccpithelial surface.

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 ) .
-
Theoero~ha~eale~ilheliumisalough,non-comifiedstratifiedsqua- Very powerful muscular contraction and peristalsis (d yrmotl1ity)can
mous epithelium, which changes abmpUy to a non-stratified columnar caurc discomfort or pain. Progressive failure ofperistalsis and a chmni-
epithelium at thegastro.oesophagealJunclion. known astheZ-line. cally hypcrtonic lower oesophageal sphincter. leading to a dilalcd, non-
Importantly, venous drainageofthe oesaphagurformr asubmucosal functioning oesophagus, is called achalasia.
venous plexus chat drains directly into thesystemic venous circulation, Forceful retching or vomiting can causc a Mallory-Weiss tear in the
avoidin~thehcpaticportal
. ~
vcinandlivcr.Thirplexusanastomoseswith oesophageal mucosa, which may bleed, causing (usually) self-limiting
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
. . hypcnensioncan bleedcatartrophically (seechapter 10).
~ ~

veins. whichenlargeand form varices. Infections of the oesophagus are rare.The mostcommon is csndidls-
sir, occurring in immunocompmmised ~ a t i e n uand those with diabetcs
Function mellitur.
Theoerophaguscunveyr food, drinkand saliva fromthepharynx lo the Squsmous cardnoma of the oesophagus is p h c u l a r l y common in
stomach, by perlslalsis. PensfaIris comprises a coordinated wave of southern Africa and may relate to diet, smoking andcarcir.ogens in the
contraction behind the bolus of food, with relaxation ahead of it, pro- soil,as well togenetic facton. Adenocarcinoma, arisingfromBarrett's
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 Chapter38).

Oesophagus 19
The stameeh is the first wholly intra-abdominal intestinal organ. It is Function
adaotedformechanicalchurning,storareanddigestion
- . offoodandcon- Food is mlxed thoroughly by the churning aclion of gastric muscle
tribulcs lo neuro-endocrine coordination of inteslinal function. The againsl aclosedpyloric sphinckr.The pylorusopens onlyto allowsuni-
basic rhythni oftheintestine, thegaslricslow wave,originates here. lisuidmaterial(chyme) through intotheduodenum.~rcventinetheras-

Structure area for morc cfficienl digestion and prevents damage to the dclicate
Tliestoniach is 'J'-shaped, wilh lesserandgreater curvatures, facing 10 intestinal mucosafromlarge, hard,imegularfoodpanicles.
the right. Thespleen lies lothc left and the pancreas lies inferiorly and Rhythmicelectric activity in thestomach produccsregular peristaltic
posteriorly. The liver lies to 1heright.Thestomach lies behind the left waveslhreelimes ominute. known as thegartricslow wave.
Ihypouhontlri;!l region an tltesurfaceof theabdomen. Gastric secretlan is stimulated by the anticipation of f w d , the sa-
The stomachcomprises five distinct regions: called cephallc phase, and by food reaching t i e stomach. the gactrfc
1 the cardla i~nmcdiatelyadjoiningtheocsophagus; phase. Acetylcholine and histamlne, acting through MY.museadnlc
1 the dotne-shapedfundusexlending lothe left of thecardia; and ~~rece~torsstimulatethesecretionof~~~. - i
3 lllc batly or corpus; Parietal cells have an extensive intracellular eanalicular system.
4 lheantrutn; numerous rnltochondria to generate energy, and a highly active K+M+
5 the pylorus, in which the circular muscle layer is rcinfareed, adenosine triphosphatase (ATPase) pump (proton pump) rhal secretes
and whiull h n n s a tight sphincter separating the stomach from the H+ into the lumen. An apical chloride channel transports C P into the
duodenum. iumcn.10 farm HCI. .
- wall reflects the general
The structure of the aastric - -
organization of At the basolateral surface. HC0,-, formed intncellularly from CO,
hollow intestinal organs, with an additional oblique muscle layer that and H,O, is exchanged far CI; so that circulating HCO,- levels rise
.. -
SUDDOrlS its mechanicalchurninefunctionand allawsittoexeand. From
outside to insidethewallsarefomdfmm:
when the stomach secretes acid ('alkali tide'). The basolateral N a + W
ATParepurnp alsoreplenishes intracellular K+levels.
serasa: Differentiation and secretion of oarietal cells is also stimulate4 bv
longitudinal muscle layer; gastr1n.Acid secretion is increasedbyexcesrgas~n, forexamplc,inthc

. ci~~culnrmusclelayer;
obliquemusclelayer;
submucosa;
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.
. muscularis mucasae;
mucosa comprising the lamina propria and columnar gastric epithe- HClactivatcs pepsinogen, toproducepepsin, iniliatingproteindiges-
lium with its pits andgiands. lion. Intrinsic factorbinds lo vitamin B,,,allowing illoescapedegra-
The coeliac artery supplies anerial blood to the stomach and venous dation in Lhe stomach and inlestine and to be safely transported to the
blood drains into the hepatic portal vein. The stomach receives rerminal ileum, where it isabsorbed. Gartraferrin binds toFe", facilitat-
parasympathetic nerves via the vagus (Xth cranial) nerve and sympa- ing absorption in theduodenurn (seeChapar21).
thetic fibres fram thesplacchnicnerves.
Most of thegastric mucosa is thrown up incoanefoldscallcd rugae. Common disorders
whilethe antral mucosa is much smoother. Alhickmucus layer ~.protects Symptoms relating to the aamach are extremely common, bur are
against mechanical trauma. HCI and proteolytic enzymes. frequently not caused by discernableorganic dircasc(seeChapter 29).
-
Gastric its arenarrov, invaeinatians oftheepitheliuminlo the lam- Typical symptoms include nausea, epigastric pain and bloating.
ins propria. Two orthree gastric glands areconnected lo each pit via a Collectively these symptoms are lermed dyspepsia and paticnts may
-
narrow isthmus. leadine" tolheneckreeianafeachnland. -
- Garlric glands
are tubular stmelures with specialized cells for lhe production of
refel to them as indigestion. With serious cnnditions of the stomach.
there may also bc vomiting, haematcmesis, melaena and lass of
HCI (parietal o r oxyntie cells) and pepsin (chlef cells), as well as weight.
mucus-producing goblet cells, undiffmntialed epilhelial 'cells. The main serious gastric conditions are peptic ulcer and gaslrltis. !
i
entem-endocrinecellsand slem cells. 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
Parietal cells are found in glands throughout lhe fundus, corpus and and the use of non-steroidal anti-inflammatory drugs (NSAmr), and i
antrum. Thcy secrete HCI. theglycoprateins intrlnricCactor and gas- gastriccarcinoma (seeChapler31). i
Imferrin, which facilitate the absorption of vitamin B,, and imn,
respctlively.
Chief cells are found predominantly in the corpus. They secrete
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
:
pepsinogen and have an exlensive rough endoplasmic reliculum and infanls.duetoacongenitally hyper(rophisdrphincter, causing projectile
prominent apical secretory granules. vomiling. In adults. a more common cause is autonomic neuropathy. i
Themainentem-endocrinecellsofrhestomachareGcells.pmducing
gastrin, D cells, producing romatorlalin, and entem-chromaffin-likc
caused, forexample, by diabetes mellltus.
1
(ECL) cells, producing l~istamine(seechapter 16).

Stomach 21 i
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-reps,lallanas EasneJ 1sw uaBoyled pozolold e s! o!lquq mp'~!~ an!~saB!paz!saqluLs S a L ~ o ~ a l u'papnpra
a aq me3 ~ u d o q ~pus
e d pau!el
'(5s B T Eua1dsq3aas)u o m w o a~18 aseas!p Ja!laoJ
p w r a q n >!]dad apqm ' a m Llsmaoxa s! wnuaponp aq, j o 12311~3
.pOolq plsaB!pLlle!uad Lq pasne3 lools j o a3umadde h e 1 pue'lla3aq1joa3epns le~!deaq~leql os'sarBo~a1ualua3e[pe~LI!I suoll
we19 a!lsualasleq~aql 'auaalaw put s ~ r a l u a ~ e m ~'e!luasue
eq asne3 -Jun[lq8!L 'xapzoq qsnlq luau!mo~ds %u!ru~oj'runnru pue SaruLzua
paq~ellepue su!a1oldo~L18Lq palaha, aIe !Il!non!m aql joa3vj~osaqL
pus u!u!qolsLaaloq~alalJas mnuaponp aqi u! sl!a>~u"~opu,-o~?lua
laldeq3aas)au!)salu!I!ewsaqlu!aauajapla!qo~?m!lue
01a)nq!lluo:,osle i e w q q m 'uawnl aql olu! ( ~ 2 1 s v ) uqnqo12ounmw1
~ u a w ! p b o ~ a m s u o d r u e ~ ~ s a ~ L m ~ ~ r u a pp qu ~e ~
r ~d~aah~. el e( l ~ a s l l a ~~ ~
qlsued pue spuel8 s,lauurug Lq paonpo~dn3uelsqnr IP!JalJeq(lue pue 's~~a3laqlopues~~a3~e!~aqropuale~nJsch's!laslsem
p ~ s e3yseS 10 UO(1JO 141 .(q P ~ U ~ U ! P US! Iuwtuol!nua IB!~OIJ!~!IU~
~ .~~. . 'sl!qdo~~nau'sa~LmqdruL~ "raZeqdo~~em 'nrelqoqy snolamtiu su!c~
us pus eualaeq luap!sa ruoq aatj LI~A!IE[~J s! au!lsalu! llerur a u -uo~e!ldoldeu!wela q ~ , ' s ~ ~ n p m o Lquamnl
~ ~ e u a q l a panauuo3aIe pue
esammqns aql u! p?leJo! are 'spuel8 s,rauunla pallea 'spUel8 lclnqnl
paq=ueq .azelnJ1!J a a ~ ! l dse umouq sploj as~ansuul~ u! dn UA\UI~I
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
-1eloFeqaw le paseala) pue suo1~!mo[Lq3uuoj 01su!aloldod!lade ql!m -nJsnm aql'al~snwqlooms j o laLel u!q1v.a8~.lamaslla3~e!la~l~!da mau
p a r a l d w o ~Y1~elnlla38~1u!
p y u a l s a - a ~ale ' l u u q u a w p!d!! 1q1ssol3e qJ!qm u o l j (uqnqJaqa!?jo) sld6.1~u!q1'8uol olu! paluapu! s! puc !IA
uo!sg!p 1331!p Lqlalua 10111sa10q~pue sp!Je &leg 'a1Lm1alua i q l olu!
n ~ L l o n ~ apuel a sppe o u y 'mans qrosqa Llan!~aeSueJqruaw le=!de
JO n8els leuy a u .uo!isaa!p lua!~yjappue p!deJ iloddns 'salholalua
leuaponp woJJ p?eealaIassulqcualua jouo!las aql Lq pue s!sLlele~olne
:ap!su!aqlol ap!srnoaql molj a s ! ~ d m o ~ L a q l ' l l cleu!lsalu!
m aql
JO uo!~ez!ueZ~o!e~ausS 1q, IJS~SJ mnuaponp aql 40 E l l B M a q l
.u!anlwuod ~!ladsqaqlo]u!ulah J~Ja)uanmlo~radns
. ~ d aql
b ~dn sale~B!mpus aql e!n s! aBeu!e~psnousn PUB wnuaponp.sq1 sarlddns b a u e x!laoJ
sale!luala#!p 'sa~e~aj!lold 1eq111a3JalqBnepauo pue [la= wals lalqsnep a q l ' l j a l aql uo reanued ?qr 01 lua~erpesa!l pue Ja)eA j o s l l n d ~ u aql s
~ u o l o n p o 01
~ dSu!p!n!p Lq 'mn!laq~!daaqua aql qs!ualdalo~L1!3ede~ e!n a=!"[ ~!~ei)l>ued pue a!!q san!aJal ued puojls ? q 'qlnq ~ aql
aq, u!slal Lau.auoz 1123 qlauedaql anoqe Isn[pale3o[ ale SllaJ UalS palle3 s! mnuaponp aq1j o ued l s ~ ay q ~ . ~ z a ~ o ) ! ~ ~ d Lllsom o J ) a l s! pue
'(91zaldsq3aas) sauouuoq J!lalualuaJ?#!p Luew ampold pue
nseqldbaaqlreau Lllueu!mopa~dpunojale s ~ ~ a ~ a u l ~ ~ o p u a . o ~ a ~ u ~
'(81 laldsq3
aas)assas!ppue wleaq leu!lsalu! u! saloJ'pauyapun'~aqlo?neq osle L e u
Lau.su!suajap pus zvased!loqdsoqd 'amLzosL1 se q ~ n su!alold
s le!~a~ 'suo!laiJasa!ialua pun a~!n[a!~caiaued
-aeq!lue u!eluo~pus uo!lalaas pue s!saqluLs &aloJd JOJ paz!le!aads ale 'apq ql!m I! %u!x!w pue qlewols aq1 ~OIJ ? w L q ~ Bu!A!ani 'au!lsalu!
IBUIS
L a u w d h ~eu!~sa~u!
~ aqljo aseq aql 1s punoj ale sllaa qlauad ?ql j o UO!S~J
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-
. ribonucleascs;
deoxyribonucleases.
Pancrealic secretion is stimulated by hormonal signals, particularly
sue producing insulin and glucagons, thus also regulating nutrition and cholecystoklnln, which is released when food enters h e duodenum.
gnstrointestinal function globally. Secrelln enhances the effect o f cholecystokinin.
The Dancrear ecreles about 2LJdav o f a blcarbonale-rich alksllne
Structure fluid lhal helps to neutralize stomach acid and provides optimal condi-
The pancreas lies transversely an the posterior abdominal wall and is lions for digeslion by pancreatic cnzymes. Centmacinar and duct cells
covered by . .~eritoneum.The head lies to the riehl,- adiacenl
. to the duo- secrete most of the fluid and alkali, by exchanging HCO; for CI-ions.
denum,andthe body andtailextendacmsstheepigasrriumtothespleen. using the cystic fibrosis transmembrane regulator (CFTR) protein.
Thesplenieveinrunsalangthesuperiorbarderafthepancreasandloops Pancreatic insufficiency therefore occurs i n cystic fibrosis, where an
ofintestineare related to it anteriorly. abnormal CRRgeneis inherited.
Branches of the coeliac and superior mesenteric aneries supply the Pancreatic islets are the only source o f lnsulln and glueagon,
- - which
gland and venous blood drains into the hepatlc portal vein, supplying are produced by pancreatic P and acells, respectively. Insulin secretioti
the liver with hormone- and growth faclar-laden blood from the - - -
is stimulaled mainly by increased blood glucose, while glucaaon sccre-
~ ~

pancrens. lion is stimulaled by hypoglycaemia. Hormones, such 3s adrenaline.

The vagus nerve and splanchnic sympathetic nerves innervate the have addilional modulatory effects on pencreatic islet secretion and
pnncrens. Sensory nerves are routed through the coeliac ganglion and islels also pmduce hormones, such as somatostatin, which modifies
pnncreatic palinmay be relieved by its surgical removalor deslruclion. entem.endocrine function locally and throudhoul the gastrointeninal
The main pnncreatic duct extends along the,lengrhof thegland and a lracl (seechapter 16).
smaller accessory duct drains thesuperior panof the headandmay open
se~nrntelvinto the duodenum. The main duct ioins the common bile Common disorders
duct hclonc o l > c ~ l i ~into
l p the duodenum through !he ampulla of Vdtcr. Pancreaticdisearcsmayremainentirely. asymptomalicuntilheyarefar
~ .
S~,lnlle!. ~pitncre;llicducts drain into the main duct. forming n 'fishbone' advanccd.They may causeabdominal pain, felt i n theepigastriumand
patlerl,. Exocrine pnncre.~lictissue is arranged in lobules composed of radiating to lhc back. Damage to lhe common pancreatic and bileducls
the finnctio~lalunits, acini. which secrete pancreatic enzymes and fluid may cause jaundiceand pancrealicerocrincinrufficiency may result in
into tlleducts. malabrorption o f food, causing diarrhoea, steatorrhoea (fat-rich
Microscopically, pancreatic cells are arranged in spherical acini. stools), weight loss and nutritlonal deficiencies. Islet damage can
. . surFncetowardr lhecenlre and the b:bsolal-
will! theil-sccl-etorvol-n~ic;ti causediobeler mellilus.
era1 surface resting on a basement membrane. Ducruies drain each nci- -
Acute pancrealitis is a serious, potentially life-threatening illness.
nus a~ldconlescelo form larger ducts lhat eventually drain into the main The mas1common causes are excess alcohol ingestion and passage o f
pnncre;tlic duct, carrying digestive juices to the duodenum. Pancreatic galistoner rhrough the amuulla o f Valer (seeChanler40). Less freouent
ocinar cells ;wr. highly specialized for prolein synthesis and secretion. causes include various drugs, abdominal traumaand viral infection.The
They have a .pyramidal crorr-section, with prominent basal rough
~
inflamed pancreas relenses enzymes into the circulation and acute pan-
endoplosmic reliculurn, where prolein synthesis occurs, extensive creatitis is a systemic illness, nffecting the whole body. Pancreatic
golgi apparntusandapical secretory (zymogen)granuler. lipases release fatty acids that interact with calcium lo fa-rm insoluble
Over 10%~oocrinepancreaticislelsarescatreredthroughoulthepan- calcium-fatty acyl salts, potentially lowering the concentralion o f cal-
creas and are supplied with a rich capillary network o f blood vessels. cium in thecirculation todangerous levels. Adrnmatic risein lheserum
They arc lnot connected by ducts lo the exocrine pancreas, but secllete lip.~seorat~lylasclevcl ltelps lodiagnose ncule pancreatitis.
direclly into the bloodstream. The principle cells i n these islets arc P Chronic pancreatitis may follow repealed bouts o f acute pancreati-
cells, which secrere insulin, acells, that secrete glucagon, and D cells. tir. The main symptoms are abdominal pain and malabsorption due to
which synthesizesomatostatin. failure of the exocrine pancreas. Patients mav also develop endocrine
pancrcaticinsufficiency (see Chapter 40).
Function Pnncrearic adenocarcinomn is n leading cause of cancer-related
The pancreas is a powerful producer o f digestive enzymes. These ale -
death and often becomes symptomatic only at an ndvanced stage. when
synthesized and stored as inactive precursors or pro-enzymes, to avoid the lumour has become inoperable. Neuro.endocrine h m o u n , which
aurodigertion o f the enzyme-producing cells and the pancreatic ducts. arise from enteric endocrine cells, are often located i n the oancreas.

