THE DIGESTIVE SYSTEM SYSTEM, THE... · Diseases of the Mouth and Oral Cavity 142 Pellagra 144...

Publishedin2011byBritannicaEducationalPublishing(atrademarkofEncyclopædiaBritannica,Inc.)inassociationwithRosenEducationalServices,LLC29East21stStreet,NewYork,NY10010.

Copyright©2011EncyclopædiaBritannica,Inc.Britannica,EncyclopædiaBritannica,andtheThistlelogoareregisteredtrademarksofEncyclopædiaBritannica,Inc.Allrightsreserved.

RosenEducationalServicesmaterialscopyright©2011RosenEducationalServices,LLC.Allrightsreserved.

DistributedexclusivelybyRosenEducationalServices.ForalistingofadditionalBritannicaEducationalPublishingtitles,calltollfree(800)237-9932.

FirstEdition

BritannicaEducationalPublishingMichael I. Levy: Executive EditorJ.E.Luebering:SeniorManagerMarilynL.Barton:SeniorCoordinator,ProductionControlStevenBosco:Director,EditorialTechnologiesLisaS.Braucher:SeniorProducerandDataEditorYvetteCharboneau:SeniorCopyEditorKathyNakamura:Manager,MediaAcquisitionKaraRogers:SeniorEditor,BiomedicalSciences

RosenEducationalServicesAlexandraHanson-Harding:EditorNelsonSá:ArtDirectorCindyReiman:PhotographyManagerMatthewCauli:Designer,CoverDesignIntroductionbyCatherineVanderhoof

Library of Congress Cataloging-in-Publication Data

Thedigestivesystem/editedbyKaraRogers,senioreditor.—1sted.p.cm.—(Thehumanbody)“InassociationwithBritannicaEducationalPublishing,RosenEducationalServices.”Includesbibliographicalreferencesandindex.ISBN978-1-61530-252-9(eBook)1.Digestiveorgans.2.Digestion.I.Rogers,Kara.QP145.D542011612.3—dc22

2010001615

Cover,pp.19,38,61,86,117,142,178,209,244,246,249© www.istockphoto.com/SebastianKaulitzki

On page 10:Thehumandigestivesystem. Mittermeier/Taxi/Getty Images

CONTENTS

30

44

Introduction 10

Chapter 1: The Beginning ofthe Digestive Tract 19

MouthandOralStructures21 TheLipsandCheeks21 TheMouth23 TheGums25 TheTeeth26 TheTongue29 TheSalivaryGlands33 Saliva35

Chapter 2: The Passage of Foodto the Stomach 38 Swallowing38 ThePharynx40 TheEsophagus43 TheStomach47 BloodandNerveSupplyofthe

Stomach50 StomachContractions51 GastricMucosa52 GastricSecretion55 GastricAbsorptionand Emptying59

Chapter 3: Anatomy of theLower Digestive Tract 61 TheSmallIntestine61 BloodandNerveSupplyofthe

SmallIntestine64 ContractionsandMotilityof

theSmallIntestine6562

AbsorptionintheSmall Intestine67 SecretionsoftheSmall Intestine72 TheLargeIntestine74 BloodandNerveSupplyofthe

LargeIntestine77 ContractionsandMotilityof

theLargeIntestine78 TheAppendix79 TheRectum81 TheAnalCanal83

Chapter 4: Digestive Glandsand Hormones 86 TheLiver86 TheBiliaryTract93 TheGallbladder95 Bile96 ThePancreas97 AcinarCells99 IsletsofLangerhans101 HormonesoftheGastrointestinal

Tract102 Insulin105 Glucagon109 IntestinalGlucagon110 Somatostatin110 Serotonin112 Cholecystokinin112 GastricInhibitory Polypeptide113 PancreaticPolypeptide113 Secretin113 VasoactiveIntestinal

Polypeptide114 EndorphinsandEnkephalins115 Prostaglandins115

80

90

OtherHormonesof Importance116

Chapter 5: Features of theDigestive Tract 117 RoleofDigestion117 UtilizationofFoodbythe

Body118 NutrientDigestion121 Carbohydrates123 DietaryFibre124 Proteins125 Fats128 Vitamins131 Calcium133 Magnesium134 Iron135 MovementofGasThrough

theDigestiveTract136 TheDigestiveTractasan

OrganofImmunity138

Chapter 6: Diseases of theUpper Digestive Tract 142 DiseasesoftheMouthandOral

Cavity142 Pellagra144 Glossitis146 VincentGingivitis147 OralCancer147 DentalCaries151 Pharyngitis152 CongenitalDefects154 DiseasesoftheSalivaryGlands154 DiseasesoftheEsophagus156 CongenitalDefects156 InflammatoryDisorders157 Strictures157

145

120

170

185

Dysphagia157 EsophagealPain158 DisordersofEsophageal

Motility159 GastroesophagealReflux

Disease160 DiverticulaoftheEsophagus163 EsophagealCancer164 DiseasesoftheStomach168 Indigestion168 UlcerativeDiseases169 Gastritis173 StomachCancer174

Chapter 7: Diseases of theIntestines 178 DiseasesoftheSmallIntestine178 Traveler’sDiarrhea179 IntestinalObstruction180 IrritableBowelSyndrome180 Malabsorption181 CongenitalMalformations182 BacterialInfections183 ParasiticInfections184 Appendicitis186 ChronicInflammations188 CeliacDisease189 TropicalSprue191 DiseasesoftheLargeIntestine192 Constipation192 Megacolon193

Diarrhea194 IntestinalGas195 DiverticulaoftheLarge

Intestine195 AbscessesoftheLarge Intestine197

188

216

233

BacterialInfectionsofthe Colon197

InflammatoryBowelDisease198 ColorectalCancer204 Hemorrhoids208

Chapter 8: Diseases of theLiver and Pancreas 209 DiseasesoftheLiver209 AcuteHepatocellular

Hepatitis210 AcuteCanalicular(Cholestatic)

Hepatitis214 ChronicActiveHepatitis215 Cirrhosis216 HepaticEncephalopathy219 PortalHypertension220 Ascites221 HepatorenalSyndrome222 LiverCancer223 DiseasesoftheBiliaryTract226 Gallstones226 OtherBiliaryTractDisorders231 Jaundice231 DiseasesofthePancreas234 Pancreatitis235 ChronicPancreatitis237 CysticFibrosis237 PancreaticCancer238

Conclusion 244Glossary 246Bibliography 249Index 251

INTRODUCTION

Humanseatformanydifferentreasons:becausetheyarehungry,becausetheyarebored,becausetheyare

stressed, or simply because the food smells and tastesgood. The biological reason for eating, however, is toreplenishnutrientsandtoprovideenergytosupportthebody’s functions.The task of the digestive system is tobreakdownfoodintotheelementsthatthebodycanuseandtoeliminateaswastewhateverisleftover.

Onemightbelievethatsuchabasicfunctionwouldbewellunderstood,withlittlelefttolearn.Infact,scientistsare constantly discovering new things about how thedigestive system does its job and how it interacts withother aspects of the body. Current research may helpexpertsunderstandelementsofhealthasdiverseashowthedigestivesystemaffects immunityaswellas its rela-tionship to such important health concerns as heartdisease, diabetes, and cancer. This book explores whathappenstofoodinitsjourneythroughyourbody.

The entrance to the digestive tract is the mouth.Althoughlittledigestionoffoodactuallytakesplaceinthemouth, itcontains importantstructuresthataid inandbeginthedigestiveprocess.Theseincludetheteeth,the tongue, and the salivary glands, which togetherreducefoodintosmallparticlesandmixitwithsalivainorder to speed its progression through the digestivesystem. Human teeth are specifically designed for anomnivorousdiet,withdifferentshapesandsurfacesforcuttingandtearingmeatandgrindinggrainsandvegeta-bles.Themusculartonguemovesfoodaroundthemouth,pushingittowardtheesophagus.Thetongueisalsocov-ered with a mucous membrane, which contains tastebuds,allowinghumanstodistinguishbetweendifferentflavours, such as sweet, salty, sour, bitter, and umami(meaty).Saliva,whichissecretedbythesalivaryglands,

11

7 Introduction 7

bothmoistensfoodandstartstodissolve itthroughtheaction of the enzyme amylase.The salivary glands makesalivatokeepthemouthmoist,buttheiractionincreaseswhenever chewing occurs. Salivary glands also increasetheiroutputinreactiontoastimulusthathasbeenassoci-ated with food in the past, such as succulent odours orevenaspecificsightorsoundrelatedtofood.So,infact,people’smouthsactuallydowaterwhenexpectingsome-thingtastysuchasasizzlinggrilledsteak.

Fromthemouth,foodpassesthroughtheesophagus,drivenbytheswallowingprocess.Swallowingisbasicallyinvoluntary–oncefoodreachesthebackofthemouththereflex to swallow takes over and cannot be retracted.Musclesintheesophagusthencarryfoodtothestomachthroughaseriesofrhythmiccontractionsknownasperi-staltic waves. These waves continuously push the fooddowntothestomach.Amazingly,ittakesonly10secondsfor food to move through the esophagus.When peopleeatinanuprightposition,liquidssimplyfalltothebottomoftheesophagusandwaitfortheactionofperistalsistoopen the lower esophageal sphincter to allow their pas-sageintothestomach.

Thestomachiswheretheprocessofdigestionbeginsinearnest.Thestomachwallscontainbothalayerknownasthegastricmucosa,whichsecretesgastricacidtodis-solvefood,andalayerofmuscles,whichcontracttomixfoodandsqueeze it throughtothesmall intestine.Veryfewnutrientsareactuallyabsorbedintothebodydirectlyfromthestomach,althoughitcanabsorbsimplesugars.Liquids also pass easily between the stomach lining andthe blood. Once the stomach has finished mashing anddissolvingthefoodwithdigestivejuices,thefoodexistsasa semiliquid substance called chyme. At that point theduodenalbulb,wherethestomachattachestothesmall

7 The Digestive System 7

12

intestine, relaxes and opens, allowing the stomach con-tentstoprogressonthenextphaseoftheirjourney.

The lower digestive tract consists of the small andlarge intestines, where nutrients are absorbed into thebodyandwasteiseliminated.Thesetwolongtubeshaveacombinedlengthofupto9metres(30feet).Inthebody,theyarefoldedandcoiledinordertofitintheabdominalcavity. The long length of the intestines as well as theuniquefoldedinnersurfaceofthesmallintestineprovidea large surface area, estimated to be some 4,500 squaremetres(5,400squareyards).Thislargesurfaceareafacili-tatestheabsorptionofnutrients.

Thesmallintestineisinfacttheprincipalorganofthedigestivetract,asthisiswheremostoftheprocessesoccurfor the breakdown of carbohydrates, proteins, and fatsintoorganiccompounds,vitamins,andmineralsthatthebodycanuse.Thelargeintestine,orcolon,completesthedigestiveprocessbyabsorbingwaterbackintothebodyand compacting the remaining waste for elimination. Italsocontributesbacteriathathelptosynthesizeavarietyofimportantvitamins.

Another organ of the lower digestive tract is theappendix, a small hollow pouch attached near to wherethesmallandlargeintestinesarejoined.Whetherornotthe appendix serves any function is still being studied.Removaloftheappendixdoesnotappeartointerferewithnormalbodilyfunction,butsomescientistssuspectthatitmayserveasareservoirofusefulbacteriaorhelpstimu-lateanddeveloptheimmunesystem.

Digestionisregulatedbyanumberofimportanthor-mones,whicharesecretedfromtheliver,thepancreas,and the gastrointestinal tract, as well as from fat cells.These hormones include leptin, which controls hungersensationsbyactingoncellsinthehypothalamusinthe

13

7 Introduction 7

brain; gastrin, which prompts the release of acid andincreasesmuscleactivityinthestomach;glucagon,whichstimulatesthereleaseofglucosefromtheliverintotheblood; and insulin, which stimulates the absorption ofglucosefromthebloodintomusclesandothertissues.

The transportation and uptake of glucose is the pri-marymechanismbywhichthebodystoresenergy.Energyoccursintheformofglycogeninmusclesandintheformof triglycerides in fat cells and is readily liberated whenneeded, such as during exercise or fasting. Inadequateproduction of insulin can lead to diabetes, in which thebody is unable to effectively regulate the body’s use ofglucose.

Asubstantialpartofthegastrointestinaltract isalsooccupiedbylymphoidtissue,partofthebody’simmunedefensesystem.Thedigestivesystemisoneofthemostcriticalpointsatwhichforeignandpotentiallydangeroussubstancescanenterthebody.Thesystem’simmunefunc-tionisfoundprimarilyinthesmallintestine.Forexample,lymphocytes,atypeofwhitebloodcell,arepresentinthesmallintestineinthebasementmembrane,intheepithe-lialcellsoftheinnermucouslayer,andinlargegroupsofnodules known as Peyer patches. When these lympho-cytes encounter a foreign substance, they respond bydestroying the foreign cell or by adhering to its surface,interferingwithitsabilitytoinvadetissueandrenderingitharmless. Lymphocytes from the Peyer patches are alsotransported from the intestine back through the lym-phatic system to the thoracic duct and dispersed fromtherethroughoutthebody.Thus,thedigestivetractalsohelpstomaintainareservoirofdefenseagainstinfectionwhereveritmightoccur.

Whenallthepartsofthedigestivesystemareworkingas they should, carbohydrates, fats, and proteins are

14


brokendownandconvertedintoenergyforthebody.Thisenergyisusedtosupportdailyactivities,toregulatebodytemperature,andtomaintainthebodilysystemsthatcon-tribute to normal physiological function. In addition tothe energy that food supplies, it also contains mineralsand vitamins, which are dissolved and absorbed duringthedigestiveprocess,andaminoacids,whichareneces-sary to the regeneration of cells.These are vital for thebody’s healthy functioning. A lack of vitamin D, forinstance,whichcomesfromeggyolks,fortifiedmilk,andevensunlight,cancauserickets.A lackof iron,foundinred meat, can cause anemia. Even the nondigestibledietary fibre in food plays an important role, providingroughage to stimulate bowel function and aiding in theelimination of potentially toxic or carcinogenic (cancer-causing)substances.

Therearemanydiseasesanddisordersthatmayinter-ferewiththeproperfunctioningofthedigestivesystem.Someoftheseconditionsarecongenital(presentatbirth).Others may be caused by infections or environmentalfactorsormaybeeffectsofnutritionaldeficienciesorofother diseases. In tropical countries, intestinal parasitessuchaspinwormsareafrequentcauseofdigestivedisor-ders. Many diseases of the digestive system are stronglylinkedtobehavioralchoices,suchasalcoholandtobaccouse.Amongthesearemalignantdiseases,suchascancerofthemouth,esophagus,stomach,orpancreas,andinflam-matory conditions, such as pancreatitis.Worldwide,cirrhosisoftheliverisoneofthemostfrequentdiseasesoccurringasaresultoflong-term,high-volumeintakeofalcohol.

Somediseasesmayalsobecausedbydigestivemalfunc-tion.Twocommonexamplesareappendicitisandgallstones.Appendicitis is an inflammation of the appendix, usually

15

7 Introduction 7

1616

occurringwhentheopeningbetweentheappendixandthelargeintestinebecomesblocked,oftenbyfecalmatter.Thispreventstheappendixfromemptyingitscontentsintotheintestine and leads to swelling and bacterial infection.Treatmentforappendicitisisusuallyremovaloftheappen-dix. Gallstones are hardened deposits that form in thegallbladder,composedprimarilyofcalciumbilirubinate(abrown-pigmentedsubstance)andcholesterol.Thesestonesare formed when the proportion of cholesterol in bileexceeds the level necessary to contain it in solution.Atthatpointcrystallineparticlesofcholesterolareformed,whichmayrangefromassmallasagrainofsandtoaslargeasagolfballinsomeinstances.Riskfactorsfortheforma-tion of gallstones include obesity and high-calorie orhigh-cholesteroldiets.

Evenhealthypeoplehaveoccasionaldigestivedistur-bances, such as heartburn, diarrhea, and nausea.Heartburn,moretechnicallyknownasgastroesophagealrefluxdisease(GERD),istheresultofcontentfromthestomach moving back up into the esophagus. It mayoccuroccasionallyafteralargemeal,butitmaybeaggra-vated by obesity or pregnancy, both of which createcrampedconditionsintheabdomenandputpressureonthe stomach. Persistent reflux symptoms can lead tomore serious diseases of the esophagus. Gastritis is aninflammationofthestomachliningthatmaybecausedby contaminated food or by excessive alcohol intake.Traveler’sdiarrhea isalmostalwayscausedby ingestionofEscherichia colibacteria,frequentlyonunwashedveg-etablesorindrinkingwater.Othertypesofindigestionmay be the result of food sensitivities or allergies; ofexcessiveintakeofacidicfoodssuchascoffee;ofimpropereating habits; or of stress. Indigestion resulting fromthesecausesmayrangeinseverityfrommildabdominal


17

7 Introduction 7

discomfortandintestinalgastothemoreseveresymp-tomsofirritablebowelsyndrome,suchaspain,cramping,andvomiting.

Ulcersarearelativelycommondiseaseofthestomachandcanalsobeaggravatedbystress.Anulceriscausedwhenthestomachliningisunabletoprotectitselffromthestomach’sownacidicgastric juices.Themostcom-mon causes for erosion of the stomach lining arelong-term overuse of anti-inflammatory drugs such asaspirin, known collectively as non-steroidal anti-inflammatorydrugsorNSAIDS,andinfectionwiththeHelicobacter pyloribacterium.Globally,H. pyloriisoneofthe most common causes of bacterial infection inhumans,beingparticularlyproblematicinless-developedcountries and even affecting roughly one-third of theU.S.population.

In this volume, readers will learn that many of themost serious diseases of the digestive system remainpoorly understood and may often be difficult to diag-nose. Because they all affect the digestive tract, a widevarietyofdiseasesmaymanifestthemselvesinsymptomssuchaspersistentdiarrhea,bloodinthestool,abdominalpain, nausea and vomiting, and loss of appetite. Manytypesofdigestivedisordersandcancershavebeenfoundtohavesomegeneticcomponent,althoughthismayonlycauseapredispositiontothediseaseratherthanbeingadirectcause.

Readerswillalsodiscoverthat,formostpeople,oneofthe most important keys to maintaining good overallhealthistreatingthedigestivesystemwithrespect.Eatingabalanceddietthatishighinfibreandlowinfat,avoidingtobacco,usingalcohol inmoderation,andmaintainingahealthyweightareallactionsthatwillhelptokeepevery-thingrunningsmoothly–notjustthedigestivesystem.

19

CHAPTER 1

19

THE BEGINNING OF THE DIGESTIVE TRACT

Thehumandigestivesystemplaysafundamentalroleinensuringthatallthefoodsandliquidsweingestare

broken down into useful nutrients and chemicals. Thedigestivesystemconsistsprimarilyofthedigestivetract,ortheseriesofstructuresandorgansthroughwhichfoodand liquids pass during their processing into forms thatcanbeabsorbedintothebloodstreamanddistributedtotissues.Othermajorcomponentsofthedigestivesystemincludeglandsthatsecretejuicesandhormonesnecessaryforthedigestiveprocess,aswellastheterminalstructuresthroughwhichsolidwastespassintheprocessofelimina-tionfromthebody.

Thedigestivetractbeginsatthelipsandendsattheanus.Itconsistsofthemouth,ororalcavity,withitsteeth,for grinding the food, and its tongue, which serves tokneadfoodandmixitwithsaliva.Then,thereisthethroat,orpharynx;theesophagus;thestomach;thesmallintes-tine, consisting of the duodenum, the jejunum, and theileum;andthelargeintestine,consistingofthececum,aclosed-endsacconnectingwiththeileum,theascendingcolon,thetransversecolon,thedescendingcolon,andthesigmoid colon, which terminates in the rectum. Glandscontributing digestive juices include the salivary glands,thegastricglandsinthestomachlining,thepancreas,andtheliveranditsadjuncts—thegallbladderandbileducts.Alloftheseorgansandglandscontributetothephysicalandchemicalbreakingdownofingestedfoodandtotheeventualeliminationofnondigestiblewastes.

20


20

The abdominal organs are supported and protected by the bones of the pelvis and ribcage and are covered by the greater omentum, a fold of peritoneum that consists mainly of fat. EncyclopædiaBritannica,Inc.

21

7 The Beginning of the Digestive Tract 7

21

Mouth and oral StructureS

Littledigestionoffoodactuallytakesplaceinthemouth.However,throughtheprocessofmastication,orchewing,foodispreparedinthemouthfortransportthroughtheupperdigestivetractintothestomachandsmallintestine,where the principal digestive processes take place.Chewingisthefirstmechanicalprocesstowhichfoodissubjected. Movements of the lower jaw in chewing arebrought about by the muscles of mastication—the mas-seter,thetemporal,themedialandlateralpterygoids,andthe buccinator.The sensitivity of the periodontal mem-branethatsurroundsandsupportstheteeth,ratherthanthepowerofthemusclesofmastication,determinestheforceofthebite.

Mastication is not essential for adequate digestion.Chewingdoesaiddigestion,however,byreducingfoodtosmall particles and mixing it with the saliva secreted bythesalivaryglands.Thesalivalubricatesandmoistensdryfood,whilechewingdistributesthesalivathroughoutthefoodmass.Themovementofthetongueagainstthehardpalate and the cheeks helps to form a rounded mass, orbolus,offood.

The Lips and Cheeks

Thelipsaresoft,pliableanatomicalstructuresthatformthemouthmargin.Theyarecomposedofasurfaceepider-mis(skin),connectivetissue,andamusclelayer.Theedgesofthelipsarecoveredwithreddishskin,sometimescalledthevermilionborder,andabundantlyprovidedwithsensi-tivenerveendings.Thereddishskin isatransition layerbetween the outer, hair-bearing epidermis and the innermucous membrane, or mucosa. The mucosa is rich in

22


22

Anterior view of the oral cavity. EncyclopædiaBritannica,Inc.

2323

mucus-secretingglands,whichtogetherwithsalivaensureadequate lubrication for the purposes of speech andmastication.

Innewborninfantstheinnersurfaceismuchthicker,withsebaceousglandsandminuteprojectionscalledpapil-lae.Thesestructuraladaptationsseemtoaidtheprocessofsucking.Mostofthesubstanceofeachlipissuppliedbytheorbicularisorismuscle,whichencirclestheopening.Thismuscleandothers that radiateout intothecheeksmake possible the lips’ many variations in shape andexpression.

The cheeks, the sides of the mouth, are continuouswith the lips and have a similar structure.A distinct fatpadisfoundinthesubcutaneoustissue(thetissuebeneaththeskin)ofthecheek.Thispadisespeciallylargeininfantsandisknownasthesuckingpad.Ontheinnersurfaceofeachcheek,oppositetheseconduppermolartooth, isaslight elevation that marks the opening of the parotidduct, leading from the parotid salivary gland, which islocatedinfrontoftheear.Justbehindthisglandarefourto five mucus-secreting glands, the ducts of which openoppositethelastmolartooth.

Thelipsaresusceptibletodiseasessuchasherpessim-plex(feverblisters,orcoldsores)andleukoplakia(whitepatches, which can be precancerous). In elderly men,ulcers on the vermilion border of the lower lip are fre-quentlycancerous.Thebordersalsomaybecomecrackedandinflamedfromexcessivedryingbytheweather,chem-icalirritants,inadequatemoisteningbecauseofinfection,orinreactiontoantibiotics.

The Mouth

The mouth, which is also known as the oral (or buccal)cavity,istheorificethroughwhichfoodandairenterthe


24


body.Themouthopenstotheoutsideatthelipsandemptiesintothethroatattherear.Itsboundariesaredefinedbythe lips, cheeks, hard and soft palates, and glottis. It isdividedintotwosections:thevestibule,theareabetweenthecheeksandtheteeth,andtheoralcavityproper.Thelattersectionismostlyfilledbythetongue,alargemusclefirmlyanchoredtothefloorofthemouthbythefrenulumlinguae.Inadditiontoitsprimaryroleintheintakeandinitialdigestionoffood,themouthanditsstructuresareessentialinhumanstotheformationofspeech.

Thechiefstructuresofthemoutharetheteeth,whichtearandgrindingestedfoodintosmallpiecesthataresuit-ablefordigestion;thetongue,whichpositionsandmixesfoodandalsocarriessensoryreceptorsfortaste;andthepalate,whichseparatesthemouthfromthenasalcavity,allowingseparatepassagesforairandforfood.Allthesestructures,alongwiththelips,areinvolvedintheforma-tion of speech sounds by modifying the passage of airthroughthemouth.

The oral cavity and vestibule are entirely lined bymucous membranes containing numerous small glandsthat, along with the three pairs of salivary glands, bathethemouthinfluid,keepingitmoistandclearoffoodandotherdebris.Specializedmembranesformboththegums(gingivae),whichsurroundandsupporttheteeth,andthesurfaceofthetongue,onwhichthemembraneisrougherin texture, containing many small papillae that hold thetaste buds. The mouth’s moist environment and theenzymeswithinitssecretionshelptosoftenfood,facili-tatingswallowingandbeginningtheprocessofdigestion.

Theroofofthemouthisconcaveandisformedbythehardandsoftpalate.Thehardpalateisformedbythehor-izontalportionsofthetwopalatinebonesandthepalatineportionsofthemaxillae,orupperjaws.Thehardpalateis

25

covered by a thick, somewhat pale mucous membranethatiscontinuouswiththatofthegumsandisboundtotheupperjawandpalatebonesbyfirmfibroustissue.Thesoft palate is continuous with the hard palate in front.Posteriorly, it iscontinuouswiththemucousmembranecovering the floor of the nasal cavity.The soft palate iscomposed of the palatine aponeurosis—a strong, thin,fibroussheet—andtheglossopalatineandpharyngopala-tine muscles. A small projection called the uvula hangsfreefromtheposteriorofthesoftpalate.

The floor of the mouth can be seen only when thetongue is raised. In the midline is the frenulum linguaewhich—inadditiontoitsfunctioninanchoringthetonguetothefloorofthemouth—bindseachliptothegums.Oneachsideofthisisaslightfoldcalledasublingualpapilla,fromwhichtheductsofthesubmandibularsalivaryglandsopen.Runningoutwardandbackwardfromeachsublin-gual papilla is a ridge (the plica sublingualis) that markstheupperedgeofthesublingual(underthetongue)sali-varyglandandontowhichmostoftheductsofthatglandopen.

The Gums

Thegums,alsoknownasthegingivae,aremadeupofcon-nective tissue covered with mucous membrane. Themucousmembraneisconnectedbythickfibroustissuetothemembranesurroundingthebonesofthejaw.Thegummembrane rises to form a collar around the base of thecrown (exposed portion) of each tooth.Thus, the gumsareattachedtoandsurroundthenecksoftheteethandadjacentalveolarbone.

Healthygumsarepink,stippled,andtoughandhavealimitedsensitivitytopain,temperature,andpressure.The


26


gums are separated from the alveolar mucosa, which isred, by a scalloped line that approximately follows thecontoursoftheteeth.Theedgesofthegumsaroundtheteetharefreeandextendassmallwedgesintothespacesbetweentheteeth(interdentalpapillae).Internally,fibresof theperiodontalmembraneenterthegumandhold ittightlyagainsttheteeth.Changes incolour, lossofstip-pling, or abnormal sensitivity are early signs of guminflammation,orgingivitis.

Gum tissue is rich in blood vessels and receivesbranchesfromthealveolararteries.Thesevessels—calledalveolar because of their relationship to the alveoli den-tales,ortoothsockets—alsosupplybloodtotheteethandthespongyboneoftheupperandlowerjaws,inwhichtheteeth are lodged. Before the erupting teeth enter themouth cavity, gum pads develop; these are slight eleva-tions of the overlying oral mucous membrane. Whentootheruption iscomplete, thegumembraces theneckregionofeachtooth.

The Teeth

Theteetharehard,whitestructuresfoundinthemouth.Usuallyusedformastication,theteethofdifferentverte-brate species are sometimes specialized. The teeth ofsnakes, for example, are very thin and sharp and usuallycurvebackward.Theyfunctionincapturingpreybutnotinchewing,becausesnakesswallowtheirfoodwhole.Theteethofcarnivorousmammals,suchascatsanddogs,aremorepointedthanthoseofprimates,includinghumans.Thecaninesarelong,andthepremolarslackflatgrindingsurfaces, being more adapted to cutting and shearing(oftenthemoreposteriormolarsare lost).Ontheotherhand,herbivoressuchascowsandhorseshaveverylarge,

27

flatpremolarsandmolarswithcomplexridgesandcusps;thecaninesareoftentotallyabsent.

Thedifferencesintheshapesofteetharefunctionaladaptations. Few animals can digest cellulose, yet theplantcellsusedasfoodbyherbivoresareenclosedincel-lulosecellwallsthatmustbebrokendownbeforethecellcontents can be exposed to the action of digestiveenzymes. By contrast, the animal cells in meat are notencased in nondigestible matter and can be acted upondirectly by digestive enzymes. Consequently, chewing isnot so essential for carnivores as it is for herbivores.Humans,whoareomnivores(eatersofplantsandanimaltissue),haveteeththatbelong,functionallyandstructur-ally, somewhere between the extremes of specializationattainedbytheteethofcarnivoresandherbivores.

Eachtoothconsistsofacrownandoneormoreroots.Thecrownisthefunctionalpartofthetooththatisvisi-ble above the gum.The root is the unseen portion thatsupportsandfastensthetoothinthejawbone.Theshapesofthecrownsandtherootsvaryindifferentpartsofthemouthandfromoneanimaltoanother.Theteethononeside of the jaw are essentially a mirror image of thoselocatedontheoppositeside.Theupperteethdifferfromthelowerandarecomplementarytothem.

Tooth Structure

Alltrueteethhavethesamegeneralstructureandconsistof three layers. In mammals an outer layer of enamel—whichiswhollyinorganicandisthehardesttissueinthebody—coverspartorallof thecrownof the tooth.Themiddlelayerofthetoothiscomposedofdentine,whichislesshardthanenamelandsimilarincompositiontobone.Thedentineformsthemainbulk,orcore,ofeachtoothandextendsalmosttheentirelengthofthetooth,being


28


coveredbyenamelonthecrownportionandbycementumontheroots.Dentineisnourishedbythepulp,whichistheinnermostportionofthetooth.

The pulp consists of cells, tiny blood vessels, and anerve and occupies a cavity located in the centre of thetooth.Thepulpcanalislongandnarrowwithanenlarge-ment, called the pulp chamber, in the coronal end.Thepulpcanalextendsalmostthewholelengthofthetoothandcommunicateswiththebody’sgeneralnutritionalandnervoussystemsthroughtheapicalforamina(holes)attheendoftheroots.Belowthegumlineextendstherootofthetooth,whichiscoveredatleastpartiallybycementum.Thelatterissimilarinstructuretobonebutis lesshardthan dentine. Cementum affords a thin covering to therootandservesasamediumforattachmentofthefibresthatholdthetoothtothesurroundingtissue(periodontalmembrane).Gumisattachedtotheadjacentalveolarboneandtothecementumofeachtoothbyfibrebundles.

Tooth Form and Function

Likemostothermammals,humanshavetwosuccessivesetsofteethduringlife.Thefirstsetofteetharecalledprimary, or deciduous, ones, and the second set arecalledpermanentones.Humanshave20primaryand32permanentteeth.

Primary teeth differ from permanent teeth in beingsmaller,havingmorepointedcusps,beingwhiterandmorepronetowear,andhavingrelativelylargepulpchambersandsmall,delicate roots.Theprimary teethbegin toappearaboutsixmonthsafterbirth,andtheprimarydentitioniscompletebyage21/2.Sheddingbeginsaboutage5or6andis finished by age 13. The primary teeth are shed whentheir roots are resorbed as the permanent teeth pushtowardthemouthcavityinthecourseoftheirgrowth.

29

Inhumanstheprimarydentitionconsistsof20teeth—four incisors, two canines, and four molars in each jaw.Theprimarymolarsarereplacedintheadultdentitionbythepremolars,orbicuspidteeth.The12adultmolarsofthe permanent dentition erupt (emerge from the gums)behindtheprimaryteethanddonotreplaceanyofthese,givingatotalof32teethinthepermanentdentition.Thepermanentdentitionisthusmadeupoffourincisors,twocanines,fourpremolars,andsixmolarsineachjaw.

