The Gastrointestinal System at a Glance

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The Gastrointestinal System at a GlanceSatish KeshavConsultant GastroenterologistJohn Radcliffe HospitalOxford, UK

Adam BaileyConsultant GastroenterologistJohn Radcliffe HospitalOxford, UK

Second edition

A John Wiley & Sons, Ltd., Publication

This edition first published 2013 © 2013 by Blackwell Publishing LtdPrevious edition 2004

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Library of Congress Cataloging-in-Publication Data

Keshav, Satish. The gastrointestinal system at a glance / Satish Keshav, Adam Bailey. – 2nd ed. p. ; cm. – (At a glance series) Includes bibliographical references and index. ISBN 978-1-4051-5091-0 (pbk. : alk. paper) I. Bailey, Adam, Dr. II. Title. III. Series: At a glance series (Oxford, England) [DNLM: 1. Digestive System. 2. Digestive System Diseases. WI 100]

612.3'2–dc23 2012007480

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover design: Meaden Creative

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1 2013

Contents  5

Contents

25 Hepaticmetabolicfunction 5826 Hepaticsyntheticfunction 6027 Hepaticdetoxificationandexcretion 62

Part 3 Disorders and diseases28 Nauseaandvomiting 6429 Diarrhoea 6630 Constipation 6831 Functionaldisordersandirritablebowelsyndrome 7032 Gastro-oesophagealrefluxandhiatushernia 7233 PepticulcerandHelicobacter pylori 7434 Gastroenteritisandfoodpoisoning 7635 Gastrointestinalsysteminfections 7836 UlcerativecolitisandCrohn’sdisease 8037 Coeliacdisease 8238 Obesityandmalnutrition 8439 Colonandrectalcancer 8640 Gastrointestinal,pancreaticandlivertumours 8841 Haemorrhoidsandanorectaldisease 9042 Gallstonesandpancreatitis 9243 Hepatitisandacuteliverdisease 9444 Cirrhosisandchronicliverdisease 96

Part 4 Diagnosis and treatment45 History,examinationandtests 9846 Diagnosticendoscopy 10047 Therapeuticendoscopy 10248 Radiologyandimaging 10449 Functionaltests 10650 Pharmacotherapy 10851 Gastrointestinalsurgery 110

Index 112

Preface 6Acknowledgements 6Listofabbreviations 7

Introductionandoverview 8

Part 1  Structure and function 1 Mouthandteeth 10 2 Salivaryglands 12 3 Tongueandpharynx 14 4 Oesophagus 16 5 Stomach 18 6 Duodenum 20 7 Pancreas 22 8 Liver 24 9 Biliarysystem 2610 Hepaticportalsystem 2811 Jejunumandileum 3012 Caecumandappendix 3213 Colon 3414 Rectumandanus 36

Part 2  Integrated function15 Embryology 3816 Entericmotility 4017 Entericendocrinesystem 4218 Entericandautonomicnerves 4419 Mucosalimmunesystem 4620 Digestionandabsorption 4821 Digestionofcarbohydrates,proteinsandfats 5022 Digestionofvitaminsandminerals 5223 Nutrition 5424 Fluidandelectrolytebalance 56

Companion website

Acompanionwebsiteisavailableat:www.ataglanceseries.com/gastro

featuring:• Interactivemultiple-choicequestions• Flashcardsofkeyfigureswithinteractiveon/offlabels

6  Preface

Preface

Organization of the bookThe Gastrointestinal System at a Glance is organized in four parts, each starting with a structural and functional overview of the main components of the system and followed by chapters dealing with integrated gastrointestinal function. The clinical relevance of aspects of anatomy, physiology and function is discussed in each chapter in order to highlight the practical importance of each subject. The third and fourth sections are more clinical, covering the most important gastrointestinal and hepatobiliary diseases and the major aspects of diagnosis and treatment. Endoscopy and radiology are described in dedicated chapters. Self-assessment questions on the accompanying website are all based on the text, and can be used to check understanding and recall.

How to use this bookThis book offers a visual and graphic scaffold for further detailed study. The aim is to provide pictures that will illustrate concepts and make them more memorable. Thus, the book can be read before starting on coursework, annotated with additional details from lectures, tutorials and self-directed study, and then used for

revision before examinations. It will therefore be useful for students approaching a subject for the first time, particularly as part of an integrated systems-based medical curriculum. The dia-grams, many of which will also be available as online flashcards, should trigger recall of facts that might otherwise be lost in plain text.