.
Pancreatic enzymes include:
trypsinagen;
althoughthey mayalroarisefr~mother~artsofth~gastrointesinaliract.
They arc gcnerally less aggressive than adenocarcinoma, but may cause
chyniot~ypsinogen; symptoms due lo their secretion o f gut hormones. Gastrin-producing -
proca1,borypeptidasesAandB: turnours (gastrlnomas) cause excess gastric acid secretion'and peptic
pro-elnstase; ulceraLion (Zolllnger-Ellison syndrome). Tumours m'ay also secrelc
phospl~alipareA: insulin, glucagon andother hormones (seechapters 16&38).
pancreatic lipase (and colipase);
pancrentic amylase;
Theliver isthelargest solidorgan inlhe body, weighing 1.5 kgin a70-kg with paniclesandcells.Numerouslymphoidcellsarepresent,including
-
adult. I t develoos from lhe embrvonic foreeut cndodem and is an inte- . and dendrltlc cells. Their function is
special subsels o f lvm~hocvtes
. .
gral part ofthe gastrointestinal system. I t performs vital metnbolic, syn- unknown, although they probably contribute to special immunalaeical
~ ~~

thetic, secrelory and excretory roles, and life cannot be sustained for properties oftheliver(seeChapter 18).
morell~ann few hours without lhe liver. , . . are large,
Hepatocvtes - cuboldal cells with a cenlral nucleus that is
occasionally tetraploid. They are functionally polarized. with slnll-
Structure soidal and cansllcular poles. Tlghtjunclionsanddesmosomessealoff
The liver lie in the rich1 . upper quadrant
~~ . o f the abdomen, directly (he canalicular membranes, across which hepatocytes secrete the con-
under1herighthemidiaphragm,protected by thelowerribs. Itcmrscrthe slituenlsofblle.Microvllli helplo increase thecellsurfacearea.
-
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 lnlracellular organelles. There is extensive smooth r n d o p l m i c
segments thntcan beidentifiedsurgically, baredon vascularsupply and reticulum for lipid and cholesterol synthesis and rough e n d o p l m l c
bilinry drainage. reticulumforproteinsynthe~is.Therearemanymllochondrlainwhich
On the ihferior surface, i n the mid-line, the p o n d vein and hcpatic melabolicreactions, such as the Krebs cycle, occurand wherechemical
artery enler and common bile d u a and lymphatic . . channels leave lhe energy is generated. There are lysosomes, peroxlsomes and endocytid
h i l u m or the liver. There structures divide into major right and left vesicles rupponing digestive functions, and storage vacuoles, glyco-
branches within theliver.The inferiorvenacava lraverses theliverpor- gen granules and fat droplels.
leriorly, where themain hepaticveinjoins it.
Thegallbladder lies under the liver to the right of the mid-lineand is Funclion
connected to thecommon bileduct by thecystic duct.The hepaticflex- The liver's complex functions have not yet been reproduced artificially.
urenftl~ecnlonlies to the rightofthegallbladder.Theliverparenchyma They include:
is enclnscrl in ;I tough fibrous capsule, which is mostly covered by peri- Regulating homeostasis of carbohydrate, lipid and-amino acid
loncutn, npxt rrom the barearea underthedomeofthediaphragm. metabolism.
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
- Storlngnutrien(ssuchasglycogen,fats andvilaminsBl,.AandK.
Producing and secreting plasma proteins and lipoproteins, including
clouingfactors andacutephasepmteins.
dl-ain;lpc is via t l ~ e hepntlcvein.
Miumscnpic:nlly the liver parenchyma is homogeneous, with repeti-
. Synlhesizingandsecrelingbllesallsforlipiddigestion.
Detoxifying and excreting bilirubin, other endogenous waste prod-
tion of the same basic organization . throughour. Hepalocytes
~. form ucts and exogenous melal ions, dmgs and toxins (xenobiotics).
three-dimensional cords and platesin the liver.These are separated by Clearing toxins and infective agents from the portal venous blood
sin~usaidsil~l.c~tgl> w h i c i ~1,lood flr~wsnlnwly.Tllcre arc lwn in;tin w;lys whilst ~noinl:~iningsyrlcmic i~nm\~nctolerance tnantige~~sinthe portal
c , l e c > ~ ~ c ~ . ~ , t ~the
; \ l itnicruscupic
~i~~g nrrangemest. I n the lobular model. circulaliun.
the hepatic venule is at thecentre, withponal vein branches at threecor- I n addition. hepatocytes retain hecapacity to prolilersle, so h a t h e
nerr of a rix-sided lobule. I n the acinar model. the ponal vein and livercan regeneratedramatically afterinjury.
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 Common disorders
centre. Liver disorders can cause many symptoms and signs., ranging from
The walls of adjacent hepatocytes form bile canaliculi. Specialized vague malaise lo fulminant liver failure, with disordered coagulation
blliary epithelinl cells line small bile ductules, larger ducls aod the and coma. Typical fenlures i<~cludeJaundice, tatlgue, loss olappelite
.gallbladder. and pain in the right upper quadrant o f the abdomen. Because of h e
Hepatic stellate cells, also known as 110 cells or fat cellr becallre they grcat reserve capacity of the liver, extensive damage may remain
colltain erorninenr droplets of fat and relinoicacid la vitamin Aderiva- asymptomalt.
live), aresituated deep totherinusoidal endorhclium.They elaborate thc Viral hepatitis is common throughout the world. Liver a b s c w m ,
connective tissue matrix of Lhe liver and respond to injury by causing causedby amoebae, bacteria and parasites, arecommonin somepartsof
fibrosis. h e world. Drugs and toxins, including med.cauons, also commonly
Endothelial cells line the sinusoids.They rest on a looreconnective affect the liver and the most impomnl of there Is alcohul. Chmnicdam-
r i x , as thesnaceofDise. andarediscontinuous.Thev
tissue ~ i ~ i ~ tknown age may cause scarring and lead lo cirrhosls. Ovenvhelming liverdam-
also contain gaps or tenestrae, which may allow molecules, parliclcr
and even cellr to easily penelratethe parenchyma from the sinusaids.
-.
age,eilheraculely orchmnicall~,causesllverfallurr.Alhoueh~riman.
liver cancer is rare, metaslatic cancers are common (see Chapters 33.
Withi,, rinomids, resident macrophages calledKupffercells interilct 38.41 &42).

Liver 27
Bile is formed by. hepatocyles
. . and modified by the specializcd biliary Active secretion of bile acids, electrolytes and organic compounds
epithelitlnl. It is an exocrine secretion necessaryfordigestion, anexcre- draws water with it and bile flow isencouraged bycwrdinatedconuac-
tion oroduct far removal of toxins and metabolic waste and a van o f the tionofcytoskeletal pmlelnsadjaeenltothecanalicu1armembrane.The
host defencesystem. canaliculi secrete450 muday and bileducts add 150mUday.
About 60mLofbileis storedin thegallbladder.Cholestemlisamajor
Structure insoluble constituent o f bile and it is stabilized by incoporation into
Macroscopically, the intrahepatic bile ducts, common hepatic duct. mixed micellcs, formed by bilesalts andphospholipids.
cystic duct, gnllbladder and common bile duct constitute the biliary Abnormalbllemaybefonedifhepatocytesareoverloadedwithone .
system. or other component; forexample, haemolysisresults inovemroduclion
The gallbladder is a pouch-like structure with a thin fibromuscular of bilirubin, which may crystallize to formgallstones.
wall located under theanterioredgeofthe liver. Itsepithelium is thrown Cholecystoklnln is released from theduodenum whenfwdarrivesin
up in complex fronds, increasing the surfacearea.Theneckof thegall- it, stimulating contraction o f the gallbladder and relaxalion of the
bladder lerds to the cystic duct, which joins the common hepatic duct. sphincter o f Oddi, thus delivering bile to the duodenum just when it is
fornied frotnthe union oftheri~htandleft intrahepaticducts, lo form the needed.
common bileduct, which leaves theliveratthehi1um.Thecommonbile Bile promotes the dlgestlon and. absorption of fats and fat-soluble
duct lies ndjncent to the hepatic anery andponal veinand joins the main vitamins in several wayr.The alkaline bile promotes emulsWeationof
pancrcaticduct beforeentering theduodenum through the ampulla of -
fats, which allows greater access to digestive enzymes.
. . and bile acids.
Vater. which is keptclosed by thesphinclerolOddl. cholestero! andphorpholipidsfommixedmlcelles,intowhichdigested
Thc hili:lwy cpill>eliamlining the major ducts and the gallbladder is fauy acids and other lipids are incorporated. l h e alkaline p H is also
composed o f a single layer of columnar or euboldal cells resting on a optimal for pancreatic lipases.
basemen1mcmbrone. ItcansecreteCI-and walerand in thegallbladder ~ r l m a r bile
y acldsaie synlherired i n the liver from cholesterol and
the s:me cells nbsorb water, to concentrate bile. 95% o f the secreted bile acids are reabsorbed in theterininal ileum and
The hilinry cnnalicutus is the primary site of bile production. I t is o carried into the portal venous circulation. These secondary blle acids.
channel for~nedfrom apposed .. surfacer of adjacent hepatocyles. TighL which have been metabolized by bacteriainthein!atiiline,arelakenupby
junctions sepnl.ate the canalicular membrane from the basolateral rur- hepatocytes and resecreted into the bile. This constituta the entero-
faceofthe hepalocyte, -
. . allowingtranrporl . proteins
. to create and maintain hepatiecirculation(reeChapter24).
concenlmtiongradients.As biliarycanaliculi convergeandenlarge,spe- Bile isthemainpathway forexcretionofhydrophobicwastessuchas
ciillizcd hili;lry epitheli;!l cellsreplace hepntncyles. bilirubin.

Functian Camman disarders

Each day, 6 0 0 m L of thick, mucoid, alkaline bile is produced. la main Jaundice, caused by accumulation o f bilirubin, is theclassic symptom !
constituents are: ofbiliary disease. Interrupting bile flow to theintestinecaurespalestool

.
a
primary bileac1ds:cholic and chenodeoxycholicacid;
secondarybi1eacids:deoxycholicandlithocholicacid;
phospla~lipids;
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
cholesterol; causc stealorrhoea, weight . loss and nutritional deficlencv. Obsmc-
bilirubin; tion and inflammation o f the biliary tract can cause pain. fever and i
conjugated drugs andendogenouswasteproducts; malaise (seeChapten33gi40).
electrolytes: Na+.CI~,HCO,~andtracemetalr,ruch as copper; Damage to hepatocytes, for example by viral hepatitis, may inhibit
secretory dimeric immunoglobulin A (sIgA) and other antibacterial bile secretion, by decreasing ATP levels, interfering with Lranrprter

-
proteins;
mucinglycoproleins.
lkansporter proteins on the basolateral surface of the hepatocyte.
. .
function and damagingcytoskeletal
-~~
proteins. This causes InIrahepatie
cholest~is,withnomacroscopicblockagetothe
dmas. can .produceasimilaieffect(seeCha~ter41).
biliarysystem.Cenain

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

Caecum nrtd appendix 35

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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 -
mences. Puboreclalis and levator an1 relax, allow in^ the anorectal
angle to straighten, and abdominal muscles conlract, to increaselnlrn-
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 abdominal pressure and help expel faeces. Conversely,iftheexlemal
vesicles in men and behind thcpouchotDouglns, uterusandvagina i n anal rphinclerdocs not relax, the urge todefecale passes.
women. Althoughthe rectum does not normally absorb nuhienls, medications
The wnli ofthe rectum is similar to thecolon, except that the longim- canbeadministered by asupposiloryoranenemasndnr~absorbcdinto
dinal muscle layer is continuous.The mucorair thrown into threesemi- thesystemiccirculation.This isparticularly usefulinbabiesandpatientr
lunar transverse folds, known as the valves of Houston, which sep- whocannolswallow.
arate flaws from faeces and prevents them entering the distal recmm
spr,ntoncously. Common disorders
Distally, the mucora forms longitudinal ridges, called rectal Anoreclal disorders typically caujc pain, itching ( p r u r l l k snl) find
cnluntns, itnd the intervening furrows terminale in rmnll folds at the bleeding (haematochesia). Pain can inhibit defecation, resulting i n
.LO~~IU:I.~~~, hardening of the stool and a self-perpetuating cycle ofconstlpalion.
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 -
lnflanlmation causer dlarrhoca and the .passage of mucus. Chmnic -
rnAcu\.#e a i d .rtermcd tnc dentaleline inflammation can reduce the ability o f the rectum to dilate, causing
-
Tilree c~shlonsof.oose conncclivc lirruc arc arranged circumfcrcn~
tialiy above the dentate line. They contain a venous plexus (haemor-
- .
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 Segmenting movements: which are randomly spaced, non-
propulsion of food from moulh toanus.It also dischargesglandularcon- propagating circular musclecontractions that mix intestinal contents.
tenls and allows sphincters lo separate inlestinal companmenls. Colonlcmassmovement: whichisapowerful.sweepingconmclion .
that occurs a few limes a day, forcing faeces into the reclum and rlimu-
Structure latingdefecation.
Apart from the moulh, tongue, pharynx and external anal sphincter, Interdigestlve migraling motor complex (IMMC): which com-
which hnve striated muscle under voluntary control. the gaslroinleslinal prises three stages lasling about an houreach, occurring between meals.
system contains non-strialed smooth muscle undcr enteric and auto- In rtagel, movement is absent. StageII,compriringofrandomregmer,t-
na~nicncrvou control. Unusually. the upper oesophagus has s~riated ina
. movements. is followed by -
. stage 111. which com~riswa forceful
musclc th;\t i s notundcrvoluntaryconlrol. wave o f contraction that migrates from lower oesophagus la terminal
The al;\in masclebulk is arrnnged inan outer longitudinal layer and ileum. This wave, sweeping the stomach and lntwtine clean of food
an lnnercirculariayer,allowinl:rhaneningandconstrictionofthe hol- debris, is lermed the 'intestinal housekeeper'.
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 ~. y ~ r i t ~ Regulation
o l ~ l l t ~ t t ~ l i ~IIICSC ~g~~~~~~ls
1;tycl.s i n lhc slonrnch and thecircular layer is thickened uruund sphinc Pcrislalsir is intrinsic lo the intestine, occurring even i n surgically ira-
-
ters, incre~sincthe constrictive force. Themain sphincters arerhe lower lated scamenls,
. and is mediated by reflex enteric nerve activiw. Nitrlc
oesopl~agealsphincter.the pyloms, the sphinclerofOddi. the ileocaecal oxlde (NO) is the main mediatorofrelaxation i n the advancing f m t o f a
valve and the anal sphincter. peristaltic wave, while acetylcholine (ACh) and other neumuansmil-
Arhin layerofmuscle,themuscularis mucosae,separatesthelamina terr mediateeontraction.
propria from thesubmucosa. Enlem-endocrine and neural pathways mediate reflex molllily
Smooth muscle cells are spindle-shaped and lack striations crealcd involvingspatially separatedp~rofthegasuointestindsystem, suchas
by organized bundles ofactinand myosin. thechalecystokinin-inducedcontraction o f the gallbladder i n response
to food in the duodenum. the garlrocolic reRex (urge lo defecate ahcr
Function eating) and the ileal brake (reduced ilwl perisklsir whcn food reaches
Commction is mediated by cross-linking of aclin and myosin, as the distalsmall intestine).
in striated muscle. Contraction is initialed by increased imracel- Serotonin (5-hydraxytryptaminc. SHT), releared by emera-
~ ~~~

lular Cal+ concentration, which is regulated by hormonal and neural endocrine cells, is a critical regulator o f intestinal motility lhraugh its
signals.
Intrinsic clectric pacemaker cells are interspersed among the
. .
effects on enteric neurons. 5HT. reccDlors mediateincreased intestinal
motilily,while5HT4receplorrmediatctheapposileeffect,andselective
muscle eclls and there provide a characteristic. low frequency wave o f inhibiton could prove to be useful therapeutically.
elccll-ic:cl clup<rlnricatinnand repolariznlion, known as the slow walvc.
Ihnl lritvcls down Ihe intestine. Pacemaker cells communicate via gap Common disorders
- -
junctions. with lhc signal travelline: faster circumferentially than Dys~notility may manifertaspain,discomfort,earlysaliety.vomiling.
tlnnsvcrscly, so that a synchronous wave is propagated along the diarrhoea or eonslipation. I t is associated with same rare but serious
intestine. Dirtinet pacemaker frequencies characterizeeach organ: for conditions andrame morecommonconditianr.
exnml>le. the gastric slow wave frequency is three contractions per Ocsophagealdysmotil~tycancaurepain(odynophagia)anddifficulty
minute. which can be measured throueh
wall (electmgastrography).
,
,
-
'
electrodes on the abdominal 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
Toniceontractions proximally, causesdysphagiaanddilatationafthedirtalaesophagur.
These are mainly sustained, low-pressure contractions that occur i n lnfantsmay deve~o~gastricoutletobstluction with penistent projcc-
-
oreans with a mnior storage . function, such as the allb bladder and rec- tilevomilingduelocongenitalhypertrophyafthepylorlcsphlncter.
turn. High-pressuretonic activity characlerizessphineterr. Followingsurgery or severeillness, generalizedparalysis oftheinles-
tine, known as paralytic lleur, may develop. This is aggravated by
Phasiccontractions hypokalaemia, hypocnlcaemia and the use o f opiate.$, which inhibi!
These short-lived. rhythmic contractions predominate in the intestine. intestinal motility. 11usually resolvcssponlaneously, althaughtheinter-
They are controlled by intrinsic pacemakers, autonomic newer and tine may dilate to such an extent that the wall becomes irchaemic and

.coordinnted reflex enteric nerve activity, and include:

Peristalsis: whichis acomelexmovementwhereby a waveofmurcu-
emergency surgery is necessary.
Less well-defined abnormalitiw o f motility may contribute to slow-
larrelax.ntion. followed by a waveof conlraction,passes dawn the intes- transit constipation, functional bowel disorders and lrrltable bowel
tinal iract proximally to distally. The wave forces intestinal contents syndrome (IBS).
bcforc it nnd is mast prominent i n the oesophagus, stomach and small Muscular spasm may be treated medically with ~elaxentssuch as
inlestine. In vomiting, peristaltic contractions move rctrogradcly mebeverine and hyorcine. Sphincter spasm may be mechanically