Incisorteetharetheteethatthefrontofthemouth,and they are adapted for plucking, cutting, tearing, andholding.Thebitingportionofanincisoriswideandthin,makingachisel-shapedcuttingedge.Theupper incisorshaveadelicatetactilesensethatenablesthemtobeusedforidentifyingobjectsinthemouthbynibbling.Nexttothe incisoroneachside isacanine,orcuspidtooth.Itfrequentlyispointedandratherpeglikeinshapeand,liketheincisors,hasthefunctionofcuttingandtearingfood.

Premolars and molars have a series of elevations, orcusps, that are used for breaking up particles of food.Behindeachcaninearetwopremolars,whichcanbothcutand grind food. Each premolar has two cusps (hence thename bicuspid).The molars, by contrast, are used exclu-sivelyforcrushingandgrinding.Theyaretheteethfarthestback in the mouth. Each molar typically has four or fivecusps.The third molar in humans tends to be variable insize, number of roots, cusp pattern, and eruption. Thenumberofrootsforeachtypeoftoothvariesfromoneforincisors,canines,andpremolarstotwoorthreeformolars.

The Tongue

Thetongueislocatedonthefloorofthemouthandisanorganthatiscapableofvariousmuscularmovements.In


30


Taste buds on the human tongue exhibit sensitivity to specific tastes.EncyclopædiaBritannica,Inc.

31

some animals (e.g., frogs) the tongue is elongated andadaptedtocapturing insectprey.Thetonguesofcertainreptilesfunctionprimarilyassensoryorgans,whereascatsandsomeothermammalsusetheirtonguesasinstrumentsforgroomingandcleaning.Inmammalsthetongueaidsincreating negative pressure within the oral cavity thatenables sucking, which is especially important for theabilityofhumaninfantsandothernewbornmammalstofeedinthefirsthoursanddaysoflife.Thetongueisalsoanimportantaccessoryorganinchewingandswallowing.In conjunction with the cheeks, it is able to guide andmaintain food between the upper and lower teeth untilmasticationiscomplete.Thetonguealsoisamajorbeareroftastebuds,isanaidtospeechinhumans,andhasglandscapable of producing some of the saliva necessary forswallowing.

The mammalian tongue consists of a mass of inter-woven, striated (striped) muscles interspaced with glandsandfatandcoveredwithmucousmembrane,whichvariesin different regions. The tongue is attached to the lowerjaw,thehyoidbone(aU-shapedbonebetweenthelowerjawandthelarynx),theskull,thesoftpalate,andthepharynxbyitsextrinsicmuscles.Itisboundtothefloorofthemouthandtotheepiglottis(aplateofcartilagethatservesasalidforthelarynx)byfoldsofmucousmembrane.

In humans the front tips and margins of the tongueusuallytouchtheteeth,aidinginswallowingandspeech.The top surface, or dorsum, contains numerous projec-tions of the mucous membrane called papillae. Theycontain tastebuds,whichare sensitive tochemicalcon-stituentsoffood,andserousglandsthatsecretesomeofthefluidinsaliva.

Thebase,orupperrearportion,ofthetonguehasnopapillae,butaggregatedlymphatictissue(lingualtonsils)


32


and serous and mucus-secreting glands are present.Theinferior,orunder,surfaceleadsfromthetipofthetonguetothefloorofthemouth.Itsmucousmembraneissmooth,devoid of papillae, and purple in colour from the manyblood vessels present. The root, the remainder of theundersidethatliesonthemouth’sfloor,containsbundlesofnerves,arteries,andmusclesthatbranchtotheothertongueregions.

An important function of the tongue is taste sensa-tion,whichisderivedfromtastereceptorcellslocatedinclusterswithintastebuds.Tastebudsareabletotransmitinformationabouttasteandflavourtothenervoussystem.In humans there may be anywhere from 50 to 150 taste

Circumvallate papillae, located on the surface of the back part of the tongue, contain taste buds (indicated by asterisks). Specialized hairlike structures (microvilli) located at the surface of taste buds in minute openings called taste pores (indicated by arrows) detect dissolved chemicals ingested in food, leading to the activation of receptor cells in the taste buds and the sensation of taste.UniformedServicesUniversityoftheHealthSciences(USUHS)

33

receptor cells within an individual taste bud.Taste budsareinnervatedbynervesthatrespondtochemicalsfromfoodinsolution,therebyprovidingthesensationoftaste.Therearefivefundamentaltastesensations:salty,sweet,sour(acid),bitter,andumami,whichrepresentsthetasteofaminoacids.Eachreceptorcellissensitivetoaparticulartaste—for example, responding only to salt or only toumami.Thetotalflavourofafoodcomesfromthecombi-nationof taste, smell, touch, textureorconsistency,andtemperaturesensations.

Among the disorders to which the tongue is subjectarecancer,leukoplakia(whitepatches),fungusinfection,congenitaldefects,andavarietyofsymptomscausedbydisease elsewhere in the body. Surgical removal of thisorganmakesspeechandswallowingdifficult.

The Salivary Glands

Foodistastedandmixedwithsalivathatissecretedbyseveral sets of glands. Besides the many minute glandsthatsecretesaliva,therearethreemajorpairsofsalivaryglands: the parotid, the submandibular, and the sublin-gualglands.Theparotidglands,thelargestofthepairs,arelocatedatthesideoftheface,belowandinfrontofeachear.Theparotidglandsareenclosedinsheathsthatlimit the extent of their swelling when inflamed, as inmumps.The submandibular glands, which are roundedinshape,lieneartheinnersideofthelowerjawbone,infrontofthesternomastoidmuscle(theprominentmuscleofthejaw).Thesublingualglandsliedirectlyunderthemucous membrane covering the floor of the mouthbeneaththetongue.

The salivary glands are of the type called racemose,fromtheLatinracemosus(“fullofclusters”),becauseofthe


34


clusterlikearrangementoftheirsecretingcellsinroundedsacs,calledacini,attachedtofreelybranchingsystemsofducts.Thewallsoftheacinisurroundasmallcentralcavityknownasanalveolus.Inthewallsoftheaciniarepyramidalsecretingcellsandsomeflat,star-shapedcontractilecellscalledmyoepithelial,orbasket,cells.The lattercellsarethoughttocontract,likethesimilarmyoepithelialcellsofthebreast,whichbytheircontractionexpelmilkfromthemilkducts.

Thesecretingcellsmaybeoftheserousorthemucoustype.Thelattertypesecretesmucin,thechiefconstituentof mucus; the former, a watery fluid containing theenzymeamylase.Thesecretingcellsoftheparotidglandsare of the serous type. Those of the submandibularglands,ofbothserousandmucoustypes,withtheserouscellsoutnumberingthemucouscellsbyfourtoone.The

The three major pairs of salivary glands. EncyclopædiaBritannica,Inc.

35

aciniofthesublingualglandsarecomposedprimarilyofmucouscells.

Thesalivaryglandsarecontrolledbythetwodivisionsof the autonomic nervous system, the sympathetic andthe parasympathetic.The parasympathetic nerve supplyregulatessecretionbytheacinarcellsandcausesthebloodvesselstodilate.Functionsregulatedbythesympatheticnerves includesecretionbytheacinarcells,constrictionofbloodvessels,and,presumably,contractionofthemyo-epithelial cells. Normally secretion of saliva is constant,regardless of the presence of food in the mouth. Theamountofsalivasecretedin24hoursusuallyamountsto1–1.5 litres (about 0.3–0.4 gallon). When somethingtouchesthegums,thetongue,orsomeregionofthemouthlining, or when chewing occurs, the amount of salivasecretedincreases.Thestimulatingsubstanceneednotbefood—drysandinthemouthorevenmovingthejawsandtonguewhenthemouthisemptyincreasesthesalivaryflow.

Thiscouplingofdirectstimulationtotheoralmucosawith increased salivation is known as the unconditionedsalivaryreflex.Whenanindividuallearnsthataparticularsight,sound,smell,orotherstimulusisregularlyassociatedwith food, that stimulus alone may suffice to stimulateincreasedsalivaryflow.Thisresponseisknownasthecon-ditionedsalivaryreflex.

Saliva

Saliva is a thick, colourless, opalescent fluid that is con-stantlypresentinthemouth.Ithasnumerousfunctions,thoughthemostimportantrelatetoitsabilitytodissolvefoodandtolubricatethesegmentsoftheupperdigestivetract.Whensalivadissolvessomeofthechewedfood,itnotonlyeasesthepassageoffoodtothestomachbutalsocreates a solution that stimulates the taste buds. The


36


lubricating actions of saliva also serve to moisten theinsideofthemouthtohelpwithspeech.

The composition of saliva varies, but its principalcomponents are water, inorganic ions similar to thosecommonlyfoundinbloodplasma,andanumberoforganicconstituents,includingsalivaryproteins,freeaminoacids,andtheenzymeslysozymeandamylase(ptyalin).Althoughsaliva is slightlyacidic, thebicarbonatesandphosphatescontainedwithinitserveasbuffersandmaintainthepH,or hydrogen ion concentration, of saliva relatively con-stantunderordinaryconditions.

Amylaseisastarch-digestingenzymethatinitiatestheprocess of enzymatic hydrolysis, which in turn dissolvesfood.Amylase splits starch (a polysaccharide containingmanysugarmoleculesboundinacontinuouschain)intomoleculesofthedoublesugarmaltose.Manycarnivores,such as dogs and cats, have no amylase in their saliva.Therefore,theirnaturaldietcontainsverylittlestarch.

The concentrations of bicarbonate, chloride, potas-sium,andsodiuminsalivaaredirectlyrelatedtotherateoftheirflow.Thereisalsoadirectrelationbetweenbicar-bonateconcentrationandthepartialpressureofcarbondioxideintheblood.Theconcentrationofchlorideinthebloodvariesfrom5millimolesperlitreatlowflowratesto70 millimoles per litre when the flow rate is high. Thesodiumconcentrationsinsimilarcircumstancesvaryfrom5millimolesperlitreto100millimolesperlitre.Thecon-centrationofpotassiuminthebloodisoftenhigherthanthat in the blood plasma, up to 20 millimoles per litre,whichaccountsforthesharpandmetallictasteofsalivawhenflowisbrisk.

Theconstantflowofsalivakeepstheoralcavityandteeth moist and comparatively free from food residues,sloughedepithelialcells,andforeignparticles.Laboratorystudies of saliva have demonstrated that it inhibits the

37

growth of bacteria. Indeed, lysozyme, the other enzymeoccurringinsaliva,hastheabilitytolyse,ordissolve,cer-tain bacteria. The secretion of saliva also provides amechanism whereby certain organic and inorganic sub-stancescanbeexcretedfromthebody,includingmercury,lead,potassiumiodide,bromide,morphine,ethylalcohol,andcertainantibioticssuchaspenicillin,streptomycin,andchlortetracycline.

Although saliva is not essential to life, its absenceresultsinanumberofinconveniences,includingdrynessoftheoralmucousmembrane,poororalhygienebecauseof bacterial overgrowth, a greatly diminished sense oftaste,anddifficultieswithspeech.


38

THE PASSAGE OF FOOD TO THE STOMACH

Thepassageoffoodintothestomachandthebreak-down of food into progressively smaller particles

withinthestomachareprocessesfacilitatedbymuscularcontractions.Forexample,musclesaidinswallowingandpushing food through the pharynx (throat). Likewise, aseries of rhythmic muscle contractions serves to moveingested products downward through the esophagus,toward the stomach. Upon entering the stomach, foodsare exposed to gastric juices, which help to dissolve theparticles.Thepowerfulgrindingcontractionsofthestomachmuscle mix the gastric contents, churning them into asemifluid mass known as chyme, which is then able toadvancetothelowerportionsofthedigestivetract.

Theactiveroleofthestomachindigestionhelpstocon-vertfoodsintochemicalformsthatthebodycanutilize.Theefficiencybywhichitdoesthisenablesthebodytoextractanabundanceofnutrientsfromchyme,especiallyasitadvancesthroughtheintestines,wherespecializedtransportersintheepithelial lining readily absorb and transfer nutrients tothebloodstreamfordistributiontothebody’stissues.

SWalloWing

Swallowingistheactofpassingfoodfromthemouth,bywayofthepharynxandesophagus,tothestomach.Threestagesareinvolvedinswallowingfood.

CHAPTER 2

39

The first begins in the mouth.There, food is mixedwithsalivaforlubricationandplacedonthebackofthetongue.Themouthcloses,andthesoftportionoftheroofof the mouth (soft palate) rises so that the passagewaybetween the nasal and oral cavities is closed off. Thetonguerollsbackward,propellingfoodintotheoralphar-ynx, a chamber behind the mouth that functions totransportfoodandair.

Once food enters the pharynx, the second stage ofswallowingbegins.Respirationistemporarilyinhibitedasthelarynx,orvoicebox,risestoclosetheglottis(theopen-ing to the air passage). Pressure within the mouth andpharynxpushesfoodtowardtheesophagus.Atthebegin-ningoftheesophagusthereisamuscularconstrictor,theupperesophageal sphincter (orcricopharyngealmuscle),which relaxes and opens when food approaches. Foodpasses from the pharynx into the esophagus.The upperesophagealsphincterthenimmediatelycloses,preventingflowoffoodbackintothemouth.

Oncefoodisintheesophagus,thefinalphaseofswal-lowing begins.The larynx lowers, the glottis opens, andbreathingresumes.Fromthetimefoodleavesthemouthuntilitpassestheuppersphincter,onlyaboutonesecondoftimeelapses,duringwhichallthesebodymechanismsspontaneously occur.After passing the upper sphincter,movementsintheesophaguscarryfoodtothestomach.Rhythmic muscular contractions (peristaltic waves) andpressurewithintheesophaguspushthefooddownward.Foldsintheesophagealwallstretchoutasmaterialspassbythemandagaincontractoncetheyhavepassed.Atthelowerendoftheesophagus,theloweresophagealsphincterrelaxesandfoodentersthestomach.Thesphincterthencloses again to prevent reflux of gastric juices and foodmaterials.

7 The Passage of Food to the Stomach 7

40


Swallowingisbasicallyaninvoluntaryreflex;onecan-notswallowunlessthereissalivaorsomesubstancetobeswallowed.Initially,foodisvoluntarilymovedtotherearoftheoralcavity,butoncefoodreachesthebackofthemouth, the reflex to swallow takes over and cannot beretracted.

Swallowingisinfluencedbybodilyposition.Liquidsswallowedwhenthebodyisinanuprightorhorizontalposition flow by gravity rapidly to the stomach. In thehead-down position, however, liquids remain at thebeginning of the esophagus, and several swallows andperistalticwavesmaybenecessarytoevacuatetheliquid.If a person swallows food connected to a string withcounterweightsattachedoutsideofthebody,hecanonlyovercome5to10grams(.17–.35ounces)ofweightresis-tance.Dogscanswallowfoodwitharesistanceof50to500grams(1.76–17.6ounces).Essentially,theswallowingcapacity of humans is much weaker than that of otheranimals.Thetemperatureoffoodsalsoaffectsaperson’sswallowingcapacity.Verycoldliquids(1–3°C[34–37°F])slow down or completely stop peristaltic movement intheesophagus.Incontrast, liquidsathightemperature(58–61°C[136–142°F])increaseperistalticmovements.

Afflictions affecting swallowing include paralysis ofthepharynx,failureoftheesophagealsphincterstoopenproperly,andspasticcontractionsoftheesophagealmusclewalls.Anyofthesemaybecausedbyphysicalorpsycho-logicalcomplications.

the pharynx

The pharynx, or throat, is the passageway leading fromthe mouth and nose to the esophagus and larynx. Thepharynx permits the passage of swallowed solids and

41

liquidsintotheesophagus,orgullet,andconductsairtoand from the trachea, or windpipe, during respiration.ThepharynxalsoconnectsoneithersidewiththecavityofthemiddleearbywayoftheEustachiantubeandpro-vides for equalization of air pressure on the eardrummembrane,whichseparatesthecavityofthemiddleearfromtheexternalearcanal.

The pharynx has roughly the form of a flattenedfunnel.Itisattachedtothesurroundingstructuresbutislooseenoughtopermitglidingofthepharyngealwallagainst them in the movements of swallowing. Theprincipal muscles of the pharynx, involved in themechanicsofswallowing,arethethreepharyngealcon-strictors, which overlap each other slightly and form


Sagittal section of the pharynx. EncyclopædiaBritannica,Inc.

42


the primary musculature of the side and rear pharyn-gealwalls.

Therearethreemaindivisionsofthepharynx:theoralpharynx, the nasal pharynx, and the laryngeal pharynx.The latter two are airways, whereas the oral pharynx isshared by both the respiratory and digestive tracts. Oneithersideoftheopeningbetweenthemouthcavityandtheoralpharynxisapalatinetonsil,socalledbecauseofitsproximity to the palate. Each palatine tonsil is locatedbetween two vertical folds of mucous membrane calledthe glossopalatine arches. The nasal pharynx, above, isseparated from the oral pharynx by the soft palate.Anotherpairoftonsilsarelocatedontheroofofthenasalpharynx.Thepharyngeal tonsils,alsoknownastheade-noids, are part of the body’s immune system.When thepharyngeal tonsils become grossly swollen (which oftenoccurs during childhood) they occlude the airway. Thelaryngealpharynxandthelowerpartoftheoralpharynxarehiddenbytherootofthetongue.

Thefirststageofswallowingconsistsofpassageofthebolusintothepharynx.Entryofthebolusintothenasalpharynx is prevented by the elevation of the soft palateagainst the posterior pharyngeal wall. As the bolus isforced into the pharynx, the larynx moves upward andforwardunderthebaseofthetongue.Thesuperiorpha-ryngeal constrictor muscles contract, initiating a rapidpharyngeal peristaltic, or squeezing, contraction thatmovesdownthepharynx,propellingthebolusinfrontofit.Thewallsandstructuresofthelowerpharynxareele-vatedtoengulftheoncomingmassoffood.Theepiglottis,alidlikecoveringthatprotectstheentrancetothelarynx,diverts the bolus to the pharynx.The upper esophagealsphincter,whichhaskepttheesophaguscloseduntilthispoint, relaxes as the bolus approaches and allows it to

43

enter the upper esophagus. The pharyngeal peristalticcontraction continues into the esophagus and becomestheprimaryesophagealperistalticcontraction.

the eSophaguS

The esophagus is a relatively straight muscular tubethroughwhichfoodpassesfromthepharynxtothestom-ach.It isabout25centimeters (10 inches) in length; thewidthvariesfrom1.5to2cm(about1inch).Anatomically,itliesbehindthetracheaandheartandinfrontofthespinalcolumn;itpassesthroughthemusculardiaphragmbeforeenteringthestomach.Inadditiontothemuscularsphinc-ters that close off both of its ends, the esophagus alsocontainsfourlongitudinallayersoftissue,whichplayaroleinenablingthetubetocontractorexpandtoallowforthepassageoffood.

Thefouresophageallayersarethemucosa,submucosa,muscularis,andtunicaadventitia.Themucosaismadeupof stratified squamous epithelium containing numerousmucous glands.The submucosa is a thick, loose fibrouslayerconnectingthemucosatothemuscularis.Togetherthemucosaandsubmucosaformlonglongitudinalfolds,sothatacrosssectionoftheesophagusopeningwouldbestar-shaped.

Themuscularisiscomposedofaninnerlayer,inwhichthe fibres are circular, and an outer layer of longitudinalfibres.Bothmusclegroupsarewoundaroundandalongthealimentarytract,buttheinneronehasaverytightspiral,sothatthewindingsarevirtuallycircular,whereastheouteronehasaveryslowlyunwindingspiralthatisvirtuallylongi-tudinal. The outer layer of the esophagus, the tunicaadventitia, is composed of loose fibrous tissue that con-nectstheesophaguswithneighbouringstructures.Exceptduring the act of swallowing, the esophagus is normally


44


The human digestive system as seen from the front.EncyclopædiaBritannica,Inc.

45

empty,anditslumen,orchannel,isessentiallyclosedbythelongitudinalfoldsofthemucosalandsubmucosallayers.

The upper third of the esophagus is composed ofstriated (voluntary) muscle.The middle third is a mix-tureofstriatedandsmooth(involuntary)muscle,andthelower third consists only of smooth muscle. The twosphinctermusclesoftheesophagusactlikedrawstringsin closing channels. Both sphincters normally remainclosed except during the act of swallowing.The upperesophageal sphincter (or cricopharyngeus muscle) islocatedatthelevelofthecricoidcartilage(asinglering-likecartilageformingthelowerpartofthelarynxwall).Theloweresophagealsphincterencirclesthe3to4cm(1.2to1.6inches)oftheesophagusthatpassthroughanopeninginthediaphragmcalledthediaphragmatichiatus.Theloweresophagealsphincterismaintainedintensionatalltimes,exceptinresponsetoadescendingcontrac-tionwave,atwhichpointitrelaxesmomentarilytoallowthe release of gas (belching) or vomiting. The loweresophagealsphincterhasanimportantrole,therefore,inprotectingtheesophagusfromtherefluxofgastriccon-tentswithchangesinbodypositionorwithalterationsofintragastricpressure.

Transportthroughtheesophagus isaccomplishedbythe primary esophageal peristaltic contractions, whichoriginate in the pharynx.Transport of material throughtheesophagustakesapproximately10seconds.Whenthebolusarrivesatthejunctionwiththestomach,theloweresophageal sphincter relaxes and the bolus enters thestomach.Ifthebolusistoolarge,oriftheperistalticcon-tractionistooweak,thebolusmaybecomearrestedinthemiddleorloweresophagus.Whenthisoccurs,secondaryperistaltic contractions originate around the bolus inresponsetothelocaldistensionoftheesophagealwallandpropelthebolusintothestomach.


46


Whenaliquidisswallowed,itstransportthroughtheesophagusdependssomewhatonthepositionofthebodyandtheeffectsofgravity.Whenswallowedinahorizontalor head-down position, liquids are handled in the samemanner as solids, with the liquid moving immediatelyaheadoftheadvancingperistalticcontraction.(Thehighpressuresandstrongcontractionsoftheesophagealperi-staltic wave make it possible for animals with very longnecks,suchasthegiraffe,totransportliquidsthroughtheesophagusformanyfeet.)Whenthebodyisintheuprightposition,however,liquidsentertheesophagusandfallbygravity to the lowerend.There theyawait thearrivaloftheperistalticcontractionandtheopeningof the loweresophagealsphincter(8to10seconds)beforebeingemptiedintothestomach.

Disorders of the esophagus include ulceration andbleeding; heartburn, caused by gastric juices in theesophagus; achalasia, an inability to swallow or to passfood from the esophagus to the stomach, caused bydestruction of the nerve endings in the walls of theesophagus; scleroderma,acollagendisease;andspasmsoftheesophagealmuscles.

In some vertebrates the esophagus is not merely atubularconnectionbetweenthepharynxandthestomachbutrathermayserveasastoragereservoiroranancillarydigestiveorgan.Inmanybirds,forexample,anexpandedregionoftheesophagusanteriortothestomachformsathin-walled crop, which is the bird’s principal organ forthetemporarystorageoffood.Somebirdsusethecroptocarryfoodtotheiryoung.

Ruminantmammals, suchasthecow,areoftensaidtohavefour“stomachs.”Actually,thefirstthreeofthesechambers(rumen,reticulum,andomasum)arethoughtto be derived from the esophagus. Vast numbers of

47


bacteriaandprotozoansliveintherumenandreticulum.Whenfoodentersthesechambers, themicrobesbegintodigestandfermentit,breakingdownnotonlyprotein,starch,andfatsbutcelluloseaswell.Thelarger,coarsermaterialisperiodicallyregurgitatedasthecud,andafterfurtherchewingthecudisreswallowed.Slowlytheprod-ucts of microbial action, and some of the microbesthemselves,moveintothecow’struestomachandintes-tine, where further digestion and absorption take place.Since the cow, like other mammals, has no cellulose-digestingenzymesofitsown,itreliesuponthedigestiveactivityofthesesymbioticmicrobesinitsdigestivetract.Muchofthecelluloseinthecow’sherbivorousdiet,whichotherwisewouldhavenonutritivevalue,istherebymadeavailabletothecow.

the StoMach

Thestomachreceives ingested foodand liquids fromtheesophagusandretainsthemforgrindingandmixingwithgastric juice so that food particles are smaller and moresoluble.The main functions of the stomach are to com-mence the digestion of carbohydrates and proteins, toconvertthemealintochyme,andtodischargethechymeinto the small intestine periodically as the physical andchemicalconditionofthemixtureisrenderedsuitableforthenextphaseofdigestion.

The stomach is located in the left upper part of theabdomenimmediatelybelowthediaphragm.Infrontofthestomacharetheliver,partofthediaphragm,andtheanterior abdominal wall. Behind it are the pancreas, theleft kidney, the left adrenal gland, the spleen, and thecolon.The stomach is more or less concave on its rightside,convexonitsleft.Theconcaveborderiscalledthe

48


The stomach has three layers of muscle: an outer longitudinal layer, a middle circular layer, and an inner oblique layer. The inner lining consists of four layers: the serosa, the muscularis, the submucosa, and the mucosa. The mucosa is densely packed with gastric glands, which contain cells that produce digestive enzymes, hydrochloric acid, and mucus. EncyclopædiaBritannica,Inc.

49


lessercurvature;theconvexborder,thegreatercurvature.Whenthestomachisempty,itsmucosalliningisthrownintonumerouslongitudinalfolds,knownasrugae.Thesetendtodisappearwhenthestomachisdistended.

The cardia is the opening from the esophagus intothestomach.Theuppermostpartofthestomach,locatedabovetheentranceoftheesophagus,isthefundus.Thefundusadaptstothevaryingvolumeofingestedfoodbyrelaxing its muscular wall. It frequently contains a gasbubble, especially after a meal.The largest part of thestomachisknownsimplyasthebody.Itservesprimarilyasareservoirforingestedfoodandliquids.Theantrum,thelowermostpartofthestomach,issomewhatfunnel-shaped, with its wide end joining the lower part of thebody and its narrow end connecting with the pyloriccanal,whichemptiesintotheduodenum(theupperdivisionofthesmallintestine).Thepyloricportionofthestomach(antrum plus pyloric canal) tends to curve to the rightand slightly upward and backward and thus gives thestomach its J-shaped appearance. The pylorus, thenarrowestportionofthestomach,istheoutletfromthestomach into the duodenum. It is approximately 2 cm(almost 1 inch) in diameter and is surrounded by thickloopsofsmoothmuscle.

Themusclesofthestomachwallarearrangedinthreelayers,orcoats.Theexternalcoat,calledthelongitudinalmuscle layer, is continuous with the longitudinal musclecoat of the esophagus. Longitudinal muscle fibres aredividedatthecardiaintotwobroadstrips.Theoneontheright,thestronger,spreadsouttocoverthelessercurva-tureandtheadjacentposteriorandanteriorwallsofthestomach.Longitudinalfibresontheleftradiatefromtheesophagus over the dome of the fundus to cover thegreatercurvatureandcontinueontothepylorus,where

50


they join the longitudinal fibres coming down over thelessercurvature.Thelongitudinallayercontinuesonintothe duodenum, forming the longitudinal muscle of thesmallintestine.

Themiddle,orcircularmuscularlayer,thestrongestofthethreemuscular layers,completelycoversthestom-ach.Thecircularfibresofthiscoatarebestdevelopedinthe lowerportionofthestomach,particularlyovertheantrumandpylorus.Atthepyloricendofthestomach,the circular muscle layer becomes greatly thickened toformthepyloricsphincter.Thismuscularringisslightlyseparatedfromthecircularmuscleoftheduodenumbyconnectivetissue.Theinnermostlayerofsmoothmuscle,called the oblique muscular layer, is strongest in theregion of the fundus and progressively weaker as itapproachesthepylorus.

The stomach is capable of dilating to accommodatemore than one litre (about one quart) of food or liquidswithoutincreasingpressureonthestomach.Thisrecep-tive relaxation of the upper part of the stomach toaccommodateamealispartlyduetoaneuralreflexthatistriggeredwhenhydrochloricacidcomesintocontactwiththemucosaoftheantrum,possiblythroughthereleaseofthehormoneknownasvasoactiveintestinalpolypeptide.Thedistensionofthebodyofthestomachbyfoodacti-vates a neural reflex that initiates the muscle activity oftheantrum.

Blood and Nerve Supply of the Stomach

Manybranchesoftheceliactrunkbringarterialbloodtothestomach.Theceliactrunkisashort,widearterythatbranchesfromtheabdominalportionoftheaorta,themainvesselconveyingarterialbloodfromtheheartto

51


the systemic circulation. Blood from the stomach isreturned to the venous system through the portal vein,whichcarriesthebloodtotheliver.

Thenervesupplytothestomachisprovidedbyboththe parasympathetic and sympathetic divisions of theautonomic nervous system. The parasympathetic nervefibresarecarried inthevagus,or10thcranial,nerve.Asthevagusnervepassesthroughtheopeninginthediaphragmtogetherwiththeesophagus,branchesoftherightvagusnervespreadovertheposteriorpartofthestomach,whiletheleftvagusnervesuppliestheanteriorpart.Sympatheticbranchesfromanervenetworkcalledtheceliac,orsolar,plexus accompany the arteries of the stomach into themuscularwall.

Stomach Contractions

Threetypesofmotoractivityofthestomachhavebeenobserved. The first is a small contraction wave of thestomachwallthatoriginatesintheupperpartofthestom-ach and slowly moves down over the organ toward thepyloric sphincter. This type of contraction produces aslightindentationofthestomachwall.Retrogradewavesfrequentlysweepfromthepyloricsphinctertotheantrumanduptoitsjunctionwiththebodyofthestomach,whichresultsinaback-and-forthmovementofthegastriccon-tentsthathasamixingandcrushingeffect.

Thesecondtypeofmotoractivityisalsoacontractingwave,butitisperistalticinnature.Thecontractionorigi-natesintheupperpartofthestomachaswellandisslowlypropagated over the organ toward the pyloric sphincter.Thistypeofgastriccontractionproducesadeepindenta-tion in the wall of the stomach. As the peristaltic waveapproaches the antrum, the indentation completely

52


obstructsthestomachlumen,orcavity,andthuscompart-mentalizes it.The contracting wave then moves over theantrum, propelling the material ahead of it through thepyloricsphincterintotheduodenum.Thistypeofcontrac-tion serves as a pumping mechanism for emptying thecontents of the gastric antrum through the pyloricsphincter.Boththemixingandtheperistalticcontractionsofthestomachoccurataconstantrateofthreecontrac-tionsperminutewhenrecordedfromthegastricantrum.Awave of peristalsis sweeps along the lower half of thestomach and along the entire intestine to the proximalcolon at two-hour intervals after meals.These peristalticwavescanbehaltedbyeatingandcanbe inducedbythehormonemotilin.

The third type of gastric motor activity is bestdescribed as a tonic, or sustained, contraction of all thestomach muscles. The tonic contraction decreases thesizeofthestomachlumen,asallpartsofthegastricwallseem to contract simultaneously. This activity accountsforthestomach’sabilitytoaccommodateitselftovaryingvolumesofgastriccontent.Thetoniccontractionisinde-pendentoftheothertwotypesofcontractions.However,mixingcontractionsandperistalticcontractionsnormallyoccursimultaneouslywiththetoniccontraction.Asfoodisbrokendown,smallerparticlesflowthroughthepyloricsphincter,whichopensmomentarilyasaperistalticwavedescends through the antrum toward it. This permits“sampling”ofthegastriccontentsbytheduodenum.

Gastric Mucosa

The inner surface of the stomach is lined by a mucousmembrane known as the gastric mucosa.The mucosa isalwayscoveredbyalayerofthickmucusthatissecreted

53


bytallcolumnarepithelialcells.Gastricmucusisaglyco-proteinthatservestwopurposes:thelubricationoffoodmassesinordertofacilitatemovementwithinthestom-achandtheformationofaprotectivelayerovertheliningepitheliumofthestomachcavity.Thisprotectivelayerisadefense mechanism the stomach has against beingdigestedbyitsownprotein-lyzingenzymes,anditisfacili-tatedbythesecretionofbicarbonateintothesurfacelayerfromtheunderlyingmucosa.