Anatomical and clinical detailThe anatomical diagrams are representations, and not exact repro-ductions, to illustrate how structure supports function, rather than to provide exact detail. For more thorough anatomy, students may use Anatomy at a Glance, also available in this series. Similarly, specific diseases are discussed to demonstrate pathogenic mecha-nisms and general principles, rather than to provide exhaustive detail. This book should be used to understand the normal physi-ology, how it goes wrong in disease, and the principles underlying modern clinical practice in gastroenterology and hepatology.

Satish KeshavAdam Bailey

Acknowledgements

We thank all the staff at Wiley-Blackwell Publishing, particularly Martin Sugden, Fiona Pattision, Ben Townsend, Martin Davies, and Karen Moore, who encouraged us through the gestation of

this edition. Professor Darrell Evans of Brighton and Sussex Medi-cine School co-authored the chapter on Embryology, for which we are grateful.

flast01.indd 6 7/11/2012 7:11:13 PM

List of abbreviations  7

List of abbreviations

ACh acetylcholineAFP α-fetoproteinAIDS acquiredimmunedeficiencysyndromeALP alkalinephosphataseALT alaninetransaminaseANCA antineutrophilcytoplasmicantibodiesAPC adenomatouspolyposiscoli5ASA 5-aminosalicylicacidASCA Anti-saccharomycescerevesiaeantibodyAST aspartatetransaminaseATP adenosinetriphosphateATPase adenosinetriphosphataseAVM arteriovenousmalformationBAT bileacidtransporterBEE basalenergyexpenditureβHCG betahumanchorionicgonadotrophinBMI bodymassindexBMR basalmetabolicrateBSE bovinespongiformencephalopathyCa2+ ionizedcalciumcAMP cyclicadenosine3′,5′-cyclicmonophosphateCCD charge-coupleddeviceCCK cholecystokininCD Crohn’sdiseaseCE capsuleendoscopyCEA carcinoembryonicantigenCFTR cysticfibrosistransmembraneregulatorcGMP cyclicguanosinemonophosphateCGRP calcitoningene-relatedpeptideCl− chlorideionCLO Campylobacter-likeorganismCMV cytomegalovirusCO2 carbondioxideCoA coenzymeACRC colorectalcancerCRP C-reactiveproteinCT computedtomographyCTC computedtomographycolonographyCTZ chemoreceptortriggerzoneCu2+ ionizedcopperDA dopamineDMT divalentmetaltransporterDNA deoxyribonucleicacidECL entero-chromaffin-likeEHEC enterohaemorrhagicEscherichia coliEPEC enteropathogenicEscherichia coliERCP endoscopicretrogradecholangiopancreatographyESR erythrocytesedimentationrateETEC enterotoxigenicEscherichia coliEUS endoscopicultrasoundFAP familialadenomatouspolyposisFe2+ ferrousironFe3+ ferricironFIT faecalimmunochemicaltestGABA γ-aminobutyricacidGIST gastrointestinalstromaltumourγGT γ-glutamyltransferaseGTN glyceryltrinitrateH+ ionizedhydrogenH2O waterH2R histaminereceptortype2HCl hydrochloricacidHCO3

− bicarbonateionHDL high-densitylipoprotein

5-HIAA 5-hydroxyindoleaceticacidHIV humanimmunodeficiencyvirusHNPCC hereditarynon-polyposiscoloncancerHPN homeparenteralnutrition5HT 5-hydroxytryptamineIBAM idiopathicbileacidmalabsorptionIBD inflammatoryboweldiseaseIBS irritablebowelsyndromeIEL intra-epitheliallymphocyteIF intrinsicfactoriFOBT immunochemicalfaecaloccultbloodtestIg immunoglobulinIL interleukinIMMC interdigestivemigratingmotorcomplexIPSID immunoproliferativesmallintestinaldiseaseK+ ionizedpotassiumLDH lactatedehydrogenaseLDL low-densitylipoproteinMAD-CAM mucosaladdressin-celladhesionmoleculeMEN multipleendocrineneoplasiaMg2+ ionizedmagnesiumMHC majorhistocompatibilitycomplexMOAT multispecificorganicaniontransporterMRA magneticresonanceangiographyMRCP magneticresonancecholangiopancreatographyMRE magneticresonanceenteroclysis/enterographyMRI magneticresonanceimagingNA noradrenalineNa+ ionizedsodiumNAPQI N-acetyl-p-benzoquinone-imineNH4