-
(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
dilated or botulinum toxin injections may induce temporary paralysis.
Bolh lechniquesareused lotreat achalasia.
Metoclopramide may stimulaleforegutmotility, as may erythromy-
-
and nlixinc- solid food. tumine: it into a semi-liquid chyme that is cin, acting on motilin receptors, and neostigmlne, aclingon murcarinic
relcase<linto tl>cduodenum. acetylcholinereceptors.
The first lhormone ever discovered was the enteric hormone secretin. least five different receptors (SHTI-, receptors), sometimes mediating
Subsequently, over30enteric(orgut) hormones havebeendescribed, all oppasiteeffects.
secreted by specialized entero-endocrine (also called ncuro-endocrine) Some enteric hormones and their receptors have very jpccific effects
cells distributed throughout the gastrointestinal system. They mainly thal have been successfully largeled therapeutically. Hlstamlne re-
control g:~rtrointcrtinnl motilily and secretion, and they mediate ceptor LypeZ(H2R)
~ .~ antagonists, such ar cimetidineandranitidine.Ihat
camrnonicntion fromonepnrt of the intestine to another and outside the reduce gastric acid secretion. are amollg the mast successful agents of
intestine. iorexan~ple,tothecensalnervoussystem. this type.
Similarly, octreollde. a modified octapeptidc (8 amino acid) homo-
Structure logue of somatostatin, is widely used to inhibit the secretion of other
Entero-endocrinecells enteric hormones, inhibit intestinal exocrine secretian and reduce
The entero-endocrine system is diffusely distributed. Mort entero- splanchnic blood flow.
endoel.ine cells a1.e found i n theepithelium of the intestine. They vilry There are now also new agents aimed at inhibiting different 5HT
in sh;~pe,although most arc pyramidal with the base of the pyramid on
~ ~
receprors.totreal aspectsofthe irritable bowel syndrome0BS). '
the basement membrane, where prominent secretory granules are Attempts to use leptin to decrease appetite and induce weight loss
located. Somecellsspan theepilhclium, with theapex incontact with the have been aenerally unsuccessful; however, now that the role ofenteric
lumen, whilc athers do not. Entero-chromafin-like cells (ECL) are hormones i n regulating body mass has been appreciated, this is e chal-
similar in structure but are located i n the submucosa or in the ~ancreatic lengingand promising areaofclinical rescarch.
islets.
Many entera-endocrine cells contain more than one hormone, and Common disorders
hormones are preferentially distributed i n cells i n different parts of the Subtle enlera-endocrine dysfunction may be rermnsiblc far very
system. Entcric hormones are alro found i n neurons i n thcenteric and common conditions ruch as the irritable bowel syndrome and obesity;
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 Most serious cntero-endocrine diseases are rare, although clinically
system therefore often overlap. silent carcinoid tumours are frequently noted alautapsy.
Symptoms caused by disorders of the enter-endocrine system are
Enteric hormones protean, reflecting the many effects of enteric hormones. To diagnose
Alnlort ail cntero-endocrine cells contain serotonin (5-hydroxytrypla- -
entero-endocrinedysfunction.cireulatine:enterichormonelevclsmav
mine. SHT), in addition to peptide hormones, while E C L cells be mcasured (in the fasting slate, as feeding alters the levels of mast
contain histamine. Most enteric hormones are short peptides that are hormones) and excess 5HTsecretion may bedetermined by measuring
synthesized as larger 'prepropeptides and modified by. for example, urinaryexcretionofS-hydroxyindoleaceticacid(S.HIAA),-
~ ~

cleavage. amidillion and sulphntian. They fall intostructural familit- Carcinoid tumours arise from entern-endocrine cells, and are rela-
and liss~tcdistl-ibulion :~ndfunction vary widely (see table in ligure tivelycommon.They maysecrelcavarietyofhormoncs andgrawthfac-
opporile). tors and 5HTsecretion is usually prominent. Carcinoids urnally wisein
theappendix,butmavoccurinother~Msot~he
.. inlestine.Thcoorialcir-
Function culation delivers 5HTfrom intestinal carcinoidr to theliver, which effi-
Enteric hormones perform a great range o f functions and work i n differ- ciently clears it, so thal patients remain asymptomatic. However. when
ent ways. Some are relatively well understood and others are only now the tumours metastasize to the liver nnd deliver their hormonesd i i c t l y
beginning to beunderrtaod.The functions ofsomepeptidehormones are intothe syslc~~~~ccirculal on. lhcy glvc rare lo the carcinoid syndrome.
shown in the tableapposite.
.. character zed by~. -
cp.rodcs of Rushina caused bv release of SKT and
Enteric hornlones may act locally (paracrinc action) i n [he im- fibrosis of !he heart and peripheral tissues, caused by gmwth facton.
such as transforminggmwth factor P (TGFp)released by the tumour.
'
mediate vicinity of where they are secreted: forexam~le,somatostatin
produced by D cells i n pancreatic islets inhibit insulin and glucagon G-cell tumours (gartrinomas) secrete excess gastrin, causing the
recrctian. They may alro first enter the circulation and then be trans- Zollinger-Ellison syndrome, which is characterized by severe gastric
poned to targets i n other parts of the intestine (endocrine acrion). All hyperacidity, mcurrenl peptic ulceration and malabsomrion due to the
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-
- - may occur sporadically, or in association with otherendocrine tumours
dercontraction.They may alsa betransponedtootherargansand, in par- i n a syndrome known as multiple endocrine neoplasla I, or MEN-I.
-
liculnr, to the central nervoussystem. Lentin and e l l n l i n are recently The syndromeis caused by an inherited abnormality i n therumoursup-
discovered exsmples, which signal satiety, and arc involved in the pressor gcneMEN1.
canlrolof nutrition. There are many other rare entcro-endocrine tumour syndmmes, ruch
Indlndual l~onnonermay also have different effeca an different tar- as glucagonomas and vasoactive intestinal peptide (VIP)-secreting
gcts,somel mcsmed vted by separate receptors Examples .nciudegns- tumours that cause the syndrome of watery diarrhoea and hypokalaemia
tun u~~~~hb~nd~toCCK-AandCCK-Breecptors,and5IIT,wh~chh~r~r (Werner-Morrison syndrome) (see Chapter38).
17 Enteric and autonomic nerves

44 Integraled function
 st sauau ?worornopuo +a,ujy
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i l o uo!lJuysLa .ulsd [eu!uopqe pue uo!)sd!lsuo~ 'eaoqme!p '2u! -110lo3aqijoa~nxay
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a q u! punoj u0;daJaJ u!ed pus aJmslldmal 'q3nol1ql se q ~ n s'sue&o
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01 a ~ n q y u oSJO~IJEJ L u s .uo!lesuas
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aqu!lndqXlosuas ~eJaJs~~jo8u!po~~e11eds amos s! waq1 q8noqllv . . . -
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puu ~!laqiedrnLs
aql Lq palUnJaUU! Bu!aq so lprn se 'ualsLs SnoAJau 3!~31ua J!PLI!.IIU!
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The gast~~ointerrinal system presents a large exposed surface ilren tho1
must be maintained and defended. Furthermore, prions, viruses, bacle- While host defences murl prevent infection and damage to the absorp-
. .
ria.. oarasites. inert articles and toxins areconstantly. innested
.. and there
is a large resident microbial flora, particularly i n the large inresrine.Tlie
tive epithelium o f thc gaslrointestinal tract. the commeiual flora ofthe
intestine is essenlial for health and thesystem musl distinguish between
mucosal immunesystem regulates how the body responds to thesechal- beneficial and harmful bacteria. Furthermore, while the intestine musl
lcnges. mounl irnnit~ne responses l o pathogens, it must also preventreaclivily to
food antigens l o avoid allergits and hypersensltlvlty. The mucosal
Structure immunesyrlem fulfils these functions in wayrlhalaresrill poorly under-
Many structures contribute lo gaslrointestinal defences, Innate defence stood. Thus while pathogens are generally repelled, om1 tolerance
mechanisms include: develops lowards lo harmless inlestinal conlenu.
The constant movement o f intestinal contents, and their periodic M cells. These Vansport intact peplides, viruses and bacteria amss
expulsion. the epilhclium and pass them on to antigen processing and presenting
The p H andchemicalcomposition ofintcslinalsecrclions; forexam. cells. The surface molecules involved i n this transpon are presently
.
ole.corrosivestomach
. -
acid and delereen1bile salls.
Anlibnclerial enzymes and peptides, ruch as lysozyme in saliva and .
unknown.
Mucosal homing. Anligenr taken orally are Vansported lo regional

-
otherexocl-incrcererianr.
Mucins form atough, slippery mucous gel.prolcctingepithelialcellr
from ~echanicaldamage.
lymph noderwherethey causcprolifera1ionnflymphocyler.Theserpe-
cific T lymphocytes and antibody-producing B lymphocyles leave the
lymphnodes and returntomucosalrurfaces.
Int~.insicecllt~lnrdcfcncer in epithelial cells. which can rcsist and Homing to the mucora is mediated by cell surface molecules h a t

-
limit invasion by pathogens.
Specialized inleslinal epilhciiai cellr, such as Paneth cellr, which
recrcle mimy ;~nlibacrerialenzymcsandpcplider.such
. . as dcfenrinr.
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-
M n s l cells, corinophils, neutrophils, macrophages and dendritic sion molecule (MAD-CAM). Specific cytokines (chcmokiner) also
. .
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 cx;tmplc, thymus ;~ndcpilhelirl expressed chemokins (TECK) attracts
nnli~et,riocelisol'tl~eadilplive immunesyrlem. cells lolhesmail inlcslinc.

- Adnplivc im~nun~edefences include:

1,sminn 1,ropria lyntpl~oeylec:thcsc B nndTcells ;,re distinct <n>m
Secretory dimcric immunoglobulin A (slgA). Mort B cellr at
mucor;al rurfaccs produce IgA, which is the most abundanl

.
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
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
through. but o~.cresidemin this position. Many ofthcsecells erprerry6 basolaleral surfaces of epithelia. The complex is transparted across
T-cell receptors, with a rcrtricted repertoire, rather lhan [he regular ap the ccll cylopiasm (transcytosed) and slgA is released at the luminal
T-cell receptors foundelsewhere.Thcy react lolipidantigcnsprcsented surface, by proteolylic cleavage of SC.
o n C D I cell surfacemolecules rather lhan pcptidcr prerented onclassic
major histocompatibility complex (MHC) class I or 11molecules, and Common disorders
may have a special role responding lo protcolipid antigens i n bacterial Thc intestinal epithelium is no1 impervious lo proteins, virurer and
ccll membranes. bacteria, as war previously assumed. Prions, such as h e bovine
Peycr'r patches: there are distinctive ruucturer wilh a specialized spongiform encephalopalhy (BSE) agent, viruses, such as human
epitheliitl lining,conlainingBandTlymphoeyterandantigenprcrenling immunodeficiency virus (HIV), nnd pathogenic bacteria, ruch as
cells. They arc [noit numerous in [he terminal ileum. The spccializcd Skigella, are taken up by M cells, allowing systemi- spread and
dome epithelit~mleckr villi andcrypls and the glycocalyx ~. formed by infection.
micravill~nnd membrane glycoprolelnr is dcfi:ienr. It conlntns rpccial- Selective I g A deficiency affectr; about 1: 500 people, wilhout much
izcd ewnc. al cells called micmfold or M cells. wh.ch lack microv~lln eifecl on cntcric immunity.
and contain membranous folds enclosing lymphocytes, macrophages Chronic immuncstimulation, for example, by Helicobocrerpylorior
and dcl~d~.itic -
cells. Thev. t r .a ~anliaenr and transoon them across the bycoelikdisease,canlcad loerc~sproliferalionofimmunecellr,neo-
cl~ilheii~l~ll.1K1 inlerialwith immunecells. plaslicchangeand inlestinallymphoma.
UndcrlhcdomeepiBelium, lymphocyter,macrophagesanddendritic Truefood allergies are rare, although they may be becoming mprc
cells form a loose T-cell-rich cortical reglon and compact B-ccli-rich frequent; particularly thosecaurcd by nut antigens.
follicles, resemblingtheorganizationoflymphnodes. Dysregulated immune responses are implicated i n coellac diseare,
Tonsils are lymphoid aggregates surrounding the opening o f the where here is hypersensitivity to peptides derived from wheal and
hypopharynx, with a broadly similar structure and function to Peycr'r other cercals and in Inflammatory bowel disease (IBD). Inflam-
~p:~lcllcs.iancl in 11,~: s l o r l ~ n ~CI~IIIII
l ~ . l ~ appcndlx,
d Peycr's pillch~slnlity ~nsliul\o!ily nunn;tlly he ttctively prevcntcd by subscls of T lympho-
be substituted by less well-defined lymphoid aggregates in lhe lamina cytes, which might have regulatory functions that are defective i n
proprin. IBD.
The main function ofthe intatine is todigestandabsorbnutriena, and it Enzymes
is variously adapled for this. Taste provides a guide lo thc nutritional Enzymes arethemoslcriticalelementofdigestion,enablingchemieslly
valueor potential toxicity offwd,and while thecolon is nolesscnlialfor complex, polymeric focils to be processed to absorbablemonomers at
nutrition it helps to conscrve water and mlts. Details o f digestion und physiological temperaturesand i n a reasonable timescale.
~ ~

absorptioll are considered in Chapters 20 and 21 and here general Enzymatic digestion starts in the mouth with sallvary amylare.
principles oreemphasized. -
whichbreaks downstarch toformsunars.Stomachacidinhibi~~amvlase
aaivity and activates gastric pcprinogen lo form. pepsin,
. thus initiating
Coordinalion protein digestion. Mort enzymatic digestion takes place i n the duc-
Hunting. gathering and nupermarket shopping all requirc exquisite denum and.jejunum,
. where pancreatic and small Intestinal enrvmes
neuromuscular eaardination, as do biting, chewing ands\vallowing. act in an aikalinc milieu. The pancreas produces a prorligiour amount
-
Thus. ~atienlswhoace weakorwho haveneurolanicaldisease. suchar a and variety o f digestive enzymes, including protelnases, amylaer.
stroke, c.an rapidly become malnourished. Once food passcs from the l i p a s s and nuclears, and pancreatic failure invariably causes malab-
mouth to the oesophagus. the involuntary enterlcnnd autonomic nerv- sorption and malnutrition.
ous s y s t ~ t ~itt~d
~ stlormanes produced hy the entcro-endocrine system Enzymes can potentially digcstcomponents o f thecells that pmduce
cnol-<linntccligestio~tnnd;~bsorption. them (autndige~tion);therefore, many are synthesizedas inactivepro-
enzymes. Other enzymes activate them by proteolytic cleavage; for
Molilily example, pancreatic trypsinogen (procnzyme) is cleaved to q p s i n by
Food moves progressively through the intestine aided by peristalsis. entemkinase secretedby duodenal enterocytes.
which is nlodificd by neuronal and endocrine signals. Anlegrade move- Enterocyter contribute a critical final stage of enzyme digestion.
ment is complemented by churning in the stomach, which mixes and whereby brush-border disaccharldases and peptldases attachcd to
~ulvcrizesfood into chvme, and the action of sohincten, which seua- theirapical sutfaces break down panially digestedsugarsand peptidesto
~.;lle i'<v><linto ;~pproprinteeomp;~nments. For example. the pyioric absorbable monomersandoligornea.
sphinctcrkeepsfood i n the stomach until il is thcconectconsistency for Within enterocyler, enzymes continue the digestive process; for
dipestion in Iheduodenum. example, fatty acids are reconslltuled inlotri~lyceridesandasrembled
. ~

into chyiomicrnnsbeforeexportat the basolateral membidneand trans-

Mechanical disruption pon lothecirculation vialymphaticchannels.
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 Special laclors
into snlnll picccs, wllilesaliva moistens and lubricates it. Panicle riles Intrinsic factor isaglycoprolein prcduccd by the stomach,whichbindr
are h~rtherreducedin thestomach, wherepowerful muscular churning vllamin D,,,
.. protcct.ng :t from breakdoan i n the proximal intestine. I n
converts food intoa thick suspension called chyme. Reducing thesizeof Ihe terminal ileum, vitamin B,, is released and absorbed. Similar ryr-
food particles increams thesurfacearea tovolume ratio,enhnncin%the tsms operate for other essential minerals and vitamins. Some nutrients.
action o f digestive cnzymcr. Chyme remains liquid until i t reacher the for example, vitamin K, may be synthesized i n the intestine by com-
large intestine. where waste is convened into semi-solid faeces by wnter mensal bacteria.