The acidity, or hydrogen ion concentration, of themucouslayermeasurespH7(neutral)attheareaimmedi-atelyadjacenttotheepitheliumandbecomesmoreacidic(pH2) at the luminal level. When the gastric mucus isremoved from the surface epithelium, small pits, calledfoveolaegastricae,maybeobservedwithamagnifyingglass.Thereareapproximately90to100gastricpitspersquaremillimetre (58,000 to 65,000 per square inch) of surfaceepithelium.Threetosevenindividualgastricglandsemptytheir secretions into each gastric pit. Beneath the gastricmucosaisathinlayerofsmoothmusclecalledthemuscula-ris mucosae, and below this, in turn, is loose connectivetissue,thesubmucosa,whichattachesthegastricmucosatothemusclesinthewallsofthestomach.

The gastric mucosa contains six different types ofcells. In addition to the tall columnar surface epithelialcells,therearefivecommoncelltypesfoundinthevariousgastricglands.

(1)Mucoidcellssecretegastricmucusandarecommontoalltypesofgastricglands.Mucoidcellsarethemaincelltypefoundinthegastricglandsinthecardiacandpyloricareasofthestomach.Thenecksoftheglandsinthebodyandfundicpartsofthestomacharelinedwithmucoidcells.

54


(2)Zymogenic,orchief,cellsarelocatedpredominantlyingastricglandsinthebodyandfundicportionsofthestomach.Thesecellssecretepepsinogen,fromwhichtheproteolytic(protein-digesting)enzymepepsinisformed.Therearetwovarietiesofpepsinogen,knownaspepsinogenIandpepsinogenII.Bothareproducedinthemucousandzymogeniccellsintheglandsofthebodyofthestomach,butthemucousglandslocatedelsewhereinthestomachproduceonlypepsinogenII.Thosestimulithatcausegastricacidsecretion—inparticular,vagalnervestimulation—alsopromotethesecretionofthepepsinogens.

(3)Gastrincells,alsocalledGcells,arelocatedthroughouttheantrum.Theseendocrinecellssecretetheacid-stimulatinghormonegastrinasaresponsetoloweredacidityofthegastriccontentswhenfoodentersthestomachandgastricdistention.Gastrinthenentersthebloodstreamandiscarriedinthecirculationtothemucosaofthebodyofthestomach,whereitbindstoreceptorsitesontheoutermembraneoftheparietalcells.Thegastrin-receptorcomplexthatisformedtriggersanenergy-consumingreactionmoderatedbythepresenceoftheenzymeATPase,boundtothemembranethatleadstotheproductionandsecretionofhydrogenionsintheparietalcells.

(4)Parietal,oroxyntic,cells,foundintheglandsofthebodyandfundicportionsofthestomach,secretehydrogenionsthatcombinewithchlorideionstoformhydrochloricacid(HCl).Theacidthatispro-duceddrainsintothelumenoftheglandandthenpassesthroughtothestomach.Thisprocessoccursonlywhenoneormoretypesofreceptorsontheoutermembraneoftheparietalcellareboundtohistamine,gastrin,oracetylcholine.Prostaglandins,

55


hormonelikesubstancesthatarepresentinvirtuallyalltissuesandbodyfluids,inhibitthesecretionofhydrochloricacid.Thedrugsomeprazole(Losec™orPrilosec™)andlansoprazole(Prevacid™)alsoinhibitacidsecretionbytheparietalcellsandareusedastreatmentsforpepticulcer.Parietalcellsproducemostofthewaterfoundingastricjuice.Theyalsoproduceglycoproteinscalledintrinsicfactor,whichareessentialtothematurationofredbloodcells,vitaminB12absorption,andthehealthofcertaincellsinthecentralandperipheralnervoussystems.

(5)Endocrinecellscalledenterochromaffin-likecellsbecauseoftheirstainingcharacteristicsarescatteredthroughoutthebodyofthestomach.Enterochromaffin-likecellssecreteseveralsub-stances,includingthehormoneserotonin.

Gastric Secretion

Thegastricmucosasecretes1.2to1.5 litres(about0.3to0.4 gallon) of gastric juice per day. Gastric juice rendersfood particles soluble, initiates digestion (particularly ofproteins),andconvertsthegastriccontentstoasemiliquidmasscalledchyme,thuspreparingitforfurtherdigestioninthesmallintestine.Gastricjuiceisavariablemixtureofwater,hydrochloricacid,electrolytes(sodium,potassium,calcium,phosphate,sulfate,andbicarbonate),andorganicsubstances (mucus, pepsins, and protein). This juice ishighlyacidicbecauseofitshydrochloricacidcontent,anditisrichinenzymes.

Thestomachwallsareprotectedfromdigestivejuicesby the membrane on the surface of the epithelial cellsbordering the lumen of the stomach.This membrane isrichinlipoproteins,whichareresistanttoattackbyacid.

56


Thegastricjuiceofsomemammals(e.g.,calves)containstheenzymerennin,whichclumpsmilkproteinsandthustakesthemoutofsolutionandmakesthemmoresuscep-tibletotheactionofaproteolyticenzyme.

Theprocessofgastricsecretioncanbedividedintothree phases (cephalic, gastric, and intestinal) thatdepend upon the primary mechanisms that cause thegastricmucosatosecretegastricjuice.Thephasesofgastricsecretionoverlap,andthereisaninterrelationandsomeinterdependence between the neural and humoralpathways.

The cephalic phase of gastric secretion occurs inresponsetostimulireceivedbythesenses—thatis,taste,smell,sight,andsound.Thisphaseofgastricsecretionisentirely reflex in origin and is mediated by the vagusnerve.Gastricjuiceissecretedinresponsetovagalstim-ulation,eitherdirectlybyelectricalimpulsesorindirectlyby stimuli received through the senses. Ivan PetrovichPavlov,theRussianphysiologist,originallydemonstratedthismethodofgastricsecretioninanow-famousexperi-mentwithdogs.

Thegastricphaseismediatedbythevagusnerveandby the release of gastrin.The acidity of the gastric con-tentsafteramealisbufferedbyproteinssothatoverallitremainsaroundpH3(acidic)forapproximately90minutes.Acidcontinuestobesecretedduringthegastricphaseinresponse to distension and to the peptides and aminoacids that are liberated from protein as digestion pro-ceeds. The chemical action of free amino acids andpeptidesexcitestheliberationofgastrinfromtheantrumintothecirculation.Thus,therearemechanical,chemical,andhormonalfactorscontributingtothegastricsecretoryresponse to eating.This phase continues until the foodhasleftthestomach.

57


Theintestinalphaseisnotfullyunderstoodbecauseofacomplexstimulatoryandinhibitorprocess.Aminoacidsandsmallpeptidesthatpromotegastricacidsecretion areinfused into the circulation, however, at the same timechymeinhibitsacidsecretion.Thesecretionofgastricacidisanimportantinhibitorofgastrinrelease.IfthepHoftheantralcontentsfallsbelow2.5,gastrinisnotreleased.Some of the hormones that are released from the smallintestine by products of digestion (especially fat), inparticular glucagon and secretin, also suppress acidsecretion.

Chyme

Chymeisathicksemifluidmassofpartiallydigestedfoodanddigestivesecretionsthatisformedinthestomachandintestineduringdigestion.Oncefoodisinthesmallintes-tine,itstimulatesthepancreastoreleasefluidcontainingahighconcentrationofbicarbonate.Thisfluidneutralizesthe highly acidic gastric juice, which would otherwisedamagethemembraneliningoftheintestine,resultinginaduodenalulcer.Othersecretionsfromthepancreas,gall-bladder,liver,andglandsintheintestinalwalladdtothetotalvolumeofchyme.

Muscular contractions of the stomach walls help tomix food and digestive substances together in formingchyme.As particles of food become small enough, theyare passed at regular intervals into the small intestine.Onceintheintestine,moreenzymesareaddedandmix-ing continues. When food particles are sufficientlyreducedinsizeandcomposition,theyareabsorbedbytheintestinalwallandtransportedtothebloodstream.

Somefoodmaterialispassedfromthesmallintestinetothelargeintestine,orcolon.Inthecolon,chymeisactedupon by bacteria that break down the proteins, starches,

58


and some plant fibres not totally digested by the otherorgans.Inboththesmallandthe largeintestine,water isnormallyabsorbedsothechymegraduallygetsthicker.Aschymepassesthroughthestomachandintestine, itpicksupcellulardebrisandothertypesofwasteproducts.Whenall of the nutrients have been absorbed from chyme, theremaining waste material passes to the end of the largeintestine, the sigmoid colon and rectum, to be stored asfecalmatteruntilitisreadytobeexcretedfromthebody.

Gastrin

Gastrinisadigestivehormonethatissecretedbythewallof the pyloric end of the stomach. In humans, gastrinoccurs in three forms: as a 14-, 17-, and 34-amino-acidpolypeptide.These forms are produced from a series ofenzymatic reactions that cleave the larger proteins intotheirsmallerforms.

Gastrin is released into the bloodstream when foodentersthestomachandiscarriedbythecirculatorysys-tem to the gastric cells in the stomach wall, where ittriggersthesecretionofgastric juice.This juiceconsistsprimarily of hydrochloric acid, which helps break apartfibrous matter in food and kills bacteria that may havebeeningested,andpepsinogen,whichisaprecursoroftheprotein-splitting enzyme pepsin. Gastrin also increasesthe motility of the stomach, thereby helping to churnfood and eventually to empty the stomach. To a lesserdegree, gastrin also increases the motility of the uppersmallintestineandthegallbladder.

The medical importance of gastrin lies in the factthattherearepancreaticislet-celltumourscalledgastri-nomas that secrete large quantities of gastrin(hypergastrinemia). Hypergastrinemia stimulates theproduction of gastric acid, which causes severe peptic

59


ulcerdiseaseanddiarrhea.Gastrinomasareonecompo-nent of the syndrome of multiple endocrine neoplasiatype1(MEN1)andarealsothedefiningtumourtypeofarare disorder known as Zollinger-Ellison syndrome,which may occur sporadically or as a part of MEN1.Treatmentconsistsofsurgicallyremovingthetumourortreatingthepatientwithadrugthatinhibitsgastricacidsecretion(aprotonpumpinhibitor).

Gastric Absorption and Emptying

Although the stomach absorbs few of the products ofdigestion,itcanabsorbmanyothersubstances,includingglucose and other simple sugars, amino acids, and somefat-soluble substances. The pH of the gastric contentsdetermines whether some substances are absorbed.At alowpH,forexample,theenvironmentisacidicandaspirinisabsorbedfromthestomachalmostasrapidlyaswater,but,asthepHofthestomachrisesandtheenvironmentbecomesmorebasic,aspirinisabsorbedmoreslowly.

Water moves freely from the gastric contents acrossthegastricmucosaintotheblood.Thenetabsorptionofwaterfromthestomachissmall,however,becausewatermoves just as easily from the blood across the gastricmucosatothelumenofthestomach.Theabsorptionofwaterandalcoholcanbeslowedifthestomachcontainsfoodstuffs and especially fats, probably because gastricemptyingisdelayedbyfats,andmostwaterinanysitua-tionisabsorbedfromthesmallintestine.

The rate of emptying of the stomach depends uponthephysicalandchemicalcompositionofthemeal.Fluidsemptymorerapidlythansolids,carbohydratesmorerapidlythanproteins,andproteinsmorerapidlythanfats.Whenfood particles are sufficiently reduced in size and are

60


nearly soluble and when receptors in the duodenal bulb(theareaofattachmentbetweentheduodenumandthestomach)haveafluidityandahydrogenionconcentrationofacertainlevel,theduodenalbulbandthesecondpartoftheduodenumrelax,allowingemptyingofthestomachtostart.

During a duodenal contraction, the pressure in theduodenalbulbriseshigherthanthatintheantrum.Thepylorus prevents reflux into the stomach by shutting.Thevagusnervehasanimportantroleinthecontrolofemptying,butthereissomeindicationthatthesympa-theticdivisionoftheautonomicnervoussystemisalsoinvolved.Severalofthepeptidehormonesofthedigestivetractalsohaveaneffectonintragastricpressureandgastricmovements,buttheirroleinphysiologicalcircumstancesisunclear.

61

ANATOMY OF THE LOWER DIGESTIVE TRACT

Once food has been processed into chyme, it is able tomove from the stomach into the lower digestive tract.This portion of the digestive tract consists of the smallintestineandthelargeintestine.Thecombinedlengthofthesetwosegmentsisabout8.2to9.1metres(27to30feet).Inordertofitwithintheabdominalcavity,thesmallintes-tine is folded repeatedly, forming a winding passagewaythat provides a large surface area for the absorption ofnutrients.Thelargeintestine,whichismuchshorterandwiderthanthesmallintestine,travelsaroundtheoutsideedgeofthelatterinaseriesoffoursections,therebysur-roundingitinasortofsquareframe.Theprimaryfunctionsof the lower digestive tract include the absorption ofnutrientsfromchymeandthecompactionoftheremain-ingwastecontents intofecalmatter,which isultimatelyeliminatedfromthebody.

the SMall inteStine

Thesmallintestineistheprincipalorganofthedigestivetract.Itsprimaryfunctionsincludethemixingandtrans-portofintraluminalcontents,theproductionofenzymesand other constituents essential for digestion, and theabsorptionofnutrients.Mostoftheprocessesthatsolubi-lizecarbohydrates,proteins,andfatsandreducethemtorelatively simple organic compounds occur in the smallintestine.

Thesmallintestine,whichis670to760cm(22to25feet)inlengthand3to4cm(1.2to1.6inches)indiameter,isthe

CHAPTER 3

62


The inner wall of the small intestine is covered by numerous folds of mucous membrane called plicae circulares. The surface of these folds contains tiny pro-jections called villi and microvilli, which further increase the total area for absorption. Absorbed nutrients are moved into circulation by blood capillaries and lacteals, or lymph channels. EncyclopædiaBritannica,Inc.

63

7 Anatomy of the Lower Digestive Tract 7

longestpartofthedigestivetract.Itbeginsatthepylorus,thejuncturewiththestomach,andendsattheileocecalvalve, the juncture with the colon.The main functionalsegments of the small intestine are the duodenum, thejejunum,andtheileum.

Theduodenumis23to28cm(9to11inches)longandformsaC-shapedcurvethatencirclestheheadofthepan-creas. Unlike the rest of the small intestine, it isretroperitoneal (that is, it isbehindtheperitoneum,themembrane lining the abdominal wall). Its first segment,knownastheduodenalbulb,isthewidestpartofthesmallintestine. It is horizontal, passing backward and to therightfromthepylorus,andliessomewhatbehindthewideendofthegallbladder.Thesecondpartoftheduodenumrunsverticallydownwardinfrontofthehilumoftherightkidney (the point of entrance or exit for blood vessels,nerves, and the ureters). It is into this part through theduodenalpapilla(papillaofVater)thatthepancreaticjuiceandbileflow.Thethirdpartof theduodenumrunshori-zontallytothe left infrontoftheaortaandtheinferiorvenacava(theprincipalchannelforreturntotheheartofvenous blood from the lower part of the body and thelegs),whilethefourthpartascendstotheleftsideofthesecond lumbar vertebra (at the level of the small of theback),thenbendssharplydownwardandforwardtojointhe second part of the small intestine, the jejunum.Anacuteangle,calledtheduodenojejunalflexure, is formedbythesuspensionofthispartofthesmallintestinebytheligamentofTreitz.

Thejejunumformstheuppertwo-fifthsoftherestofthesmallintestine.It,liketheileum,hasnumerouscon-volutionsandisattachedtotheposteriorabdominalwallby the mesentery, an extensive fold of serous-secretingmembrane. The ileum is the remaining three-fifths ofthesmallintestine,thoughthereisnoabsolutepointat

64


whichthejejunumendsandtheileumbegins.Inbroadterms, the jejunum occupies the upper and left part ofthe abdomen below the subcostal plane (that is, at thelevel of the 10th rib), while the ileum is located in thelowerandrightpart.Atitsterminationtheileumopensintothelargeintestine.

The arrangement of the muscular coats of the smallintestine isuniformthroughoutthe lengthoftheorgan.Theinner,circularlayeristhickerthantheouter,longitu-dinal layer.Theoutermost layerof thesmall intestine islinedbytheperitoneum.

Blood and Nerve Supply of the Small Intestine

Thesuperiormesentericartery(abranchoftheabdominalaorta) and the superior pancreaticduodenal artery (abranch of the hepatic artery) supply the small intestinewithblood.Thesevesselsrunbetweenlayersofthemes-entery, the membrane that connects the intestines withthewalloftheabdominalcavity,andgiveofflargebranchesthatformarowofconnectingarchesfromwhichbranchesarisetoenterthewallofthesmallbowel.Thebloodfromtheintestineisreturnedbymeansofthesuperiormesen-tericvein,which,withthesplenicvein,formstheportalvein,whichdrainsintotheliver.

The small intestine has both sympathetic and para-sympathetic innervation. The vagus nerve providesparasympatheticinnervation.Sympatheticinnervationisprovided by branches from the superior mesentericplexus,anervenetworkunderneaththesolarplexusthatfollows the blood vessels into the small intestine andfinallyterminatesintheAuerbachplexus,whichislocatedbetween the circular and longitudinal muscle coats, andtheMeissnerplexus,which is located inthesubmucosa.

65


Numerous fibrils, both adrenergic (sympathetic) andcholinergic(parasympathetic),connectthesetwoplexuses.

Contractions and Motility of the Small Intestine

Thecontractionsofthecircularandlongitudinalmusclesare regulated by electrical impulses that begin with thepassageofcalciumionsintothemusclecell.Theduodenalpacemakersendselectricalimpulsesdownthesmallintes-tine at a rate of 11 cycles per minute in the duodenum,graduallydecreasingto8cyclesperminuteintheileum.Theseelectricalchangesarepropagatedinthelongitudinalmusclelayerofthewallofthesmallintestine.

Occurringsimultaneouslywiththeslow-waveelectricalactivitymaybefast,spikelikeelectricalcharges.Thistypeofelectricalactivityoriginatesinthecircularmusclelayerof the intestinal wall and occurs when the circular layercontracts.Thedepolarizationofthemusclecellmembranes,oranexcessofpositivechargesontheinsideofthecell,causesthemyofibrils(thecontractingcomponentsofthemyofilamentsthatconstitutethemuscletissues)tocontract.Therateofthesecontractionsisgovernedbytherateofdepolarizationofthemusclecellmembrane.Thetwospiralmuscle layers then contract, causing the motor activitythat permits the mixing and transporting of the food inthesmallintestine.

Theprimarypurposesofthemovementsofthesmallintestinearetoprovidemixingandtransportofintraluminalcontents.Acharacteristicofsmallintestinemotilityistheinherentabilityofthesmoothmuscleconstitutingthewalloftheintestinetocontractspontaneouslyandrhythmically.This phenomenon is independent of any extrinsic nervesupply to thesmall intestine.Inthemyentericplexus (anetworkofnervefibresinthewalloftheintestine),there

66


are several other messenger substances and receptorscapable of modulating smooth muscle activity, includingsomatostatin, serotonin (5-hydroxytryptamine), and theenkephalins. With at least seven such substances in andaroundthesmoothmuscle,thereissomeconfusionastotheirrespectiveroles.Thecontractionsofthesmallintes-tinecreatepressuregradientsfromoneadjacentsegmentoftheorgantoanother.Thepressuregradients, inturn,areprimarily responsible for transport within the smallintestine.

Withinthesmallintestine,twotypesofmotoractivityhavebeenrecognized:segmentingcontractionsandperi-staltic contractions. The predominant motor action ofthesmallintestineisthesegmentingcontraction,whichisalocalizedcircumferentialcontraction,principallyofthecircularmuscleoftheintestinalwall.Segmentingcontrac-tionsmix,separate,andchurntheintestinalchyme.Thecontractioninvolvesonlyashortsegmentoftheintestinalwall,lessthan1to2cm(about1inch),andconstrictsthelumen,tendingtodivideitscontents.Asthechymemovesfrom the duodenum to the ileum, there is a gradualdecreaseinthenumberofsegmentingcontractions.Thishas been described as the “gradient” of small intestinemotility.

Although segmenting contractions usually occur inanirregularmanner,theycanoccurinaregularorrhyth-mic pattern and at a maximum rate for that particularsite of the small intestine (rhythmic segmentation).Rhythmic segmentation may occur only in a localizedsegmentofsmallintestine,oritmayoccurinaprogressivemanner, with each subsequent segmenting contractionoccurring slightly below the preceding one (progressivesegmentation).

Aperistalticcontractionmaybedefinedasanadvancingring,orwave,ofcontractionthatpassesalongasegment

67


ofthegastrointestinaltract.Itnormallyoccursonlyoverashortsegment(approximatelyevery6cm[2.4inches])andmovesatarateofabout1or2cmperminute.Thistypeofmotoractivityinthesmallintestineresultsinthetransportofintraluminalcontentsdownward,usuallyonesegmentatatime.

Whenaninflammatoryconditionofthesmallbowelexists, or when irritating substances are present in theintraluminal contents, a peristaltic contraction maytraveloveraconsiderabledistanceofthesmallintestine;thisiscalledtheperistalticrush.Diarrheaduetocommoninfections is frequently associated with peristalticrushes. Most cathartics (e.g., laxatives) produce theirdiarrheiceffectbyirritatingtheintestinalmucosaorbyincreasingthecontents,particularlywithfluid.

Absorption in the Small Intestine

Althoughthesmallintestineisonly3to4cm(1.2to1.6inches)indiameterandapproximately7metres(23feet)inlength,ithasbeenestimatedthatitstotalabsorptivesurfaceareaisapproximately4,500squaremetres(5,400squareyards).Thisenormousabsorptivesurface ispro-vided by the unique structure of the mucosa, which isarrangedinconcentricfoldsthathavetheappearanceoftransverseridges.Thesefolds,knownasplicaecirculares,areapproximately5to6cm(2inches)longandabout3mm(0.1inch)thick.

Plicae circulares are present throughout the smallintestineexceptinthefirstportion,orbulb,oftheduo-denum,whichisusuallyflatandsmooth,exceptforafewlongitudinal folds. Also called valves of Kerckring, theplicaecircularesarelargestinthelowerpartoftheduo-denumandintheupperpartofthejejunum.Theybecomesmallerandfinallydisappearinthelowerpartoftheileum.

68


The folds usually run one-half to two-thirds of the wayaroundtheintestinalwall.Occasionally,asinglefoldmayspiralthewallforthreeorfourcompleteturns.Ithasbeenestimatedthatthesmallintestinecontainsapproximately800 plicae circulares and that they increase the surfaceareaoftheliningofthesmallbowelbyfivetoeighttimestheoutersurfacearea.

Anotherfeatureofthemucosathatgreatlymultipliesits surfacearea is thatof tinyprojectionscalledvilli.Thevilli usually vary from 0.5 to 1 mm (0.02 to 0.04 inch) inheight. Their diameters vary from approximately one-eighthtoone-thirdtheirheight.Thevilliarecoveredbyasinglelayeroftallcolumnarcellscalledgobletcellsbecauseoftheirroughresemblancetoemptygobletsaftertheyhavedischargedtheircontents.Gobletcellsarefoundscatteredamongthesurfaceepithelialcellscoveringthevilliandareasourceofmucin,thechiefconstituentofmucus.

Atthebaseofthemucosalvilliaredepressionscalledintestinalglands,orLieberkühnglands.Thecellsthatlinetheseglandscontinueupandoverthesurfaceofthevilli.Inthebottomoftheglands,epithelialcellscalledcellsofPanetharefilledwithalphagranules,oreosinophilicgran-ules,socalledbecausetheytakeuptherose-colouredstaineosin. Though they may contain lysozyme, an enzymetoxictobacteria,andimmunoglobins,theirprecisefunc-tionisuncertain.

There are three other cell types in the Lieberkühnglands:gobletcells,endocrinecells,andundifferentiatedcells,whichhavethepotentialtoundergochangesforthepurpose of replacing losses of any cell type. The mainfunctionsoftheundifferentiatedcellsintheseglandsarecellrenewalandsecretion.Undifferentiatedcellshaveanaverage life of 72 hours before becoming exhausted andbeingcastoff.

69


Theappearanceandshapeofthevillivaryindifferentlevelsofthesmallintestine.Intheduodenumthevilliarecloselypacked,large,andfrequentlyleaflikeinshape.Inthe jejunum the individual villus measures between 350and 600μm in height (there are about 25,000μm in aninch)andhasadiameterof110to135μm.Theinnerstruc-ture of the individual villus consists of loose connectivetissuecontainingarichnetworkofbloodvessels,acentrallacteal(orchannelforlymph),smoothmusclefibres,andscatteredcellsofvarioustypes.Thesmoothmusclecellssurroundthecentrallactealandprovideforthepumpingactionrequiredtoinitiatetheflowof lymphoutofthevillus.Asmallcentralarteriole(minuteartery)branchesatthetipofthevillustoformacapillarynetwork;thecapil-laries,inturn,emptyintoacollectingvenulethatrunstothebottomofthevillus.

Aremarkablefeatureofthemucosavilliistherough,specialized surface of the epithelial cells. This plasmamembrane, known as the brush border, is thicker andricherinproteinsandlipidsthanistheplasmamembraneon the epithelial cells at the side and base of the villus.Waterandsolutespassthroughporesinthesurfaceepi-thelium of the mucosa by active transport and solventdrag;i.e.,solutesarecarriedinamovingstreamofwaterthat causes an increased concentration of solute on thesideofthemembranefromwhichthewaterhadoriginallycome.Thesizeoftheporesisdifferentintheileumfromin the jejunum.This difference accounts for the variousratesofabsorptionofwateratthetwosites.

Theenterocytesarejoinedneartheirapexbyacontactzone known as a “tight junction.” These junctions arebelievedtohaveporesthatareclosedintherestingstateanddilatedwhenabsorptionisrequired.Thebrushborderisfusedtoalayerofglycoprotein,knownasthe“fuzzycoat,”

70


where certain nutrients are partly digested. It consists ofindividualmicrovilliapproximately0.1μmindiameterand1μm in height; each epithelial cell may have as many as1,000 microvilli.The microvilli play an important role inthe digestion and absorption of intestinal contents byenlarging the absorbing surface approximately 25 times.They also secrete the enzymes disaccharidase and pepti-dase that hydrolyze disaccharides and polypeptides tomonosaccharides and dipeptides to amino acids,respectively.

Molecularreceptorsforspecificsubstancesarefoundonthemicrovillisurfacesatdifferentlevelsinthesmallintes-tine. This may account for the selective absorption ofparticular substances at particular sites—for example,intrinsic-factor-bound vitamin B12 in the terminal ileum.Suchreceptorsmayalsoexplaintheselectiveabsorptionofiron and calcium in the duodenum and upper jejunum.Furthermore,therearetransportproteinsinthemicrovillusmembrane associated with the passage of sodium ions,D-glucose,andaminoacids.Actinisfoundinthecoreofthemicrovillus,andmyosinisfoundinthebrushborder.Becausecontractility is a function of these proteins, the microvillihavemotoractivitythatpresumablyinitiatesthestirringandmixingactionswithinthelumenofthesmallintestine.

Beneaththemucosaofthesmallintestine,asbeneaththat of the stomach, are the muscularis and the submu-cosa.The submucosa consists of loose connective tissueandcontainsmanybloodvesselsandlymphatics.Brunnerglands, located in the submucosa of the duodenum, arecomposedofacini(roundsacs)andtubulesthataretwist-ingandhavemultiplebranching.Theseglandsemptyintothe base of Lieberkühn glands in the duodenum. Theirexact function isnotknown,buttheydosecreteaclearfluid that contains mucus, bicarbonate, and a relatively

71


weak proteolytic (protein-splitting) enzyme. In the sub-mucosaofthejejunum,therearesolitarynodules(lumps)oflymphatictissue;thereismorelymphatictissueintheileum,inaggregatesofnodulesknownasPeyerpatches.

Paneth Cells

Paneth cells, also called Davidoff cells, are a specializedtypeofepithelialcellfoundinthemucous-membranelin-ingofthesmallintestineandoftheappendix,atthebaseof tubelike depressions known as Lieberkühn glands.Namedforthe19th-centuryAustrianphysiologistJosephPaneth, the cell has one nucleus at its base and denselypackedsecretorygranulesthroughouttherestofitsbody.Thecells’functionisnottotallyknown,noristheirmannerofdischargingtheirgranules.

Paneth cells secrete large amounts of protein-richmaterialandarethoughttosecretetheenzymepeptidase,whichbreakspeptidemoleculesintoaminoacidssuitableforassimilationbythebody.Inhumansthegranulesarefound to contain carbohydrates, proteins, and zinc. Inmiceaspecificprotein,lysozyme,knowntodestroysomebacteria, is believed to be present in the granules.ThissuggeststhatthePanethcellmightalsohaveanantibacte-rialfunction.

Argentaffin Cells

Argentaffincellsareroundorpartlyflattenedcellsoccurringin the lining tissue of the digestive tract and containinggranulesthoughttobeofsecretoryfunction.Theseepi-thelial cells, though common throughout the digestivetract, are most concentrated in the small intestine andappendix.The cells locate randomly within the mucousmembraneliningoftheintestineandintubelikedepressionsinthatliningknownastheLieberkühnglands.

72


The granules of argentaffin cells contain a chemicalcalledserotonin,whichstimulatessmoothmusclecontrac-tions. Functionally, it is believed that serotonin diffusesoutoftheargentaffincellsintothewallsofthedigestivetract,whereneuronsleadingtothemusclesarestimulatedto produce the wavelike contractions of peristalsis.Peristalticmovementsencouragethepassageoffoodsub-stancesthroughtheintestinaltract.

Peyer Patches

Peyer patches are nodules of lymphatic cells. They areformed when lymphatic cells aggregate into bundles orpatches,whichoccursusuallyonlyinthelowestportion(ileum)ofthesmallintestine.Peyerpatchesarenamedforthe17th-centurySwissanatomistHansConradPeyer.

Peyerpatchesareroundorovalandarelocatedinthemucous membrane lining of the intestine.They can beseenbythenakedeyeaselongatedthickenedareas,andtheirsurfaceisfreeoftheprojections(villi)anddepres-sions(Lieberkühnglands)thatcharacterizetheintestinalwall.Usuallythereareonly30to40patchesineachindi-vidual.Inyoungadultstheymaybemorenumerous,andasapersonagestheytendtobecomelessprominent.

ThefullfunctionofPeyerpatchesisnotknown,buttheydoplayaroleinimmunologicresponseandcontainBand T cells similar to those found in peripheral lymphnodes.Intyphoidfever,thesepatchesmaybecomesitesof inflammation, in which case they may develop intoulcerations,hemorrhages,orperforations.

Secretions of the Small Intestine

There are many sources of digestive secretions into thesmall intestine. Secretions into the small intestine arecontrolledbynerves, including thevagus,andhormones.

73


Themosteffectivestimuliforsecretionarelocalmechanicalor chemical stimulations of the intestinal mucous mem-brane.Suchstimulialwaysarepresentintheintestineintheformofchymeandfoodparticles.Thegastricchymethatisemptiedintotheduodenumcontainsgastricsecretionsthatwillcontinuetheirdigestiveprocessesforashorttimeinthesmallintestine.

Oneofthemajorsourcesofdigestivesecretionisthepancreas, a large gland that produces both digestiveenzymesandhormones.Thepancreasempties itssecre-tions into the duodenum through the major pancreaticduct(ductofWirsung)intheduodenalpapilla(papillaofVater)andtheaccessorypancreaticducta fewcentime-tresawayfromit.Pancreaticjuicecontainsenzymesthatdigestproteins,fats,andcarbohydrates.Secretionsoftheliveraredeliveredtotheduodenumbythecommonbileductviathegallbladderandarealsoreceivedthroughtheduodenalpapilla.