+ ammoniumionNO nitricoxideNPY neuropeptideYNSAIDs non-steroidalanti-inflammatorydrugsOAT organicacidtransportPBC primarybiliarycirrhosisPET positronemissiontomographypIgA polymericimmunoglobulinAPLA2 phospholipaseA2

POMC pro-opiomelanocortinPYY peptideYYPSC primarysclerosingcholangitisPT prothrombintimeRNA ribonucleicacidSBP spontaneousbacterialperitonitisSC secretorycomponentSGLT sodium–glucoseco-transportersIgA secretorydimericimmunoglobulinASOD sphincterofOddidysfunctionSTa heat-stableenterotoxinTECK thymusandepithelialexpressedchemokineTGFβ transforminggrowthfactorβTIPSS transjugularintrahepaticporto-systemicshuntTNFα tumournecrosisfactorαTPN totalparenteralnutritiontTG tissuetransglutaminaseUC ulcerativecolitisUDP uridinediphosphateUSS ultrasoundscanningVC vomitingcentreVIP vasoactiveintestinalpeptideVLDL verylow-densitylipoproteinsWHO WorldHealthOrganization

Introduction and overview

Functional anatomy

Diseases and disorders

Endocrine system

Bloodvessels

Mouth

OesophagusPeripheral

nerves

Centralnervoussystem

Digestion, absorption, nutrition

Stomach

Liver

Gallbladder

Hepatic portal vein

Pancreas

Small intestineColon

Rectum

Anus

Mucosa

Submucosa

Serosa

Muscularispropria

Muscularismucosae

Entericendocrine

cells

Epithelium

Immunecells

Intrinsicnerves

Extrinsicnerves

The Gastrointestinal System at a Glance, Second Edition. Satish Keshav and Adam Bailey.8  © 2013 Blackwell Publishing Ltd. Published 2013 by Blackwell Publishing Ltd.

Introduction and overview  9

Structure and functionThe gastrointestinal system comprises the hollow organs from mouth to anus that form the gastrointestinal tract, the pancreas, which mainly secretes digestive juices into the small intestine, and the liver and biliary system, which perform vital metabolic func-tions in addition to their contribution to digestion and the absorp-tion of nutrients.

The intestinal tractA hollow tubular structure into which nutrient-rich food is coerced, and from which wastes are expelled, this is found in the most primitive multicellular organisms, from the hydra onwards. In humans, the tract is highly specialized throughout, both structur-ally and functionally. The mouth and teeth are the first structures in this tract and are connected by a powerful muscular tube, the oesophagus, to the stomach. The stomach stores food after meals and is the site where major digestive processes commence. The small intestine is the main digestive and absorptive surface. The large intestine acts mainly as a reservoir for food waste and allows reabsorption of water from the mainly liquid material leaving the small intestine; it can be affected by a number of common, serious diseases, such as inflammatory bowel disease and colorectal cancer.

The pancreasDigestive enzymes are produced in many parts of the gastrointes-tinal tract, including the mouth (salivary glands) and small intes-tine (enterocytes), although the exocrine pancreas is the most prodigious producer of digestive enzymes. Pancreatic failure causes malabsorption, which can be reversed by artificial enzyme supplements.

The liver and biliary systemWithout the liver, survival is measured in hours, and no artificial system has yet been devised to substitute for hepatic function. The liver is the largest solid organ in the body, and its essential func-tions include regulation of protein, fat and carbohydrate metabo-lism, synthesis of plasma proteins, ketones and lipoproteins, and detoxification and excretion. Via the hepatic portal circulation, it receives and filters the entire venous drainage of the spleen, gas-trointestinal tract and pancreas. Through the production of bile, it is also essential for digestion and absorption, particularly of dietary fats and fat-soluble vitamins.

Integrated functionThe gastrointestinal system is controlled by both intrinsic and extrinsic neuronal and endocrine mechanisms. Enteric nerves and endocrine cells are particularly important in coordinating motility, digestion and absorption, and in regulating feeding and overall nutrition, including the control of body weight.