Surlace area
Abroqtion o f digested food depcndr critically on a well-adaotsd and
Solubilizalion ample surface area.The small lnleslineis the main absorptive surface,
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
-
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
lumen is nctively secreted by theintestineandexccrineglands. Itissub- the hcad').
sequently reabsorbed, to maintain fluid balance. Pllcae circulare nrctransvene folds, which increase the surface area
threefold, and villi are finger-like projections inlo the lumen, which
Emulsification and micellelormation increase inte7tinal surface area 10-foid. Micmvilli, which are micro-
Mnsl dictnl.y fill is too hydrophobic lo dissolve in wdter, so mixing in scopic, linger-like projections on thc apical surface o f enterocyter.
tile alkaline intestinal lumen emulsifies it, creating tiny panicles increase theabsorptive sutface area 20-fold. so that overall the surface
and inc~.ensinpthe surface area available for lipid-digesting enzymes.
area is increased 600xover thatofasimplchoilow tube.
A ~ n p l ~ i l ~ l tbilcsalts,phospholipidr
ilie nndcholcrlero1,esterssecreted in . .
bile form micellcr, which are microscopic particles withn hydrophobic specialized absorptivesurlaces
ctrrc ;tnrl the Ihy~lropllilicp:ms o f the molecules on theoutside. nigesled , Entemcyte~arc crq! lritcly adapted lor abcorption by capresing the
lipi~ls.suvl~ ;Is I'atly acids, pal-titioointo ti~ehyd~ophobiccore;~nde:~nbc nppropr.ittccell mctnl, anc lransportersandchannels lnaddilion,rcc-

absorbed from ~teintertinallumen. 1.0"s of the intestine arc specialized for absorbing panicularnutricrts:
--
for exarnplc, folic acid is mostly abscrbcd in the leiunum and vitamin
Acidification and alkalization n,,and blle.~cldsarc mostly ahsorbzd in lhetermlnal Ileum
Optimal digustion in thestomach requires an acid environment, created Enterocytes can regulate the extent o f absorption; forexample, Iron
by HCI, secreted by gastricparietalcells. Conversely, optimal digestion transportis inhibited when there aresufficientbody stores and, ingenetic
by pancreatic enzymes requires an alkaline medium, provided by haemochromatosls, regulation malfunctions and paticntr accumulate
HCO;,secrcted i n the bileand pancreaticjuice. 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- Control of body mass
-
tem. whichnlsorenulates -
theirdistribution,stora~eanddisoosal. Conse- Maintaining healthy body weight and proportion lhmugh life is acorn-
quenrly, gastrointestinal dysfunction causes disordered nutrition and plex featofneuralandendocrlnecontml. thedetails ofwhich anonly
disordered ntlllilion has profoundeffects on thegartrointertinolsyrtem. now being discovered.
-
The sloean: 'what we eat. what we are and what wcdo' encaorulales
nutrition. An adequate supply of nutrients must be available, the recipi-
Food and calorie intake is regulated behavlourally and neumnal
control involves the conex and centres in the hypothalamus and
~ ~

en1 must be in a slate to metabolize nulrienls to build and repair tissues brainstem. Many n e u r o t r a ~ m l l t e r s including
, peptide Y (PY), pro-
andutilizechemicalenere~.and -.. whatultimateuseirmadcofnutrientsis opiomelanocortin (POMC), noradrenaline (NA) and serotonin (5-
determined by what the recipient doer. hydroxylryptamine, SHT), are involved in the control of aowtite. ..
Thus. :Isedentary office worker user food diflercntly lo an Olympic POMC- and PY-containing hypothalamic neurons integrate signals and
athlete or n critically ill patient on a mechanical ventilator. In each case
what they do is potentially enhancedor limited by nutrition.
-
communicate with the brainstem. which in tumssienalstothehvwthal-
amur using NA.
.
,

Leplin is a critically important peplide hormone rrlearcd by

Basic nutritional concepts adipocytes and lntesllnzil cells lo signal that adequate calories have
.
The main foods.. orotein. corbahvdrilte and fat. are maeronulrlenls
required i n llelntivcly large quantities to provide energy and organic
been consumed and stored as fat. Ghrelin, released fmm the intestine.
mediates long-ten control ofeating andbody mass.
building m.aterinls. Micronulrienls are required in milligram ormicro- Body masscan also becontrolled by regulatingenergyexpendllure.
gramqt~antiliesforrpcciolbioshemicalfunctions;thesearemainlyvita- In rodents, the basal metabolic rate (DMR) is increased by adaplive
mims. ~nincl.illsand csscnlial fatty acids. Non-digestible plant material. thermogcncsis. whereby energy expenditure is increased in brown fat.
- - is needed foroplimal intestinal function.
called libreor rouahaec. generating heat. Humans havelittle brown fat, althoughBMRrimwith
Energy intake must at least equal output. Even in a slate of total rest. regular exercise, which may explain how regulai exercise impmves
energy is requircd for metabolism-the basal energy expenditure weight control. However, BMR falls as body weight decreases, counter-
(BEE). Basal energy expeiditure varies with age and sex and most actingslimmers'effortr toloseweight.
people must consume 1.3-1.5xtheir BEE to remain in equilibrium.
although l h i ~may increaseto2xBEEwilh severemetabolicstress. Gastrointestinal disease and nutrition
Metabolic energy is stored in the chemical bonds in organic com- Gastrointestinal disease inevitably interferes with nutrition. Rcduced
pounds, with fats being the most energy dense, with the highest number intake may be due lo nausea andvomiling, poordcntition,or dysphagia
of calories per g n m weight, followed by carbohydrates and then secondary to oesooha~eal
. . disease. Pancreatic. biliarv and intcslinal
proteins. diseases cause malabsorption. Coeliac disease and Cmhn's disease in
Glucose isessential forenergy supply to thebrainand red bloodcellr. particular are associated with multiple deficiencies, including calcium
It is usually derived from ingested polyraccharider, and the liver can and vitamin D deficiency leading lo orteo~orosis.
mainlain blood glucose levels from stored glycogen (glycogenolpsis) Chronic liver disease is characterized by nutritional abnormalities
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 absorption offatnandfat-rolublevilamins.
in starvation means that the brain can use fatty acids and ketones for Gastrointestinaldiseasescanalsocausespecificnutrientdeficiencier.
someof its energy requirements.
Amino acids are required to produce proteins, which are constantly
~. -
ruchar atrophicgaslriliscausingvitamin ..
B,,deficiency.
Metabolic derangemen1 caused by systemic disease is aggravated
renewed and replaced. even in adulthood when growth has ceased. when the intestine, livcroroancreas is involved. as theoatient'rahililvto
~ ~

Amino acid flux is measured in terms of nitrogen balance, as dietary assimilate nutrients is compromised.
nitrogen is almostentirely containcdin aminoacidsand nitrogen - excre.
lion, via ores. is mainly due to amino acid breakdown. Thedietary pro- Enteral and parenteral nutrition
tein resuirement to remain in nilroeen
. balance varies with nee. sex and High caloric Itquid dicts that can be administered by inmavenour infu-
metnboliestate. sion have made tolal pamntcral nulrilion rrPM. oosrBle.
. Total oar-
enteral nutrition is used when patienls cannot be fed enterally, for
Assessing nutrition example, because of intestinal failure, orsurgery.
In children, growth ehsrls help todetect potential nutritional problems. WithTPN, homeostaticmechanisms regulatingdigestion andabsorp
Other simple clinical measurer include the body mass Index (BM1) tion arebypasred; therefore, nutientlevels mustbecarehrlly monitored
(weighfieighl'), measured in kilograms and metres, giving a global and the feed modified accordingly. This, and therisk ofinfection asso-

fold thlcknesr,refleeling bbdy fat.

-
measure. mld-arm circumfemnce. reflectine muscle mass. and skln- ciated with infusing nutrient-rich solutions, make TPN demanding and
potentially dangerous.
S.mple blood tests can tdcntify deficiencies in iron, calci~m.n n c . Furthermore, the lack of enteral feeding atrophies the intestinal
copgcr,
.. v~taminrA. D , K. B,,,- and folste. and nitrogcn
. balance can be epithelium and may increase bacterial translocation and the risk cf
csti~n;\ledby oiensuring urinary urea excretion. sepsis.Thus,enteral or panialentcral nutrition is preferred.
 .uo!~d~osqea~
.nlum~aqu"jBu!lqeua'uodsue~o~Lue joluapuadapu! uo!~d~osqe +EN
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~suo!a~!~~uL~~c~!~ornso
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snql puu )no ruo! +EN? ? J ~ I~ oaaucq~ra
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d orle s! aJaqL 'sauelqmam leqde pun lmate[oseq
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a1eln8s~pus s?ua!ped u!elu!em q q m ' s l l a ~le!laql!da aql sson aloj
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pue palen!eAa Qlyare3 aq ?loj?laq plnoqs uo!leJpLH 'p?qs!u?ld
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Buguup'~a~amoq S
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o s l e Xlpv
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pueln!q 10qUOJi~all!ms~em~lna~ asn
c Se u ~ r s a l d o s e ~ pua'Ll!!e[owso
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p a s e ~ ~ ~ u ! L q ~ o ) p a l e s u a d m o ~ a q u e ~ u o l o ~ a q l B u ! q 3 ~ a ~ s ~u!
j o 1 ~ ~ 1 3majd e u e q alom Bu!sol pue pa1e~a101 L l ~ o o ds! uol~rupLqaa
uo!)eln0ay
~ a L srl n m w aw ow! uapsms - 5 0 3 ~'q3ewols aql u l 'snlnmleue9 .L!le~s!ppaqmsqaa aJa taqt raa!n[an!rsaB!p alanas SPUCIB
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!
I UO!I
-amasjo ~d au!pqle %u!u!ea!ern JOJlueuodw! s! uo!)anas - ( 0 3 ~ -&osqc Lq paJelda~ale pue D p l a d Jalem j o ~ 0001
u )seal IC 01lunowo
'(dN33)
aleqdsoqdouom au!souenB J![JLJ Lq asaqL 'sBunl aql qBno~qlpue saJatj 'auun 'learns u! sassol L~o)eBllqo
pa1eln8aiamslal;uaqa-l3laq1oal!qm'n~3joBu!uadoaq1alelnaaJ
sla JOJdn axem 01 Ll!ep paqs!ua!da~aq lsnm salLlollsala pue sp!ny Lpog
rtorcs before a competition by eating a carbohydrate-rich meal Amino aclds and prolelns
(cnrbo-Innding). Essenlialamlnoacidscannolber)n~hesizedinsufficientamoun~sfmm
The livcralsoproducesglucosefromamlnoacldsby gluconeogene- precunon and must be derived f i m the diet. The L i v c p d u c e s a 611
sls. whereby transaminares removethe amine -eraup . and feed the prod- com~lemenlofaminoacidsbv lranramlnallonsnd other modifications ~~~