Thecompositionofthesuccusentericus,themixtureof substances secreted into the small intestine, variessomewhatindifferentpartsoftheintestine.Exceptintheduodenum,thequantityofthefluidsecretedisminimal,evenunderconditionsofstimulation.Intheduodenum,for example, where the Brunner glands are located, thesecretioncontainsmoremucus.Ingeneral,thesecretionofthesmallintestineisathin,colourlessorslightlystraw-colouredfluid,containingflecksofmucus,water,inorganicsalts,andorganicmaterial.The inorganicsaltsarethosecommonly present in other body fluids, with the bicar-bonate concentration higher than it is in blood. Asidefrommucus,theorganicmatterconsistsofcellulardebrisand enzymes, including a pepsinlike protease (from theduodenumonly),anamylase,alipase,atleasttwopepti-dases,sucrase,maltase,enterokinase,alkalinephosphatase,nucleophosphatases,andnucleocytases.

74


the large inteStine

Thelargeintestine,orcolon,servesasareservoirfortheliquidsemptied into it fromthesmall intestine.Ithasamuch larger diameter than the small intestine (approxi-mately2.5cm,or1inch,asopposedto6cm,or2.4inches,inthelargeintestine),butat150cm(5feet),itislessthanone-quarterthelengthofthesmallintestine.Theprimaryfunctions of the colon are to absorb water; to maintainosmolality, or level of solutes, of the blood by excretingand absorbing electrolytes (substances, such as sodiumandchloride,thatinsolutiontakeonanelectricalcharge)fromthechyme;andtostorefecalmaterialuntilitcanbeevacuated by defecation. The colon also contains largenumbersofbacteriathatsynthesizeniacin(nicotinicacid),thiamin (vitamin B1) and vitamin K, vitamins that areessential to several metabolic activities as well as to thefunctionofthecentralnervoussystem.

Thelargeintestinesecretesmucus,whichaidsinlubri-catingtheintestinalcontentsandfacilitatestheirtransportthrough the bowel. Each day approximately 1.5 to 2 litres(about0.4to0.5gallon)ofchymepassthroughtheileocecalvalvethatseparatesthesmallandlargeintestines.Thechymeisreducedbyabsorptioninthecolontoaround150ml(5fluidounces). The residual indigestible matter, together withsloughed-offmucosalcells,deadbacteria,andfoodresiduesnotdigestedbybacteria,constitutethefeces.

The large intestine can be divided into the cecum,ascendingcolon,transversecolon,descendingcolon,andsigmoidcolon.Thececum,thefirstpartofthelargeintes-tine,isasacwithaclosedendthatoccupiestherightiliacfossa,thehollowoftheinnersideoftheilium(theupperpartofthehipbone).Guardingtheopeningoftheileum(the terminal portion of the small intestine) into thececumistheileocecalvalve.

75


The mucosa of the large intestine is punctuated with numerous crypts that absorb water and are lined with mucus-secreting goblet cells. At the lower end of the rectum, the circular and longitudinal muscle layers terminate in the internal and external anal sphincters. EncyclopædiaBritannica,Inc.

76


The circular muscle fibres of the ileum and those ofthececumcombinetoformthecircularsphinctermuscleof the ileocecal valve. The ascending colon extends upfromthececumatthe levelofthe ileocecalvalvetothebend in the colon called the hepatic flexure, which islocated beneath and behind the right lobe of theliver.Behind,itisincontactwiththerearabdominalwalland the right kidney.The ascending colon is covered byperitoneumexceptonitsposteriorsurface.

Thetransversecolonisvariableinposition,dependinglargely on the distention of the stomach, but usually islocatedinthesubcostalplane—thatis,atthelevelofthe10thrib.Ontheleftsideoftheabdomen,itascendstothebendcalledthesplenicflexure,whichmaymakeaninden-tationinthespleen.Thetransversecolonisboundtothediaphragmoppositethe11thribbyafoldofperitoneum.

Thedescendingcolonpassesdownandinfrontoftheleft kidney and the left side of the posterior abdominalwalltotheiliaccrest(theupperborderofthehipbone).The descending colon is more likely than the ascendingcolontobesurroundedbyperitoneum.

Thesigmoidcoloniscommonlydividedintoiliacandpelvicparts.Theiliaccolonstretchesfromthecrestoftheilium,orupperborderofthehipbone,totheinnerborderofthepsoasmuscle,whichliesintheleftiliacfossa.Likethedescendingcolon,theiliaccolonisusuallycoveredbyperitoneum.Thepelviccolonliesinthetruepelvis(lowerpartof thepelvis)andformsoneortwo loops, reachingacrosstotherightsideofthepelvisandthenbendingbackand,atthemidline,turningsharplydownwardtothepointwhereitbecomestherectum.

Thelayersthatmakeupthewallofthecolonaresimilarinsomerespectstothoseofthesmallintestine;therearedistinct differences, however.The external aspect of thecolon differs markedly from that of the small intestine

77


because of features known as the taeniae, haustra, andappendicesepiploicae.Thetaeniaearethreelongbandsoflongitudinalmusclefibres,about1cm(0.4inch)inwidth,thatareapproximatelyequallyspacedaroundthecircum-ference of the colon. Between the thick bands of thetaeniae,thereisathincoatingoflongitudinalmusclefibres.Becausethetaeniaeareslightlyshorterthanthelargeintes-tine,theintestinalwallconstrictsandformscircularfurrowsof varying depths called haustra, or sacculations. Theappendicesepiploicaearecollectionsoffattytissuebeneaththecoveringmembrane.Ontheascendinganddescendingcolon,theyareusuallyfoundintworows,whereasonthetransversecolontheyformonerow.

The inner surface of the colon has many crypts thatarelinedwithmucousglandsandnumerousgobletcells,anditlacksthevilliandplicaecircularescharacteristicofthe small intestine. It contains many solitary lymphaticnodules but no Peyer patches. Characteristic of thecolonicmucosaaredeeptubularpits,increasingindepthtowardtherectum.

Theinnerlayerofmuscleofthelargeintestineiswoundinatightspiralaroundthecolon,sothatcontractionresultsin compartmentalization of the lumen and its contents.Thespiraloftheouterlayer,ontheotherhand,followsaloose undulating course, and contraction of this musclecausesthecontentsofthecolontoshiftforwardandback-ward.Thebulkofthecontents,inparticulartheamountofundigestedfibre,influencesthesemuscularactivities.

Blood and Nerve Supply of the Large Intestine

Thearterialbloodsupplytothelargeintestineissuppliedbybranchesofthesuperiorandinferiormesentericarteries(bothofwhicharebranchesoftheabdominalaorta)and

78


thehypogastricbranchoftheinternaliliacartery(whichsuppliesbloodtothepelvicwallsandviscera,thegenitalorgans, the buttocks, and the inside of the thighs).Thevesselsformacontinuousrowofarchesfromwhichvesselsarisetoenterthelargeintestine.

Venousbloodisdrainedfromthecolonfrombranchesthat formvenousarches similar to thoseof thearteries.Theseeventuallydrainintothesuperiorandinferiormes-entericveins,whichultimatelyjoinwiththesplenicveintoformtheportalvein.Theinnervationofthelargeintes-tineissimilartothatofthesmallintestine.

Contractions and Motility of the Large Intestine

Local contractions and retrograde propulsions ensuremixing of the contents and good contact with themucosa. Colonic motility is stimulated by masticationand by the presence of fat, unabsorbed bile salts, bileacids,andthepeptidehormonesgastrinandcholecysto-kinin.Thehormonessecretin,glucagon,andvasoactiveintestinalpeptideacttosuppressmotility.Theelectricalactivityofthemusclesofthecolonismorecomplexthanthatofthesmallintestine.

Variations from the basic rhythmic movements ofthe colon are present in the lower (distal) half of thecolon and in the rectum. Slow-wave activity that pro-duces contractions from the ascending colon to thedescendingcolonoccursattherateof11cyclesperminute,andslow-waveactivityinthesigmoidcolonandrectumoccursat6cyclesperminute.Localcontractionsmigratedistally in the colon at the rate of 4 cm (1.6 inches) persecond.Retrograde,orreverse,movementsoccurmainlyintheupper(proximal)colon.

79


The Appendix

Theappendixisavestigialhollowtubethatisclosedatoneendandisattachedattheotherendtothececum,apouch-like beginning of the large intestine into which the smallintestineempties itscontents.It isnotclearwhethertheappendixservesanyusefulpurposeinhumans.Suspectedfunctions include housing and cultivating beneficial gutflorathatcanrepopulatethedigestivesystemfollowinganillness that wipes out normal populations of these flora;providingasitefortheproductionofendocrinecellsinthefetus that produce molecules important in regulatinghomeostasis; and serving a possible role in immunefunctionduringthefirstthreedecadesoflifebyexposingleukocytes(whitebloodcells)toantigensinthegastrointes-tinal tract, thereby stimulating antibody production thatmayhelpmodulateimmunereactionsinthegut.Whilethespecificfunctionsofthehumanappendixremainunclear,thereisgeneralagreementamongscientiststhattheappen-dixisgraduallydisappearingfromthehumanspeciesoverevolutionarytime.Theappendixisofmedicalsignificancebecauseitsblockagecanleadtoappendicitis,apainfulandpotentiallydangerousinflammation.

Theappendixisusually8to10cm(3to4inches)longand less than 1.3 cm (0.5 inch) wide. The cavity of theappendixismuchnarrowerwhereitjoinsthececumthanit is at its closed end.The appendix has muscular wallsthatareordinarilycapableofexpellingintothececumthemucoussecretionsoftheappendicealwallsoranyoftheintestinal contents that have worked their way into thestructure.Ifanythingblockstheopeningoftheappendixorpreventsitfromexpellingitscontentsintothececum,appendicitismayoccur.Themostcommonobstructionintheopeningisafecalith,ahardenedpieceoffecalmatter.

80


Swellingoftheliningoftheappendicealwallsthemselvescanalsoblocktheopening.

Whentheappendixispreventedfromemptyingitself,aseriesofeventsoccurs.Fluidsanditsownmucoussecre-tionscollectintheappendix,leadingtoedema,swelling,and the distention of the organ. As the distentionincreases,thebloodvesselsoftheappendixbecomeclosedoff,whichcausesthenecrosis(death)ofappendicealtissue.Meanwhile,thebacterianormallyfoundinthispartoftheintestine begin to propagate in the closed-off pocket,worseningtheinflammation.Theappendix,weakenedbynecrosisandsubjecttoincreasingpressurefromwithinbythe distention, may burst, spilling its contents into theabdominalcavityand infectingthemembranesthat line

The appendix is a hollow tube that is closed at one end and is attached at the other end to the cecum at the beginning of the large intestine.EncyclopædiaBritannica,Inc.

81


the cavity and cover the abdominal organs. Fortunately,peritonitisisusuallypreventedbytheprotectivemecha-nismsofthebody.Theomentum,asheetoffattytissue,oftenwraps itselfaroundthe inflamedappendix,andanexudatethatnormallydevelopsintheareasofinflamma-tionbehaveslikeglueandsealsofftheappendixfromthesurroundingperitonealcavity.

The Rectum

Therectum,whichisacontinuationofthesigmoidcolon,beginsinfrontofthemidsacrum(thesacrumisthetrian-gularbonenearthebaseofthespineandbetweenthetwohipbones). It ends in a dilated portion called the rectalampulla,whichinfrontisincontactwiththerearsurfaceoftheprostateinthemaleandwiththeposteriorvaginalwall in the female. Posteriorly, the rectal ampulla is infrontofthetipofthecoccyx(thesmallboneattheverybaseofthespine).

Attheendofthepelviccolon,themesocolon,thefoldofperitoneumthatattachesthecolontotherearwalloftheabdomenandpelvis,ceases,andtherectumisthencoveredbyperitoneumonlyatitssidesandinfront.Lowerdown,the rectum gradually loses the covering on its sides untilonlythefrontiscovered.About7.5cm(3inches)fromtheanus, the anterior peritoneal covering is also folded backontothebladderandtheprostateorthevagina.

Near the termination of the sigmoid colon and thebeginningoftherectum,thecolonictaeniaespreadouttoform a wide external longitudinal muscle coat. At thelowerendoftherectum,musclefibresofthelongitudinalandcircularcoatstendtointermix.Theinternalcircularmusclecoatterminatesinthethickroundedinternalanalsphinctermuscle.Thesmoothmusclefibresoftheexternal

82


longitudinalmusclecoatoftherectumterminatebyinter-weavingwithstriatedmusclefibresofthelevatorani,orpelvicdiaphragm,abroadmusclethatformsthefloorofthepelvis.Asecondsphincter,theexternalanalsphincter,iscomposedofstriatedmuscleandisdividedintothreeparts known as the subcutaneous, superficial, and deepexternal sphincters. Thus, the internal sphincter iscomposed of smooth muscle and is innervated by theautonomicnervoussystem,whiletheexternalsphinctersareofstriatedmuscleandhavesomatic(voluntary)inner-vationprovidedbynervescalledthepudendalnerves.

Themucosal liningoftherectumissimilartothatofthesigmoidcolonbutbecomesthickerandbettersuppliedwithbloodvessels,particularlyinthelowerrectum.Arterialbloodissuppliedtotherectumandanusbybranchesfromtheinferiormesentericarteryandtherightandleftinternaliliac arteries.Venous drainage from the anal canal andrectum is provided by a rich network of veins called theinternalandexternalhemorrhoidalveins.

Twotothreelargecrescentlikefoldsknownasrectalvalvesare locatedintherectalampulla.Thesevalvesarecaused by an invagination, or infolding, of the circularmuscleandsubmucosa.Thecolumnarepitheliumoftherectal mucosa, innervated by the autonomic nervoussystem, changes to the stratified squamous (scalelike)type, innervated by the peripheral nerves, in the lowerrectumafewcentimetresabovethepectinateline,whichisthejunctionbetweenthesquamousmucousmembraneofthelowerrectumandtheskinliningthelowerportionoftheanalcanal.

Onceortwicein24hours,amassperistalticmovementshiftstheaccumulatedfecesonwardfromthedescendingandsigmoidsectorsofthecolon.Therectumisnormallyempty,butwhenit isfilledwithgas, liquids,orsolidsto

83


theextentthattheintraluminalpressureisraisedtoacertainlevel,theimpulsetodefecateoccurs.

The musculus puborectalis forms a sling around thejunction of the rectum with the anal canal and is main-tained in a constant state of tension.This results in anangulationofthelowerrectumsothatthelumenoftherectumandthelumenoftheanalcanalarenotincontinuity,a feature essential to continence. Continuity is restoredbetweentheluminaofthetwosectorswhentheslingofmusclerelaxes,andthelongitudinalmusclesofthedistalandpelviccoloncontract.Theresultingshorteningofthedistalcolontendstoelevatethepelviccolonandobliter-atestheanglethatitnormallymakeswiththerectum.Thestraightening and shortening of the passage facilitatesevacuation.

Theactofdefecationisprecededbyavoluntaryeffort,which,inturn,probablygivesrisetostimulithatmagnifythevisceralreflexes,althoughtheseoriginateprimarilyinthedistensionoftherectum.Centresthatcontroldefeca-tionreflexesarefoundinthehypothalamusofthebrain,in two regions of the spinal cord, and in the ganglionicplexusoftheintestine.Astheresultofthesereflexes,theinternalanalsphincterrelaxes.

The Anal Canal

The anal canal is the terminal portion of the digestivetract,distinguishedfromtherectumbecauseofthetran-sition of its internal surface from a mucous membranelayer(endodermal)tooneofskinliketissue(ectodermal).Theanalcanalis2.5to4cm(1to1.6inches)inlength;itsdiameterisnarrowerthanthatoftherectumtowhichitconnects.Thecanalisdividedintothreeareas:theupperpart, with longitudinal folds called rectal columns; the

84


lower portion, with internal and external constrictivemuscles (sphincters) to control evacuation of feces; andtheanalopeningitself.

Theanalcanalconnectswiththerectumatthepointwhereitpassesthroughamuscularpelvicdiaphragm.Theupperregionhas5to10rectalcolumns,eachcolumncon-taining a small artery and vein. These are the terminalportionsofthebloodvesselsthatfurnishtherectalandanalareas; they are susceptible to enlargement, commonlyknown as hemorrhoids. The mucous membrane of theupperportionissimilartothatintherestofthelargeintes-tine.Itcontainsmucus-producingandabsorptivecells.

Thelowerportionsoftheanalcolumnsarejoinedbysmallconcentriccircularfoldsofthemucousmembraneknown as anal valves. Between the valves are small analsinusesthatopentolymphductsandglands.Thesesome-timesbecomeabscessedandinfected,especiallyinpersonswhohavechronicdiarrhea,constipation,ordiabetesmel-litus.The internal wall of the anal canal is first lined bymoist,softskinthatlackshairorglands;itthenbecomesa tough (keratinized) layer of skin containing hair andglands.Thekeratinizedlayeriscontinuouswiththeskinoftheanalopeningandexternalbody.Boththeupperandlowerportionsoftheanalcanalhavecircularandlongitu-dinalmusclelayersthatallowexpansionandcontractionofthecanal.Theanalopeningiskeratinizedskinthathasseveralfoldswhilecontracted.Whenopen,thefoldsallowtheskintostretchwithouttearing.Intheskinaroundtheanalopeningbutnotimmediatelyadjacenttoitareglandsthatgiveoffperspiration.

Theloweranalcanalandtheanalopeningarecomposedoftwomuscularconstrictionsthatregulatefecalpassage.Theinternalsphincterispartoftheinnersurfaceofthecanal.Itiscomposedofconcentriclayersofcircularmuscletissue and is not under voluntary control. The external

85


sphincterisalayerofvoluntary(striated)muscleencirclingtheoutsidewalloftheanalcanalandanalopening.Onecancauseittoexpandandcontractatwill,exceptduringtheearlyyearsof lifewhen it isnotyet fullydeveloped.Nervesintheanalcanalcausesphincterresponseandthesensationofpain.Thelowerpartofthecanalisverysensitivetoheat,cold,cutting,andabrasion.

Wasteproductspasstotheanalcanalfromtherectum.Nerve responses from the rectum cause the internalsphinctertorelaxwhiletheexternalonecontracts.Shortlythereafter the external sphincter also relaxes and allowsfecal discharge. The pelvic diaphragm and longitudinalmuscles draw the anus and rectum up over the passingfecessothattheyarenotextruded(prolapsed)outoftheanalopeningwiththefeces.Numerousbloodvesselssur-roundtheanalcanalandmaybesubjecttoenlargementand rupture.This condition, commonly called a hemor-rhoid,orpile,maycausepain,bleeding,andprojectionofthevesselsfromtheanus.

86

DIGESTIVE GLANDS AND HORMONES

Thesecretionofhormonesandothersubstancesfromthedigestive glands plays an important role in coordinatingtheactivitiesofdigestionandinfacilitatingtheutilizationof nutrients by the body’s tissues. Digestive hormonessendimportantsignalstothebrainthatconveydifferenttypesof information,suchas thatconcerninghungerorsatiety.Thesecretionofsubstancessuchasbileisfundamen-taltothebreakdownofcertaintypesoffood;bilefunctionsspecificallyinthedigestionoffats.Examplesofdigestiveglandsincludetheliverandthepancreas,whichsecretestwohormones—insulinandglucagon—thatarecentraltothemetabolismofcarbohydrates.

the liver

Theliverisnotonlythelargestglandinthebodybutalsothe most complex in function. The liver consists of aspongymassofwedge-shapedlobes,withtissuemadeupofcellstunneledthroughwithbileductsandbloodvessels.Thisarrangementunderliestheabilityofthelivertoper-formitsmanyimportantfunctions.Themajorfunctionsoftheliveraretoparticipateinthemetabolismofprotein,carbohydrates,andfat;tosynthesizecholesterolandbileacids; to initiate the formation of bile; to engage in thetransportofapigmentknownasbilirubin;tometabolizeandtransportcertaindrugs;tocontroltransportandstorageof carbohydrates, vitamins, and other substances; to syn-thesizeblood-clottingfactors;toremovewastesandtoxic

CHAPTER 4

87

7 Digestive Glands and Hormones 7

Anterior and posterior views of the liver. EncyclopædiaBritannica,Inc.

88


matterfromtheblood;toregulatebloodvolume;andtodestroyoldredbloodcells.

Thecellsoftheliversynthesizeanumberofenzymes.Theyalsoplayaroleintheconversionofnutrientsenteringtheliverfromtheintestineintoformsthatareusablebythebodycellsorthatcanbestoredforfutureuse.Fatsareconvertedintofattyacidsandthenintocarbohydratesorketonebodiesandtransportedbythebloodtothetissues,wheretheyarefurthermetabolized.Sugarsareconvertedintoglycogen,whichremainsstoredintheliveruntilitisneededforenergyproduction.Itisthenreconvertedintoglucoseandreleasedintothebloodstream.Theliverman-ufactures blood serum proteins, including albumin andseveral clotting factors, and supplies them to the blood.The liver also metabolizes nitrogenous waste productsanddetoxifiespoisonoussubstances,preparingthemforeliminationintheurineorfeces.

Theliverliesunderthelowerrightribcageandoccupiesmuchoftheupperrightquadrantoftheabdomen,withaportionextendingintotheupperleftquadrant.Theorganweighsfrom1.2to1.6kg(2.6to3.5pounds)andissomewhatlarger inmenthan inwomen.Itsgreatesthorizontalmea-surementrangesfrom20to22cm(approximately8inches);vertically,itextends15to18cm(about6to7inches),andinthicknessitrangesfrom10to13cm(about4to5inches).Theliverisdividedintotwounequallobes:alargerightlobeandasmallerleftlobe.Theleftlobeisseparatedonitsanterior(frontal)surfacebythedensefalciform(sickle-shaped)liga-ment that connects the liver to the undersurface of thediaphragm.Ontheinferiorsurfaceoftheliver,therightandleftlobesareseparatedbyagroovecontainingtheteresliga-ment,whichrunstothenavel.Twosmalllobes,thecaudateandthequadrate,occupyaportionoftheinferiorsurfaceofthe right lobe.The entire liver, except for a small portion

89


thatabutstherightleafofthediaphragm,isenvelopedina capsule of tissue that is continuous with the parietalperitoneum that lines the abdominopelvic walls anddiaphragm.

Themajorbloodvesselsentertheliveronitsinferiorsurfaceinacentrallyplacedgroovecalledtheportahepatis,which anatomically separates the quadrate and caudatelobes.The liver has two sources of blood supply. Fullyoxygenatedbloodcomesfromthehepaticartery,whichisa major branch of the celiac axis (the main artery thatcrossestheabdomen)afteritsemergencefromtheabdom-inal aorta. Partially oxygenated blood is supplied by thelargeportalvein,whichinturnreceivesallvenousbloodfrom the spleen, pancreas, gallbladder, lower esophagus,andtheremainderofthegastrointestinaltract,includingthe stomach, small intestine, large intestine, and upperportionoftherectum.

Theportalveinisformedbythejunctureofthesplenicveinwiththesuperiormesentericvein.Attheportahepatis,a groove that separates the two lobes of the liver at therightside,theportalveindividesintotwolargebranches,eachgoingtooneofthemajorlobesoftheliver.Theportahepatisisalsotheexitpointforthehepaticducts.Thesechannels are the final pathway for a network of smallerbileductulesinterspersedthroughouttheliverthatserveto carry newly formed bile from liver cells to the smallintestineviathebiliarytract.

Themicroscopicanatomyoftheliverrevealsauniformstructureofclustersofcellscalledlobules,wherethevitalfunctionsoftheliverarecarriedout.Eachlobule,measur-ing about 1 mm (0.04 inch) in diameter, consists ofnumerouscordsofrectangularlivercells,orhepatocytes,that radiate from central veins, or terminal hepaticvenules, toward a thin layer of connective tissue that

90


separatesthelobulefromotherneighbouringlobules.Thecords of liver cells are one cell thick and are separatedfromoneanotheronseveralsurfacesbyspacescalledsinu-soids, or hepatic capillaries. Sinusoids are lined by thinendothelialcellsthathaveopeningsthroughwhichfinger-like projections (microvilli) of the hepatocytes extend,allowing direct accessibility of the hepatocyte to thebloodstreaminthesinusoids.

Liver cells, or hepatocytes, have direct access to the liver’s blood supply through small capillaries called sinusoids. Hepatocytes carry out many metabolic func-tions, including the production of bile. Kupffer cells line the liver’s vascular system; they play a role in blood formation and the destruction of cellular debris.EncyclopædiaBritannica,Inc.

91


The other major cell of the liver, the Kupffer cell,adheres to the wall of the sinusoid and projects into itslumen.Itfunctionsasaphagocyte(acellthatengulfsanddestroysforeignmaterialorothercells).Smallspaces(Dissespaces)arepresent inplacesbetweenthehepatocyteandthesinusoidalendothelium,probablyforthetransportoflymph. On neighbouring surfaces the hepatocytes areboundtooneanotherbydense,tightjunctions.Theseareperforated by small channels, called canaliculi, which aretheterminaloutpostsofthebiliarysystem,receivingbilefromthehepatocyte.Theyeventuallyjoinwithothercana-liculi,formingprogressivelylargerbileductsthateventuallyemergefromtheportahepatisasthehepaticduct.

Hepatocytesoccupyabout80percentofthevolumeoftheliver,andtheircytoplasm(theareasurroundingthenucleus) contains many mitochondria, which providetheenergyneededforthemanysyntheticandmetabolicfunctionsofthelivercell.Thecytoplasmalsocontainsaseriesoflongtubules,calledtheendoplasmicreticulum,whichprovidesmanyenzymesessentialtoliverfunction.Some of the membranes of the endoplasmic reticulumappeargranular,orrough,owingtothepresenceofribo-somes, which are responsible for forming specificpolypeptide(protein)chainsafterhavinghadtheaminogroupremoved(deamination)andhavingbeenconvertedinto glucose through a process called gluconeogenesis.The ammonia released from gluconeogenesis is con-vertedtoureainthehepatocytebywayoftheureacycle.

Thenonribosomal,orsmooth,endoplasmicreticulumiswherecytochromes(combinationsofhemefromhemo-globin with various proteins) and certain enzymesundertake the important hepatic functions of drug andhormonal metabolism and also cholesterol synthesis.Hepatocytesalsoconjugatewithcarbohydratecomponents

92


of bilirubin and other fat-soluble metabolic and foreigncompounds and thereby are made soluble in water.Bilirubinistheproductofhemoglobinmetabolismthatisformedinthebonemarrowandthelymphatictissueandis carried to the liver after becoming bound to plasmaalbumin.Itisreleasedatthehepatocyticsinusoidalmem-brane and is transported to the smooth endoplasmicreticulum,whereitisconjugatedwithoneortwomoleculesofglucuronicacidandtherebybecomessolubleinwaterandexcretableinbile.

The Golgi apparatus, a series of tubular structuresbetweentheendoplasmicreticulumandthecanaliculus,acts as a transport station for newly made proteins andother hepatocytic products before they are conveyed tootherpartsofthecelloroutofthecellentirely.Lysosomes,anotherimportantcytoplasmicconstituent,areresponsibleforthe intracellularstorageofpigments, suchas ironorcopper,andforthedigestionofcertaincontents,suchasglycogenorforeignparticles.Thenucleusofthehepato-cyte guides replication of the cell and transmits geneticmaterial in the form of messenger ribonucleic acid(mRNA)fromdeoxyribonucleicacid(DNA)toorganelleslocatedinthecytoplasm.

Theproductionofbile isadefiningcharacteristicoftheliver.Eachdaytheliversecretesabout800to1,000ml(about1quart)ofbile,whichcontainsbilesaltsneededforthedigestionoffatsinthediet.Thepresenceoffatintheduodenumstimulatestheflowofbileoutofthegallbladderand into the small intestine. Senescent (worn-out) redblood cells are destroyed in the liver, spleen, and bonemarrow. Bilirubin, formed in the process of hemoglobinbreakdown, is released intothebile,creating itscharac-teristicgreenishorangecolour,and isexcretedfromthebodythroughtheintestine.

93


Acommonsignofimpairedliverfunctionisjaundice,a yellowness of the eyes and skin arising from excessivebilirubinintheblood.Jaundicecanresultfromanabnor-mallyhighlevelofredbloodcelldestruction(hemolyticjaundice),defectiveuptakeortransportofbilirubinbythehepaticcells(hepatocellularjaundice),orablockageinthebileductsystem(obstructivejaundice).Failureofhepaticcells to function can result from hepatitis, cirrhosis,tumours, vascular obstruction, or poisoning. Symptomsmayincludeweakness, lowbloodpressure,easybruisingand bleeding, tremor, and accumulation of fluid in theabdomen.Bloodtestscanrevealabnormallevelsofbiliru-bin, cholesterol, serum proteins, urea, ammonia, andvarious enzymes.A specific diagnosis of a liver problemcanbeestablishedbyperforminganeedlebiopsy.

Theliverissubjecttoavarietyofotherdisordersanddiseases.Abscesses can be caused by acute appendicitis;those occurring in the bile ducts may result from gall-stones or may follow surgery. The parasite that causesamebicdysentery,aprotozoancalledEntamoeba histolytica,canproduceliverabscessesaswell.Variousotherparasitesprevalent in different parts of the world also infect theliver.Livercanceriscommon,occurringmostlyassecondarytumours originating elsewhere in the body. Glycogen-storagediseases,agroupofhereditarydisorders,generateabuildupofglycogenintheliverandaninsufficientsupplyof glucose in the blood. Certain drugs may damage theliver,producingjaundice.

the biliary tract

Thebiliarytractbeginswiththeappearanceoftwolargeducts,therightandlefthepaticducts,attheportahepa-tis.Justbelowtheportahepatis,these1-to2-cm(about

94


half-inch)ductsjointoformthehepaticduct,whichpro-ceeds for another 2 to 3 cm and is joined by the cysticduct, leading from the gallbladder. The resulting com-monbileductprogressesdownwardthroughtheheadofthepancreas.There it is joinedbythemainpancreaticduct(ductofWirsung)ataslightlydilatedareacalledthehepatopancreaticampulla(ampullaofVater),whichliesinthewalloftheinnercurveofthedescendingduode-num,andterminatesinthelumenoftheduodenumata2-to3-cmelevationcalledtheduodenalpapilla(papillaofVater).

Thecommonbileductaveragesabout10cm(about4inches)inlength,andflowofbilefromitslowerendintotheintestineiscontrolledbythemuscularactionofthehepato-pancreatic sphincter (sphincter of Oddi), located in theduodenal papilla.The cystic duct varies from 2 to 3 cm inlength and terminates in the gallbladder. Throughout its

The gallbladder and bile ducts in situ. EncyclopædiaBritannica,Inc.

95


length,thecystic duct is lined by a spiral mucosal eleva-tion,calledthevalvulaspiralis(valveofHeister).

The Gallbladder

Thegallbladderisamuscularmembranoussacthatstoresand concentrates bile. Situated beneath the liver, thegallbladderispear-shapedandhasacapacityofabout50ml(1.7fluidounces).Theinnersurfaceofthegallbladderwall is lined with mucous-membrane tissue similar tothat of the small intestine. Cells of the mucous mem-brane have hundreds of microscopic projections calledmicrovilli, which increase the area of fluid absorption.Theabsorptionofwaterandinorganicsaltsfromthebilebythecellsofthemucousmembranecausesthestoredbiletobeabout5times—butsometimesasmuchas18times—moreconcentratedthanwhenitwasproducedintheliver.

Contraction of the muscle wall in the gallbladder isstimulated by the vagus nerve of the parasympatheticsystemandbythehormonecholecystokinin,whichispro-duced in the upper portions of the intestine. Thecontractions result in the discharge of bile through thebileductintotheduodenumofthesmallintestine.

If food is present in the small intestine, bile that isflowingfromthetwolobesoftheliverintothehepaticand common bile ducts will continue directly intotheduodenum.Ifthesmallintestineisempty,however,the sphincter of Oddi will be closed, and bile flowingdown the common duct will accumulate and be forcedback up the tube until it reaches the open cystic duct.Thebileflowsintothecysticductandgallbladder,whereit is stored and concentrated until needed.When foodenters the duodenum, the common duct’s sphincter

96


opens,thegallbladdercontracts,andbileenterstheduo-denumtoaidinthedigestionoffats.