The gastrointestinal system presents a huge surface area that has to be protected against injury, particularly from microbial patho-gens that are ingested with food and from the large, diverse popu-lation of commensal bacteria that populate the intestine. Estimates of the total number of species of bacteria vary from 500 to 1000,

and may be greater. In faeces, the number of bacteria is huge, 108 to 1010 per gram, so that the total number of bacterial cells in the body may be approximately 1013. The mucosal immune system is critically important in regulating how the intestine responds to these challenges, providing protection and not reacting inappro-priately to normal components of the diet.

Diseases and disordersNausea, vomiting, diarrhoea and constipation are common symp-toms, and their basic pathophysiology illustrates important aspects of gastrointestinal function.

Gastrointestinal symptoms are frequently not associated with any discernible pathological abnormality. These medically unex-plained symptoms are often labelled functional disorders and, as our understanding of gastrointestinal physiology becomes more sophisticated, we may discover new explanations and treatments that are more effective.

Gastrointestinal system infections are common and are associ-ated with significant morbidity and mortality worldwide. They range from self-limiting food poisoning to life-threatening local and systemic infections. Even peptic ulceration is most frequently caused by infection, with the Helicobacter pylori bacterium.

For some major diseases, such as inflammatory bowel disease, the aetiological agent has not been identified, despite rapidly advancing genetic and molecular research. Conversely, coeliac disease, another serious and common gastrointestinal inflamma-tory disease, is caused by a well-characterized immune response to wheat-derived proteins.

Colon cancer is a major cause of cancer-related death, and our molecular and cellular understanding of its pathogenesis, and the pathophysiology of other gastrointestinal, pancreatic and liver tumours, is rapidly increasing.

Liver damage is often caused by infections or drugs and may be acute or chronic. Acute liver disease can rapidly progress to liver failure, or can resolve, either spontaneously or with appropriate treatment. Chronic liver disease may cause cirrhosis, which is char-acterized by a variety of signs and symptoms and changes through-out the body, including the effects of hepatic portal venous hypertension.

The gastrointestinal system is essential to nutrition, and disor-dered nutrition is a major issue worldwide – both through under-nutrition and starvation and through overnutrition, which causes obesity, possibly the single most important modern health problem in the affluent world.

Diagnosis and treatmentClinical assessment, including a focused history and examination, is the foundation of diagnosis. In addition, the gastrointestinal system can be investigated by endoscopy, radiology and specific functional tests. Endoscopy and radiology may also be used thera-peutically, and pharmacotherapy and surgery for gastrointestinal disorders exploit many unique features of the structure and func-tion of the system.

The Gastrointestinal System at a Glance, Second Edition. Satish Keshav and Adam Bailey.10  © 2013 Blackwell Publishing Ltd. Published 2013 by Blackwell Publishing Ltd.

1 Mouth and teeth

Vermillion border

Soft palateand uvula

Fauces

Tonsils

Floor of mouthTongue

Lips

Teeth

Nasopharynx

Oropharynx

Hypopharynx

Hard palate

Soft palateOral cavity

Mandible

Nasal cavity

Orbicularis ori

Trigeminal(Vth) nerve

Temporalis

Masseter

Facial (VIIth) nerve

Pterygoid muscles

Buccinator

Mandible

Maxilla

Zygomatic arch

Permanent teeth

Muscles of mastication

Crow

n

Milk teeth

6 months to 3 years

2 incisors (cutting)

1 canine(gripping)

3 molars

Root

Erosion of enamel

Dental plaque

Gingival retraction

Enamel

Dentine

Pulp

Squamousepitheliumof mouth

Gingivaltissue (gum)

Alveolar bone

Periodontalmembrane(joint)

Nerves(trigeminal)

Bloodvessels

Tooth structure

Tongue

Hyoid

2 premolars(grinding)

Cementum

Mouth and teeth Structure and function  11

The mouth and teeth admit food into the gastrointestinal tract. They cut and break large pieces, chop, grind and moisten what can be chewed, and prepare a smooth, round bolus that can be swal-lowed and passed on to the rest of the system. Of course, the lips and mouth also serve other functions.

StructureThe sensitive, flexible, muscular lips that form the anterior border of the mouth can assess food by palpation, and their flexibility enables them to seal off the oral cavity and form variously a funnel, suction tube or shallow ladle to ingest fluids and food of varying consistency. The main muscles of the lips are orbicularis ori.