uctr into the Krebs cycle. Fatty acid metabolism also producer the of dietary amino acids and expons these for use i n protein synthesis
two-carbon-containing acetyl coenzyme A (acetyl-CoA) molecule that thmughout the body.
-
fceds into the Krebscycle; however, new six-carbonruearr.ruchar elu- - Excess amino acids are metabolized by removal o f lheaminogmups.
cost, cannnt be synthesized from fatty acidr via the Krebs cycle. Thus releasingammonla, whichis potentially toxicand is convenedintourea
rugarcon be laiddown as fat, but fat cannot beconvened tosugar. in the livcr, via the urea cycle, and excreted in the urine. Tbe eerbon
Hormones such as insulin, glueagons, growth hormone. corlica- rkelelans are used for ellergy prod~~ction or convened into glucme for
steroids and catecholamines, acting via cell-surface and inlracellular storage or expon. Thus, during fasting, stmation or savereillnerr;,thc
receptors in the hepatocyte, determine the balance of glycogcn synthe- liver can conven muscle protein and other tissues into essentialenergy.
sis, glycogenalyrir and glucaneogenesir. The liver synthesizes many proteins, includinz
~ ~ .enzymes
. ior in own
metabolic processes, and plasma proteins l o r export. Tbe liver pro-
Lipids duces albumin, which conslilutes 50% of plasma protein, caagulallan
Dlclary lipidscarried, far example, i n chylomicmns, are laken upfmm factors (including 11, VII. I X and X, which arepost-translationally mod-
the circulillion bv the liver and broken down into comooncnt parts ified by vitamin K-dependent?-carboxylatlon) complement pmleinr.
including fatty acids, phospholipids and cholesterol.
~~~
circulating protease inhibitors, apolipopralelns
~ ~ . . . and carrier omlelns
The liver then repackages there lipids as lipoproteins, for expon to that bind hormones and othersmall molecules i n thecirculation.
the rest o f the body via the bloodstream. Li~apmleinr .. arc macromo- Inflammation causes the release o f circulating pcptide mcdiatarr
lecular conlplexer formed from lipids and rpccific proteins called called eylokines, of which interleukin 6(IL-6), is particularly
. impnanl
.
apolipoprateinr.lhey allow hydrophobiclipids to bctranrponcdinthe i n stimulating the hepatic acute phase response, whereby the liver
blood, and specific receptors that bind to different apolipoproteins allow rapidly increaser its synthesis o f host defence proteins and reducer
targeting to thedifferent tissues that express the necessary receptarr.The albumin synthesis. Acute phase proteins include C-reactive protein
main lipoproteins exported from the hepatocyte are very low-density .
(CRP),semm am~loidA,recreto~y~hos~holi~areA?andcoanulation
.. .
lii,oproleins ( v L D L ) ~ hi ~ g~h-densit y lipoproteins (HDL). and complementproteinr.
The liver also takes up and recycler lipoproteins
. . and free fany acidr
from thecirculation, funller regulating the dinrihutian of lipidr arodnd Metabolic and synthetic failure
the body. A l l hepatocytes can pcrfotm basic metabolic and synthetic functions.
Thc liver is themajorriteafcholesteralsynthesisand most circulat- so thereis a vast reserveolpacil~.Dis~~tedcar~hvdrate.oratein
. ~ . .. and
ing cl~olcsterolis derived fmm hepatic synthesis rather than directly lipid metabolism results in laligue, wasting o f body muscle and fat
froln the rlia. The rtatin drugs, which are the most effective treatment resewer, and biochemical abnomalitics including hjpglyeaemia.
for hypercholerterolaemin. act pr.rnar.1~an the liver, by inhlbattng ihc hypoalbuminaemlnandreducrd coagulation lactors.
r;~ie.ltoul ~.z c n.~ y r nincho.e;reralsyniner~r.
e HMC-CoA reductarc Hypoalbuminaemia can cause oedema, due lo reduced plarma
Cholesleml is urcd to synthesis bilesalts, which are then conjugated oncotic pressure allowing extravasntion offluid Fromcapillaries intotir-
with taurine andelveine
-. .[amino acids) andseereled i n bile. sues. Reduced clotting factors cause a coagulopathy, with a prolonged
Ketones are synthesized from acetyl-CaA, derived from the oxida- pmlhrombintime(PT).
tion offatry acids andprovidcarourceofcirculatingmetabolicfuel dur- Coagulation factors have a half-lifeof few hours i n thecirculation and
ingfarlingandrtarvation.Cellssucharncuronr,whichnormallyrequire rapidly disappear when the liver fails suddenly.Albumin has a half-life
glucorc, can adapt theirmetabolirmtourc kaoncr 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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s
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parsam! Lq pame3 q Lsm e!maou!qn~!l!q~adLqpaiean!uo3u" !I
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s! n~Krnledaqu! u!qm!l!q pa~eanluoaISOW ,u!qnJ!!!q Bu!rlnm!~'pa~eB Lq pasne3 ~a!punc!pus s!qi say!dB rus!loqelam u!qn~!l!a .au!ln 10
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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 example, pain. emotional upset, feverand serious physical illness. Veri-
an imporlnnt defence against noxious agents that could be swallowed abllity in the way that these stimuli are pmcessed may aecountforwhy
with food, nnd the process is tightly controlled. Vomiting is coordinated somepcople vomit more readily thanothers.
by
. risnnlr
. fmm the intestine, body and brain. reaching nerve centres i n Sensory inputs from the gastminteslinal met and other viscera. car
the brainstem, which control voluntary and involuntary muscles in the ried by the ";gal and splanchnic autonomic ncrves, also stimulate the
-
nbdomen.chest and eastmintestinal andres~iratorytracts. VC, so that -aastrointestinal distension, infection and inflammation can
Nausea is the dysphoric desire to vomit, often accompanied by dis- all inducevomiting.
taste for food and loss of appetite (anorexia). Although nausca usually The autonomic centres regulating sweating, lacrimation, salivation
orecedes vomit in^,
. either may occur in isolation. and head rate all lie close to the VC and these autonomic ohenomena
Retching is the rhythmic reverse peristaltic activity of the stomach are all stimulated in thc surge of neuronal activity that accompanies
. - . accomoaniedbv conuaction ofabdominal muscles and
and oesoohaeus.
deep,sighingrespiratorymovemenlsthat oftenprecedeactualvomiting.
vomiling.
. - ~ ~
Retching is 'dry', i.e. whileitfeelsasthoughoneis abouttovomit,there Commoncauses
is naefflilx of vomilus.Duringretchina.
. . -
. theoesopha~usdilaresand may Common causes are detailed i n the figure. Neumgenlc or psychic
accull~olatevomitus that is subsequently expelled. stimuli, chemlcnls end mechanlcal or chemical irritation of ihe
Vomiting is the forceful expulsion of loud out ofthe mouth, usually lnlcsllnal lract itself may stimulate vomiting. I n many instances the
accompallied by increased salivation, sweating . and tachycardia. exactpathway remains unknown.
Vomiting is different from passive regurgitation, where acid stomach
contents and partly digested food reflux into the mouth. Eflectsand consenuences
Physiologically, vomiting expels noxious material fmm the gasuoin-
Muscular coordination testinal tract. Normally, neuromuscular reflexes pmtect the respiratory
Intrinsic muscles o f the stomach and oesophagus relax the gastro- tract, but i n inebriated or unconscious individuals ~rotectivemecha'
oesophngenlsphinctcrandforcegastriccontentsoutofthcstomach and nisms may fail, allowing espiralion o f vomitus, which can cause
ocn<ll~ltspas by reverse perislalsis. Vomitus rarely cont.linr material asphyxiation or chemical inflammation and bacterial infection of the
fmln beyond the ileocaecal valve, although reverse peristalsis can con- iungs(pneumonla).
vey intestinal contentsall theway from the ileum. Thc strongproplstbe forces generated dunngrelch~ngandvorml.ng
Abdominal muscles, including the diaphragm, contract, greatly cancause a tear in the oesophageal
. . mucora(Mallory-Welsstear).nts
increasing intrc-abdominal and intrathoracic pressure, thus helping lo typically causes haematemesis (vomiting blood). Generally the tear is
empty theupper gnstrointesliml tract. superficial and heals rapidly.
Simollaneously, the epiglattir shuts off the larynx, which is Chmnic vomiting, as in bulimia,cancauseacid damagelothe teeth
dmwn forwa~.dand upwards by muscles i n the jaw and neck. The and gums. Furlhermore, prolonged or profuse vomiting can deplete
sofl p:!l;tlc i s dwwn upwards, closing off the nasopharynx. These fluid and electrolytes, leading to dehydration and altered blood chem-
cnorclin:~lcd il~oscutitrmovements protect the airway as vomitus is istry. Vomiting o f gastric conlenLr typically causes hypokalaemia,
expelled. In unconscious or inebriated individuals these protective hyponatraemla and melabolicalkalarir, whileloss o f HC03-in inles-
mecllanislns are disrupted and vomitus may be aspirated into the tinal contents can cause metabolic acidosls.
airway.
Treatment
Neural control Vomiting should generally be viewed as a protective mechanism and
Thevomitingcenlre(VC),inthed~nalparlofthereticularformationo~ auentionshould befocusedon treatingtheunderlylngcaure,whilesup-
the medulla oblongata, is the main site o f neural control o f vomiting. porlive measures for the patient should aim to replace fluidand elec-
The VC is essential for vomiting, whatever the primary stimulus, as it trolytelossas. ?
receives and coordinates signals fmm a number of other centres and Inothercases, however,nauseaandvomitingarertimulatedby minor
coordinates theoutout. events, or by an essential treatment, such as chemotherapy for cancer. .
The chemoreceplor trlgger zone ( a ) i n the floor of the fourth and must be treated even while the inducing agent is present F o m - !
ventricle lies outside the blood-brain barrler and therefore senses nately, powerful drugs that intempt vomiling in. different ways are
blood-bolne chetuical stimuli that induce vomitxng, such as dmgs like available. These include ecelylcholine (ACh) receptor antagonis& and
i
I
morphine and d~goxin.The.CI2 i n turn stimulates the VC to lnduce histamine I11 reccpar antngorusts, which arc panicularly useful for
I
vomline. - motion s~ckncrsand vcrtibulocochlear dvsfuncl~on, d o ~ a m i n eDl i
Motion sickness and diseases ofthe inner earcause vomitingby send-
-
ine newe sienals from the nucleus o f the vestibulocoehlear (VIIIth
receptor antagonists, such as phenothiazines and metoclopramide, that
block stimuli from the CTZ serotonin (5-hydroxytryplamine. SHT)
1
:
cranial) neweto theVC, possibly via t h e m . SHT,receptor antagonists, such as ondansctron, that block the VC and
Other areas of the brain, suchas thecortex, thalnmus andhypolhal- afferenls from the gastrointestinal lract; and cannablnoids, whose 1
amus, also signnl to the VC, mediating vomiting associated with, for mechanismof action is still unknown. f

Nosseo and vomiting 63

Inl'cctiot~sditurhoea is not only a nuisance to travellers-it also causes disaccharide in milk, into the absorbable monosaccharides glucose and
major ~norbidityand monality in pans o f the world where sanitation. galactose. Without lactase, ingested lacloseremains In theinlestim.cre-
cletin drinking water and nutrition areinadequate.Diarrhoeacan nlsobe ating an osmotic load. Hereditary lactase deficiency is more freqwnt i n
symptomatic of serious underlying gastrointestinal diseases, such as populations wheremilkisaminorpanofthetraditionaldiet,andcanalso
inflammatory boweldisease (IBD) and colorectalcancer beacquired as aresult ofdamage to the intestinalepithelium,caused by.
B y delinition, diarrhoea implies that an e x c w volume o f stool is for example, gastroenterills.
passed, and this is usually accompanied by lncresscd frequency . . of Other causes o f osmotic diarrhoea include the useof "on-absorbable
defecation and increased liquidity o f the stool. Normal stool volume food sweeteners, such as sorbitol, and laxallves, such ar IacNloseand
varies betweell individuals and is about 200-300 mlidav. magnesiumsulphate.
Diarrhoea m.ay be accompanied by abdominal and rectal pain. Malabsorption of other dietarycomponents can alsocause dianhoea.
urgency to defecate and incontinence o f faeccs. Whcn diarrhoea is although generalized malabsorption, such as i n pancreatic failure.
caused by f~od'~oisoning.theremay bcconcurrcnlvomlting. predominantly causes steatorrhoea, which is increased faecal fat
Diarrhoea1 stool is usually more liquid. I t may also contain more fat content, causing large, pale stools that float on water and have an
when c.aused by malabsorption (ateatorrhoea) and i t may contain pus unpleasant odour, panly due to metabolism o f fatty acids by colonic
and blood when caused bv intestinal inflammation (see Chapters 34 & bacteria.

Diarrhoea is usually acute; that is, sudden i n onset and shon-lived. Inflammation
Damageto the intestinal lining, caused by bacterialor viral infection, or
-
although it can be chronlc.The causes, mechanisms and treatment are
immune-mediated processes, causes infiltrationof fluid and inflamma-
genernlly different in acute and chronic diarrhoea.
tory cells into the intestinal wall and exousion ofthis inflammatoryem-
Mechanisms dateinto theinlcrtinal lumen. Excess mucus may also besecretedbylhe
Although the mechanisms are considered separately, for any onc cause damaged epithelium. ~nfiammationalso increases fluid secretion and
inhibitsreabsorption (seeChapters32&34).
ofdiarrhoea m u l r i ~ l mechanisms
e may .
. operate. Forexample, ulcerative
Pain and urgency oftcn accompany inflammatory dianhoea and leu-
colitis causer inflammation and also increased secretion and motility
recandnry to thestimulationafenteric neuro-endocrine pathways. cocylesand blood are foundmixed inwith thestool.
Common caurcr include bacterial and amoebic dysentery and IBD.
Secretory diarrhoea Dysmotility
Whcn increased secretion into the intestine exceeds the capacity of the Increased motility can incrcasc the frequency ofdefecation, andwheni t
sm;,ll and large intestine to mbsorb fluid, stool volume increases. isseveretheremay bcinsulficicnttimefor nomalreabsorpllonoffluid
Incl-c;tscd rccrclian by entemeytes is often aggravated by a concurrent from the stool, resulting i n increased stool volumes. Dysmotility may
abao~ptivedefect. occur with aulonornlc neumpalhy, for example, in diabetes melliNs.
Cholcra is n common, serious and well-characterimd example. Other causes include thyrotoxicosls and motility-stimulating drugs.
where hypersecretion is mediated by the bacterial exotoxin of Wbrio such as acetylcholineste~seinhibitors used l o m a t myasthenia gravis
cholcrrrc. Cholera toxinA irreversibly nctivates adcnyl cyclase 10 pro- (see Ch;~ptersI 5 & 17).
duce cyclic adenosine 3'5'-cyclic monophosphnte
. . (eAMP), which
stimulates runained chloride secretion into the intestinal lumen by the Treatmenl
-
cvslic fibrosis transmembrane reeulator (CFTRI. Nat nnd wmer are
secl.eted wilh CI-, maintaining eleclronculrality and osmotic balance
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
Cholera can kill i n a few houn by causing profound dehydration. The against infection, antidiarrhoealr should be used with caution. Treat-
stool may bevirtually clear electrolyte-rich fluid, known as 'rice-water ment should be rflainly supponivc, to prevent dehydration and elec-
stool'(s;e~ha~ter%). trolytedepletion.
Cholera is spread via the faecal-oral route, so diarrhoea enhancer Hydration can be maintained using a slightly hypotoni~and alkaline
infectivity and aids the organism's survival. Conversely, diarrhoea oralrebydrationsolutioncontainingglucoseandsodiuminthecorrect
clears bacteria from the intestine and is pan of the body's defence ratio to exploit active absorption via the apical Na+-glucose m
system. vansponer on enterocytes, which draws water into the cells along the
Otherbncterialtoxina, hormoneselaboratedby hormone-producing osmotic gradient(see Chapter23).The WHOrehydrationformulationis
lumours, particularly earcinolds and vasoactive intestinal peptide 3.5gNaCI. I.SgKC1, 2.9gNa citrate and 2.0g glucose per litre. ?his
(VIP).amar, and tubulovillaua colonic adenomas that secrete fluid provides 90muNat. 20mM Kt, 8 0 m ~ C I - . I O m cilrate and l l l m ~
and i?keus fmm the abnormal epithelium can also cause secretory glucose. In more severely ill patients Intravenous hydration may be
di;t~.rl~oca.Excess bilesalts thaturenotrcabsorbed intheterminal ileum. required.
as n result of terminal ileal disease or rcscction, can induce colonic Spccllic causescan also betreated, for example, antiblollcs for bac-
hypersecretinn. terial or amoebic dysentery and rtemlds and 5.amlnosalicylates for
IBD. Malabsorption caused by pancreatic insufficiency can be treated
Osmotic diarrhoea with oral pancreatic enzyme supplemenls, while secretory dianhoea
Anon-alraorbable ormotlc load i n the intestinecon overload the intes- caused by hormone-secreting tumoun can be convolled using somato-
tillc's c:q>;!city ibr renbrarbing wilter "guinsl theosmotic gradient.Thus slotln, which reduces hormonc secretion.
more fiuid remains in the intestinal lumen and is excreted, causing The most frequently used anlldiarrhoeals an the opiates codeine
diarrhoen. An example is inherited or acquired lactase deficlency. and loperamide, which inhibit intcstinal motility and increase the time
Lactare is the enzyme that normally splits lactose, the predominant available for intestinal fiuid reabsorption.

Diarrhoea 65
Constipation is one of the commonest gastrointestinal complaints. I n Neurological damage to the braln a n d splnsl cord, for example.
addition, people often auribute symptoms such as tiredness. lethargy. i n mulllple sdemsk and pedpheral neumpathy can lead 16chmnic
nausea and headache to what they,perceive as constipation. Often no constipation as well as incontinence. . . , :,:.
medical explanation is found and there is no proven link between infre-
quentdefeearion and general illhealth. Local causesand obstruction
Local obstn~ction,for example, by a tumour, may cause pain anddiffi-
Causesand mechanisms cully i n defecation. Painful local lesions, such as pmlapsed haemor-
Irregular bowel habit can exacerbate constipation, as the colon and rhoids and anal fissure, inhibit the urge l o defecate. Constipation 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. fissure.
I n severe chronic constipation, parlicularly i n the elderly, faeces may
becomeso hard, dry andimmovable (Isecal impacllon) that they cannot Clinical features
be passed without medical or surgical assistance, leading lo intcslinal The normal frequency of defecation (bowel movement, bowel open-
obstruction ing)variesinthepopulationfromaroundthreetimesaday toonceevery
3days,althoughmany peoplelieou&idethisrange. . . . L::. ,,,: '

Reducedmotility
Reduced colonic motility . may becongenital as i n Hirschsprun~'sdir-
~ ~.
ease, where myenteric nerves are absent from the distal colon, causing
-
True constipation implies reduced defecation frequency or stool vol-
chronic obstmction and a massivelv dilated, faeces-filled ~ r o x i m a l ume, although patients also complain o f slralning during defecation.
colon (megacolon). pain on defecation and hard, dark stool.'lhe wnreof incomplef.ieyi&;
Paralytic ileus occurs after abdominal surgery, or with electmlyle ation is called tenesmus. : . .: ,,:: ?t::p;?!,:c,:agt:
abnormalilles, such as hypakalaemia.
.. Intestinal motility may be
~ ~
Paradoxically, chronic constipation and faecal impaction:pacticu-
reduced acutely by stress,due to sympathetic autonomic nerveactivily, larlyin thcelderly, may cause incontinknceandpassageoffluidprre;-
and .ueoule
. who are severely. iniured
. or otherwise unwell may become tum, so-called overflow incontinence.
constipated for severaldays.
Ncurnnriueular dysfunction caused by hypercalcaemia directly Diagnosis
reduces intestinal motility. Perceived and actual problems mustbedistinguished.Amrefulhktory
Reduced colonic motility may also be constitutive, i.e, normal for ofdietary habits and any dmgs that might cause constipation should be
thal penon(slow transit constipation). taken. !,<;
Faecal impaction alid local lesions, including anal and rectal cancer.
Drugs. can be detected by digital rectal examination. Faecal loading o f the
Drugs such as opiates, antidepressants and others with anlicholinergic colon may be seen on plain abdominal X-ray. Timing the passage of
effects reduce intestinal motililv. Similareffccls are seen with oral iron radio-opaque markers through the intestine (shape lest) is used todiag-
supplements and aluminium-containing antacids. nose slow transit constipation. , . :. ,