Thegallbladderiscommonlysubjecttomanydisorders,particularly the formation of solid deposits called gall-stones. Despite its activity, it can be surgically removedwithoutseriouseffect.

Bile

Bile,alsoknownasgall,isagreenishyellowsecretionthatisproducedintheliverandpassedtothegallbladderforconcentration,storage,ortransport intothefirstregionofthesmallintestine,theduodenum.Itsfunctionistoaidinthedigestionoffatsintheduodenum.Bileiscomposedof bile acids and salts, phospholipids, cholesterol, pig-ments,water,andelectrolytechemicalsthatkeepthetotalsolutionslightlyacidic(withapHofabout5to6).Bileiscontinually secreted from the cells of the liver into thecommonbileductandgallbladder;onceinthegallbladderit becomes highly concentrated. The amount of bilesecretedintotheduodenumiscontrolledbythehormonescholecystokinin, secretin, gastrin, and somatostatin andalsobythevagusnerve.

Bilesaltsarecomposedofthesaltsoffourdifferentkinds of free bile acids (cholic, deoxycholic, chenode-oxycholic, and lithocholic acids). Each of these acidsmay in turn combine with glycine or taurine to formmorecomplexacidsandsalts.Bilesaltsandacidscanbesynthesized from cholesterol or extracted from thebloodstreambytheliver.Theypassfromtheliverintothe small intestine, where they act as detergents toemulsifyfatandreducethesurfacetensiononfatdrop-lets to prepare them for the action of pancreatic andintestinal fat-splitting enzymes. The salts are large,

97


negativelychargedionsthatarenotreadilyabsorbedbytheupperregionof thesmall intestine.Consequently,theyremaininthesmallintestineuntilmostofthefatisdigested.

In the lower small intestine, the salts and acids areabsorbedandpassedbackintothebloodstreamuntiltheyareonceagainextractedbytheliver.Thiscycle,fromthelivertothesmallintestineandbloodandthenbacktotheliver, is called enterohepatic circulation. Some salts andacidsarelostduringthisprocess;thesearereplacedintheliverbycontinualsynthesisfromcholesterol.Therateofsynthesis is directly related to the amount of acids andsaltslost.Bilesaltsdonotnormallyreachthecolon.Whentheydo,however,theymayinhibittheabsorptionofwaterandsodium,causingawaterydiarrhea.

Bile salts and acids are transported in a fluid thatcontainswater,sodium,chloride,andbicarbonates.Thisfluid is produced in the liver, and it serves to neutralizehydrochloricacidpassedfromthestomachintothesmallintestine.Water-insoluble wastes that the liver removesfromblood,suchascholesterol,steroids,drugs,andhemo-globinpigments,arecarriedinthefluidtotheexcretorysystem.Hemoglobinpigmentsarebrokendown,producingseveral bile fluid compounds, including bilirubin, whichhas no known function other than that of a colouringagent.Tracesofothersubstancescanalsobefoundinbileincluding mucus, serum proteins, lecithin, neutral fats,fattyacids,andurea.

the pancreaS

Thepancreasisalong,narrowglandthatissituatedtrans-versely across the upper abdomen, behind the stomachandthespleen.Themidportionofthepancreasliesagainst

98


Acinar cells produce digestive enzymes, which are secreted into tiny ducts that feed into the pancreatic duct. Islets of Langerhans are clusters of cells that secrete hormones such as insulin and glucagon directly into a capillary net-work, which also joins the pancreatic duct. EncyclopædiaBritannica,Inc.

99


thevertebralcolumn,theabdominalaorta,andtheinferiorvenacava.

Thepancreasisbothanexocrine(ductal)andendocrine(ductless) gland.The exocrine tissue, called acinar tissue,produces important digestive enzyme precursors that aretransmitted into the small intestine, while the endocrinetissue (contained in the islets of Langerhans) produces atleast two hormones (insulin and glucagon) that areimportant in the regulation of carbohydrate metabolism.Twootherhormonesproducedbythepancreas,vasoactiveintestinal polypeptide and somatostatin, are pivotalelementsinthecontrolofintestinalsecretionandmotility.

Individual acinar cells have the shape of a truncatedpyramid,arrangedingroupsaroundacentralductallumen.Thesecentralductsemptyintoprogressivelylargerinter-calated and collecting ducts that eventually join thepancreaticduct(ductofWirsung).Thepancreaticductinturn enters the hepatopancreatic ampulla (ampulla ofVater) of the duodenum, where, in about 80 percent ofinstances, it is joined by the common bile duct.Occasionally the junctionwiththecommonbileduct isproximaltotheampulla,andinafewcasesthepancreaticduct and the common bile duct join the duodenumseparately.

Acinar Cells

The acinar cells constitute more than 95 percent of thecellular population of the exocrine pancreas. They pro-duceavarietyofdigestiveproteins,orenzymes,involvedprincipally with the degradation of dietary proteins(proteases),fats(lipases),andcarbohydrates(amylases)inthe intestine.Otherproteinsecretions includeatrypsininhibitor,aso-called“stoneprotein”thatkeepscalciumin

100


solution, and various serum proteins, including albuminandimmunoglobulins.

In the acinar cells almost all enzymatic proteins aresynthesizedonribosomesfromaminoacidscarriedtothepancreasbythebloodstream.Enzymeprecursorsarecon-jugatedintheGolgiapparatusandthenconcentratedintomembrane-wrappedzymogengranules,whicharestoredinthecytoplasmbeforesecretion.Enzymaticsecretionismediated by stimulants such as secretin, a hormonereleasedfromtheduodenumbytheintroductionofgastricacid;cholecystokinin,releasedbythepresenceofdietaryfat; amino acids; hydrochloric acid; and acetylcholine,whichisproducedasaresponsetothesensoryaspectsoffeeding and to the physical effects of chewing andswallowing.

Uponbindingofspecificreceptorsitesontheacinarmembrane with cholecystokinin or acetylcholine, thezymogengranulesmigratetotheapexoftheacinarcell,where theyareextruded intothecentralductal lumen.Bindingofvasoactiveintestinalpolypeptideorsecretintoacinarreceptorscausesincreasedproductionofbicar-bonate,sodium,water,andenzymesbyacinarcellsandsmall ductal cells. Bicarbonate is secreted in exchangeforchloride,andsodiumisexchangedforhydrogen,witha resultant increased acidity of the blood leaving theactively secreting pancreas. Binding of cholecystokinincauses production of bicarbonate and enzymes by theacinarcells.

In the absence of cholecystokinin and acetylcholine,asinfastingsubjectsorinpatientsbeingfedintravenously,thesynthesisofzymogenbytheacinarcells ismarkedlyreduced. Pancreatic atrophy also occurs after removalof thepituitarygland,probablyowingtotheabsenceofgrowth hormone. Thus, cholecystokinin, acetylcholine,

101


and growth hormone are pancreatotrophic, or pancreas-feeding, hormones. The pancreas itself also appears tosecreteanas-yet-unidentifiedhormonethatistrophic,ornutritive,totheliver.

Islets of Langerhans

Theislets,orislands,ofLangerhansareirregularlyshapedpatchesofendocrinetissuelocatedwithinthepancreasofmostvertebrates.TheyarenamedfortheGermanphysi-cianPaulLangerhans,whofirstdescribedthem in 1869.The normal human pancreas contains about 1,000,000islets.Theisletsconsistoffourdistinctcelltypes,ofwhichthree(alpha,beta,anddeltacells)produceimportanthor-mones. The fourth component (C cells) has no knownfunction.

The most common islet cell, the beta cell, producesinsulin,themajorhormoneintheregulationofcarbohy-drate,fat,andproteinmetabolism.Thereleaseofinsulinfromthebetacellscanbetriggeredbygrowthhormone

The islets of Langerhans contain alpha, beta, and delta cells that produce glu-cagon, insulin, and somatostatin, respectively. These hormones regulate one another’s secretion through paracrine cell-cell interactions.EncyclopædiaBritannica,Inc.

102


(somatotropin) or by glucagon, but the most importantstimulator of insulin release is glucose.When the bloodglucoselevelincreases—asitdoesafterameal—insulinisreleased to counter it.The inability of the islet cells tomakeinsulinorthefailuretoproduceamountssufficientto control blood glucose level are the causes of diabetesmellitus.

ThealphacellsoftheisletsofLangerhansproduceanopposing hormone, glucagon, which releases glucosefromtheliverandfattyacidsfromfattissue.Inturn,glu-coseandfreefattyacidsfavourinsulinreleaseandinhibitglucagonrelease.Thedeltacellsproducesomatostatin,astronginhibitorofsomatotropin,insulin,andglucagon;its role in metabolic regulation is not yet clear.Somatostatinisalsoproducedbythehypothalamusandfunctionstheretoinhibitsecretionofgrowthhormonebythepituitarygland.

horMoneS of the gaStrointeStinal tract

Control of the activity of the specialized cells in thedigestive system that are concerned with motor andsecretory functions depends upon signals received attheir cell membranes.These signals originate in eitherendocrineornervecellsandarecarriedtothetargetcellby amino or peptide “messenger” molecules. Whensecreted,thesesubstanceseitherdiffuseintothetissuespacesaroundthecellsandaffecttargetcellsinthevicinityoraretakenupinthecirculatingbloodanddeliveredtotargetcellssomedistanceaway.Inbothcircumstancesthemessengers are hormones, but those exerting their effectlocallyarecalledparacrine.Thoseexertingtheireffectatadistancearecalledendocrine.

103


Thedifferencebetweenparacrinesignalingandendo-crinesignalingisillustratedbythehormonessomatostatinand gastrin. Somatostatin has inhibiting effects on theproductionofacidinthestomach,themotoractivityofthe intestine, and the release of digestive enzymes fromthepancreas.Theseeffectsareachievedbylocaldiffusionofsomatostatinfromdeltacellsinthevicinityofthetargettissue(deltacellsarefoundintheisletsofLangerhans,theintestines,andthestomach).Ontheotherhand,gastrin,ahormone produced by the granular gastrin cells in themucosa of the gastric antrum (the lower part of thestomach),issecretedintotheblood.Thus,itproducesitseffectsatasitedistantfromthesiteofitsrelease.

Peptidesarecomposedofanumberofaminoacidsstrungtogether in a chain.The amino acids occur in an orderedsequence that is peculiar to each peptide. The biologicalactivityofthepeptide(i.e.,theabilitytostimulatethetargetcells)mayresideinonlyafractionofthechain—forexample,ina four-orfive-amino-acidsequence.Inother instancestheentirechainmustbeintacttoachievethispurpose.

Gastrinexemplifiesthebiologicalcapabilityofafractionofthemolecule.Thesefractionshaveamolecularstruc-ture that fits the receptor site on the membrane of thetarget cell and therefore can initiate the intracellulareventsintheproductionoftheacid.Thegastrincellsoftheantrumofthestomachprimarilyproduceamessengerpeptideconsistingof17aminoacids,whereasthoseintheduodenum and jejunum of the small intestine primarilyproduce a messenger peptide with 34 amino acids. Theshortermoleculeismorepotent.Thechaincanbecleavedtoonlyfouraminoacids(thetetrapeptide),however,and(provided that the sequence remains the same as in theparentmoleculeandthefragmentistheoneattheaminoterminal of the whole molecule) the cleaved amino acid

104


chainretainsbiologicalactivity,althoughitislesspotentthanthelargermoleculesofgastrin.

Certainmessengerpeptideshavebeenfoundtoorigi-natenotinendocrinecellsbutinneuralelementswithinthegastrointestinaltract,tobereleasedduringelectricaldischarge within the nerves. For example, vasoactiveintestinal polypeptide released from nerve terminals inthebrainalsoisabundantinthenervousstructuresofthegut,includingthesubmucosalandmyentericnerveplexuses.Occasionally vasoactive intestinal polypeptide coexistswith acetylcholine, the messenger molecule of the auto-nomicparasympatheticnervoussystem.

Peptidesthatbindwithtargetcellreceptorsandstim-ulatethecelltoreactareknownasagonists.Othersthatfitthereceptorbutdonotinitiateintracellulareventsareknownasantagonists.Theabilityofantagoniststooccupyreceptors and thereby deny access to an agonist is thebasisofthetreatmentofpepticulcerdiseasewithhista-mine(H2)receptorblockers.Byoccupyingthereceptorson the parietal cells, antagonists deny histamine theopportunity to initiate the production of hydrochloricacid,oneofthechiefcausativeagentsofpepticulcers.

Similareventsstimulateorsuppresstheproductionofthemessengerpeptidesintheirendocrineorneuralcelloforigin. For example, the discharge of granules of gastrinfrom the gastrin cells occurs when a meal is consumed.While the concentration of hydrogen ions (the acidity)remains lowbecauseof thebufferingeffectof the food,thereleaseofgastrincontinues.Asdigestionproceedsandthe stomach begins to empty, however, the acidityincreasesbecauseofthediminishingneutralizingeffectofthe food.Whenthecontentsof thestomach incontactwith the mucosa of the antrum reach a certain level ofacidity (pH of 2.5 or less), the release of gastrin stops.

105


Failureofthismechanismleadstoinappropriatesecretionofacidwhenthestomachisemptyandmaycausepepticulcersintheduodenum.Someendocrinecellshavemicro-villi on their surface that project into the lumen of theglandor into themainchannelof thestomachor intes-tine. These cells probably have an ability to “sample”continuouslythelumenalcontentsintheirvicinity.

Whenproductionandsecretionofapeptidehormoneisexcessive, it inducesan increase in thenumberof thetarget cells and may increase the size of the individualcells. This is known as trophism and is similar to theincreaseinsizeofskeletalmuscleinresponsetoappropri-ate exercise (work hypertrophy). Such trophism isobservedincertaindiseasestatesthatinvolvethegastro-intestinalhormones.Thus,whengastrin issecreted intothebloodbyatumourofgastrincells(gastrinoma)ofthepancreas, it is a continuous process because there is nomechanismatthatsitetoinhibitthesecretion.Thisbringsaboutamassiveincreaseinthenumberofparietalcellsinthestomachandanoverproductionofacid.Thisinturnoverwhelmsthedefensesofthemucosaoftheuppergas-trointestinal tract against autodigestion and results inintractableandcomplicatedpepticulceration.

Eighteen different endocrine cells can be identifiedwithin the gastrointestinal tract, but it is probable thatseveral of these and their particular peptides are evolu-tionaryvestigesthatfunctionedinotherstagesofhumandevelopment,whileothersmayrepresentdifferentstagesofmaturationofthesameendocrinecell.

Insulin

As mentioned previously, insulin is a hormone that regu-lates the level of sugar (glucose) in the blood and that is

106


Hormones secreted from adipose tissue, the gastrointestinal tract, and the pancreatic islets of Langerhans regulate a variety of physiological processes.EncyclopædiaBritannica,Inc.

107


producedbythebetacellsoftheisletsofLangerhansinthepancreas.Insulinissecretedwhenthelevelofbloodglucoserises—asafterameal.Whenthelevelofbloodglucosefalls,secretionofinsulinstops,andtheliverreleasesglucoseintotheblood.Insulinwasfirstisolatedasapancreaticextractin1921bytheCanadianscientistsSirFrederickG.BantingandCharlesH.Best.

Insulinisaproteincomposedoftwochains,anAchain(with21aminoacids)andaBchain(with30aminoacids),which are linked together by sulfur atoms. Insulin isderived from a 74-amino-acid prohormone moleculecalled proinsulin. Proinsulin is relatively inactive, andunder normal conditions only a small amount of it issecreted.Intheendoplasmicreticulumofbetacells,theproinsulinmoleculeiscleavedintwoplaces,yieldingtheAand B chains of insulin and an intervening, biologicallyinactive C peptide. The A and B chains become linkedtogetherbytwosulfur-sulfur(disulfide)bonds.Proinsulin,insulin,andCpeptidearestored ingranules inthebetacells,fromwhichtheyarereleasedintothecapillariesoftheisletsinresponsetoappropriatestimuli.Thesecapil-lariesemptyintotheportalvein,whichcarriesbloodfromthe stomach, intestines, and pancreas to the liver. Thepancreas of a normal adult contains approximately 200unitsofinsulin,andtheaveragedailysecretionofinsulinintothecirculationinhealthyindividualsrangesfrom30to50units.

Several factorsstimulate insulinsecretion,butbyfarthemostimportantistheconcentrationofglucoseinthearterial(oxygenated)bloodthatperfusestheislets.Whenblood glucose concentrations increase (i.e., following ameal),largeamountsofglucosearetakenupandmetabo-lized by the beta cells, and the secretion of insulinincreases. Conversely, as blood glucose concentrations

108


decrease, the secretion of insulin decreases. However,evenduringfasting,smallamountsofinsulinaresecreted.Thesecretionofinsulinmayalsobestimulatedbycertainaminoacids,fattyacids,ketoacids(productsoffattyacidoxidation),andseveralhormonessecretedbythegastro-intestinal tract. The secretion of insulin is inhibited bysomatostatin and by activation of the sympathetic ner-voussystem(thebranchoftheautonomicnervoussystemresponsibleforthefight-or-flightresponse).

Insulin acts primarily to stimulate glucose uptake bythree tissues—adipose (fat), muscle, and liver—that areimportant in the metabolism and storage of nutrients.Like other protein hormones, insulin binds to specificreceptors on the outer membrane of its target cells,therebyactivatingmetabolicprocesseswithinthecells.Akeyactionofinsulininthesecellsistostimulatethetrans-locationofglucosetransporters (moleculesthatmediatecell uptake of glucose) from within the cell to the cellmembrane.

In adipose tissue, insulin stimulates glucose uptakeandutilization.Thepresenceofglucoseinadiposecells,inturn, leads to increased uptake of fatty acids from thecirculation,increasedsynthesisoffattyacidsinthecells,andincreasedesterification(whenanacidmoleculebindstoanalcohol)offattyacidswithglyceroltoformtriglycer-ides,thestorageformoffat.Inaddition,insulinisapotentinhibitor of the breakdown of triglycerides (lipolysis).Thispreventsthereleaseoffattyacidsandglycerolfromfat cells, saving them for when they are needed by thebody (e.g., when exercising or fasting).As serum insulinconcentrations decrease, lipolysis and fatty acid releaseincrease.

In muscle tissue, insulin stimulates the transport ofglucoseandaminoacidsintomusclecells.Theglucoseis

109


storedasglycogen,astoragemoleculethatcanbebrokendown to supply energy for muscle contraction duringexerciseandtosupplyenergyduring fasting.Theaminoacidstransportedintomusclecellsinresponsetoinsulinstimulation are utilized for the synthesis of protein. Incontrast, intheabsenceof insulintheproteinofmusclecellsisbrokendowntosupplyaminoacidstotheliverfortransformationintoglucose.

Insulinisnotrequiredforthetransportofglucoseintolivercells,butithasprofoundeffectsonglucosemetabo-lisminthesecells.Itstimulatestheformationofglycogen,anditinhibitsthebreakdownofglycogen(glycogenolysis)andthesynthesisofglucosefromaminoacidsandglycerol(gluconeogenesis).Therefore,theoveralleffectofinsulinis to increase glucose storage and to decrease glucoseproductionandreleasebytheliver.Theseactionsofinsu-linareopposedbyglucagon,anotherpancreatichormoneproducedbycellsintheisletsofLangerhans.

Inadequateproductionofinsulinisresponsibleforthecondition called diabetes mellitus. Severe diabeticsrequire periodic injections of insulin. The first insulininjectionsutilizedhormoneextractsfrompigs,sheep,andcattle, but by the early 1980s, certain strains of bacteriahadbeengeneticallymodifiedtoproducehumaninsulin.Todaythetreatmentofdiabetesmellitusreliesprimarilyonaformofhumaninsulinthat ismadeusingrecombi-nantDNAtechnology.

Glucagon

Glucagon is a 29-amino-acid peptide that is producedspecifically by the alpha cells of the islets. It has a highdegree of similarity with several glucagon-like peptidesthat are secreted by cells scattered throughout the

110


gastrointestinaltract.Glucagonsecretionisstimulatedbytheingestionofprotein,bylowbloodglucoseconcentra-tions (hypoglycemia), and by exercise. It is inhibited bythe ingestion of carbohydrates, an effect that may bemediatedbytheresultantincreaseinbloodglucosecon-centrations and insulin secretion. Glucagon stronglyopposestheactionofinsulin;itraisestheconcentrationofglucoseinthebloodbypromotingglycogenolysisandbystimulatinggluconeogenesis.Byincreasingtheconcen-tration of glucose in the bloodstream, glucagon plays acriticalroleinmaintainingbloodglucoseconcentrationsduringfastingandexercise.

Intestinal Glucagon

Intestinalglucagon(enteroglucagon)issecretedbyLcells,whicharefoundthroughoutthegastrointestinaltract,inresponse to the presence of carbohydrate and triglycer-idesinthesmallintestine.Intestinalglucagonmodulatesintestinalmotilityandhasa strongtrophic influenceonmucosalstructures.

Somatostatin

Somatostatin is a polypeptide that inhibits the activityof certain pancreatic and gastrointestinal hormones.Somatostatin exists in two forms: one composed of 14aminoacidsandasecondcomposedof28aminoacids.Thenamesomatostatin,essentiallymeaningstagnationofa body, was coined when investigators found that anextractofhypothalamictissues inhibitedthereleaseofgrowthhormonefromthepituitarygland.Somatostatinsubsequentlywasfoundtobewidelydistributedthrough-out the central nervous system and to occur in othertissues.

111


Inthepancreas,somatostatinisproducedbythedeltacellsoftheisletsofLangerhans,whereitservestoblockthesecretionofbothinsulinandglucagonfromadjacentcells.Insulin, glucagon, and somatostatin act in concert tocontroltheflowofnutrientsintoandoutofthecirculation.Therelativeconcentrationsofthesehormonesregulatetherates of absorption, utilization, and storage of glucose,aminoacids,andfattyacids.Theanatomicproximityofthebeta, alpha, and delta cells in the islets of Langerhans isimportant. Somatostatin and glucagon appear to have aparacrinerelationship,eachinfluencingthesecretionoftheother,withbothaffectingtherateofinsulinrelease.Somatostatin also inhibits the secretion of several gas-trointestinal hormones—including gastrin, secretin,cholecystokinin, and vasoactive intestinal polypeptide.This results in the inhibition of many functions of thegastrointestinaltract,includingthesecretionofacidbythestomach,thesecretionofdigestiveenzymesbythepancreas, and the absorption of nutrients by theintestine.

Few examples of somatostatin deficiency have beenfound.Alzheimer disease appears to cause a decrease insomatostatinlevelsinbraintissue,althoughitisnotclearwhatrolethisplaysinthecourseofthedisease.Inthelate1970s, a rare somatostatin-producing tumour called asomatostatinoma was first identified. Since thensomatostatinomas have been well characterized. Thetumours tendtodevelop in thepancreas,duodenum,orjejunum,anddiagnosisisbasedonplasmalevelsofasub-stance called somatostatin-like immunoreactivity (SLI),whichmaybe50timesgreaterthannormalinindividualswithasomatostatinoma.Theexcesslevelsofsomatosta-tin may cause abdominal cramps and pain, persistentdiarrhea,highbloodglucoseconcentrations,weightloss,andepisodicflushingoftheskin.

112


Serotonin

Serotonin, or 5-hydroxytryptamine, is an amine that isformed from the amino acid 5-hydroxytrytophan in theenterochromaffin cells (EC) and in other similar cellscalledenterochromaffin-likecells(ECL).Thesecellsalsosecretehistamineandkinins,whichlikewisehaveimportantmessengerfunctionsinglandularsecretionsandonbloodvessels.Serotoninactsinparacrinefashion.BothECandECLcellsarewidelydistributedintheepithelialliningofthegastrointestinaltract.

Cholecystokinin

Cholecystokinin(orCCK;formerlycalledpancreozymin)isadigestivehormonereleasedwithsecretinwhenfoodfromthestomachreachestheduodenum.Cholecystokininand pancreozymin were once considered two separatehormonesbecausetwodistinctactionshadbeendescribed:the release of enzymes from the pancreas, an actionascribedtopancreozymin;andthecontractionofthegall-bladder,whichforcesbile intotheduodenum,anactionascribed to cholecystokinin. However, today these twoactionsarerecognizedasbelongingtooneenzyme,nowknownsolelyascholecystokinin.

Cholecystokininissecretedbycellsoftheuppersmallintestine.Itssecretionisstimulatedbythe introductionofhydrochloricacidorfattyacidsintothestomachortheduodenum.Cholecystokininstimulatesthegallbladdertocontractandreleasestoredbileintotheintestine.Italsostimulates the secretion of pancreatic juice and mayinduce satiety. There are several hypotheses regardingcholecystokinin’sabilitytoinducesatiety.Onehypothesisis that meal-induced secretion of cholecystokinin acti-vatesthesatietycentreofthehypothalamusinthebrain

113


so that the person feels full and stops eating.A secondhypothesisisthat,becausecholecystokinininhibitsemp-tyingofthestomach,thesensationofsatietymaybetheresultofdistensionofthestomach.

Gastric Inhibitory Polypeptide

Gastricinhibitorypolypeptideisahormonesecretedbycellsoftheintestinalmucosa.Itactstoblockthesecretionof hydrochloric acid into the stomach, and it increasesinsulin secretion from the beta cells of the islets ofLangerhans.Thislatteractioncausesanincreaseinseruminsulin concentrations that is significantly larger afteringestingglucosethanafterintravenousadministrationofthesameamountofglucose.

Pancreatic Polypeptide

Pancreatic polypeptide is a hormone consisting of 36aminoacidsthatissecretedbytheF(orPP)cellsoftheisletsofLangerhans.Itssecretionisstimulatedbyeating,exercising,andfasting.Itcaninhibitgallbladdercontrac-tionandpancreaticexocrinesecretion,butitsroleinthemetabolismofnutrientsisuncertain.

Secretin

Secretinisadigestivehormonemadeupof27aminoacidsthat is released from the wall of the duodenum. It wasdiscoveredin1902byBritishphysiologistsSirWilliamM.BaylissandErnestH.Starling.BaylissandStarlingplaceddilutehydrochloricacid intoasegmentofadog’sbowelfromwhichthenervesupplyhadbeensevered.Theythencollectedanextractofthebowelliningandinjecteditintoanotherdog.Theresultwasanincreaseinthesecretionof

114


pancreatic juice in the dog that received the injection.Theynamedthematerial intheextract“secretin.”Withthisdiscoveryemergedtheconceptthatchemicalmessagescouldactatdistantsitestoregulatebodilyfunctions.

Whenhydrochloricacidpassesfromthestomachintotheduodenum,secretinisreleasedintothebloodstreamandstimulatestheacinarcellsofthepancreastosecretewaterandbicarbonateintothepancreaticductsthatdrainintotheduodenum.Bythismechanism,hydrochloricacidsecreted by the stomach, which can be damaging to theintestinal lining, is promptly diluted and neutralized.Secretin also inhibits the secretion of gastrin, whichtriggers the initial release of hydrochloric acid into thestomach,anddelaysgastricemptying.

Vasoactive Intestinal Polypeptide

Vasoactive intestinal polypeptide is a 28-amino-acidhormonesecretedbyendocrinecellsornerveendingsinthegastrointestinaltract.Itinhibitsthereleaseofgastrinandthesecretionofacid,isamildstimulantofbicarbonatesecretionfromthepancreas,andisapowerfulstimulantofthesecretionofwaterandelectrolytesbythesmallandlargeintestines.

Studieshave indicatedthatvasoactive intestinalpoly-peptide is capable of acting as a neurotransmitter (achemicalagentreleasedbyneuronstostimulateneighbour-ingneurons).Thismodeofactionhasbeenassociatedwiththehormone’sabilitytoinducearelaxationeffectinsometissues. Certain other gastrointestinal hormones aresuspectedtoactasneurotransmittersaswell.Thesehormonesincludemotilin,neuropeptideY(whichinteractswithghrelintoregulateappetite),gastrin-releasingpeptide(bombesin-likepeptide),glucagon,andsomatostatin.

115


Somepancreaticislet-celltumourssecreteexcessiveamounts of vasoactive intestinal polypeptide (a condi-tion called Verner-Morrison syndrome, or pancreaticcholera).Thesetumourscausesevere,intractable,debili-tating watery diarrhea and an associated loss of largequantitiesofpotassium.Theresultingdehydrationmaybelife-threatening.

Endorphins and Enkephalins

Endorphinsandenkephalins,eachcomprisingfiveaminoacidsinthemolecule,arepresentinthevagusnervesandthemyentericplexus.Theyhavethepropertiesofopiate(opium-derived)substancessuchasmorphine.Theybindtothesamereceptorsandareneutralizedbytheopiateantagonist naloxone. There is no evidence that endor-phinsandenkephalinsarecirculatinghormones,buttheenkephalins may have a physiological paracrine role inmodulatingsmoothmuscleactivityinthegastrointestinaltract,andendorphinsmayserveinmodulatingthereleaseof other peptides from endocrine cells in the digestivesystem.

Prostaglandins

Prostaglandins are hormonelike substances involved inthe contraction and relaxation of the smooth muscle ofthegastrointestinaltract.Prostaglandinsarealsoabletoprotectthemucosaofthealimentarytractfrominjurybyvarious insults (boilingwater,alcohol,aspirin,bileacids,stress)byincreasingthesecretionofmucusandbicarbon-ate from the mucosa, which in turn stimulates themigration of cells to the surface for repair and replace-mentofthemucosallining.

116


Other Hormones of Importance

Ahormoneknownasmotilinissecretedbetweenmeals.A high level of motilin in the blood stimulates the con-tractionofthefundusandantrumandacceleratesgastricemptying. It contracts the gallbladder and increases thesqueezepressureoftheloweresophagealsphincter.Ahor-monecalledneurotensinissecretedbytheNcellsoftheileuminresponsetofatinthesmallintestine.Neurotensinmodulatesmotility,relaxestheloweresophagealsphincter,andblocksthestimulationofacidandpepsinsecretionbythevagusnerve.

SubstanceP—whichispresentinsignificantamountsinthevagusnervesandthemyentericplexus—stimulatessalivaproduction,contractionofsmoothmusclecells,andinflammatory responses in tissues, but it is uncertainwhetheritisanythingotherthananevolutionaryvestige.Apeptidecalledbombesinisfoundintheintrinsicnervesof the gastrointestinal tract. It stimulates the release ofgastrinandpancreaticenzymesandcausescontractionofthegallbladder.Thesefunctionsmaybesecondary,how-ever, to the release of cholecystokinin. It is uncertain ifbombesinhasaphysiologicalroleorifitisanevolutionaryvestige,similartosubstanceP.

117

FEATURES OF THE DIGESTIVE TRACT

Throughtheactofeating,oringestion,nutrientsenterthebody,anditistheroleofthedigestivesystemto

thenrenderthesenutrientsusefultocells.Manynutrientmoleculesaresolargeandcomplexthattheymustbesplitintosmallermoleculesbeforetheycanbeusedbycells.Thisprocessofbreakingdownfoodintomolecularparticlesofusablesizeandcontentiscalleddigestion.Eachsegmentofthe digestive tract carries out a specific function in thelarger process of digestion, and collectively the entiresystemenablestheefficientextractionofnutrientsandthedisposalofwastes.Thus,nutrientdigestionandabsorptionformthetwomajorfunctionsofthedigestivesystem.

Thedigestivetract isalsoequippedwithspecial fea-tures to deal with nonnutrient entities from the externalenvironmentthatenterthebody.Forexample,itisdesignedtofacilitatethemovementofgasessuchasairswallowedwith food and methane produced by gut bacteria, and toprotectagainstinfectiousorganismsthatmayaccompanyfoodintothebody.Infact,thedigestivesystemservesasanimportant resource for immune defense, with uniqueepithelial barriers and supplies of immune cells calledlymphocytes,whichareconstantlyreadyfordispatchuponentryanddetectionofapotentiallyharmfulagent.

role of digeStion

Cellsrequireaconstantsourceofenergyinordertofunc-tion. In humans this energy comes primarily from the

CHAPTER 5

118


nutrients found in foods. Some nutrients serve as rawmaterials for the synthesis of cellular material. Others(e.g., many vitamins) act as regulators of chemical reac-tions;andstillothers,uponoxidation,yieldenergy.Notallnutrients,however,are ina formsuitable for immediateusebythebody.Somemustundergophysicalandchemicalchangesbeforetheycanserveasenergyorcellsubstance.Thisfunctionisfulfilledbydigestion.