The maxilla and mandible support the roof and floor of the mouth, respectively. The arch of the mandible supports a sling of muscles that forms the floor, including the tongue. The maxilla is continuous with the rest of the skull and forms the roof of the mouth anteriorly and, simultaneously, the floor of the nasal cavity and paranasal maxillary sinus. Posteriorly, the roof is formed by the soft palate, composed of connective tissue.

The sides of the mouth comprise the cheek muscles, chiefly the buccinator, and supporting connective tissue. Posteriorly, the oral cavity opens into the oropharynx, and the tonsils are situated between the fauces laterally, marking the posterior limit of the oral cavity.

The entire mouth, including the gingivae or gums, is lined with a tough, mainly non-cornified stratified squamous epithelium, which changes to skin (cornified stratified squamous epithelium) at the vermillion border of the lips.

Teeth arise in the alveolar bone of the mandible and maxilla. Infants are born without external teeth and with precursors within the jaw. A transient set of 20 ‘milk’ teeth erupts through the surface of the bone between 6 months and 3 years of age. They are shed between 6 and 13 years of age, and permanent teeth take their place. There are 32 permanent teeth and the most posterior molars, also known as wisdom teeth, may only erupt in young adulthood.

Teeth are living structures with a vascular and nerve supply (derived from the trigeminal, or Vth cranial, nerve) in the centre of each tooth, which is termed the pulp. Surrounding the pulp is a bony layer called dentine, and surrounding this is an extremely hard, calcified layer called cementum within the tooth socket, the enamel crown protruding into mouth. Teeth lie in sockets within the alveolar bone, and the joint is filled with a layer of tough fibrous tissue (the periodontal membrane) allowing a small amount of flexibility. The margins of the tooth joint are surrounded by gingivae, which are a continuation of the mucosal lining of the mouth.

FunctionThe lips, cheeks and tongue help to keep food moving and place it in the optimal position for effective chewing. The main muscles

of chewing or mastication are the masseter and temporalis, which powerfully bring the lower jaw up against the upper jaw, and the pterygoids, which open the jaws, keep them aligned, and move them sideways, and backwards, and forwards for grinding. The trigeminal (Vth cranial) nerve controls the muscles of mastication.

Teeth are specialized for different tasks as follows:• Incisors have flat, sharp edges for cutting tough foods, such as meat and hard fruits.• Canines have pointed, sharp ends for gripping food, particularly meat, and tearing pieces away.• Premolars and molars have flattened, complex surfaces that capture tiny bits of food, such as grains, and allow them to be crushed between the surfaces of two opposed teeth. As people get older, the grinding surfaces of the molars are gradually worn down.

Certain drugs can be absorbed across the oral mucosa and may be prescribed sublingually (under the tongue). In this way, the need to swallow is avoided and the absorbed drug bypasses the liver and avoids hepatic first-pass metabolism. Glyceryl trinitrate is one of the most common drugs administered in this way.

Common disordersHerpes simplex infection of the mouth is very common, causing cold sores, which often erupt on the lips when people have other illnesses. Serious oral infections, usually caused by a mixture of anaerobic bacteria, are less common.

The corners of the mouth may be ulcerated or fissured in patients who cannot take care of their mouths, for example after a stroke, so careful oral hygiene is important in these cases. Nutritional deficiency, particularly of B complex vitamins and iron, is also associated with fissures at the edge of the mouth, known as angular stomatitis.

Shallow ‘aphthous’ ulcers in the mouth are common and are usually not associated with a more serious condition. Rarely, squa-mous cell carcinoma can develop in the mouth. Risk factors for this include smoking and chewing tobacco or betel nut, which is particularly common on the Indian subcontinent.

Dental caries is the commonest disorder of teeth, resulting in tooth loss with advancing age. It is caused by the action of bacte-ria, producing acids that demineralize the teeth. There is also infection of the gums and periodontal membrane, encouraged by carbohydrate and sugar-rich food residues left in the mouth. Bac-teria grow in the gap between the tooth enamel and gums, forming a layer called plaque, within which they multiply. Their metabolic products, including organic acids, damage tooth enamel. Gradual erosion of enamel and retraction of the gingivae weakens the tooth joint. Infection can penetrate the pulp causing an abscess, and chronic infection can destroy and devitalize the pulp.

Dental hygiene, including brushing and flossing and having fluo-ride in drinking water, which strengthens tooth enamel, reduces the incidence of caries.