Excessive, chronic use of stimulant laxatives, such as senna, can
reducc motility, presumably by damaging ordcpletingenteric neurons. Treatment
causingcolonicatonia. Stopplng drugs that cause constipation and ensuring thal sufficient
SHT, mccplor antagonisls that have been used lo treat diarrhoea in fibreand fluid are ingested areessential. Increasing dietary fibre forms
irritablebowel syndrome (IBS) can also cause severe constipation. the basis of laxatives that rely on increasing stool bulk, althoughenccss
fibrecanexacerbatecnnslipation. : ,.. ,:,~'.;.
Stool b u l k Where psychological or social factors are implicated, itis important
Stool volu~ucandthefrcquencyofdefecationvary withdiet. fluidintake thattheyareidentified.
and iotcntinal secrclion. Dietnry Ahrc. which mainly comprises nnn- Comcting cleclrnlylc abnormalities and allowine the bowel time to
diecnii~lopti~ntpolysacchnrides, draws water around itself. incrctaing
stool volume. Thus,chronic constipation is often caused by lack o f . - r

dieta~yiibre andlor Inadequate fluid Intake, which is required to cally, Painful or obslmctive pri-anal and rectal condition; may also
t~ydr:~te(lietnrvAhreand tosoften thestnol. requiresurgery. . . .. . ..: ., ~,,.:.::
'
,
. :. : ,;:
Will, lasting, the frequency o f defecslion deciines, panly becuuseof Where constipation does not respond to simple d i e m i o r lifestyle
reduced reflex colonic activitv and also because of reduced stool vol- measures, and is nut caused by identifiable pathology, laxatives may be
ume, although a large proporlion o f the solid material in stool actually used. They work in a number o f different ways, including increasing - .
cam~xiscscnlcl-icbacteriarnthcr than food residue. stool bulk, increasing osmotlc fluid secretion, soiteningstool, stlmu-
laling secretion and motility viaenteric neuro-endocrinepathways'and
Neuro.psychological dysfunction directly stimulating neuro-endocrineresponses by receptor-targellng.
Defecation is imbued with social and psychosexual constraints Thesearedetailed in the table within the figurebpposite. ,: : :
that influence bowel habit, and it can be inhibited volunprily via the
externnl anal sphincter and by cortical signals acting on autonomic
"ewes.
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
~ J 'ah!snla -y!uB!r inoql!m u ~ n q p s se
~ qqans 'suo!r!puoa uowwo3 apnlau! asaqL
sraplos!p l e I e q d o s a 0
'qxcasapus ~ u a u ~ c a r
's!souBc!p rs!sss 01 yauyap LIICUIJOJ
uaaq aneq ' p a l a a ~ ~uca ~ s h sleu
.U!~~JOUO!EE!~EU -!rnalu!a~lnea
NI aqlja ued aq~o18u!p103aepay!srs~s'samolpuLrarZ3s!a
~wjuaaaql aanpal rnql pus 'u!mq aq1 01SIOUB!~u!sd Lahuoa leql s u o ~ uo!le,!llssela
-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 lying flat, and by reducing inlra-abdontinal pressurc. which encourages
angle; which also tends to seal the junction. Funhennore, while the the stomach toreium to the abdomen.
lower oesophagus and gastro-oesophageal junction remain i n the Less frequently, a fold of gastric cardia may herniate through the
abdominal cavity, . any . increase i n lntrs-abdominal pressure, which diaphragmatic hiatus alongside the mophagus, creating a mlllog
lends lasqueezegarlriccontentsoutofthestomach,alsoimpingesonthe hiatus hernia, whichcan becomestrangulated.
iunction and counteracts thiseffect.
Stomach contcntsdo regularly reflux through thegartro-oesophageal Clinical lealures
sphincter. even i n normal individuals. wheh the lower oesophageal Heartburn is described by patients as an acid, buminp sensationin the
sphincter relaxes to allow food, drink and swallowed saliva to enter the .-
e~izaslrium or lower chest, often localized to iusl behind the ncmum
stomael~.Thisphysiological reflux is probably notharmful. (relrosternnlly). I t is the typical symptom of gaslro-oesophagealrcflux.
However, whenoesophagealanddiaphragmaticmuscletonedeclines Patients may also complain of eplgastrlc paln and dyspepsia aggra-
nnd intra-nbdominal pressure is chronically increased, for example, by vated by meals, alcohol and lying flatin bed.
nhesity. 1p;ll-ticul;!rly i n older individunls, reflux may bccotne mnre frc. Stnmach conkntn may reflux into the mouth and occasionally be
qucol iandscvcre. aspirated into the larynx, cauringeough and hoarseness. Reflur may
Rcll!$r o l g;lstric cnnvnts stimulates nerve endings in thc lower also be completely asymptnmatlc and, paradoxically, the development
nemph:\gus, which can cause pain and discamfort. Chronic stimulation of Barrett's oesophagus, which is relatively resistant to acid damage,
m;ny allso inulaase the sensitivity of nerve endings, causing - pain even
~
may improverymptoms.
i n tile absence o f concurrent reflux. Severe and prolonged reflux can
damnze and emde the lower oesophageal . . epithelium
. and provoke Diagnosis
inflammation (oesophagitis). Upper gastrointestinal endoscopy is the main diagnostic test. Bioprics
Citronic rcflux can also induce metaplastic chanae . in the epithelial are fakentodistinguish oesophapitir and Bamtt'roesophagus hlriolog-
lining of the lower oesophagus, which is normally a non-cornified lcally. A barium swallow can demonslrate hiaNr hernia and reflm o f
-
stratified rtlunmous e~ithelium.and can chanae to a simple columnar stomach contents into the oesophagus, as well as revere d e w o f
epithelium, with gastric or small intestinal features. This gastric o r oerophagitis.
intestinal metaplasia is known as Barrett's oesophagus, which may Oesophagcaland gasl~icp H can be measured directly visa nasogas-
undergo dysplssia and can go on tadevelop into adenocarcinoma (see trically placcd sensor Episodes ofreduce pHcan then becorrelated with
Chaptel.s4 & 381. symptoms and in the Bernstein test, acid is infused into the lower
Themost likely causeofdamageduetorefluxisgastrichydrochloric oesophagus, i n an attempt to reproduce the symptoms and confirm the
acid (HCI), although other gastric contents, such as enzymes, and bile diagnosis (seeChapter46).
acids from the duodenum, may also contribute. Bile acids, chemically Oesophageal manometry helps to distinguirhdysmotilityfmm reflux
altered by acid, may be particularly imponant in inducing metaplasia. (seeChapter46).
dyrplasia and cancer.
Helicobaclerpylori infection tends to reduce gastric acid secretion. Treatmenl
particularly whenitcauseschronie gastritis,so that, theoretically, eradi- Lifestyle changes such as having smaller meals, giving up smoking.
cation o f hi. 10'lori infection, which reduces the risk o f gastritis, peptic reducingalcohol intake, losing weight and sleeping withthe headofthe
ulcer and onslric cancer, may actually exacerbate acid reflux (see bed raised can effectively reduce symptoms. Simple antacids arr also
chapter31) effective, althoughselective histamine HZ receptor antagonists, such
--
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
as ranitidine, and the proton pump inhibilors, such hs omcprazole;
which irreversibly block acid producti~nby parietal cells, an the most
(or gap) in the diaphragm through which the oesophagus enters the effectivelreatment.
aWamen.Araresult,thehemiatedponionofthestomachcamerroliein Hiatus hernia usually does not require specific !xeatmenr, such ar
thc thnr:tx. Ilsunlly the gastm-oe5ophngealjunction and gastric cnrdia nurzery, although it cnn be repaired by fundopliestlon, whereby the
- -
slidc opwards. cl.eating a slldinc hiatus hernia, which compromiser gastric fu'ndus is partially wrapped around the lower oesophagus.
sphincter function by straightening out the angle of the gastm- strengthening the sphincter and preventing migration Wough the
aesaphngeal junction and removing the diaphragmatic contribution diaphragmatic hiatus. Fundoplicaiion can also be used to weat
to sphincter function. Furthermore, as thejunction now lies within the intractable refluxin the absenceofahiatur hernia.
thorax, which has a law pressure, increased inlra-abdominal pressure. Baneu's oesophagus is premalignant and, therefore, regulru.
transmitted through the stomach, tends to force gastric contents endoscopic surveillance with biopsies to detect. dyrplaria is'
through the rphincrer. advocated. If dysplasia i s detected, the patient may undergo
Asliding hiatus hemiaeanrpontaneously reduce, for example, when oesophagectomy.
.-
4 - . i r r < 'n
N ?!k,,,0
" 3 -.LP
s g.%pi&E
g "P
- O m S R
:=.a
2 a
e 5 s lv g
5 .!.<so 0
E*
P O .

z B-,i p
0 - 0 ,
g ~
-'g :-.q -1,"" g

ps i.:oc=$mz8 e-4*
4I:sp
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r r - z o o j .
x LIB 2
s:$g:
z a0 p- .- .E= - .
45.. =
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Pathogenesis Peptic ulcer may cause major acute bleeding, leadingto haemateme-
~ ~ 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 sb andlor melaena, which is a msdical emergency. Similarly, peptic
.
by O cells in the antrum.. acetylcholine -
released by the vaaus nerve and ulcers may perforate the stomach or duodenum, causing perltonlllr.
histamine released by entem-chmmaffin-like (ECL) cells. ail of which Peptic ulcer may penelrate into the pancreas and cause pancroatills.
stimulate reeepton on acid-pmducingparlelalcells. Scarring of the duodenum by chronic ulceration may cause intestinal
-
Duodenal ulcers areexceedinely- rare in .people . who do not produce
gastric acid and multiple, recurrent ulcers occur when acid production
obstruction.

is greatly increased, for cxample, by gastrin-secreting tumours (see Diagnosis

Chapters 16 & 38). However, gastric acid production is usually low in Uppergasfrointestinal endoscopy is the bestdiagnorticest. Ulcencan
peoplewith gastric oiccrs and this may betheresuitofchronicgastritis. also be dctccted by barlum contrast X-rays.
- ..
Prortaelandinr.Thc riskof oeoticulceris increased in vatients who
usenon-steroidal anti-inflammatorydrugs (NSAIDs), inciudingarpirin.
H. pylori infcction can be diagnosed serologlcally, orby the urease
breath t a t , in which I1C-labelled urea is taken orally and themulling
which mhibil prostaglandin production by epithelial cells. Furlhermore "CO, released by the urease enzyme is measured on the b m h (see
the r sk cf .peptic
. ulcer is reduced by an arlificial .prorlag'andin
- EZ ngo- Chapter 46). H. pylori organisms
~ ~ . can be demonstrated hislolonlcall~
" .
~nist,~n~isol~rostil. and the urwse enzyme can bedeteclul using a simplecolorimellictest
Smoklna, -
. slcohol. nenetlcs and s t r s s . Other risk factors include (CLOtest,forCompylobocfer-likeorganism) inmucosal biopsicstaken
smoking tobacco and drinking alcohol, although the mechanisms by duringendoscopy (seeChapter46).
which these act areunknown. Inaddition. thereisasmall genetic - vredir- Gastric ulcers may be caused by carcinoma or lymphoma, io they
position. There is little evidence that stress or lifestyle factors play any must always be blopsied locheck that they arenol malignant Duodenal

.
role.
Helicoboeterpyiori. Spiral bacteria in the stomach had been noted for
over a hundred years, yet thcir significance only became apparent in
ulcers are very rarely malignant.

Treatment
1982 whenWarrenandMarshallculturcd&pylon'from I I patientrwith Surgery. Exccpt ioremergencies, surgical Malmentir now obsolete.
garaitis and Dr Marshall then dcmonshated that it caused gastritis by Partial gastreclomy to remove pan of the gastrin-producing. G-cell-
intestine
. .n test dare himself. He was subsequently . . curcd by antibiotic rich antrum was once routinely performed. ~ n o t h eapproach
i was to
treatment. selectively section branches of the vagus nerve (selective vagotomy)
H. pylori infection is present in the majority of paticntr with peptic that stimulated acid secretion, sparing fibres that controlled th.ipyloric
ulcer, although only about 15% of infected people dcvclop ulcers. sphincter.
Eradicating H. pylori infection permanently cures peptic ulcer in the Simpleantacidsandanticholinergirrarereiativeiyineffecti~e~ha~e
majority of carer.
H. pylori infection of the gastric antrum, which stimulates gastrin
production, causer the greatest hyperacidity and duodenal ulceration,
.
tobe taken frequently and produceside-effccts. . .. . ,
The first effective medical Malment for peptic ulcer emerged when
rclcctive histamineH2receptorantagonisls weredeveloped.Forsome
while infcction ofthe gastriceorpus, wheremart parietal cellsare pres- time drugs such as cimetidine and ranitidine were the mbst widely pre-
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

-
scribed medications worldwide. . .
Proton pump inhibitors, which irreversibly block acid production
by parietal cells, have ovcnaken the HZ receptor antagonists, and
- clusters.Thur both host factors and thebacler-
by various bacterial gene omeprazole, the first proton pump inhibitor, accounts for the greatest
iai strain determine theoutcomeof infection. worldwideexpenditureon a single dmn. .
Peptic ulceration results fmm an imbalanee between gaslroprotec- Helicoboeterpylori eradlcatlon provides a permanent cure for most
live fnctors, such as the mttcur layer and prostaglandins. nnd aggresrivc cases a i peptic ulcer. Successiul eradication requires combined ther-
factors, such us stomach ucid and the effecls of smoking, alcohol apy with an acid suppressor and two or three antibiotics. Most standard
and NSAIDr. H. pyiori infection dramatically tips the balance against
protection.
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-
Clinical features gency surgical or endoscopic therapy, such as injection of adrenaline
Epigastric pain, often aggravatedby hunger or by meals and relieved around an exposed vessel, to arrest haemorrhage.
by antacids, suggests peptic ulceration or gastritis. There may be
nausca, vomiting and anorexia. Anaemia may develop from chronic
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
% "ag g,s, $ B 3
r.0 l 0o ;$ - 2 5 g
9
% oo xm n - s
9 a a . - $ %
(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 disappearing.Duodenal biopsy demonstralcsblunt villiand hyperplas-
various othergastrointeslinal system-relatedillness. Furthermore, there liccrypts. resembling cocliacdiscnsc, and antibiotics mcurativc.
-
is a laree resident or commensal .population
h e ~ l t and
h disease remains unknown.
. o f bacteria, whose role in
Systemlc Inlecllon, abscesses and masses
Intestinal bacteria can migrate into the portal veln and f o m llver
Commensal llora abscesses, while some entcric organisms, especially. slreotococcifrom.
Bacteria colonire the entire intestinal tracl, with the greotest number. the mouth and gut, can cause infective endocardllls. Therefore, p p l c
10'2/g,in the lnrgeinlestine.They apparenlly causenoharm andpoten- ..
with valvular heart disease have .proohvlactic antibiotics before dental
tinlly benefit thc host, possibly by excluding pathogenic species. There and same endoscopic procedures. Salmonella ryphi causes syslemic
;we nvcrSt10 llillcrenl spcclcs and the dominvnl specics and gcncr;! arc inleclion and in immunocomprnmised patienu. less virulent, non.lyphi
,Tsclrericl,in coli. U$dobocferio andLocrobocillus. Solmanella species can alsocauseosteomyellUs. bralnabscw,endo-
E, coli. Enremcoccus, Srreprocohus, Closlridio and others retain the cnrdilis.etc.
ability to cause disease. either by -
. acquiring
. virulence faclors, which are Enlamoeba hirrolyfica causes liver a b s w s and abdomind wall
usually plasmid or phagc DNA-cncoding toxins, adhesins, etc.. or by masses (ameoboma) as well as acutedysentery. . .
exploiting reduced host defence. Closfridium dificile, for example. Echinococcus species (hydatld worm), acquired from shecp and
causes diarrhoea when antibiotic ueatmenl upscts thc normal microbial dogs,invadetheinlestinalwall,spreadsystemicallyandformlarge,egg-
populalion, allowing it to produce its cytotoxin. filledcysts i n theliver, lungsandotherorgans. ...
Liver abscesses typically cause abdominal pain, fever and abnormal
Bacterial overgrowth blood tests, although they may be asymptomatic. Ultrasound and com-
The small intestine normally contains very few bacteria because o f thc puarizedtomography (~~scanning&usedtomakethedia~nosisand
constant movement o f foodand theeffectof antimicrobial proteins pro- - - . are used l o &Ibacterial
antibiotics, with or without sur~icaidrainage.
duced by Paneth cells, for example. Bacteria overgrow, however, when and amoebic abrcesses. Hydatid dise~erequirrssurgicaltreatment.~
the normal anatomy is disrupted, for example surgically, or where dis- Perl-anal abscesses, arising from anaerobic infeclion o f the deep
eases like sysfcmicsclerosiscausedysmotilityand stasis. anal glands, are relatively common and are mated by incision and
Thebacleriamerabolizenulrients, thusdepriving thepatient.andpro- drainage and antibiotics. Recurrent peri-anal sepsis may indicate
. .
duce excess intestinal gas, damage the mucosa and cause malabsorp- anorectal Crohn's disease.
lion.Symptomsincludeabdaminalpainandflatulence.Brealhtestscan
be used to establish the diagnosis. Antibiolics and corrective surgery Inflammatory bowel disease
may benecessary. -
I B D is notcaused by a discreteintestinal infection,although bothulcer-
alive colitis (UC) and Crohn's are lriggered by cnvirontnental factors
Worms and parasites lhat arc almosl certainly enteric microbes or their ~ m d u c kAntibiotics
.
Mulricellular worms and parasites commonly infest the intestine. aregenerally ineffective in UC, but do improvcsomcforms of Crohn'r
particularly where sanitation is poor. Hookworms. (apeworms and disease,andadministering pmbiolics,whicharclivccomensalbacte-
round!vorms can remair: i n the intestine for many yean, causing ria, ameliorates some forms of lBD.
chronic dianhoea, malabsorption and anaemia. Roundworms invade Intestinal infection with Mycobocrerium fuberculosir and Yerrinia
the intestine and migrate through the lungs
- as part
. of their life cycle. species can slrikingly
- . resemble ileoc~ecal Crohn's disease. Similarlv.. .
causing systcmic disease. The pork tape-worm, Toenia solium, leaves bacterial and amoebic dysenlery, cytomegalovirus and herpes simpler;
encysted eggs throughout the body, causing cyslicercosir. Treatment virus infection can cwse bloody diarrhoea. abdominal pain and intes-
requires helminthicides such as albendazole. tinal ulceration that can be confused withUC.

Candidiasis Clinical presentation anddiagnosis

Co~zdidnololbicn~zs,
theonly major fungal pathogen of the intestinal trilcl. Chronic inteslinaliniectionscancauseabdominalpain,dimhoea.flatu-
. .
is a commensal i n most oeoole. Reduced immunilv. .
.. as i n neulrooenia.. lence, weight loss, malabsorption andior anaemia.
diabetes mellitur, stetoid usc or acquired immune deficiency syn- Stool culture can detect bacterial pathogens and micmscopy can
drome(A1DS) allows Condido to invadethe superficial epithelial layers detect ova, cysts and parasites. Radiological imaging, endoscopy with
of the tongue, mouth, pharynx and oesophagus, causing inflammation biopsy and culture, blood culture and serological tesk detect deep-
and pain. Diagnosis is confirmed by detecting fungal hyphaein cytolog- seatedabrcerreranddislanlinfwtion. ; . ' ,' j .~~~ !'':,;:!>': ':; . ,;
ical specimens, or by cullure. Topical or systemic antifungals such as
nystatin orfluconazoleareeffectivetherapy. Treatment
The potential role of enleric commensals i n health and disease is
Whipple'sdisease a reminder that anliblotics should be used cautiously. Conversely,
This rare, chronic, intestinal infection caused by Zhpherymo whippelii live bacteria or probiollcs may be used therapeutically i n certain
typically affects middle-aged Caucasian males, resulting i n diarrhoea. circumstances.
~labsorptionandfevcr.Duodenalbiopsyshowrmacmphagesconlain- Selecllve entcric decon(aminaUon, with non-absorbedantibiotics.
ing mnlly bnc1eri.a and thetreatment isa prolongedcourseofnnlibiolics. such as neomycin and norfloxacin, cen be used before IntesUnnl
surgery and i n chronic liver disease, l o e a t hepatic encephalopalhy
Tropical sprue and lo prevent spontaneous bacterial peritonltb. The intestine is not
Chronic diarrhoea and malabsorplian, associated with enteric infection, sterilized butthe balanceofspeciesir altered.
which used lo be common in long-term rcsidents of the tropics is now

Gosrminlesrinal rprem infections 77

Two diseases constitute idiopathic inflammatory bowel disease (IUD): I n CD, terminal ileitis may cause diarrhoea or constipation, abdomi-
.
ulceralivecolitis(UC)and. . . .
Crohn'sdisease~CD).Thevaredistinct but nal pain and a palpable Inflammatory m a u i n $e right iliac fms8.