Once food is broken down mechanically and is con-vertedchemically, itcanbeabsorbedbycellsandusedtomaintain vital bodily functions. The amount of energyderivedfromfooddependsonthenutrientsthatthefoodcontains,aswellasonthebody’sabilitytoabsorbthechem-icallyconvertedsubstances.Theroleofdigestionthenistoprocess foods to the point where they can be readilyabsorbedintothebloodstreamanddeliveredtocells.

utilization of food by the body

The human body can be thought of as an engine thatreleases the energy present in the foods that it digests.This energy is utilized partly for the mechanical workperformedbythemusclesandinthesecretoryprocessesandpartlyfortheworknecessarytomaintainthebody’sstructureandfunctions.Theperformanceofworkisasso-ciatedwiththeproductionofheat.Heatlossiscontrolledso as to keep body temperature within a narrow range.Unlikeotherengines,however,thehumanbodyiscontin-ually breaking down (catabolizing) and building up(anabolizing)itscomponentparts.Foodssupplynutrientsessentialtothemanufactureofthenewmaterialandpro-videenergyneededforthechemicalreactionsinvolved.

Carbohydrate, fat, andproteinare, toa largeextent,interchangeableassourcesofenergy.Typically,theenergy

119

7 Features of the Digestive Tract 7

providedbyfoodismeasuredinkilocalories,orCalories.Onekilocalorie isequalto1,000gram-calories (orsmallcalories),ameasureofheatenergy.However,incommonparlance,kilocaloriesarereferredtoas“calories.”Inotherwords,a2,000-caloriedietactuallyhas2,000kilocaloriesofpotentialenergy.Onekilocalorieistheamountofheatenergyrequiredtoraiseonekilogramofwaterfrom14.5to15.5 °C (58.1 to 59.9°F) at one atmosphere of pressure.Another unit of energy widely used is the joule, whichmeasuresenergyintermsofmechanicalwork.Onejouleistheenergyexpendedwhenonekilogramismovedadis-tanceofonemetrebyaforceofonenewton.Therelativelyhigherlevelsofenergyinhumannutritionaremorelikelyto be measured in kilojoules (1 kilojoule = 103 joules) ormegajoules (1 megajoule = 106 joules). One kilocalorie isequivalentto4.184kilojoules.

Theenergypresentinfoodcanbedetermineddirectlybymeasuringtheoutputofheatwhenthefoodisburned(oxidized) in a bomb calorimeter. However, the humanbodyisnotasefficientasacalorimeter,andsomepotentialenergyislostduringdigestionandmetabolism.Correctedphysiological values for the heats of combustion of thethreeenergy-yieldingnutrients,roundedtowholenumbers,areasfollows:carbohydrate,4kilocalories(17kilojoules)pergram;protein,4kilocalories(17kilojoules)pergram;and fat, 9 kilocalories (38 kilojoules) per gram. Beveragealcohol (ethyl alcohol) also yields energy—7 kilocalories(29kilojoules)pergram—althoughitisnotessentialinthediet.Vitamins,minerals,water,andotherfoodconstituentshavenoenergyvalue,althoughmanyofthemparticipateinenergy-releasingprocessesinthebody.

The energy provided by a well-digested food can beestimated if the gram amounts of energy-yielding sub-stances(non-fibrecarbohydrate,fat,protein,andalcohol)inthatfoodareknown.Forexample,asliceofwhitebread

120


containing12gramsofcarbohydrate,2gramsofprotein,and1gramoffatsupplies67kilocalories(280kilojoules)ofenergy.Foodcompositiontablesandfoodlabelsprovideusefuldataforevaluatingenergyandnutrientintakeofanindividualdiet.Mostfoodsprovideamixtureofenergy-supplyingnutrients,alongwithvitamins,minerals,water,and other substances. Two notable exceptions are tablesugarandvegetableoil,whicharevirtuallypurecarbohy-drate(sucrose)andfat,respectively.

Throughout most of the world, protein suppliesbetween 8 and 16 percent of the energy in the diet,althoughtherearewidevariations intheproportionsof

fat and carbohy-drate in differentpopulations. Inmore prosperouscommunitiesabout12 to 15 percent ofenergy is typicallyderived from pro-tein, 30 to 40percent from fat,and 50 to 60percent from car-bohydrate. On theother hand, inmany poorer agri-cultural societies,wherecerealscom-prise the bulk ofthe diet, carbohy-drate provides aneven larger per-centage of energy,

First Lady Michelle Obama gets help from students with the harvest of the White House garden. MarkWilson/GettyImages

121


with protein and fat providing less.The human body isremarkablyadaptableandcansurvive,andeventhrive,onwidelydivergentdiets.However,differentdietarypatternsareassociatedwithparticularhealthconsequences.

nutrient digeStion

There are four means by which digestive products areabsorbed:activetransport,passivediffusion,facilitateddiffusion,andendocytosis.Activetransportinvolvesthemovement of a substance across the membrane of theabsorbingcellagainstanelectricalorchemicalgradient.Itiscarrier-mediated;thatis,thesubstanceistemporarilyboundtoanothersubstancethattransportsitacrossthecellmembrane,whereitisreleased.Thisprocessrequiresenergyandisatriskofcompetitiveinhibitionbyothersubstances. That is, other substances with a similarmolecularstructurecancompeteforthebindingsiteonthecarrier.

Passivediffusionrequiresneitherenergynoracarrier.Thesubstancemerelypassesalongasimpleconcentrationgradient from an area of high concentration of the sub-stance to an area of low concentration until a state ofequilibrium exists on either side of the membrane.Facilitateddiffusionalsorequiresnoenergy,butitinvolvesacarrier,orproteinmoleculelocatedontheoutsideofthecellmembranethatbindsthesubstanceandcarriesitintothe cell. The carrier may be competitively inhibited.Endocytosistakesplacewhenthematerialtobeabsorbed,onreachingthecellmembrane, isengulfed intothecellinterior.

Absorptionoffoodbythesmallintestineoccursprin-cipally in the middle section, or jejunum. However, theduodenum, although the shortest portion of the small

122


intestine,hasanextremelyimportantrole.Theduodenumreceives not only chyme saturated with gastric acid butpancreaticandliversecretionsaswell.Itisintheduodenumthattheintestinalcontentsarerenderedisotonicwiththebloodplasma;i.e.,thepressuresandvolumesoftheintes-tinalcontentsarethesameasthoseofthebloodplasma,sothatthecellsoneithersideofthebarrierwillneithergainnorlosewater.

Bicarbonatesecretedbythepancreasneutralizestheacid secreted by the stomach.This brings the intestinalcontentstotheoptimalpH,allowingthevariousdigestiveenzymes to act on their substrates at peak efficiency.Anumberofimportantgastrointestinalhormonesregulategastricemptying,gastricsecretion,pancreaticsecretion,andcontractionofthegallbladder.Thesehormones,alongwithneuralimpulsesfromtheautonomicnervoussystem,provideforautoregulatorymechanismsfornormaldiges-tiveprocesses.

Most salts and minerals, as well as water, are readilyabsorbedfromallportionsofthesmallintestine.Sodiumisabsorbedbyanactiveprocess,thenecessarymetabolicenergybeingprovidedbytheepithelialcellsofthemucosaofthesmallintestine.Sodiumismovedfromthelumenofthe intestine across the mucosa against a concentrationgradient(i.e.,aprogressiveincreaseintheconcentrationofsodium)andanelectrochemicalgradient(i.e.,agradualincrease in the concentration of charged ions). Sodiumions are absorbed more readily from the jejunum thanfromotherpartsofthesmallintestine.Chlorideisreadilyabsorbedinthesmallintestine,probablyasaconsequenceofsodiumabsorption.

Potassiumisabsorbedatabout5percentoftherateofsodium. It is thought that potassium moves across theintestinalmucosapassivelyorbyfacilitateddiffusionasa

123


consequenceofwaterabsorption.Theabsorptionofwaterappearstobesecondarytotheabsorptionofelectrolytes(substancesthatdissociateintoionsinasolution).Waterabsorptionoccursthroughoutthesmallintestine,thoughchiefly in the jejunum. Water moves freely across theintestinalmucosabothways,butittendstomoveinthedirection of the hypertonic solution (the solution intowhichanetflowofwateroccurs)andawayfromthehypo-tonicsolution(onefromwhichanetflowofwateroccurs).Thus, if thecontentsof the lumenarehypotonic,watermoves rapidly from the lumen to the blood. If the con-tentsoftheintestinallumenarehypertonic,watermovesmorerapidlyfromthebloodintothelumen.Thistwo-waymovementofwatertendstomaintaintheintestinalcon-tentsinanisotonicstate.

Carbohydrates

Carbohydratesareabsorbedasmonosaccharides(simplesugarssuchasglucose,fructose,andgalactosethatcannotbefurtherbrokendownbyhydrolysis)orasdisaccharides(carbohydratessuchassucrose,lactose,maltose,anddextrinthat can be hydrolyzed to two monosaccharides).Thesesimpler molecules, however, must be obtained by thebreaking down of polysaccharides, complex carbohy-dratesthatcontainmanymonosaccharides.Chiefamongtheseisamylose,astarchthataccountsfor20percentofdietarycarbohydrate.Amyloseconsistsofastraightchainofglucosemoleculesboundtotheirneighboursbyoxygenlinks.Thebulkofthestarchisamylopectin,whichhasabranchchainlinkedinafterevery25moleculesofglucoseonthemainchain.

Onlyasmallamountofstarchisdigestedbysalivaryamylase. Most is rapidly digested in the duodenum by

124


pancreaticamylase.Buteventhisenzymehaslittleeffectonthebranchchainsofamylopectinandevenlessonthelinkages in cellulose molecules. This accounts for theinability of humans to break down cellulose. There areseveral formsofamylase inpancreatic juicewhosefunc-tionistohydrolyzecomplexcarbohydratestodisaccharidesand trisaccharides and amylopectins to dextrins. In thebrushborder(comprisingultrafinemicrovilli)andthesur-face membrane of the epithelial enterocytes are thedisaccharidaseenzymes,lactase,maltase,sucrase,andtre-halase, which hydrolyze maltose and the dextrins to themonosaccharidesglucose,galactose,andfructose.

Glucose—which is one of the two monosaccharidecomponents of table sugar (sucrose) and milk sugar (lac-tose)—iscombinedwithphosphateinthelivercellandiseithertransportedtoperipheraltissuesformetabolicpur-poses or stored in the hepatocyte as glycogen, a complexpolysaccharide.Specificenzymesystemsarepresentinthehepatocytefortheseconversions,aswellasforthetransla-tion of other dietary monosaccharides (fructose fromsucroseandgalactosefromlactose)intoglucose.Thehepa-tocyte(livercell)isalsoabletoconvertcertainaminoacidsandproductsofglucosemetabolism(pyruvateandlactate)intoglucosethroughgluconeogenesis.

Fructose appears to be absorbed by simple diffusion,but glucose and galactose are transported by an energy-usingprocess,probablybindingtoaspecificproteincarrierwithattachedsodiumions.Thesugarisreleasedinsidetheenterocyte,sodiumispumpedout,andthesugarsthendif-fuseintothecirculationdownaconcentrationgradient.

Dietary Fibre

Dietary fibre, the structural parts of plants, cannot bedigested by the human intestine because the necessary

125


enzymes are lacking. Even though these nondigestiblecompoundspassthroughthegutunchanged(exceptforasmallpercentagethatisfermentedbybacteriainthelargeintestine), they nevertheless contribute to good health.Insoluble fibre does not dissolve in water and providesbulk,orroughage,thathelpswithbowelfunction(regu-larity)andacceleratestheexitfromthebodyofpotentiallycarcinogenicorotherwiseharmfulsubstancesinfood.

Typesof insolublefibrearecellulose,mosthemicellu-loses,andlignin(aphenolicpolymer,notacarbohydrate).Majorfoodsourcesofinsolublefibrearewholegrainbreadsandcereals,wheatbran,andvegetables.Solublefibre,whichdissolvesorswellsinwater,slowsdownthetransittimeoffoodthroughthegut(anundesirableeffect)butalsohelpslowerbloodcholesterollevels(adesirableeffect).Typesofsoluble fibre are gums, pectins, some hemicelluloses, andmucilages.Fruits(especiallycitrusfruitsandapples),oats,barley, and legumes are major food sources. Both solubleand insoluble fibre help delay glucose absorption, thusensuringaslowerandmoreevensupplyofbloodglucose.Dietary fibre is thought to provide important protectionagainst some gastrointestinal diseases and to reduce theriskofotherchronicdiseasesaswell.

Proteins

The digestion of protein entails breaking the complexmolecule first into peptides, each having a number ofaminoacids,andsecondintoindividualaminoacids.Thepepsinsareenzymessecretedbythestomachinthepres-enceofacidthatbreaksdownproteins(proteolysis).Thepepsins account for about 10 to 15 percent of proteindigestion.Theyaremostactiveinthefirsthourofdiges-tion,andtheirabilitytobreakdownproteinisrestrictedby the necessity for an acidic environment with a pH

126


between 1.8 and 3.5. The trypsins (proteolytic enzymessecreted by the pancreas) are much more powerful thanpepsins,sothegreaterpartofproteindigestionoccursintheduodenumandupperjejunum.Therefore,evenaftertotalremovalofthestomach,proteindigestionusuallyisnotimpaired.

Pancreatic secretion contains inactive protease pre-cursorsthatbecomeenzymaticallyactiveafterinteractingwith another enzyme, enterokinase, which is secretedfrom the microvillous component of the enterocytes intheduodenalandjejunalmucosa.Trypsinogenisactivatedintheintestinebyenterokinase,whichis liberatedfromduodenal liningcellsbythe interactionofbileacidsandcholecystokinin.Thisactivationoftrypsinogentotrypsinisinitiatedbythecleavagefromitofsixterminalaminoacid residues.The other proteases are activated by free

Meat—such as this steak—is an important source of protein. Other protein-rich foods include eggs, beans, and milk. MiguelMendez/AFP/GettyImages

127


trypsin. The net effect of these proteases is to reducedietaryproteinstosmallpolypeptidechainsoftwotosixaminoacidsandtosingleaminoacids.

Trypsin activates the other pancreatic proteases,including chymotrypsin and elastase. Trypsin, chymo-trypsin,andelastaseareknownasendopeptidasesandareresponsiblefortheinitialbreakdownoftheproteinchainstopeptidesbyhydrolysis.Thenextstep—thebreakdownofthesepeptidestosmallermoleculesandthento indi-vidual amino acids—is brought about by the enzymicactivityofcarboxypeptidases,whicharealsosecretedbythepancreas.

Peptidaseactivitycommencesoutsidetheenterocytes(inthemucusandbrushborder)andcontinuesinsidethecell.Adifferentpeptidaseappearstobeinvolvedineachstage of the breakdown of protein to amino acids.Likewise,thetransportofdifferentpeptidesinvolvesdif-ferentmechanisms.Dipeptides(peptidesthatreleasetwoaminoacidsonhydrolysis)andtripeptides(peptidesthatrelease three amino acids) are moved from the surfacebrushborderintothecellbyanenergy-requiringprocessinvolvingacarrierprotein.Smallpeptideswithfewaminoacidsareabsorbeddirectlyassuch.Thegreaterpartofthebreakdownofpeptidestoaminoacidstakesplacewithinthe enterocyte. Curiously, small peptides are absorbedmore rapidly than amino acids, and, indeed, the precisedetails of the mechanism for absorption of amino acidsare largelyunknown.It isknownthatsomeaminoacidshave a specific individual transport system while othersshareone.

Aminoacidsmaybeclassifiedintogroups,dependingupon their optical rotatory characteristics (i.e., whetherthey rotate polarized light to the left, or levo, or to theright,ordextro)andintermsofreactivity,oracidity(pH).

128


Levorotatoryaminoacidsareabsorbedextremelyrapidly—muchmorerapidlythanaredextrorotatoryaminoacids.In fact, levorotatory amino acids are absorbed almostasquicklyastheyarereleasedfromproteinorpeptide.Neutralamino acids have certain structural requirements foractivetransport,and if thesespecificstructuralarrange-mentsaredisturbed,activetransportwillnotoccur.Basicaminoacids,whichhaveapHabove7,aretransportedatabout5to10percentoftherateofneutral levorotatoryaminoacids.

Fats

Almostalldietaryfatisstoredastriglycerides.Solubilityinwaterisnecessaryinorderforfattobetransferredfromthe lumenof the intestineto theabsorptivecells.Manyfactors,suchasthelengthofthefattyacidchainsofthetriglycerides, play an important role in determining thissolubility. Triglycerides have three long chains of fattyacids(LCFA)attachedtoaglycerolframework,andtheyare insoluble inwater.Theremainderaremedium-chaintriglycerides(MCT),whichcanbeabsorbedintactbythemucosaofthesmallintestine.

Lipases,whichincludephospholipase,esterase,colipase,andlipase,functiontoreduceMCTstofreemonoglyceridesand medium-chain fatty acids (MCFA), which are moresolubleinwaterthantheLCFAsandmovequicklythroughthecellsandpassintotheportalcirculationandthentotheliver.Lipasesrequirethepresenceofbileacidsintheintestinallumenfortheformationofmicellarsolutionsoffatpriortooptimaldigestion.

Long-chainfattyacidsattachedtothetriglyceridesareattackedbythepancreaticenzymelipase.Twoofthethreefattyacidchainsaresplitoff,leavingoneattachedtothe

129


glycerol (forming a monoglyceride). In the presence ofexcesslevelsofbilesalts,however,thisactivityofpancreaticlipaseisinhibited.Alipasemaybepresentingastricjuice,butitisnotcapableofdigestingMCFAsandLCFAs,andtheproportionofsmall-chainfattyacidsinfoodissmall.Thus,littledigestionoccursinthestomach.

Anotherpancreaticenzyme,colipase,bindstothebilesalts, leaving lipase available to attack the triglycerides.Themonoglyceridesthatresultfromthesesplittingpro-cesses combine into a complex called a micelle. Themicelle permits fat components to be soluble in water.Becausebilesaltshaveahydrophobic,orwater-repellingregion,andahydrophilic,orwater-attractingregion,themicelleisformedwithbilesaltsarrangedaroundtheout-sidewithhydrophobicendsfacinginsideandhydrophobicfatty acids, monoglycerides, phospholipids, and choles-terol,aswellasthefat-solublevitaminsA,D,E,andK,inthecentre.

Thereisa layeroffluidoverlyingthesurfacecellsofthemucosaofthesmallintestineknownasthe“unstirred”layer.Itisacrossthislayerthatthemicellesmustpasstoreachthecellmembranes.Therateofdiffusionthroughtheunstirredlayerisdeterminedbythethicknessofthelayerandthegradientinconcentrationsofthevariousele-ments of the transport system from the lumen of theintestinetothecellmembrane.Underneaththeunstirredlayer is a glycoprotein layer known as the “fuzzy coat,”which mainly comprises mucus. Beneath the fuzz is thebrushborderonthesurfaceofthecellmembrane.Ithasadoublelayeroflipidthatiseasilypenetratedbythefattyacidsandmonoglyceridesthataresolubleinlipids.

Once the micelle has passed through the fuzzy coatandthebrushborder,itentersthecellsofthetissuesthatlinetheintestine.Themicelledisintegrates,thebilesalts

130


diffusebackintothelumen,andacarrierproteinpicksupthe fatty acids and the monoglycerides and transportsthem to the endoplasmic reticulum, a tubular structurerichinenzymes,inthecellinterior.Atthissitethetriglyc-erideissynthesizedagainundertheinfluenceofanenzymecatalystcalledacyltransferase.

The triglycerides pass to the membrane of anothertubular structure, known as the Golgi apparatus, wheretheyarepackagedintovesicles(chylomicrons).Thesevesi-clesaresphereswithanoutercoatingofphospholipidsandasmallamountofapoprotein,whiletheinteriorisentirelytriglycerideexceptforasmallquantityofcholesterol.Thechylomicronsmigratetothecellmembrane,passthroughit,andareattractedintothefinebranchesofthelymphaticsystem,thelacteals.Fromtherethechylomicronspasstothethoracicduct.Thewholeprocessofabsorption,fromtheformationofmicellestothemovementoutofthecellsandintothelacteals,takesbetween10and15minutes.

The medium-chain triglycerides are broken down tomedium-chainfattyacidsbypancreatic lipase.Medium-chainfattyacidsaresolubleinwaterandreadilyenterthemicelles.Ultimately,aftermovingacrossthemembraneoftheenterocyte,theypassintothecapillarytributariesoftheportalveinandthentotheliver.

The liver metabolizes fat by converting stored fattyacids to their energy-releasing form, acetylcoenzyme A(acetyl CoA), when hepatic glucose and glycogen storesareexhaustedorunavailableformetabolicpurposes(asindiabeticketoacidosis).Theliveralsoplaysaroleinthefor-mation of storage fats (triglycerides) whenevercarbohydrates,protein,orfatexceedstherequirementsoftissuesforglucoseortheneedsoftheliverforglycogen.Furthermore,theliversynthesizescellmembranecompo-nents (phospholipids) and proteins (lipoproteins) thatcarrylipids(fatsandcholesterol)intheblood.

131


Vitamins

Fat-solublevitaminspasswiththechylomicronsintothelymphaticsystem.VitaminA,firstpresentingasthepre-cursorbeta-carotene,iscleavedtoformretinol,whichisthenrecombinedwithfattyacidsbeforeenteringthechy-lomicron. Vitamins D and D3 diffuse passively into thechylomicron. The absence of bile salts from the intes-tine—whichoccursinjaundiceduetoobstructionofthebiliarytract—severelyimpairsvitaminKabsorptionandblood clotting, with risk of hemorrhage. Vitamin E, amixtureofoilsknownas tocopherols, ispresent ineggsandissynthesizedbysuchplantsassoybeans,corn(maize),and wheat. It passes through the enterocyte with theotherlipidsofthemicelleandisultimatelystoredintheliver.

Folic Acid

Folicacid(pteroylglutamicacid)isnecessaryforthesyn-thesisofnucleicacidsandforcellreplication.Folicaciddeficiencyresultsinanimpairedmaturationofredbloodcells (erythrocytes). Folates are synthesized by bacteriaandplantsandarehydrolyzedtofolicacidintheintestine.Milkandfruitarethemainsourcesoffolicacid,providingon average 500 micrograms daily. Folic acid is stored intheliver.

The hydrolysis of the folates, a necessary step toabsorption, takes place on the brush borders of jejunalenterocytes and is completed on lysosomes—structureswithin the cell that contain various hydrolytic enzymesand are part of the intracellular digestive system.Whenhydrolysis of folates is disturbed, anemia develops.Thisprocessisinterferedwithbycertaindrugs,especiallyphe-nytoin, used in the management of epilepsy, and by thelong-termuseofsulfonamides inthesuppressionofdis-ease.Amethylgroupisaddedtopteroylglutamicacidin

132


theenterohepaticcirculationintheliverandisexcretedin the bile. Approximately 100 micrograms are utilizedeachday.Themethodofabsorptionisuncertain.

Vitamin B12Vitamin B12, also called cobalamin because it containscobalt,isessentialtotheformationofbloodcells.Itisacoenzymethatassiststheenzymesresponsibleformovingfolateintothecellinterior.VitaminB12isaproductofbac-terial metabolism. Although bacteria in the colon alsoproducevitaminB12,itcannotbeabsorbedatthatsite.

VitaminB12occursinaboundforminfoodandisliber-ated by proteolytic activity in the stomach and smallintestine.Itthenbindswithintrinsicfactor(IF),aglyco-protein produced by the same parietal cells that formhydrochloric acid. Intrinsic factor is essential to trans-port, and the B12 protein complex, known astranscobalamin II, is necessary to transfer the vitaminfromtheintestinetotherestofthebody.OncetheIFisattached, further proteolytic digestion of the boundvitaminisprevented.Absorptionisconfinedtothedistal100 cm of ileum, especially the last 20 cm, where thecomplex binds to receptors in the brush border of theenterocytes. The process is slow; it takes three hoursfrom its presentation in food to its appearance in theperipheral blood via the enterohepatic circulation andhepaticveins.ThedailyrequirementofvitaminB12isonemicrogram.VitaminB12isstoredprimarilyintheliver.

Vitamin D

VitaminDisessentiallyahormoneandisavailablefromtwosources.First,undertheinfluenceofphotosynthesismade possible by ultraviolet rays from the Sun, a sterolcompound from the liver (dehydrocholesterol) is con-vertedtovitaminD3.ThissuppliesenoughvitaminD3for

133


human needs. In the absence of exposure to sunlight,dietarysupplementsbecomenecessary.Eggs, liver,forti-fied bread, and milk are the main sources of vitamin D.DeficiencyofvitaminDoccurswhenthereislackofsun-light and inadequate vitamin D in the diet. It may alsoresult from disease or after resection of the small intes-tine, which may cause malabsorption. In thesecircumstancessofteningofbone(osteomalacia)andricketsmayoccur.

Inthe jejunumvitaminDis incorporatedalongwithbilesaltsandfattyacidsintothemicelles.Subsequently,astheprovitaminD1,vitaminDisabsorbedintheileumandthenpassesintothecirculationviatheportalvein.Aspecificbloodborneprotein,analpha-1–globulin,carriesittotheliver,wheretheprocessofchemicalchangetotheactivehormonebeginsbyhydroxylationtocholecalciferol.Thederivativesareconveyedfromthelivertovarioustissues,including the skin, bone, and parathyroid glands. In theintestine vitamin D influences the permeability of thebrushbordersoftheenterocytestocalcium.

Calcium

Calciumisrequiredfortheconstructionofbone.Itformspartofthesubstancecementingtogetherthewallsofadja-centcells,anditisvitalintheresponsivenesstostimuliofmuscleandnervecells,whichdeterminestheirexcitability.Themainsourcesofcalciumaremilkandmilkproducts;meat,inwhichitisboundtoproteins;andvegetables,inwhich it is bound to phytates (phytic acid) and oxalates(thesaltofoxalicacid).

Theabsorptionofcalciumisinfluencedbyconditionswithinthelumenofthesmallintestine.Theacidsecretionfromthestomachconvertsthecalciumtoasalt,whichisabsorbed primarily in the duodenum. Unabsorbed

134


calciumisprecipitatedintheileumandisexcretedinthefeces.Lactose,thesugarofmilk,aidscalciumabsorption,whereasexcessfattyacidandhighconcentrationsofmag-nesiumandoxalatesinterferewithit.

Calcium is absorbed across the brush border of theenterocytecellmembranebyamechanismthatrequiresenergy.VitaminDisessentialtothisprocess,and,whenitis deficient, the active transport of calcium stops.Parathyroidhormone(parathormone)andgrowthhormonefromthepituitaryglandalsoinfluencecalciumabsorption.Anaveragedietcontains1,200mgofcalcium,one-thirdofwhichisabsorbed.Inthepassageofthebloodthroughthekidney,99percentofthecirculatingcalciumisreab-sorbed.Thus,inkidneyfailureaswellasinmalabsorptionstates,excessivelossesofcalciumoccur.Incalciumdefi-ciency,calciumisresorbedfromthebone,whichtherebyweakensandsoftenstheskeletalstructure.

Magnesium

Anaveragedietcontainsaround300mgofmagnesium,ofwhichtwo-thirdsisabsorbed.Halfoftheabsorbedmag-nesiumisexcretedbythekidneys,whichcanregulatetheamountwithinarangeof1to150millimolesperday.Thiscontrolissubjecttotheinfluencesofparathormoneandthe thyroid hormone calcitotonin. Magnesium is impor-tanttoneuromusculartransmission.Itisalsoanimportantcofactorintheenzymicprocessesthatformthematrixofboneandinthesynthesisofnucleicacid.Magnesiumdefi-ciencycanresultfromtheoveruseofdiureticsandfromchronic renal failure, chronic alcoholism, uncontrolleddiabetesmellitus,andintestinalmalabsorption.

Magnesiumhasaninverserelationshipwithcalcium.Thus,iffoodisdeficientinmagnesium,moreofthecal-cium in the food is absorbed. If the blood level of

135


magnesium is low, calcium is mobilized from bone.Thetreatmentofhypocalcemiaduetomalabsorptionincludesadministrationofmagnesiumsupplements.

Iron

Iron is necessary for the synthesis of hemoglobin, theoxygen-carryingcompoundoftheredbloodcells.Italsohasanimportantroleasacofactorinintracellularmetab-olism.Themaindietarysourcesaremeat,eggs,nuts,andseeds.The average daily diet contains approximately 20mg of iron. Humans are unable to excrete iron that hasbeenabsorbedinexcessofthedailyrequirementof1mg.

The acid in the stomach prevents the formation ofinsolublecomplexes,asdoesvitaminC.Someaminoacidsfrom dietary protein stabilize the iron in low molecularweightcomplexes.Phosphatesandphytatesofvegetable

Halibut is an excellent source of magnesium. Other magnesium-rich foods include artichokes, whole wheat flour, almonds, beans, and spinach. Express/HultonArchive/GettyImages

136


origin, some food additives, and the inhibition of acidsecretionimpedetheabsorptionofiron.

Ironisalmostwhollyabsorbedintheduodenumbyaprocessthatinvolvesmetabolicactivityrequiringenergy.Mostof the ironremains trapped in thesurfaceentero-cytesandislostwhenthecellsdieandareshedintotheintestine.Theamountofironlostseemstoberelatedinsomewaytothestateofthebody’sironstores,althoughthiscanbeovercomeifverylargedosesofironaretakenorally. Alcohol in the stomach and duodenum increasesthe rate of absorption. Transport of the iron from theenterocyte is achieved by binding to a carrier, a plasmaproteincalledtransferrin.Fromtheintestineitpassesintotheportalcirculationandtheliver.Whenthelossofironisincreased,asinexcessivemenstruationandinbleedingdisorders,therateofabsorptionissteppedupfromlessthan1mgperdayto1.5mgormore.

MoveMent of gaS through the digeStive tract

Themovementofgasthroughtheintestinesproducesthegurglingsoundsknownasborborygmi.Intherestingstatethereareusuallyabout200mlofgasinthegastrointestinaltract.Itscompositionvaries:between20and90percentisnitrogen,upto10percentisoxygen,upto50percentishydrogen, up to 10 percent is methane, and between 10and30percentiscarbondioxide.

Mostoftheairthatpeopleswallow,whiletalkingandeatinginparticular,iseitherregurgitated(asinbelching)or absorbed in the stomach. Anxiety or eating quicklyinducesfrequentswallowingofairwithconsequentbelch-ingorincreasedrectalflatus.Althoughsomeofthecarbondioxideinthesmallintestineisduetotheinteractionof

137


hydrogen ions of gastric acid with bicarbonate, some isgenerated in the jejunumbythedegradationofdietarytriglyceridestofattyacids.Highlevelsofcarbondioxideinrectalflatusreflectbacterialactivityinthecolon.

Methanecannotbeproducedbyanycellandisentirelytheresultofbacteria’sactingonfermentabledietaryresi-duesinthecolon,althoughthereappearstobeafamilialfactorinvolvedinthis,asnoteveryonecangeneratemeth-ane. In the colon bacterial production of hydrogen ismarkedly elevated when the diet contains an excess ofvegetablesaccharides.Thisisparticularlynoticeableafterconsumingbeans,forexample.Gasismoreoftenrespon-sibleforthebuoyancyofstoolsthanisexcessiveresidualfatinmalabsorptionstates.

The gradient between the partial pressures (or thepressureexertedbyeachgasinamixtureofgases)ofpar-ticular gases in the intestinal lumen and the partialpressuresofgasesinthecirculatingblooddeterminesthedirection of movement of gases. Thus, because oxygentends to be in low pressure in the colon, it diffuses outfromthebloodintotheintestine.Thediffusionofnitro-gen from the blood into the intestine occurs because agradient is established by the carbon dioxide, methane,andhydrogenthatresultfrommetabolicactivitiesofthecommensalbacteria.Thepartialpressurecontributedbynitrogeninthecolonis lowered,stimulatingnitrogentoentertheintestinefromtheblood.