similar, and both are chronic, relapsing and remitting conditions. Chronic terminal ileitis may interfere with absorption o f dtamln
Together they affect about 150/100000 o f the population i n Western B,t and bile salts, causing anaemla and predisposing to gallstones.
counlrics. Inflammation may also cause strictures, resulting i n inteslinal
obstuction.
Aetiology I n CD, because the inflammation extends mnsmurally, intestinaliis-
The intestine is constantly i n contact with the harsh digestive environ- tulaeanddcep-seated abscessesoccur.
ment and-may be regarded as being in a state o f chronic low-grade Thesystemic inflammatory responsechdracterired by fever,malabe
inflammation. Challenges to the intestine include p H extremes. and welghl loss tends lo be milder i n U C and more pronounced in
mechanical trauma, ingested bacterialand viralpathogensand toxlns. CD.
and the microorganisms that comprise the resident commensal Extra-intestinal features o f I B D include skin rsshcs. such as
microflora o f the bowel. Immunological reactivity may, therefore. pyoderma gangrenosum and erythema nodosum, srthralgia and
develop tocomponents o f thedietor themicroflora. arthritis (in up to 15% of patients), and inflammation o f thc eyes
The aetiology o f 1BD remains unknown and it probably results from (Irllls and uveilis). Apthous ulcem i n the mouth are pMicularly
one or more envlronmental trlggers acting against a background of common.
inherited gcnclicpredisposllion. Longstanding UCpredisposes tocolmcancerandprimary sclerosing
Recently. C D of the terminal ileum has been genetically linked to chalangitis (PSC) occurs i n a b u t s % ofpatiena with UC.
-
mutations i n theNOD2eene. which is ~robablvanintracellularrecerrtor
for bacterial cell wall components, expressed i n monocytes and Paneth Diagnosis
cells. The mainstay of diagnosing colitis is to perform sigmoidoscopy and
Furthermore, experimentally disrupting the immune system i n colonoscopy, with mucosal biopsies10 histologically confirm thediag-
laboratory animals often leads to intestinal inflammation, which only naris. A barlum meal and rollow-thwugh examination visualizer 6 c
develops when enteric bacteria are present. terminal ileum, demonstrating inflammation, fistulae and stricmw.
Uicertnive colitis and C D may have a number o f differem primary TherearenospecificbloodlestsforUCorCD, butanaenia,vitaminBII
c;n!ser.a l l rcntlting in ri~nil;~rclinicnl
and pathological outcomes. JeficienCy, and raised inflammatory marken, such as the C-readlve
protein, are common. 11 a proportion of U C patiena, antineutmphil
Macroscopic pathology cytoplasmic antibodies (ANCA) are found, while i n CD, antibodies to
Ulcernlivc colitis only nffcctr the 1.1rge intestine and does not extend a, Soechrrmmyce.~ccrevi.~ioe (ASCA) may bedetected.
thesm;~llintestine.Furthermore,therectumisslmostinvariablyaffeeled
and infln~n~nntion extends proximaliy la avariableexlent. Treatment
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
- 5-Aminasalicylic acid (SASA, mesalarine). This camp?und hw a
lrrcal anti-inflammatory action, particularly in the colon, and can be
nnnrect:~li~~fl;~mm;ttinn. An individual patient could have one, two or administered rectally or orally. Slow release formulations (pentara or
three ol'lhcse ;wens niiected, in any combination. Furthermore, while asacal) dissolve in the colon, while conjugated farms o f SASA (rul-
infl.nm~n;ttion in U C is contiguous, extending for a variable distance phasalarine, alaalazine and balsalaride) are enzymatically released i n
from the rectum. in CDthere mav benormal areas inters~ersed between thecolon by bacterin.
inflsn~cdsegmenls:'skip lesions'. Corticnslemids. Steroid treatment is usually effective at inducing
remission and is used pnnicul.~rlyto treat acute exacerbations. It may be
Microscopic pathology administered parcnlcrally, orally or rectally. Prolonged systemic steroid
The mucasd is ulcerated and there is an inflammatory reaction in the treatment has many advcrsc cffects, including worsening osteopomsis.
laminnpropl.ia. Uudeso~~ideisasynthelicstcroidthatisnpidly metabolized by theliver,
I n UC. there are reduced numbers nfgoblet cells (gohlet ccll dcplc- resulting in low systcmic levcls, and it may bcpillticularly effective far
tion) and increased numbers of Paneth eells. Furthermore, while nor- terminal ileal CD.
mal colonic cryptsareshort andstraight, inUCthey aredistorted and In~munosupprersives. Dmgs such as azathioprine, bmercapto-
branched. Another typical feature is a collection of neutrophils within purine and methotrexaa are used, parricularly when freo!~ent relapses
..
thecryrrtlumen, formingcryptabscwes.
. ~. necessitate repeated steroid use. Antibodies to the eyiokine Nmour
Within the lamina propria there are increased numben of inflamma- necrosis factor a (TNFa) are dramatically effective in a proportion o f
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
.
people wilhCD.
Antibiotics. Metronidazolc may induct remission i n some cases of
CD but is not effecliveinUC.
itre gr:~nlulatnas in CD, consisting of activated lymphrlcyles ilnd Probiotics. Live bacteria, to restore the normal balance of enteric
macrophnges. flora, are used with somesuccess.
Surgery. Panprnctocolectomy (removal o f thecolon and rectum) is
Clinical features cur;tlive lor UC und is used is a lasl resort for Severe disease or where
Colitis (UC ar Crohn's colitis) causes diarrhoea, which usually con- dysplaaia develops.CD almost invariably recunafieraurgery; therefore
tains blond i l n d p ~ ~ s o r m u cIn
~ snddilian.theremay
. benhdonlinnl pain the use o f surgcry is largely liniited to, for example, relieving aympto-
and n~nlaiscduclo thesystemicrespanaela inflammation. maticstrictures ordrainingabscessses.

Ulcerurive coliris and Crohn'sdiseme 79

Coeliac disease is also known as glulen enteropathy because it is caused by iron deficiency is frequent. Malabsorplion of calcium and
caused by immune reactivity triggered by glulamine- and proline-rich vitamin Dincreaseslheriskofdevelopingosleopomsls.
glulenproteins,found mainly inwlleat,rye, barleyandoa(s.Theillness Nutrients that are mainly absorbed i n the proximal small intwlinc.
may become apparent at any age, from infancy to old age. may remain such as i r o n and calclum, are most affected by coeliac disease, while
asymplomalic.and may be detected incidentally. nulrienlspredominanlly absarbedinthejejunumandilel;m,suchasfollc

Aetiology and pathogenesls disease.

.-
acid, vllamln C and vilamin B,, are affected onlv i n more advarced

The healthv small inlestinal eoithelium is maintained bv constant cell Patients may complain o f abdominal pain and U R d n e v and, for
turnover, nnd the balance between normal shedding a f old epithelial - -
unknown reasons, neurological com~lalnts,ranging from mild.perioh- .
cells at lhe lips o f villi and the formation of new cells from stem era1 neuropalhy to more severe central nervous syslem disfurtmce,
cells i n the crypts maintains a 2: 1 ratio between villus height and occurinuoto IO9oof oatients.
crypl deplh. The lamina propria contains a small number of lym- Asmall number of peopledevelop a blistering rashcalled dematitls
phocytes. m.ncrophages, fibroblasls, capillary endathelial cells and herpetitormis,associatedwithantibodiesto~TGreactingwihafamof
other cells. The epithelium itself contains a population of resident thisenzyme indermalcells.
intrnepilhclinl lymphocytes that maintain surveillance against Possibly as the result o f chronic inflammation, people with uncon-
potenlinl pnthogens. trolled coeliac disease are at increasedriskofdeveloping intestinal neo-
In genetically susceptible individuals, immunological reaction lo plasms, panicularly intestinal lymphoma. This risk is substantially
gluten-derived gliadin peptides develops upon dietary exposure. The reduced by slricl adherenccloagliadin-freediet(seeChapter38).
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
All thesesigns and syrnptamsdisaoDear
. .
Ihediet and reappear i l i t is reintroducrd.
-
.. when eliadinis omilted from
strongly~- associated with the condition. Early dietary . exposure
. to gluten.
panicularly after weaning from milk, may increase the risk of dcvelop- Diagnosis
ing thedi.;e:trc. Uncxplatned ~nnemi;landvagueabdominal andncuralogicalsymploms
The ilhifluitaus cellular enz.yme tissue lransglulaminase (CCG). shobld prompt the physiclan to check for cocliac disease, as it is often
wllicll mw~n:tllycrr,s.;-linksglulsn~ineresidueswithlysineincon.ective missed and is parliculrrly common in some pap~~latians, such as people
tissueprolein.i,plnyr an essential ralein the pathogenesis, byconvening originating from western Ireland. Conversely, i t remains rare among
glutnmineresidues in nativcgliadinpeptides lo glutamate,creating more Africans.
imm~~nogenicpeptides. Howevernodisease-associaledpolymorphisnis Circulating antibodies lo tTC otFer an excellent ser~logicalmarker
in thcf7%gc~~el~nvc been irlentilied. of coeliac disease, with sensilivity and specificity approaching 100%.
Lymphocytes
. . . - ..
react with the modifiedaliadinoe~tides an the surface Thetest wasfir~tdescribedasdetectinganunknownanti~kinthelining
.
o f nntigcn-presenling cells and proliferate, increasing the number o f of oesophageal smooth muscle (endomysium), hence lhe term anti-
intrnepithelial and lamina propria lymphocytes. Activated lymphocytes endomysial antibody. This test replaces the anligliadin anti-body lest
secrete inflammalor] mediators, including the cytokines, y-interferon lhathaslowersensilivily and specificity. Serological tesls rely on dcrecl-
and tumour necrosis faclor u(TNFa), recruiting and aclivaling mare ingimmunoglabulin A(1gA) intibodies andkunreliable in theI : 500
inflammatarycellr.alteringtheproliferativcrsteofinteslinalepiihelial individuals with selective IgA deficiency..(seechapter 18).
stem cells, and increasing the rateofprogrammedcell death (apoptasis) Upper gastrointestinal endoscopy and duodenal mucasal blopsy, to
i n mature enterocytes. This creates an aedematous, swollen intestinal confirm subtolal vlllus atrophy and lymphocytic infilmtion, is per-
mucosa, wilh short, thick, blunt villi and deeper than normal crypts formed before treatment, after initiating a gliadin-free
~ - diet, and azain-
(subtotal villus atrophy), and the reduced epithelial surface area afterreinlroduclionofagliadinchallengediel,andislhegoldstandardof
and compromised epithelial digestive and absorptive capacity leads to -
diagnosis. With the advent o f reliable serological testinn,
-. it is now used
mnlabsorptian. lersliequently.
Theconcentration of dietarygluten is highestpmximally in the intes- Rare forms o f small intestinal disease, such as Whipple's disease.
tine and therefore caeliak disease affects the duodenum and proximal Crohn's disease o f the small intestine and troplcal sprue may mimic
jejunum mast severely. coeliacdiseaseand hereaduodenalorjejunal biopsy may @panicularly
hclpful i n thc diagnosis.
Clinical features
Coeliac disease can become apparent at any age, allhough most Treatment
cases are diagnosed i n enrly childhood or in middle age. Coeliac The mainstay o f trealment is for patients to follow a gluten-free diet.
<lisc;~scrimy rc~nsincli~~ic;\lly
silent and people with circu1.1ting inpti- Wheat, rye and barley proteins are present in many ready-made meals
hodies to ITG, hut no avert palholagy, may be considered l o have lnlenl andsnacks, sothe helpaf s professional dietician ahd a oatients'asraci-
disc:lsc. ation,such as !he c o c ~ i a c s h c ~ien~t yh e ~ ~ , s h o ube~nlisledto
ld main-
Malabsorption causes diarrhoea and weight loss. Inability lo tain vigilance. I n severe, uncontrolled coeliac disease. acute intestinal
absorb fats rcsults i n steatarrhaea, wilh bulky, pale, foul-smelling inflammation can be treated with conicostemids, but this is hazardpus
stools that float in water, because of their high fat content. Anaemia. and rarely indicated.

Coeliac disease 81
m
N

: Basel mcUlbollc re* (BMR)

0
CL
9s
L
P
I

BMI
Obesity options. Cosmetic surgery has only short-term knehts and risks
Obesity is arguably the most prevalent health problem i n the Western scarring and infeclion. GasMinteslinal surgery is raerved for mating
-
world and ils incidence is increasing worldwide. Body -
. weight is tighlly
- . morbid obesity. Jejuno-Ileal bypass is no longer performed, kcsuse i t
regulated so thatst~ategiesto gain or lose weight muslovercomestrong caused severe liver disease (steatohepalllls). Jaw-wlrlng, whiehlimits
homeostatic mechanisms (reeChapterZ2). 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
Measuringobesity reservoir, ore the most frequent operations for obesity (se~Chapter48).
Obesity implies anabnormal ratioofadiposetissuetoleanmarr(mainly
bone and muscle). The body mars index (BMI) (weighl in kg/(height in Starvation, malnutritionandanorexia
m)>) is a practical guide to healthy body weight. The normal B M I is Malnutrition has many causes, of which economic deprivation is the
between 18and25; over25isoverweight,over30isobeseandover40is commonest. However, even i n wealthy societies, ill health, gaswin-
morbidly obese. Skin-fold thickness also measures body fat stores, as tertinal diseases, such as oesophageal cancer, and anorexia nervosq as
does totnl body impedance to a low frequency electrical current, and well as voluntaryfasting,canallcausemalnutritionandstarvation.
total body density, whichcan bedetermined in rescarchseltings.
Obesity is nssocialed with excessive rates o f illness, particularly Measurlng malnutrition
hypcrtcnrion, diabetes mellitus, stroke, vascular thrombosis and The B M I is abnormally low and other measures, such as skin.fold
henrl discnse. A simple measure of overweight that correlates with the lhickness and muscle strength and mars, are low. Listlessness and
risk of c;s~liovasculardisease is the waist: hlp ratio, with the normal lethargy occur and with severe starvation, mulllple organ failure may
rario being less than one. occur. I n women, menst~atlonceases.Theremay also besigns ofspe-
cific vitamin and mineral deficiencies.
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.
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
Sornc~lialsrcstrict fluid intoke and dehvdration causer ranid b u t s ~ u r i - reduced. This atrophy occurs whenever the intestine is not used, so
our weight iorr.To maintain weightcontml, diets must besustainable palientr whoarefedparenterally arealsoatrisk.Malnourishedchildren
and nutritionally adequate and not lack essential vitamins, minerals or havestunled growthand, due to mucosalalrophy andageneralreduclion
macmnutrients. Very low calorie diets, carry the risk o f undernutrition i n immune competence, are paRicularly susceptible to infections.
and should be supervised by a physician, while law calorie diets, for such as gastroenteritis, which aggravates the malnutrition and may be
examole. thoreadvocated bv -
. WeightWalchersm, aresafer. fatal.
Large portions and a preponderance of caloric-dcnrc foods, that is. Metabolic adaptation, which reducer dependence on glucose and
fats, lend to increase calorie intake. Ideally the proportion of calories lowers the BMR, allows the organism to survive for longer at a lower
consumed as fat should be between20and 309oofthetolal. energy .~ -
intake, An imponant consequence is that rapid refeedine:after a
Excrcirc. Regularexercise helps tolimit body weight, panly by eon- periodofstarvationcaninduceseriousmetabolicabnormalities(rrIe~d-
suming calories to provide energy to muscle and alsb by suppressing lngsyndrome).
appetiteand raising thc basalmetabolicrate(BMR) (seeChapler22). Kwashiorkor, or protein-energy malnutrition, occurs when protein
Pharmacolherapy. The medical consequences of obesity are being deficiency is greater than overall calorie deficiency. lissue and blood
increasingly recognizedandeffectiveLreatmentsactively sought, paRly pmleins areinadequately renewed,causingrkin, hair andserum pmtein
slimulated by-!he discovery o f leptin and other endogenous appetile- abnormalities and, characterirlica:ly, peripheral aedema. Mararmus.
suppressants, and the results ofresearch into neuro-endocrinecontrol o f i n contrast. is global malnbtrition, withautoedema.
body~. weight. Specific micronutrient deficicncier also occur i n malnutrition and.
The most effective appetite suppressants were the amphetamine paradoxically, global malnutrition may mask specific vilamin dehcien-
derivatives dexfenfluramine and phenteramine, which unfortunately . .
c i a . For example, malnourished alcohol-dependent oeoole. who
caused major cardiac side-effects and were withdrawn from use. Sibu- neglect nutrition i n favour o f alcohol, may be lhlamlne (vitamin B,)
..
trnmine is another effective appetite rupprersanl
.. - -
acting through sero- deficient The dehcieney may not be clinically apparent while they con-
toninerglc pathways. Orlistat is aspecific pancreatic liparelnhibltor sumea diet laclang carbohydrales.However, ifthey areadmined to hos-
-
thnt -?uses fat malabsomtion and weiehtlorr. Side-effects. ruch as oilv
stool and fat-soluble vilamin deficiencies, limit its use.
pital and given lntravenuur glucose or a good meal, acute thiamine
deficiency occurs, becausethiamineis an essential cofaclorforthe .pym-
~

Oe~asianally,obesity is caused by endocrine dysfuncljon, ruch as vale dehydrogenaseenzyme, which metabolizes glucose i n cells. Acute
and treat in^
-hqpolhqroidisrn,
.. . .the underlying
. .condition is effective.
Surgery. Surgical removal of fat, for example, by liposuction and
thiamine deficiency is a nicdical emergency
- . and can cause wmanenl
neurological damage (Wernicke's encephalopathy) ifthiamine is not
gastrointestinal surgery to limit food intake and absorption are the main administered immedintely.
. .. .--T.-l-
*.a .-.lI.,..---I.,-,II...,.--.... I....A. . . ~ . * , . .. .. ...,,,.,..? ~
./..#,.. ', ' . -.. . . . .. ..... , -
Gastrointestinal cancers impose a major health burden: colon and rectal cases.This occurs becauseeachcolonoeytealready camesonemutared
cancer (colorectal cancer. CRC) is the second commonest cause of APCgene, so that environmental carcinogens only have to mutate and
cnncer-rcl;!tcd death in the Western world. while gastric, oesophageal. inactivate the sinxleremnining copy to produceopolyp, whichcnn then
p;tncrc:ttic ttl~dIivercnncerilrealsorelatively frequent. goon todevelopintoncancer.
HNPCC doer not involve a polyp-forming stage and is asswiated
Pathology with mutations in the genes rerpocsible far ensuring that rnist&es i n
The development ofcalareclal cancer follows a characteristic pnuerni n copying D N A during mitosis are repaired (mlsmalch repair genes).
most cases. with the earliest lesion being a microscopic focus o f aber- Patients lose the ability to correct genelic mistakes and thus armmulate
rant epithelial cells. With time these form a small dysplastic polyp. mutations i n neoplasia-inducinggenes,including ACP, pS3 and Am.
which enlarges, comprising epithelial cells with increasing numbers
of mutations i n cancer-related genes and a progressively dysplaslic Clinlcalfealures
phenotype. Exceptinfamilialsyndmmcr.CRCisrarebeforetheagcofSOyeanand
Some cells may became malignant, forming a focus ofcarcinoma in it increases i n incidcnce thereafter. Early cancers and'adertomar in the
silt,, which is confined to the epithelium of thepolyp.These malignant colon may remain entirely Bsymplomatic. Larger adenomas and can-
cells may penetrate the basement membrane and invade first the inles- cers may bleed micmrcopically over time, causing nnneda. Larger
tin;bl w,dl snd then lymphatics via which they are carried to regional lumoursmay causeoven rectal bleedingandaltered bowelhabil(con-
ly~npllno<les.Finallythey may invade blood vessels and r o melaslaslze slipation and/or diarrhoea). Intestinal abrtmction, abdominal pain and
todistant organs such as the livcr and lungs. weight loss occur when thediseaseis funheradvanced.
Thc D t ~ b c s s t n ~isi n~iscd
~ lo determine prognosis nnll op1im;i 1rc;tl-
mcnt (sce ligure). Diagnosis
Barium enema and colonoscopy are the main diagnosticfests. H i t o l -
Aetiology and pathogenesis o n ofcolonic polyp biopsies can demonstrate dysplasia and neoplasia
Environmental factors including diet influence the incidence of CRC. (see Chapters 44& 45).
Western dietsthat are high i n fat and red meat and low i n fibre predis- Stool examination may demonstrate occult bleeding. Faecal occult