Inareaswherelactase,theenzymethatbreaksdownlactose(milksugar),ismissingfromthegroupofdisaccha-ridasesofthesmallintestine,lactosepassesintothecolonundigested. In a lactase-deficient person, the unhydro-lyzedlactoseentersthecolon,wheretheamountoflactosenormallypresentinaglassofmilkiscapableofliberating,afterbacterialfermentation,theequivalentoftwotofour

138


cups(500–1,000ml)ofgas(hydrogen).About15percentofthegasdiffusesbackintotheblood,withtherestpassingasflatus.

Hydrogen generated in the colon is partly absorbed,passes inthecirculatingbloodtothe lungs,anddiffusesinto the respiratory passages, where its presence can beeasilydetermined.Thetimetakenforhydrogentoappearinthebreathafteringestionofastandardloadofglucoseorlactoseisusedtodeterminewhethertheupperareaofthe gastrointestinal tract is colonized by bacteria.Hydrogenthatappearswithin30minutesoftheingestionofthesugarloadsuggestsheavycolonizationofthesmallintestine.

the digeStive tract aS an organ of iMMunity

Thebodyiscontinuouslyexposedtodamagebyviruses,bacteria, and parasites; ingested toxins and chemicals,includingdrugsandfoodadditives;andforeignproteinofplant origin.These insults are received by the skin, therespiratorysystem,andthedigestivesystem,whichcon-stitutetheinterfacebetweenthesterilebodyinteriorandtheenvironment.

Thedefenseofthebodyisvestedlargelyinthelym-phaticsystemand its lymphocytes.Asubstantialpartofthegastrointestinaltractisoccupiedbylymphoidtissue,whichcanbedividedintothreesectors.Thefirstisrepre-sented by the pharyngeal tonsils, the appendix, and thelarge aggregates of nodules known as Peyer patcheslocated at intervals throughout the small intestine.Thesecondsectorincludesthelymphocytesandplasmacellsthatpopulatethebasementmembrane(laminapropria)ofthe small intestine, the area of loose connective tissue

139


abovethesupportingtissueofthemucosalliningextendingintothevilli.Thethirdsectorcompriseslymphocytesthatliebetweentheepithelialcellsinthemucosa.Theinterac-tionbetweenthesecellsofthelymphaticsystemandthethreateningagentisthebasisofdefenseinthegastroin-testinaltract.

Lymphocytesareoftwotypes,BandT,accordingtowhethertheyoriginateinthebonemarrow(B)orinthethymus gland (T), located in the chest. On leaving theirtissueoforigin,bothtypesendupintheperipherallym-phoid structures. These include the peripheral lymphglands,thespleen,the lymphnodes inthemesenteryoftheintestine,thePeyerpatches,andthespacesbetweentheepithelialcellsofthemucosa.

Lymphocytesareimmatureuntiltheycomeintocon-tactwithantigens.Ifforeignmaterialisrecognizedassuchby T cells (T lymphocytes), the lymphocytes undergo aprocessofmaturationinwhichtheyproliferateanddivideintosubclasses.Thefirstsubclasscomprisesthe“helper”Tcells,whicharemediatorsofimmunefunction.Thesec-ondclassconsistsof“suppressor”Tcells,whichmodulateandcontrolimmuneresponses.Thethirdclasscomprisesthe“killer”Tcells,whicharecytotoxic(i.e.,theyareableto destroy other cells). Most of the lymphocytes lyingbetweentheepithelialcellsofthemucosaarekillerTcells.

When B cells (B lymphocytes) recognize antigen,theyalsomature,changingtotheformknownasplasmacells.These cells elaborate a highly specialized proteinmaterial, immunoglobulin (Ig), which constitutes anti-bodies.Therearefivevarietiesofimmunoglobulin:IgA,IgM,IgG,IgD,andIgE.Bcellsandplasmacellsarefoundmainlyinthecellsinthespacesofthebasementmembrane.Another group of specialized cells are known as M cells.Thesearestretchedoverandaroundordinaryepithelial

140


cellsofthemucosa.TheMcellspackageantigenicmaterialinto vesicles and move it through the cell and into thesurroundingspaces.

LymphocytesofthePeyerpatchespassthroughlymphvessels to the nodes in the mesentery and then to thethoracicduct.Thisisthecollectingchannelintheabdo-men,whichpassesupthroughthethoraxtodrainintothevenoussystematthejunctionoftheleftinternal jugularandleftsubclavianveins.Thevariousramificationsoftheabdominal lymphatics all drain into the thoracic duct.Fromtherethelymphocytesarecarriedbacktotheintes-tineaswellasbeingdispersedtootherorgans.Itisthesemigrated lymphocytes that come to populate the base-ment membrane and to occupy the spaces betweenepithelialcells.

MostcellsinthemesentericnodesandthebasementmembraneareplasmacellsthatproduceimmunoglobulinofclassIgA.IgMand,toalesserextent,IgEareproducedbyothercells,andIgGisformedbycellsinthespleenandperipherallymphnodes.TheIgAofplasmacellsissecretedinto the lumen of the intestine, where it is known as“secretory IgA” and has a different molecular structurefrom that of the IgA circulating in the blood. Whensecreted, it is accompanied by a glycoprotein that is pro-ducedbytheepithelialcellsofthemucosa.Thissubstance,when attached to the IgA molecule, protects it fromdigestionbyprotein-splittingenzymes.ThisIgAcomplexcan adhere to viruses and bacteria, interfering with theirgrowthanddiminishingtheirpowertoinvadetissue.Itisalsocapableofrenderingtoxicsubstancesharmless.FormedbyBcells,IgEcoatsthesurfaceofmastcells,whicharespeciallyadaptedtodealwiththeallergicchallengeposedbyparasitesandworms.

Thenewborn infant isprotectedbyalready-maturedimmunoglobulin with which the colostrum, the initial

141


secretion of the lactating breast, is richly endowed. Astime passes, the gastrointestinal tract of the infant isincreasinglyexposedtovarious insults, andthe lympho-cytes and other cells of the immune system becomeadapted to deal with these. In this way, the body alsodevelopsatolerancetopotentiallyoffendingsubstances.Ifinvasionoftissueoccursdespitethesevariousdefenses,thenageneralizedsystemicimmunereactionismarshaled.Someofthefeaturesofthisreaction,suchasfeverandamassiveincreaseinthewhitebloodcells,aretheevidenceofillness.

142

DISEASES OF THE UPPER DIGESTIVE TRACT

Diseases of the upper digestive tract can affect thestructuresoftheoralcavity,includingtheteethand

tongue, as well as the pharynx, the salivary glands, theesophagus,andthestomach.Examplesofcommoncondi-tions that affect these portions of the digestive systeminclude dental caries (cavities), peptic ulcer, and gastro-esophagealrefluxdisease.Insomecases,conditionssuchascrackededgesofthelips,discolorationofthetongue,orinflammationofthetongue(glossitis)mayarisesecondarytonutritionaldeficiencyorsystemicdisease.Inaddition,somediseasesoftheupperportionsofthedigestivetracthavesymptomsthatinvolvetheorgansofthelowerdiges-tive tract. Thus, diseases of the upper digestive systemsometimesrequiremultiplediagnosticteststorevealtheirtrueoriginsandcauses.

diSeaSeS of the Mouth and oral cavity

Besides local disease, features characteristic of systemicdisordersareoftenpresentonthemouthandintheoralcavity.Forexample,lipsthatarefissuredanderodedatthecornersmayindicateriboflavindeficiency.Likewise,mul-tiple brown freckles on the lips, when associated withpolypsinthesmallintestine,arecharacteristicofPeutz-Jegherssyndrome.InFordycedisease,alocalizedconditionoftheoralcavity,aggregatesofsmallyellowspotsoccuronthebuccalmucosaandonthemucosabehindthelips.The

CHAPTER 6

143

7 Diseases of the Upper Digestive Tract 7

spotsareduetothepresenceofenlargedsebaceousglandsjustbelowthemucosalsurface.

Themostcommonmouthulcersareduetoaphthousstomatitis. These ulcers affect one out of every fiveCaucasians. The manifestations of this condition rangefromoneortwosmallpainfulvesiclesrupturingtoformround or oval ulcers, occurring once or twice a year andlastingsevento10days,todeepulcersofonecentimetre(about half an inch) or more in diameter.The ulcers arefrequently multiple, occur anywhere in the mouth, andmaypersistformonthsatatime.Symptomsrangefromamild local irritation to severe distressing pain that pre-ventstalkingandeating.Scarringcanbeseenatthesitesofpreviousulcers.

Aphthous ulceration is sometimes associated withstress,butitmayalsobeareflectionofanunderlyingmal-absorptive disease such as celiac disease. Treatment isdirectedtothepredisposingcause.Topicalandsystemiccorticosteroids are the most effective treatment. Localanestheticagentsandanalgesicsmaypermiteasiertalkingandeating.Inamoreseriouscondition,Behçetsyndrome,similarulcersoccurinthemouthandonthegenitalia,andtheeyesmaybecomeinflamed.

Discolorationofthetongue,commonlywhite,isduetodepositsofepithelialdebris,effete(orworn-out)bacteria,andfood.Italsooccursincircumstancesinwhichthereisreducedsalivaproduction.Thismaybeacute,asinfever,whenwaterlossthroughtheskinisexcessive.Discolorationofthetonguebecomeschronicfollowingatrophyofthesalivaryglandsandintheabsenceofgoodoralhygiene.Ifthe person is a heavy smoker, the deposit is colouredbrown. Black discoloration of the tongue with the for-mationinthecentreofadensepellicleoffurlikefiliformpapillae(blackhairytongue)maybeduetoafunguswith

144


pigmented filaments. Occasionally it simply representsexcessiveelongationofthefiliformpapillae.

Adeeplyfissuredtongue(scrotaltongue)maybedueto a congenital variation in the supporting tissue of thetongue,but itcanbecausedbysyphilis,scarletfever,ortyphoidfever.Thereisamilddegreeofinflammationinthefissures,whichcausesaslightburningdiscomfort.Otherimportant diseases of the oral cavity include glossitis,Vincentgingivitis,oralcancer,anddentalcaries.

Pellagra

Pellagraisanutritionaldisordercausedbyadietarydefi-ciencyofniacin(alsocallednicotinicacid)orbyafailureofthebodytoabsorbthisvitaminortheaminoacidtryp-tophan,whichisconvertedtoniacininthebody.JosephGoldberger of the United States Public Health Servicewasthefirsttoassociatepellagrawithanutritionaldefi-ciency. In 1937 it was shown that dogs with a disordersimilartopellagraknownasblacktonguecouldbecuredbytheadministrationofniacin.

Inhumanspellagraischaracterizedbyskinlesionsandbygastrointestinalandneurologicaldisturbances.Theso-calledclassicalthreeDsofpellagraaredermatitis,diarrhea,anddementia.Skinlesionsresultfromanabnormalsensiti-zation of the skin to sunlight and tend to occursymmetricallyontheexposedsurfacesofthearms, legs,and neck.They may look at first like a severe sunburn,later becoming reddish brown, rough, and scaly.Gastrointestinal symptoms usually consist of diarrhea,withanaccompanyinginflammationofthemouthandthetongueandfissuringanddryscalingofthelipsandcornersof the mouth. Neurological signs appear later in mostcases, when the skin and alimentary manifestations are

145


prominent. The dementia, or mental aberrations, mayincludegeneralnervousness,confusion,depression,apathy,anddelirium.

In humans, pellagra is seldom a deficiency of niacinalone. Response to niacin therapy tends to be partial,whereasthetherapeuticadministrationofawell-balanced,high-proteindietandmultivitaminscommonlybringsswiftrecovery.Mildorsuspectedinstancesofniacindeficiencycanbeeffectivelytreatedwithawell-balanceddietalone.

Pellagraisseldomencounteredincountriesinwhichthepopulationgenerallyeatsawell-balanceddiet,butitstilloccursinmostcountriesinwhichpeopleliveonadietthat consists predominantly of corn (maize)—which islowintryptophan,andcontains littleornoprotein-richfood.Suchfoodsasmilkandeggs,althoughlowinniacin,willprotectthebodyfrompellagrabecausetheirproteins

This patient exhibits dermatitis of her hands, one of the symptoms of pellagra. This disorder is caused by a lack of niacin. CDC

146


containsufficienttryptophanforthesynthesisofniacin.Pellagra can also be a side effect of chronic alcoholism.SymptomscloselyresemblingthoseofpellagraareseeninHartnupdisease.

Glossitis

Glossitis isaninflammationofthetonguecharacterizedbylossofthesurfacepapillae,aconditionthatgivestheaffectedareaasmooth,redappearance.Glossitismaybetheprimarydisease,ormaybeasymptomofoneofseveralhereditary and acquired conditions—such as certainformsofanemia,pellagra,syphilis,ornutritionaldeficien-cies.Theremay,however,beamildburningsensationthatcanbecontrolledwithtopicalanesthetics.

Abaldtongue(atrophicglossitis),withasmoothsur-faceduetocompleteatrophyofthepapillae,isassociatedwith malnutrition, severe iron deficiency anemia, perni-cious anemia, and pellagra.The condition is endemic inunderdeveloped countries in which there are periods offamine.Atrophic glossitis may heal spontaneously whentheunderlyingcauseiscorrected.

Geographictongue(benignmigratoryglossitis)referstothechronicpresenceof irregularlyshaped,brightredareasonthetongue,surroundedbyanarrowwhitezone.Normal tongue epithelium may grow back in one areawhilenewareasofglossitisdevelopelsewhere,makingthediseaseseemtowander.Thesechangesusuallygiverisetonosymptomsor,atthemost,toamildburningsensation.Thecauseisunknown,andtheconditionmaypersistforyears.Thereisnotreatment.

Median rhomboid glossitis refers to a single rough,lozenge-shaped area of glossitis in the midline of thetongue. It appears to be a combination of anomalous

147


fetal development and a yeast infection.Though someindividualsfearthatglossitisiscancerous,malignancyisrarelyassociatedwiththecondition.

Vincent Gingivitis

Vincent gingivitis—which is also known by a variety ofother names, includingVincent stomatitis, acute necro-tizingulcerativegingivitis,andtrenchmouth—isanacuteandpainfulinfectionofthetoothmarginsandgumsthatiscausedbythesymbioticmicroorganismsBacillus fusiformisand Borrelia vincentii. The chief symptoms are painful,swollen,bleedinggums;small,painfululcerscoveringthegumsandtoothmargins;andcharacteristicfetidbreath.Theulcersmayspreadtothethroatandtonsils.Feverandmalaisemayalsobepresent.

Vincentgingivitiscanoccurafteraprolongedfailuretobrushone’steeth,thoughtherearemanyotherpredis-posing factors, such as vitamin deficiencies, emotionalstress,andsoon.Itisendemicincountrieswherethereisseveremalnutritionandpoororalhygiene.Itisuncertainifitistransmittedbytheexchangeofsalivainkissing,butitsepidemicincreaseinwartimeanditsfrequencyinthesexuallypromiscuoussuggestthis.

Theinfectionisreadilytreatedbybedrest,theadmin-istrationofpenicillinorotherantibiotics,andtheuseofantiseptic mouth rinses. It may also be treated by trim-ming the gum margins to eliminate subgingival pockets.Regulartoothbrushingisthechiefpreventivemeasure.

Oral Cancer

Oral cancer is a disease characterized by the growth ofcancerous cells in the mouth, including the lips. Oral

148


cancer is often associated with cancers of the cavitylocated behind the tonsils and the back of the throat(oropharyngeal cancer). It is sometimes caused bychronicthermalirritationinheavysmokersandisoftenpreceded by leukoplakia (plaquelike patches arising onthemucousmembranesofthecheeks,gum,ortongue).Similarly,oralcancercanbecausedbythehabitofkeepingtobacco in thespacebetweenthecheekandtheteeth.Cancersofthesalivaryglandsandofthemucousmembranesofthecheekscausepain,bleeding,ordifficultyinswallow-ing. The lymphomas and other tumours of lymphoidorigin may first appear in the tonsillar or pharyngeallymphnodes.

Mostcasesoforalcanceroriginatefromtheflattenedcellsthatmakeuptheliningoftheoralcavity(squamouscellcarcinomas).Oralcancerscanspreadintothejawandmay occur simultaneously with cancers of the larynx,esophagus,orlungs.Cancerofthetongueandofthebonystructuresofthehardpalateorsinuses,forexample,mayprojectintothemouthormayburrowdeepintothesur-roundingtissues.

Causes and Symptoms of Oral Cancer

Severalfactorshavebeenidentifiedthatincreasetheriskofdevelopingoralcancer.Tobaccoandalcoholusearetheleading factors, with each increasing the risk sixfold.Tobaccouseincludescigarettes,cigars,pipes,andchewingtobacco. Oral cancer affects men at twice the rate ofwomen,probablybecausemenhavegenerallybeenmorelikelytousetobaccoandalcohol.VitaminAdeficiencyisalsoariskfactor,andsomestrainsofhumanpapillomaviruscaninfectthemouthandmayincreaseriskoforalcancer.Exposuretoultravioletradiationfromthesunisresponsibleforsomecancersofthelips.

149


Symptomsoforalcancervarydependingontheloca-tion of the cancer. The most common symptom is amouth sore that does not heal. Some early visual signsincludewhiteorredpatchesinthemouth.Whitepatches(leukoplakia) progress to cancer in about 5 percent ofcases.The red patches (erythroplakia) bleed easily, androughlyhalfofthembecomecancerous.Othersymptomsoforalororopharyngealcancerincludelumpsorswellinginthecheek,neck,orjaw,difficultyswallowingormovingthetongueor jaw,andpaininthe jaworteeth.Virtuallyanytypeofcontinuingmouthpainmayindicateoralcancerandshouldbeinvestigatedbyaphysician.

Diagnosis of Oral Cancer

Once cancer is suspected, a thorough examination isconducted to determine its type and stage. Suspected

Detail of a person’s mouth with leukoplakia, a precancerous lesion that devel-ops on the tongue, gums, or the inside of the cheek. It is caused by chronic irritation, such as smoking. AmericanCancerSociety/GettyImages

150


tumoursareanalyzedbybiopsy,andthemouth,pharynx,andlarynxareexaminedvisuallywithsmallmirrorsoralaryngoscope—a flexible tube that contains a light andlensattheend.Insomecasesamoreextensiveexamina-tionoftheheadandneckmaybeconductedundergeneralanesthesia. Several imaging methods may also be used,such as chest and head X-rays, computed tomography(CT)scans,ormagneticresonanceimaging(MRI).Aswal-loweddoseofbariummayberequiredbeforeadministeringX-raysinordertoprovidebetterimagecontrast.

Onceoralcancerhasbeendiagnosed,itsstageisdeter-minedtoindicatehowfarthecancerhasprogressed.Stage0oropharyngealcancerisconfinedtotheepithelialcellsthatlinetheoralcavityorpharynxandissometimescalledcarcinomainsitu.StageIandIIcancersarelessthan2cm(about3/4ofaninch)andbetween2and4cm,respectively,and have not spread to nearby lymph nodes. Stage IIItumours are either larger than 4 cm (1.5 inches) or aresmallercancersthathavespreadtoonelymphnodeonthesame side of the neck as the tumour. Stage IV tumourshavespreadtootherregionsoftheneck,thelymphnodes,orotherorgansinthebody.Survivalisconsiderablyhigherwhenthecancer isdetectedearlybutvery lowoncethecancerhasspreadtodistantorgans.

Treatment and Prevention of Oral Cancer

Likemostcancers,oralandoropharyngealcancerscanbetreatedwithsurgery,radiation,orchemotherapy.Surgeryisoftenthefirstmodeoftreatment.Inordertominimizetissueloss,superficialcancersofthelipmaybeshavedoffa layeratatimeuntilnocancerisdetected.Smallearly-stage tumours can be removed along with somesurroundingtissuewithminimalsideeffects.Ifthecancerhasspreadintothesurroundingbone,partorallofthejawmay have to be removed (mandible resection) or a

151


maxillectomyperformedtoremovethehardpalate.Bothof these procedures require subsequent reconstructivesurgery.Ifthecancerhasspreadintothelymphnodesoftheneck,thesenodeswillalsoberemoved.

Oralandoropharyngealcancersmaybetreatedwithradiation, using either external beams or surgicallyimplanted radioactive pellets. For oral cancer, externalradiationisthemostcommonapproach.Radiationisusuallyemployed in conjunction with surgery to destroy smallamountsofremainingcanceroustissue.

Oral cancer is almost completely preventable if thekeyriskfactorsofsmokingandalcoholconsumptionareavoided.AhealthydietcontainingsufficientvitaminAisalso recommended. Regular dental examinations maydetectoralcancerearly.Denturesshouldberemovedandcleanedatnighttoavoidtrappingcancer-causingagentsagainstthegums.

Dental Caries

Dental caries, also known as cavities or tooth decay, arelocalized diseases of the teeth. Caries result from thedestructionofthedentalenamelandunderlyingtissuesbyorganicacids.Theseacidsareformedbybacteriagrowingin debris and food accumulated in pockets between thebase of the teeth and the gum margins. Decay typicallybegins at the surface of the tooth and may progressthrough the dentine into the pulp cavity. The proteinstructureofthedentineisdestroyedbyenzymaticactionand bacterial invasion. This periodontal infection ulti-matelyleadstotheinvolvementandinflammationofthetooth’snerve,causingtoothache.

An abscess may form at the apex of the tooth andextend into the jawbone, causing osteomyelitis (inflam-mation of the bone), or into the soft tissues around the

152


rootsoftheteeth,causingcellulitis(inflammationofthesoft tissues).Halitosis (foulbreath) isduetotherottingdebrisinthepocketsunderthegummargins.Eventuallytheteethloosenandfalloutorneedtobeextracted.

Malnutrition,alcoholism,andmalabsorptionofvitaminD (rickets)orofproteins (as inceliacdisease), initiateoraggravate caries. Structural defects of the teeth andhereditycanalsoaffectone’schancesofdevelopingcaries.

There are an estimated 600 species of bacteria thatnormallyinhabitthehumanoralcavity.Thus,thebacte-rialcompositionoftheoralcavityissuspectedtoplayanimportantroleinthedevelopmentofcariesandgumdisease.In 2008 the discovery of a bacterial species namedPrevotella histicola, which is present in both healthy andcancerousoraltissuesandwhichgeneratesacidicmetabo-lites,suchasaceticacidandlacticacid,thatcandamagetoothenamel,underlinedtheneedtobetterunderstandoralmicroorganismsandtheirroleintoothdecay.

Treatment of caries includes attention to diet, oftenentailingtheavoidanceofsweets,andcareoftheteethbycleansing and by restoring teeth that have cavities.Theadditionofsodiumfluoridetofluoride-deficientmunicipalwatersupplieshasbeenobservedtoreducetheincidenceofcariesbyasmuchas65percent.Thesealingofthebit-ingsurfacesofteethwithadhesiveplasticshasalsogreatlyreducedtheincidenceofcaries.Todayscientistsareinves-tigatingwaystoinfluenceoralterthebacterialcompositionof the oral cavity for the prevention and treatment oftoothdecay.

Pharyngitis

Pharyngitisisaninflammatoryillnessofthemucousmem-branesandunderlyingstructuresof thethroat (pharynx).

153


Inflammation usually involves the nasopharynx, uvula,softpalate,andtonsils.Pharyngitisisverycommon,espe-ciallyinyoungpersons.

Pharyngitis can be caused by bacteria, viruses, myco-plasmas,fungi,andparasitesandbyrecognizeddiseasesofuncertaincauses.InfectionbyStreptococcusbacteriamaybeacomplicationarisingfromacommoncold.Thesymptomsof streptococcal pharyngitis (commonly known as strepthroat)aregenerallyrednessandswellingofthethroat,apustulantfluidonthetonsilsordischargedfromthemouth,extremely sore throat that is felt during swallowing,swellingoflymphnodes,andaslightfever.Sometimesinchildrenthereareabdominalpain,nausea,headache,andirritability.

Diagnosisisestablishedbyadetailedmedicalhistoryand by physical examination; the cause of pharyngealinflammationcanbedeterminedbythroatculture.Usuallyonlythesymptomscanbetreated—withthroatlozengesto control sore throat and acetaminophen or aspirin tocontrol fever. If a diagnosis of streptococcal infection isestablished by culture, appropriate antibiotic therapy,usuallywithpenicillin,isinstituted.Withinapproximatelythreedaysthefeverleaves.Theothersymptomsmaypersistforanothertwotothreedays.

Viralpharyngitisinfectionsalsooccur.Theycanproduceraised whitish to yellow lesions in the pharynx that aresurrounded by reddened tissue. Lymphatic tissue in theupperpartofthepharynx,aswellastissuesattherootofthe tongue, may be similarly involved.Viral pharyngitiscausesfever,headache,andsorethroatthatlastsfor4to14days. A number of other infectious diseases may causepharyngitis, including tuberculosis, syphilis, diphtheria,and meningitis. In diphtheritic pharyngitis, the membra-nous exudate is more diffuse than in other types of

154


pharyngitis,itistougher,anditextendsoveramuchlargerpartofthemucousmembraneofthemouthandnose.

One of the complications of pharyngitis may be aperitonsillar abscess, also called quinsy, adjacent to onetonsil.Thisappearsasanextremelypainfulbulgingofthemucosa in the area. Surgical incision and draining aresometimesnecessaryifantibioticsarenotgivenpromptly.

Congenital Defects

Thereareseveralcongenitaldisorders(conditionsarisingduringfetaldevelopment)thatcanaffectthestructuresoftheoralcavity.Cleft lip,alsoknownasharelip, isacon-genitaldeformityinwhichthecentraltomediallipfailstofuseproperly,resultinginafissureinthelipbeneaththenostrils.Otherdisordersarerelatedtoanabnormalpositionoftheteethandthejaws,resultingininefficientchewing,andtotheabsenceofoneormoreofthesalivaryglands,which may lessen the amount and quality of saliva thatthey produce. Neurological defects that provide inade-quate stimulation to the muscles of the tongue and thepharynxcanseriouslyimpairchewingandevenswallowing.Sensory-innervation defects may not allow the usualreflexes to mesh smoothly, or they may permit harmfulingestantstopassbyundetected.

diSeaSeS of the Salivary glandS

Thesecretionofsalivaismarkedlydiminishedinstatesofanxietyanddepression.Theconsequentdrymouthinter-fereswithspeech,whichbecomesthickandindistinct.Intheabsenceofthecleansingactionofsaliva,fooddebrispersistsinthemouthandstagnates,especiallyaroundthebaseoftheteeth.Thedebrisiscolonizedbybacteriaand

155


causes foul breath (halitosis). In the absence of saliva,swallowing is impededbythe lackof lubricationforthechewing of food that is necessary to form a bolus.Theconditionisaggravatedinstatesofanxietyanddepressionwhendrugsthathaveananticholinergic-likeactivity(suchas amitriptyline) are prescribed, because they furtherdepresstheproductionofsaliva.

Thesalivaryglandsareseverelydamagedandatrophyin a number of autoimmune disorders such as Sjögrendisease and systemic lupus erythematosus. The damageoccurs partly by the formation of immune complexes(antigen-antibodyassociations),whichareprecipitatedinthe gland and initiate the destruction. In these circum-stances,thelossofsalivaispermanent.Somesymptomaticreliefisobtainedbytheuseof“artificialsaliva,”methylcel-lulose mouthwashes containing herbal oils such aspeppermint.As some of the salivary glands retain theirfunction,theymaybestimulatedbychewinggumandbya parasympathomimetic agent such as bethanecol. Theproductionofsalivamaybealsoimpairedbyinfiltrationofthesalivaryglandsbypathologicallymphocytes,suchasinleukemiasandlymphomas.Intheearlystagesofthesediseases,theglandsswellandbecomepainful.

Excessiveproductionofsalivamaybeapparentincon-ditions interfering with swallowing, as in Parkinsondisease, or in pseudobulbar paralysis from blockage ofsmallarteriestothemidbrainregions.Truesalivaryhyper-secretionisseeninpoisoningduetoleadormercuryusedincertainindustrialprocessesandasasecondaryresponseto painful conditions in the mouth, such as aphthousstomatitis(certainulcersoftheoralmucosa)andadvanceddentalcaries.

Acuteandpainfulswellingofsalivaryglandsdevelopswhensalivarysecretionisstimulatedbythesight,smell,

156


and taste of food, but saliva is prohibited from flowingthrough an obstructed salivary duct. Swelling and painsubside between meals. Diagnosis can be confirmed byX-ray. Persistent swellings may be due to infiltration bybenignormalignanttumoursortoinfiltrationbyabnormalwhitebloodcells,asinleukemia.Themostcommoncauseofacutesalivaryswellingismumps.

diSeaSeS of the eSophaguS

Difficultyinswallowing(dysphagia)maybetheonlysymp-tomofadisorderoftheesophagus.Sometimesdysphagiaisaccompaniedbypain(odynophagia),orpainmayoccurspontaneously without swallowing being involved. Theesophagusdoesnothingtoalterthephysicalorchemicalcomposition of the material it receives, and it is poorlyequippedtorejectmaterialsthathavegotpasttheintricatesensorsofthemouthandthroat.Consequently,itisvulner-abletomucosalinjuryfromingestantsaswellastomaterialsthat reflux into its lower segment from the stomach.Althoughtheesophagealmusclecoatsarethick,theesoph-agusisnotprotectedwithacoveringofserousmembrane,asareneighbouringorgansinthechest.

Congenital Defects

Congenitaldefectsoftheesophagusaremostoftenseenininfancy,primarilyasafailuretodevelopnormalpassage-ways.Infantsbornwithopeningsbetweentheesophagusand trachea cannot survive without early surgery. Thelowerendoftheesophagusissubjecttovariousdevelop-mentalabnormalitiesthatshortentheorgansothatthestomach is pulled up into the thoracic cavity.Abnormalities of the diaphragm may contribute to asimilaroutcome.

157


Inflammatory Disorders

Inflammatory disorders of the esophagus result from avarietyofcauses,fromtheingestionofnoxiousmaterials,the lodgment of foreign bodies, to a complex of eventsassociatedwithrefluxofgastriccontentsfromthestom-ach into the lower esophagus. Inflammation resultingfromsurfaceinjurybycausticsubstancesiscalledcorrosiveesophagitis.The term “peptic esophagitis” is applied toinflammation that is associated with reflux and involvesboththemucousmembraneandthesubmucosallayer.Anumberofotherdiseasesmaycauseinflammationoftheesophagus—forexample,scleroderma,adiseaseinwhichthesmoothmuscleoftheorgandegeneratesandiseven-tually replaced by fibrous tissue, and generalizedcandidiasis, a disease in which the esophagus is ofteninvolvedinasepticprocesscharacterizedbymanysmallabscessesandulcerations.

Strictures

Fibrous (scar) tissue contracts over time. Consequently,when fibrous tissue develops around a tube, as in theesophagus, inresponsetoinflammation,thecontractingscarnarrowsthelumen,causingastricture,andmayeven-tually obstruct it completely. Strictures are readilydiagnosedbyX-rayoresophagoscope.

Dysphagia

Dysphagia is characterized by difficulty in swallowingcausedbylesions,failuretotransportabolusthroughtheesophagus, or mechanical obstruction by stricture,tumours,or foreignbodies in theesophagus.Inpersonsover 50 years of age, the sensation of food “sticking” is

158


more often caused by a disease process, frequently atumour,involvingthewalloftheesophagusandprovidinga mechanical rather than a functional obstacle to thepassage of food.The neural arc of swallowing involvesthe medulla of the brain stem, the vagus (10th cranial)nerves, and the glossopharyngeal, trigeminal, and facialnerves. Consequently, dysphagia may also result frominterferencewiththefunctionofanypartofthispathway.Thus, it occurs commonly, but usually transiently, instrokes.Dysphagiamaybeprominentindegenerativedis-eases of the central nervous system, especially of theganglia at the baseof the brain. In these circumstances,thebehaviourofthesmoothmuscleofthepharynxandtheupperesophagealsphincterisdisturbed.