pose In CRC, while vegetables, vitamins, trace elements, such as sele- blood testing is bared on the guiaic chemical reaction with haem, and
nium, and non-steroidal anti-inflammatoly drugs (NSAlCs:, such as false positives may be caused by dietary haem, far example, frommeal
sulindac, seem to bcprotective. Smokingtobacco also increases the risk (seeChapter43).
of CRC. High-fat diets induce the production o f carcinogens, while Blood tests may show iron deficiency or anaemia. Increaredcirculat-
reduced dietaly flbrecauses canstipationsothatthecarcinogenr remain ing levels o f an embryonic protein, carcino<mblyonic antigen (CEA),
incantact with theepithelium for longer. are associated with CRC and can be used io manitorNmaurrecurrence
Chronic intestinal inflammation. as i n ulcerative colilis, also after rurgely and chemotherapy. . ,
increaser the risk. possibly by increasing epithelial cell turnover, and Removal o f adenomatouspolyps before they become malignant dra-
thus increasing thechance ofgenetic mutations. matically reduces the risk ofdeveloping CRC. Therefore, because CRC
There is a strong genetic element and the risk o f CRC is increased in is so common, some nuthbritier advocate population screening, using
people who haveoneor moreaffected firstdegree relatives.Thesludy of barium enema. colonorcopy or faecal occult blood testing for people
familial forms o f CRC, panicularly aulosomal dominant familial ade- overtheageof50 years.
nomatous polyposis (FAP) and hereditary non-polyposls colon a n - I n FAP, the panproctocolectomy (surgical removal of the whale
cer (HNPCC), have helped to elucidate the molecular pathogenesis of colon and rectum) i n early adulthood prevents CRC.
CRC, bnscd on the 'two-hil' and multiple gene theory o f how tumour
suppressor genes function. Trealment
Colonic epithelial cells undergo p r o g r w l v e change from normal. Surgery. simple adenomas may be removed during colanoscopy by
through increasing dyrplaria. to carcinoma. These cellular changes are snaringandexcision (polypectomy), whileCRC has toberemavedsur-
causedby genetic changes: Someaf which may be inherited and others aicallytoaether withs m a r ~ i nofnormal tirrueto ensure taralresection.
acquired through the effect ofcarcinagens. Mutation o f a single allele f f CRC isdetected early, particularly if it has not extended beyond the
is usunlly insufficient to alter cellular function, so, for each gene, both intestinal wall. theoveration mavbecurative. MetastaticCRC cannotbe
alleles must bcmulated. cured, although surgely may palliate symptoms, such as bleeding.
I n genetic CRC syndromes, one mutant allelc is inherited, so only a obslruction and pain.
single sccond mutation i n that gene is required. To produce cancer, Chemotherapy and radiotherapy: adjuvant chemotherapy may
numerous genes mustbc mutated; therefore, ittakes many years to accu- lncreasesurvrval after rurgely and radiotherapy may be used to reduce
mulatesr~fficienlmutations. Forcxample.FAPir caused by mutations i11 tumourbolk.
the adenornatous polyposis coli (APC) gene, which is frequently Prevention: adletthat is low in fat and red meat andhighincarbahy-
mutated even i n sporadic, non-familial CRC. Patients with FAPdevelop drate and fibre is recommended, and the use o f N S A D s is being
many hllndredsaf polyps and thencanccr i n their early 20s i n almost all invwegated.

Colon andrecfolconcer 85
Tumourrofthecolon,oesophagus,stomach,pancreasandlivcrarccom- Eradicating H. pylori infection. or prolonged antibiotic treatment of
mon worldwide. Colon cancer is the most common (see Chapter 37). IPSID, may cure earlv cases. In coeliac disease. strict adherence to a
~ ~~ ~~

There is marked geographlcal and raclal varlatlon in the incidence of

~ ~
gluten-free diet removes the antigenic stimulus to lymphocylu and
gastric, oesophageal, pancreatic and liver cancer In cirrhosis, primary reduces the riskof lymphoma.
livercanceris eommonandtheliverisalsoafrequentsiteformetaslasls
from many othercancers. Pancreatlccancer
Pancreatic adenocarcinomas may present with abdominal pain or,
Gastric cancer when they occur in the head of the pancreas, may obslruct hecommon
Gastric cancer is particularly prevalent in Japan, but the incidence Is bile duct, causinglaundice. Very early cancers may be m l e d bywide
-
decreasinc worldwide. Environmental factors, such as smoked foods. excision of the pancreas, duodenum and related slruciures (W3lpple's
.play a role and chronlc gastritis, causcd by autolmmune disease, or
~
operailon). . .,,,.% ..
more commonly by Helicobnelerpylon' infection, predisposes Lo both
adenncn~.cinnmaandgastric lymphoma (sceChnpter3 I). Neuro-endocrine tumours and carclnolds
Synlpla!ns includenbdotninnl pain, dyspepsia.anaemia and occullor Tumoun arising from entero-endocrine tissue may be benign or malig-

theepignrtri~~ni
-
ovcrl intcstin:tl hlee~lin~.Advnncedcnncermavc.~usearralrrahlem;~ssin
. .
andlymphaticsprelid may ereatcapalpable lymph nodc
n.ant, and may occur spnradically or as part of inherited multiple
endocrineneoplasia(MEN)syndmmes.Theymay
. ~ . . bearvm~tomalicfor
. .
in theneck-'Virchow's node'. many years, or mayproducesymptoms by virtueofaberrant hormone
Endoscopy !nay revenl a gastric ulcer. All gastric ulcers should be secretion.cvcnwhilethetumouritselfisextremelvsmalland~hvaicallv .. .
biopsied and a rccond endoscopy performed after2 months oftreatment inapparent; for example, lumoun of G-cell origin pmduce gastrin.
toarsess henling: "on-hcalinggastriculcen may bemalignant. resulting in excess stomach acid production and peptic ulceration
(Zollinger-Elllson syndromc). Other tumours may produce insulin;
Oesophageal cancer glucagon or vasoactive intestinal peptide (VIP), causing diarrhoea a i d
Squamous cell carcinoma of the oesophagus is the commonest farm hypokaiaemia (Verner-Morrlson syndrome) ( a. e. r 16. .' .';'
~

and is particularly prevalent in parts ofsouthern Africa. In the Western Carclnoids are typically slow-growing Nmoun h a t pmduce an
world, however. the incidence of oesophageal sdenocsrcinoma is excess of serotonin (5-hydroxytryptaminc. SHT) and peptide p w h
increasing. facton. They usually remain asymptomatic, as the liver npidiy maa-
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 5HTis released directly intothesystcmiccirculation,causingsymptoms
. .
~redirooseto adenocarcinoma. Chronic reflux can cause mctaolaria such as flushing and diarrhoea, which constitute thecarelnoid
of the oesophageal epithelium, from stratified squamous to simple syndrome.
columnar, intestinal-lype epithelium. This change is termed Barrett's Hormonal effects are oflen the fin1 sign of neuro-endocrine tumours.
oerophaeus,
. - ..
which carrier ariskofdvsplasia -
and subsequent maliananl Anatomical localizationcan be difficult and relieson CTandMRI imag-
transformation (seechapters 4&30). ing and radionuclide-based scans to localile tumour cells expressing
Dysphagia (food sticking) and odynophagia (pain on swallowing) surfacc somatostatin receptors, which are present on most neuro-
signify oesophagcal disease and may be accompanied by weigh1 loss. endocrine tumours (octreotide scan). Excess urinary excretion of 5-
Malignant trachco-oesophageal fiselae may cause recurrent aspiration hydroxy-indoic acetic acid (5-HIAA), a metaboliteof5HT, can beused
pneumonia. Barium swallow, endoscopy, biopsy and brush cytology to diagnosccarcinoid syndrome.
confirm thediagnosis. Octreotidc or somatostatin injections may alleviatesymptoms by s u p
Very early disease may becured by oesophagectomy but usually the pressing hormone secretion, and surgery is potentially curative.
cancer is non-resectable and patients receive palliative trealmcnt by
dilatation ofrtrictures,placementofmcchanieaistentsorlasertreatment Liver cancer and masses
tored\~cetumourbulk. Primarylivercancer (hepatoma) is nre,exccpt inchronieliverdisease
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 virus infection. People with primary sclerosing cholangitis (PSCj are
and trintedearly particularly prone to develop cancer of the biliary epithelium, cholan-
giocsrcinoma.Non-malignanthepatlcadenomaissssociatedwihhe
Gastrointestinal lymphoma
Gastric and intestinal lymphomas are rare and are usually causcd by
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.
chronic inflammation and activation of the local immune systcm, as colon,pancreasand breast
with H. pylon' infection, coeliac diseasc and immunnproliferative Typical symptoms ~ncludenghl upper
~ .~ quadrant pain and, if h e
~

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
and bilirubin may bc raised. In heontoma, elevated circulatine
levels of the embryonic protein, a-fetoprotein (AFF) may be
-
abdominnl pain. Diagnosis is hampered by the difficulty in reaching detected.
parts of thesmallintestineby endoscopy (seeChapter44). Bariummeal Ultrasound. CT and MRI scans and a liver biopsy may be needed
and follow-through examination,computcrizedtomography(CT), mag- lo confirm the diagnosis and lo distinguish cancer from benign cysts.
~ ~

netic rest>ll2lnceimaging (MRI) scanning and exploratory laprrotomy haemungiomas. abscesses and benign lumours (seechapten 33 & 45).
with intcslinal biopsy are often used to makerhc diagnosis (see Chapter Treatment remains unsatisfactory. '

45).

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 obstmcled and Infected. m i s causes deep-sealed peri-anal absnsses
treatable. 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
Haemorrhoids may persist and can become chronically infected. dlscharglng mucus
Heamorrhoids are commonly known as piles. They may cause rectal and pus. Anorectal fistulae may also occur after surgical incision and
paln and bleeding and may interfere withdefecation. drainageofabscesses.
Externel piles are actually dilated superficial veins in the peri-anal Abscesses and fistulae may be deeper than clinically apparent and
skin. which become thrombosed and exquisitely painful. Occasionally. computerized tomography (CT) and magnetic resonance imaging
thethrombosedpilemay blced.Whenthey heal,anexternal skin tag may (MRI)scannlngofthepeivis may be helpful beforesurgical matment.
remain. Surgical lnclslon a n d dralnage are usually required and bmad-
Internal haemorrholdsarisefromsuperficial veins in themucosaof speclrumantlbloties, including melronidazole lo trealanaembic infec-
the lower rectum, which become engorged through chronically raised tion. are used.
intra-abdominalprerrureandstralningduringdefecation.Theveinsare Chronic and recurrent anorectal sepsis may be caused by anoreclal
supponed by cushionsof soft connective tissue, which hypertrophy and Cmhn's disease, in which case additional anti-inflammatory treabnenl
contribute to the swelling (see Chapter 14). Chronic straining is the is also required (see Chapter34).
commonest cause of haemorrhoidal vein enlargement and contributing
factors include pregnancy,obesity and weightlifting. Proctitis
First-degree internal haemorrhoids comprise hypenrophied cush- Superficial inflammation of the rectal mucosa, causing bleedine. -. diar-
ions, wilh enlarged veins that may bleed but do not protrude out of the rhbea, urgency of defecation and mucus discharge, may be caused by
rectum intotheanus. ulcerative colitis or Crohn's disease. In many cases..~inflammation
Second-degree haemorrhoids prolapse through theanus, but reduce remains confined to the recmm and never extends proximally. Recral
sponlnneously. steroids and 5-aminosalicylic acid (SASA, mesalazine) are usually
Third-degree haemorrhoids require manual reduction of the pro- effective and long-term treatment with oral SASA may h
lapse and lnurth-dcgrce haemorrhoids cannot be reduced manually. initiated.
Internal haemorrhoids generally do not cause pain unless they pro-
~ ~
Radiation proctltis. Pelvic irradiation, for example, to treat cervical
lapse and ulcerate. They may cause a sense ofrectal fullness, diseomfon cancer in women,orprosualecancerinmen, may causechronic varcular
and intomplete evacuation (tenesmus). m e most common symptoms . . damage and mucoral fibrosis, with the formation of friable, abnormal
include bleeding, typically at the end of defecation, and the effects of blood vessels that bleed spontaneously. 'The symptoms of diarrhoea.
prol.apre, which includechronic leakageof mucus and subsequentperi- rectal .bleeding and discharge may develop years after the initial
anal itching (prurllisani) andexcoriation. radiotherapy.
The diagnosis is confirmed by careful examination of the peri-anal
region and anal canal using a proctoscope. Barium enema and Pruritis ani
colonorcopy may beneeded toexcludeother causes of rectal bleeding. Poorperinealhygeine may cause imtationofhperi-analskin and,con-
Medical treatment includes altering diet to avoid constipation. versely, overzealous cleaning with soaps may dry the skin,also causing
using stool softeners and changing behaviour toavoid straining during .
irritation. Infestation with pinworms (Enlembiw vermiculnrisl.. which
defecation. crawl onto theperi-anal skin, may albo cause prurltis, as might chronic
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. Proclalgia fugax
Proetalgna fugax is a stabbing pain in *herectum, oftenafter defecation,
Anal fissure and usually has no direemable organzc cause and is hard to Mat (see
Asplit in the skin of the anal canal causer acute tearing paln, panieu- Chapter29).
larly ondefecation.Theremay also besomebleeding.Thecause iscon-
~ L i p i l lnlld
i ~ ~hnrd stool. Anal wartsandsexually transmitted infections
On examination, there is a linear tear in the skin. Ninety percent of Infection with human papillomavirus may cause pen-anal w a s that are
tears are porlerior and 10% anterior. m e r e may be a skin tag, called a treated m rhesame way as genilal wans. Syphilis may alsocause w m -
sentinel pile,al theedgc of achronic tear. like papules, as well as pen-anal ulcers. Other sexually transmined
~ ~

Stool softeners and alleviating constipation are the main treatments diseases, such as herpes simplex virus infection and gonorrhoea, may
and, in the acute state. local application
.. of glyceryl
.~ trinllrateoinlment.
~
cause pen-analinflammationandulceration.
whichrclaxesthcanalsphincter,mayallow thefisruretoheal.Inchronic
cases, surgical division of the internal anal sphincter (splrlncterotomy) Peri-anal tumours
may be performed Squamous cellcarcinomais the most common anal Nmour and may be
associated with infection by human papillomavirus 16 and 18. Chronic
Anorectal abscess and fistula hypertrophic ulcers with rolled edges are the typical manifslation and
The deep anal glands, which secrete mucus into the anal canal, extend 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 inflammatory disorders. Treatment includes supportive c ~ eanalgesia
,
is unstable and cholesterol may cryslallize amund a micmscopic pani- andantlblotls.
cle or nidus. such as a bacterial cell. Initially crystals are very small. Gallstonesareonly removed whenthey causeclinicslproblerns.Dur-
forming sludge or biliary sand, but they grow by accretion over time. ing an episode of acute obstrucllon, infection or pancreatitis, they may
Eighty-five percent of gallstones are cholesterol stones, formed in this be removed urgently by ERCPor surgery. More usually. the gallbladder
way. and stones are removed surgically (cholecystectomy). when theacute
Less frequently,
. . bile withexcessively. hiahconcenlrationsofbilepig-
. ~ - episode has settled (seeChapter48).
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
Pancreatitis
Pathogenesis
snla.lncreases the riskof gallstone formation. Obstruction and damage to pancreatic ducls by stoner, hlmours o r
- duct tissue. inid-
trauma releases pancreatic enzymes that auto-dieest
Pathogenesis sting aself-perpetuatingcycleoftissuedamageand enzyme relearethat
Most gallstones remain in the gallbladdcr and are asymptomatic. can rapidly destroy large pads ofthe pancreas. Bacterial lnfectlon and
although
. there is a slightly
. . increased risk of gallbladder cancer, which leakage of enzymes into the bloodstream often accomvanv. . this tissue
itselfis very rare.Gallstonesejectedfromthegallbladder,however, may damage, causing severe tissue damage at distant sites, particularly the
. .
obstruct the bile ducts and are the main causeofsvmotomatic -
eallstone lungs.~usacutepancreatitisisaseveremultisystemdirorderthatcan
disease. A stone i n the cystic duct can obstruct the gallbladder, which berapidly talal.
may then become infected, causing cholecystitis. Impacted stones in The same mcchanismr can be initiated by chemical damage to thc
the common bile duct cause intrahepatic and extrahepatic biliary pancreas caused by drugs, panicularly excess alcohol, which is thesec-
obstruction and, if theobstructed bileductsbecomeinfected, ascending ond commonest cause of acute pnncreatitis. Pancmtitis may also bc
eholaneitis results. Stones in the common bile duct or the a m ~ u l l aof caused by trauma, for example following ERCP, and by Infection, for
Vatermay causepancreaticobstruction,resultinginpancreatitisaswell example with themumps virus.
as cholnngitis.
Clinical presentation
Clinical presentation Abdominal paln,anorexia,vomllingandfeverarethemainsymptamr.
Biliary disease often causes nausea and anorexia. Symptoms may be Multisystem failure, with hypotension, hypoxia and widespread
aggravated by falty meals, which stimulate cholecyslokinin release. inlravascular haemorrhage, occurs in severecases.
whichi~~tl~rnstimulatesgallbladdercontraction.Abdominal pain,local-
ized to the right upper quadrant, is caused by distension of the gall- Diagnosis
bladder and bile ducts, and a tender, inflamed gallbladder may be Blood lesu show greatly elevated circulating levels of pancreatic
palpnble.Thepain islypically colicky, orepisodic,aggravated by waver enzymcs, panicularly
. amylase
. and lbase. Inflammatorv marken such
of ineffective peristalsis. Pancreatitis and bacterial infection cause as C-reactive pmlein areraiscd. Hypoxia and hypoealeapmia indicate
severt.~crrirtent~ain, whichmav bea=companied by teverandrieors. - severe ~ancrealilis.Abdominal ultrasound and CT or MRI scannine
Biliary obstruction causes jaundice, pale stools, due to abscnt bile may demonstrate an enlarged. oedemalaus pancreas.
-
.viemena in the intestine. and dark urine. due la urinarv excretion of
conjuguled bilirubin. Inadequate excretion ofpruritogenic substances. Treatment
which have not been well characterized. causes itchinc. - Persistent To minimize pancreatic enzyme production, the patient is kept nil-by-
biliary obstruction results in malabsorption of fats and fat-soluble mouth and thc stomach is empllcd by nasogartrlcsuction. Antiblotis
vitamins due to thelackofbilesaltsin theintestine. for presumcd lnfcct~onand supponlte measures are the mainstay of
Symptoms may be transient, as stones can be spontaneously ejected treatment S~cclficlnhibltorrof~ancma~csec~tion.andof~anmatic
through thesphincter ofOddi. enzymcs, have notyct provedclinically useful.

Diagnosls Chronicpancreatitis
Blood tests show raised biliary enzymes, conjugated bilirubin and Repeatedpassageofstonesandchmnic alcoholexcessmay causerecur-
inflnmmnrory markers, ruchasC-reacllveproteln(seeChapter41).
Ultritsotand scanning of [he nbdomen sensitively dctects gnllstones (CFTR),
-
rent pancreatitis. Inherited abnormalltier in the cystic Rbmsls eene
which regulates CI-secretion in duct cells, also predisposes to
and also shows if they are causing obsuuction. Computerized tomogra- chmnic pancreatitis. Repealeddamaae - affects exocrlneand endocrine
phy (CT)and magneticresonanceimaging(MR1)seanningmay alsobe pancreatic function, causing malabsorption due to p&cmtic enzyme
used (see Chapter45). , In addition.
deficiency and diabeler mellitus due to insulin deficiencv.
Endoscopic relragrade cholangiopancrealography(ERCP) provides damageta sensory ncrves and scarring and obsuuction ofthepancreatic
-
contrast-enhaneedimaaesofthe . . -
biliarvlract,demonstratinaobstruction duct cause abdominal pain, which can be enlreme.
and slones in clear detail. In addition, stones can be removed endoscopi- The s c m d pancreas may develop calcified areas that are visible on
cally,or thesphincterof Oddi cut (sphlncterotomy), allowingstoner lo plain abdominal X-ray.
pass sponlnneously. Treatment involves replacing pancreatic enzymes wilh oral rupple-
menls, treating diabetes wilh Insulin injections and relieving pain.
Treatment which may bedifficult. . .
Cl~oleqslitis,cl~olnngilisnnd pnncreatitis are serious multisystem