Mostindividualscanlocatethesiteofdysphagiaandthedistributionofthepainwithaccuracy.Asenseoffoodstickingorofpainonswallowing,however,maybefelttobeinthethroatoruppersternumwhentheobstructionordiseaseis infactatthelowerendoftheesophagus.Thesensationofa“lumpinthethroat,”or“globushystericus,”isnotconnectedwitheatingorswallowing.Thesensationmayresultfromgastroesophagealrefluxorfromdryingofthe throat associated with anxiety or grief.Treatment isdirectedtowardthecauseofthedisorder.

Esophageal Pain

Thenervesconveyingthesenseofpainfromtheesophaguspass through the sympathetic system in the same spinalcordsegmentsasthosethatconveypainsensationsfromthemuscleandtissuecoveringsoftheheart.Asaresult,episodesofpainarisingfromtheesophagusasaresultofmusclespasmortransientobstructionbyamedicinetabletor other object may be experienced in the chest and

159


posteriorthoraxandradiatetothearms.Thispainthusmimics pain of cardiac origin (angina).The pain due totransientobstructionmaybefeltnotonlyinthechestbutalso,throughradiationtotheback,betweentheshoulderblades.It isverysimilar topain fromgallstones;attackslast10to30minutes.

Inmiddle-agedandelderlypersons,spontaneousanddiffuse spasm of the smooth muscle of the esophaguscauses considerable discomfort as well as episodes ofdysphagia.Alternativenamesfortheconditionare“cork-screw” esophagus and diffuse spasm of the esophagus.TheappearanceoftheesophagusseenonanX-rayscreenwhile a barium bolus is swallowed resembles that of theoutlineofacorkscrewbecauseofthemultiplesynchro-nized contractions at different levels of the spirallyarranged smooth muscle.The pain of esophageal spasmmayberelievedbymedicationsthatrelievecardiacangina,especiallynitroglycerinornifedipine.

Disorders of Esophageal Motility

Disorders of the motility of the esophagus tend to beeither caused by or aggravated during times of stress.Eating rapidly is another trigger, as this demands moreprecise and rapid changes in muscle activity than eatingslowly.Achalasia,formerlycalledcardiospasm,isaprimarydisturbanceintheperistalticactionoftheesophagusthatresultsinfailuretoemptytheorganofitscontents.Thelower sphincteric portion of the esophagus does notreceive its normal signal to relax and, over time, maybecomehypertonic,resistingstretching.Acycleoccursinwhichthemainportionoftheesophagusslowlybecomesdistended,holdingacolumnoffluidandfoodthatitcannotpropel downward to a lower esophageal sphincter that

160


stays closed because of a failure in its neural system. Inmost persons with this disorder, there is a shortage ordiseaseofganglioncellsofthemyentericplexus(Auerbachplexus),oradiseaseofthenetworkofnerveswithinthemusclesoftheesophagus,sothatcoordinatedperistalsisbecomesimpossible.

InChagasdisease,parasitescalledtrypanosomesinvadetheneuraltissueanddirectlydestroyganglioncells.Theseorganisms are not present in the temperate zones of theworld,however,andthereasonforganglioncelldegenera-tioninachalasiaisgenerallyunknown.Effectivetreatmentisachievedbydestroyingtheabilityoftheloweresophagealsphincteroftheesophagustocontract.Thismaybedonebyforcibledilatation,usingaballoon,oftheesophagusintheareathatistonicallycontracted.Theobjectiveis to rupture the circular muscle at the site, and this isgenerallyachievedwithoneortwodilatations.Ifthisfailstoovercomethecontractionorifthecontractionrecurs,surgeryisrequiredthatinvolvesopeningtheabdomenandcutting throughthecircularmuscles fromtheoutsideof theesophagus.The disadvantage of both methods oftreatment is that the anti-reflux mechanism is therebydestroyed.Consequently,ifprecautionsarenottaken,theindividual may lose the symptoms and risks of achalasiabutmaydevelopthesymptomsandsignsofrefluxpepticesophagitis.

Gastroesophageal Reflux Disease

Inhealthyindividuals,refluxofgastriccontentsintotheesophagus occurs occasionally. This causes the burningsensationbehindthesternumthatisknownasheartburn.Some of the refluxed material may reach the pharynxwhereitalsomaybefeltasaburningsensation.Refluxis

161


mostlikelytooccurafterlargemeals,especiallyifphysicalactivity,includingbending,stooping,orlifting,isinvolved.In these circumstances, the esophagus responds withperistalticwavesthatsweepthegastriccontentsbackintothestomach,withreliefoftheheartburn.

Persistentrefluxsymptomsareinvariablyduetoinad-equatefunctioningoftheanatomicalcomponents,suchastheloweresophagealsphincter,whichkeepthecontentsofthestomachbelowthediaphragm,delayedesophagealclearanceoftherefluxedmaterial,anddelayedemptyingofthestomach.Thedisordercanalsobecausedbyobesity.Excessivefatonthetrunkisalmostalwaysaccompaniedbylargedepositsoffatwithintheabdomen,especiallyinthemesentery(thecurtainlikestructureonwhichmostof the intestine is hung). Consequently, when intra-abdominal pressure is increased, such as in physicalactivity,thereisinsufficientroomwithintheabdomentoaccommodate the displacement of the organs, and theresultingpressureforcesthestomachupward.

Theweakpointisthecentreofthediaphragmattheopening (hiatus) through which the esophagus passes tojoin the stomach. The upper portion of the stomach ispushedthroughthehiatus,andthedistortionofthepositionof the organs brings about impaired functioning of theanti-reflux mechanisms. In the early stages the stomachmayslidebackintotheabdomenwhentheincreaseintheintra-abdominalpressureeases,buteventually,ifthecir-cumstancesareunchanged,theupperpartremainsabovethediaphragm.

A common contributory cause of gastroesophagealreflux inwomen ispregnancy.As theuteruscontainingthedevelopingfetuscomestooccupyalargepartoftheabdomen, the effect is the same as in obesity. Becausegravity is the only force that keeps the gastric contents

162


within the stomach, if a hernia develops, the reflux andthesymptomsfromitwillpromptlyoccurwhentheindi-vidualliesdown.Persistingrefluxofgastriccontentswithacidanddigestingenzymesleadstochemicalinflammationof the lining of the esophagus and ultimately to pepticulceration. If inadequately treated, the process leads tosubmucosal fibrosis and stricturing, and, besides thesymptoms of heartburn and regurgitation, the patientexperiencespainoneatingandswallowing.

The treatment of peptic reflux esophagitis includeslosingweight,avoidingacidicandfattyfoodsandbeverages,remaininguprightfortwotothreehoursaftermeals,givingupsmoking,andraisingtheheadofthebedhighenoughtodiscouragenocturnalgastroesophagealreflux.Antacidsareeffective,asaremedicationsthatreducethesecretionofacidbythestomach,suchashistaminereceptorantag-onists and proton pump inhibitors. If a stricture hasformed,itcanbedilatedeasily.Ifthedisorderisnotover-comewiththeseconservativemeasures,surgicalrepairisperformedthrougheitherthechestortheabdomen.

Someindividualswithseverepepticrefluxesophagitisdevelop Barrett esophagus, a condition in which thedamagedliningoftheesophagusisrelinedwithcolumnarcells.Thesecellsaresimilartothoseliningtheupperpartofthestomachandarenottheusualsquamouscellsthatlinetheesophagealmucosa.Insomepersonsinwhomthistransformationoccurs,acarcinomadevelopssome10to20yearslater.Thedecisionastothetreatmentofahiatalherniabyconservativemeansorbysurgeryisinfluencedbysuchfactorsasage,occupation,andthelikelihoodofcompliancewithastrictregimen.

Thereisamuchlesscommonformofhiatalhernia,calledaparaesophagealhernia,inwhichthegreatercur-vatureofthestomachispushedupintothethoraxwhile

163


the esophagogastric junction remains intact below thediaphragm. Such individuals experience dysphagiacaused by compression of the lower esophagus by thepart of the stomach that has rolled up against it.Thisrarerformofherniaismoredangerous,oftenbeingcom-plicatedbyhemorrhageorulceration,andrequiresreliefbysurgery.

Diverticula of the Esophagus

Pouches in the walls of the structures in the digestivesystem that occur wherever weak spots exist betweenadjacentmusclelayersarecalleddiverticula.Intheupperesophagus,diverticulamayoccur intheareawherethestriatedconstrictormusclesofthepharynxmergewiththesmoothmuscleoftheesophagusjustbelowthelar-ynx.Somemalesover50yearsofageshowprotrusionofasmallsacofpharyngealmucousmembranethroughthespace between these muscles.As aging continues, or ifthere is motor disturbance in the area, this sac maybecomedistendedandmayfillwithfoodorsaliva.Itusuallyprojectstotheleftofthemidline,anditspresencemaybecome known by the bubbling and crunching soundsproducedduringeating.Oftenthepatientcanfeelitintheleftsideoftheneckasalump,whichcanbereducedbypressureofthefinger.Sometimesthesacmaygetsolarge that it compresses the esophagus adjacent to it,producing a true obstruction. Treatment is by surgery.Small diverticula just above the diaphragm sometimesarefoundaftertheintroductionofsurgicalinstrumentsintotheesophagus.

Boerhaavesyndromeisararespontaneousrupturetothe esophagus. It can occur in patients who have beenvomiting or retching and in debilitated elderly persons

164


with chronic lung disease. Emergency surgical repair ofthe perforation is required.A rupture of this type con-finedtothemucosaonlyatthejunctionoftheliningsofthe esophagus and stomach is called a Mallory-Weisslesion.At this site, the mucosa is firmly tethered to theunderlyingstructuresand,whenrepeatedretchingoccurs,thispartoftheliningisunabletoslideandsuffersatear.Thetearleadstoimmediatepainbeneaththelowerendofthesternumandbleedingthat isoftensevereenoughtorequire a transfusion. The circumstances preceding theeventarecommonlytheconsumptionofalargequantityofalcoholfollowedbyeatingandthenvomiting.Thelarg-est group of individuals affected are alcoholic men.Diagnosis is determined with an endoscope (a flexible,lens-containing tube). Most tears spontaneously stopbleeding and heal over the course of some days withouttreatment.Iftransfusiondoesnotcorrectbloodloss,sur-gicalsutureofthetearmaybenecessary.Analternativetosurgery is the use of the drug vasopressin, which shutsdown the blood vessels that supply the mucosa in theregionofthetear.

Esophageal Cancer

Esophageal cancer is a disease characterized by theabnormal growth of cells in the esophagus. Esophagealtumoursmaybebenignormalignant.Generally,benigntumoursoriginateinthesubmucosaltissuesandprincipallyare leiomyomas (tumours composed of smooth muscletissue)orlipomas(tumourscomposedofadipose,orfat,tissues).

Malignanttumoursareeitherepidermalcancers(squa-mouscellcarcinomas),madeupofunorganizedaggregatesofsurface(squamous)cells,oradenocarcinomas,inwhichthere are glandlike formations. Approximately half of

165


esophagealcancersaresquamouscellcarcinomas.Cancersarisingfromsquamoustissuesarefoundatalllevelsoftheesophagus,whereasadenocarcinomasaremorecommonatthelowerendwhereanumberofglandsofgastricoriginarenormallypresent.

Worldwide, men are more than twice as likely todevelop esophageal cancer than women. In the UnitedStates,blacksarethreetimesmore likelythanwhitestodevelop the disease.Tumours of the esophagus seem tovary greatly in their worldwide distribution. In NorthChina,forexample,theincidenceofesophagealcancerinmenis30timesthatofwhitemenintheUnitedStatesand8timesthatofblackmen.

Causes and Symptoms of Esophageal Cancer

The exact causes of esophageal cancer are not known.However, several risk factors have been identified thatincrease the likelihood of developing esophageal cancer.Somefactors,suchasage,sex,andrace,areimpossibletocontrol. However, tobacco and alcohol use increase risk,andthesebehaviourscanbecontrolled.Peoplewhoacci-dentlyswallowedlyeaschildrenalsohaveahigherriskofesophagealcancerasadults.Long-termproblemswithacidrefluxmayleadtoBarrettesophagus,inwhichthenormalsquamous cells that line the esophagus are replaced withglandularcells.Thiscondition increasescancerrisk.Raredisorderssuchastylosisandachalasiaarealsoriskfactors.Women may be predisposed by long-standing iron defi-ciency,orPlummer-Vinson(Paterson-Kelly)syndrome.

Dysphagiaisthefirstandmostprominentsymptom.Later swallowing becomes painful as surrounding struc-turesareinvolved.Hoarsenessindicatesthatthenervetothelarynxisaffected.Othersymptomsmayincludepainortightnessinthechest,unexplainedweightloss,orfre-quenthiccups.

166


Diagnosis of Esophageal Cancer

Esophagealcancersareusuallydiagnosedoncesymptomshave appeared, but by this time the cancer has usuallydevelopedtoarelativelyadvancedstage.ThediagnosisissuggestedbyX-ray,althoughseveralotherimagingmethodsmay be employed as well, including CT scans or ultra-sound.Thereisnodefinitivelaboratorytestforesophagealcancer.However,diagnosiscanbereinforcedbyremovingquantities of cells with a nylon brush for examinationunderamicroscope(exfoliativecytology).Indeed,endos-copywithmultiplebiopsiesfromtheareaofabnormalityoftenconfirmsdiagnosis.

Onceesophagealcancerhasbeendiagnosed,itsstageisdeterminedtoindicatehowfarthecancerhasprogressed.Stage0esophagealcancerisalsocalledcarcinomainsituandisconfinedtotheinnerlayerofepithelialcellsliningtheesophagus.StageIcancershavespreadintothecon-nective tissue layer below the epithelium but have notinvaded the underlying muscle layer. Stage II cancerseitherhavespreadthroughthemusclelayertotheouterboundariesoftheesophagusorhavespreadonlyintothemusclelayerbuthavereachednearbylymphnodes.StageIIIesophagealcancershavespreadthroughtheesophagealwall to the lymph nodes or other local tissues. Stage IVcancers have metastasized, or spread, to distant organssuchasthestomach,liver,bones,orbrain.

Thesurvivalrateforesophagealcanceris lowerthanfor many other cancers. When the cancer is detectedbefore it has invaded the underlying tissue layers of theesophagus, five-year survival is high, but fewer than 25percentofesophagealcancersarediagnosedatthisstage.Ifthecancerhasmovedtothetissueimmediatelyunderlyingthemucosalsurface,five-yearsurvivalisreducedtoabout

167


50percent,andtheratedropssignificantlyoncethecancerhasmovedfromtheesophagustonearbylymphnodesorothertissues.Oncethecancerhasspreadtodistanttissuesinthebody,five-yearsurvivalisextremelylow.

Treatment and Prevention of Esophageal Cancer

Esophagealcancersarebesttreatedsurgicallywhenpos-sible.Ifthecancerisconfinedtotheupperregionoftheesophagus,anesophagectomymaybedonetoremovethecancerousportion,alongwithnearbylymphnodes,andtoreconnect the remaining esophagus to the stomach. Forcancers of the lower esophagus, it may be necessary toperform an esophagogastrectomy, in which a portion ofthe esophagus is removed along with a portion of thestomach.Thestomachisthenreattacheddirectlytotheremainingesophagus,orasegmentofthecolonisusedtolinkthestomachandesophagus.Bothofthesesurgeriesare difficult and often result in serious complications.Other,less-drasticsurgeriesmaybeusedtorelievesymp-toms, especially when surgical cure is not possible. Inadvancedcases,atubemaybeinsertedintotheesophagustokeepitopen.Wherethechannel isgreatlynarrowed,thesizeofthetumourcanbereducedbydestroyingthetissuewithlasers.

Radiationtherapyisusedtorelievesymptoms.Itisusedformalignanciesoftheupperesophagusandastreatmentfor those at the lower end.The side effects of radiationtreatmentincludevomiting,diarrhea,fatigue,andesopha-geal irritation. Chemotherapy is also used for someesophageal cancers in order to relieve symptoms. Sideeffectsofchemotherapyresemblethoseofradiationtherapy.Althoughneitherchemotherapynorradiationtherapyarecurative,theyplay importantcomplementaryroles intheoveralltreatmentofesophagealcancer,sincetheynotonly

168


relievesymptomsbutalsomaybeabletoshrinktumourspriortosurgery.Lesseningtheeffectsofthedisease,withrestoration of eating ability, is very important, becauseotherwisetheinabilitytoswallowevensalivaisdistressing,andstarvationmayresult.

Esophagealcancercannotbecompletelyprevented,butrisk can be lowered by reducing alcohol consumption andavoiding tobacco. Individuals who are at high risk shouldreceiveregularscreeninginordertoincreasetheprobabilityofearlydetection.Becausethereisnobloodtestavailableforesophageal cancer, screening requires regular biopsies andviewingoftheesophaguswithanendoscope.

diSeaSeS of the StoMach

Diseases that affect the stomach can hinder the break-down of food and the absorption of nutrients. Manydisorders of the stomach involve abnormalities of acidsecretion and tend to be painful and distressing to thepatient.Amongthemostcommonlyoccurringconditionsthataffectthestomachareulcer,gastritis,andcancer.

Indigestion

Indigestion, also called dyspepsia, is any or all of theunpleasant symptoms that are associated with the mal-functioning of the digestive system. Indigestion may becaused by a disease, but it primarily occurs because ofstressorimpropereatinghabits,smoking,drinkingexcessivequantitiesofcoffeeoralcohol,orhypersensitivitytopar-ticularfoods.

Any disorder that affects the coordination of thestomachmusclesiscapableofproducingsymptomsrangingfrom those that are mildly unpleasant to others that arelife-threatening.Symptomsincludeabdominaldiscomfort,

169


belching, flatulence, anorexia, nausea, vomiting, diarrhea,constipation,andheartburn.Anorexiaandnauseaseemtobe mediated through the central nervous system, withreflexinputfromnerveendingsinthestomachandduo-denum.Sometimestheentiredurationofanausea-vomitingepisode is so short that it appears to be vomiting alone,obscuringthepresenceofnausea.Thisischaracteristicallynoted in persons with primary diseases of the brain,especiallythosewithtumoursormeningitis inwhichthecerebrospinal fluid is under increased pressure. In manydiseases,vomitingmaynotbeprecededbynauseaatall,and in others there may be a long time lag between thetwo. Seasickness is the best-known example of thisrelationship.

The intrinsic muscles of the stomach are innervatedby branches of the vagus nerves, which travel along theesophagus from their point of emergence in the brainstem.Gastricretentionmayresultfromthedegenerationof these nerves that can result from diabetes mellitus.Obstructionduetoscarringintheareaofthegastricoutlet,or to tumours encroaching on the lumen, causes thestomachtofillupwith itsownsecretionsaswellaswithpartially digested food. In these circumstances, vomitingleads to dehydration and to electrolyte losses, whichthreatenlifeifnotcorrected.Theingestionofsolublealkaliinthissituationmayaggravatethedisturbanceintheacid-base balance of the body. Bulimia, a nervous disordercharacterized by compulsive eating followed by vomitingand purging, can cause severe dehydration and even arupturedstomach,anditcanprovefatal.

Ulcerative Diseases

Ulcersareproducedwhenexternalfactorsreducetheabilityofthemucosalliningtoresisttheacidiceffectsofgastric

170


juice.Theareaofthestomach inwhichacidandpepsinaresecretedhasthehighestresistancetopepticulcer.Themucosa elsewhere is less well protected, and its break-downmayleadtoulceration.Ifthelesionisconfinedtothesuperficiallayersofthemucosa,itiscalledanerosion.If itextendsthroughtheintrinsic layerofmuscleofthemucosaintothetissuesbelow,itisknownasanulcer.

Erosionsandulcerscanbeacuteorchronicaccordingto how readily they heal. Infection with the bacteriumHelicobacter pyloriandlong-termuseofnonsteroidalanti-inflammatorydrugs(NSAIDs)arethetwomajorcausesofulcers.Inspecialcircumstances,suchasthestateofshockproduced by large burns, intracranial surgery, coronaryocclusion,andsepticemia,acuteandrapidlypenetratingulcersmayoccur.

In theWestern world, duodenal ulcer is much morecommonthangastriculcer,occursmoreofteninmenthan

This illustration shows stages of a stomach ulcer, from erosion to a chronic ulcer. 3D4Medical.com/GettyImages

171


in women, and is aggravated by stress. In Japan gastriculcerismorecommonthanduodenalulcerandisthoughttoberelatedtotherawfishandaceticacidpicklesofthetraditionaldiet.Duodenalulcerismostcommonbetweenages25and35,whereasgastriculcerisuncommonbeforeage40andhasapeakfrequencybetweenages55and65.Genetic factors are also involved in the development ofulcers. Inheriting blood group O may render a personmore likely to develop duodenal ulceration. There arefamiliesinwhomthesecretionofpepsinogenIisexcessiveand renders them prone to duodenal ulcer since excessacid secretion is linked to excess secretion of thishormone.

Pain is the major symptom of duodenal ulcers. Thepainisaburningorgnawingsensationfeltinthemidupperabdomen.Ingastriculcer itcomesonsoonaftereating,whereasinduodenalulceritcomesonwhenthestomachisempty—oneandahalftotwohoursaftermealsandduringthenighthours.Intheearlystagesofthedisease,thepainiseasilyandimmediatelyrelievedbyantacidsand,induodenalulcer,bylightfood.

Gastric ulcers almost always recur in the same sitewithinthestomach,butduodenalulcersareoftenmultiple,and recurrence may be anywhere in the duodenal bulb.Furthermore,duodenalulcersareusuallyaccompaniedbyan inflammation affecting the whole bulb (duodenitis).Multiple erosions varying in size between 0.5 and 5 mm(0.02 and 0.2 inch) are frequently scattered over themucosa.With gastric ulcers the inflammation is usuallyconfinedtotheimmediatevicinityofthecraterand,asarule,isnotaccompaniedbyerosions.Theexceptionsaregastriculcersintheantrumandprepyloricareaassociatedwith the use and abuse of analgesics and NSAIDs forarthriticdisorders,inwhichmultipleerosionsarecommonlypresent.

172


Themostcommonsiteofgastriculcersishalfwayuptheinnercurvatureofthestomachatthejunctionofthelower one-third with the upper two-thirds of the organ.Thismaybebecausebloodflowtothissiteismoreeasilyreducedthanelsewhere.Chronicgastriculcersatthissiteare strongly associated with obstructive disease of theairways (chronic bronchitis and emphysema). Smokingimpairsthehealingofbothgastricandduodenalulcers.

InfectionwithH. pylori isthemostcommonbacte-rialinfectioninhumans.ThisbacteriaispervasiveintheThirdWorld,andintheUnitedStates,itaffectsaboutathird of the population.Among those who suffer frompepticulcers,asmanyas90percentofthosewithduodenalulcersand70percentwithgastriculcersarebelievedtobe infectedwithH. pylori.Thisbacteriumconvertstheabundant waste product urea into carbon dioxide andammonia.Theprocesscausesthemucosalliningtobreakdown.Initsweakenedconditiontheliningcannotwith-stand the corrosive effects of gastric acid, and an ulcercanform.

The complications of peptic ulcers are hemorrhage,perforation,andobstructionoftheoutletofthestomach(pyloricstenosis)byscarringoftheduodenalbulborofthepyloricchannel.Scarringoftenleadstoboutsofvomitingand accompanying malnutrition and requires surgery.Bleeding may be obscured because of oozing from theflooroftheulceranddetectableonlybylaboratorytestingofthefeces,orbleedingmaybebrisk,leadingtothepassageof tar-coloured stools (melena). Occasionally, when theulcererodesintoa largevessel,bleedingisexcessiveandlife-threatening.The mortality associated with bleeding ishighintheelderlybecauseofchronicchangesinthelungs,heart,andbloodvessels,whichreducescardiorespiratoryreserves.Thisisfurtheraggravatedbysmoking.

173


Briskbleedingisusuallyaccompaniedbythevomitingof blood (hematemesis), which requires treatment bybloodtransfusion.Intheelderly,hardeningofthearteries(atherosclerosis) prevents the vessel from closing downaroundthelesion.Ifbleedingpersistsorrecurs,surgeryisnecessary.Ulcersthatpenetratethebackwallofthestomachor duodenum erode into the pancreas, and back painbecomesprominent.If theulcerpenetratestheanteriorwall,freeperforationintotheabdominalcavitymayoccur.This causes immediate, intense pain and shock, and theabdominal wall becomes rigid. In most instances thisrequires emergency surgery with drainage of theabdomen.

Surgery for chronic ulceration is used less frequentlysincetheintroductionofdrugsthatstopthesecretionofstomach acid. Histamine-receptor antagonists, such ascimetidine,ranitidine,andfamotidine,blocktheactionofhistamine on the acid-secreting parietal cells of thestomach. Proton pump inhibitors, such as omeprazole,lansoprazole,andrabeprozale,inhibittheATPaseenzymeinside the parietal cell and prevent acid secretion. MostpepticulcersnotcausedbyH. pyloriinfectionresultfromtheingestionoflargequantitiesofNSAIDs.WithdrawalofNSAID treatment usually allows the ulcer to heal.TreatmentforH. pylori–inducedulcersareantibioticsandaprotonpumpinhibitor.

Gastritis

Adiffuseinflammationofthestomachlining,gastritisisusuallyanacutedisordercausedbycontaminatedfood,byalcoholabuse,orbybacterial-orviral-inducedinflamma-tion of the gastrointestinal tract (gastroenteritis). Suchepisodesareshort-livedandrequirenospecifictreatment.

174


Painisgeneralizedintheupperabdomenandiscontinuous,butitprogressivelysubsidesovertwoorthreedays.

AspirinandNSAIDstakenforarthritiscauseerosionsintheantrumofthestomachandinsomeinstancescausebleedingandchroniculceration.InfectionbythebacteriaH. pyloriisalsoacommoncauseofchronicgastritis.Thisusuallyrespondstothewithdrawaloftheoffendingdrugsandtreatmentwiththesameagentsusedtotreatpepticulcersofthestomachandduodenum.

Anotherformofgastritis isgastricatrophy,inwhichthethicknessofthemucosaisdiminished.Gastricatrophyisoftentheculminationofdamagetothestomachovermanyyears.Diffusegastricatrophyleadstopartiallossoftheglandularandsecretingcellsthroughoutthestomachand may be associated with iron deficiency anemia.Atrophyofthemucosaconfinedtothebodyandfundicregionsofthestomachisseeninperniciousanemiaandisdue to the formation of antibodies to intrinsic factorsecretedbytheparietalcells.IntrinsicfactorisnecessarytotheabsorptionofvitaminB12.

Stomach Cancer

Stomach cancer, also called gastric cancer, is a diseasecharacterizedbytheabnormalgrowthofcellsinthestom-ach. The incidence of stomach cancer has decreaseddramatically since the early 20th century in countrieswhere refrigeration has replaced other methods of foodpreservation such as salting, smoking, and pickling.Stomach cancer rates remain high in countries wheretheseprocessesarestillusedextensively.

Causes and Symptoms of Stomach Cancer

Ninety-fivepercentofmalignantstomachcancersdevelopfromthecellsthatformtheinnermostlining,ormucosa,

175


ofthestomach.Thesetumoursarecalledadenocarcino-mas. Other stomach cancers can develop from thesurrounding immune cells, hormone-producing cells, orconnectivetissue.

Multipleriskfactorshavebeenidentifiedthatincreasea person’s probability of developing this cancer. Theseinclude a diet high in salted, smoked, or pickled foods,tobacco and alcohol use, or a family history of stomachcancer. Infection by the bacterium H. pylori, which cancausesignificantdamagetogastrictissuesandisacauseofpepticulcers,canalsoleadtostomachcancer.Otherfac-torsthatmayincreasetheriskofstomachcancertovaryingdegrees are previous stomach surgery, blood type A,advanced age (60–70 years), or chronic stomach inflam-mation.Malesdevelopstomachcanceratapproximatelytwicetherateoffemales.

RaredisorderssuchasperniciousanemiaorMenetrierdisease and congenital disorders that lead to increasedriskforcolorectalcancermayalsoincreasestomachcancerrisk.The symptoms of stomach cancer are prevalent inmanyother illnessesandmayincludeabdominalpainordiscomfort, unexplained weight loss, vomiting, poordigestion,orvisibleswellingintheabdomen.

Diagnosis of Stomach Cancer

Nospecificlaboratorytestforstomachcancerexists,andthediseaseisthereforeusuallydiagnosedthroughacombi-nationofvisualmeans.Aphysiciancaninspecttheliningofthestomachwithanendoscope.Theendoscopecanalsobeusedtotakesamplesfrompotentiallycanceroustissuesforbiopsy.Thesesamplesareexaminedunderamicroscopeforsignsofcancer.Anendoscopemayalsobemodifiedwithaspecialprobethatemitssoundwavesinthestomach,whichallowsthephysiciantocreateanimageofthestomachwall.X-rays are also employed, usually after the patient has

176


swallowedabariumcompoundthatcoatsthestomachandprovidesbetterimagecontrast.OtherimagingtechniquessuchasCTscansandMRIarealsoused,especiallywhenthecancerisbelievedtohavespread.

Oncestomachcancerhasbeendiagnosed,itsstageisdetermined.Thestageisanindicatorofhowfarthecan-cer has progressed. Staging for stomach cancer iscomplicatedandisbasedonacombinationofhowfarthecancer has grown through the stomach wall and on thenumberoflymphnodesaffected,ifany.Stage0stomachcancerisalsocalledcarcinomainsituandisconfinedtothe mucosal lining of the stomach. Stage I and stage IIcancershavespreadintotheconnectivetissueormusclelayers that underlie the mucosa, but they have reachedfewerthansixnearbylymphnodes.StageIIIandIVcan-cers are more advanced and may have metastasized todistanttissues.

Averyhighpercentageofindividualssurvivestomachcancerforatleastfiveyearsifthecancerisdiagnosedveryearly,andmanyofthemgoontolivelong,healthylives.Unfortunately,onlyasmallpercentageofstomachcancersare identified and treated at such an early stage.At thetime when most lower-stomach cancers are diagnosed,roughly half the patients survive for at least five years.Cancersoftheupperstomachhavealowersurvivalrate,andifthecancerhasspreadtodistanttissuesinthebody,thesurvivalrateisextremelylow.

Treatment and Prevention of Stomach Cancer

Surgery is theonlymethodavailable forcuringstomachcancer,althoughradiationorchemotherapymaybeusedinconjunctionwithsurgeryortorelievesymptoms.Ifthecancerislocalized,thecancerousportionsofthestomachareremovedinaprocedurecalledapartialgastrectomy.In

177


some cases, the entire stomach must be removed alongwiththespleenandnearbylymphnodes.

Repair of the stomach generally requires permanentchanges in dietary habits and may demand intravenousadministrationofvitaminsupplements.Ifacancercannotbecured,surgerymaystillbeusedtorelievesymptomsordigestive discomfort. Radiation therapy is sometimesusedinconjunctionwithsurgerytodestroyanyremainingcancercells.Whenstomachcancerhasspreadtodistantorgans, chemotherapy may be required so that as manycancercellsaspossiblecanbesoughtoutanddestroyed.Both radiation therapy and chemotherapy may produceseveralsideeffectssuchasvomitinganddiarrhea.

Stomachcancercannotbecompletelyprevented,butpeoplecandecreasetheirriskofdiseasebyadoptingadietthatislowinsalted,smoked,andpickledfoodsandhighin fruits and vegetables. Elimination of tobacco use andreduction in alcohol consumption also help lower risk.ResearchhasindicatedthatprompttreatmentofH. pyloriinfectioncanreversegastrictissuedamage,therebyreducingstomachcancerrisk.

178

DISEASES OF THE INTESTINES

Diseasesthataffectthesmallandlargeintestinescanarise from a variety of causes and range from rela-

tivelyharmless,withverylittlepainandrequiringminimaltherapeutic intervention, to severe, causing acute orchronicpainandpotentiallynecessitatingtheremovalofa portion of the intestinal tract. Examples of commonconditions of the intestines include traveler’s diarrhea,parasiticinfection,andinflammation.Becausetheintes-tinesplayaprominentroleintheabsorptionofnutrientsduringthedigestiveprocess,manychronicdiseasesthatinvolvethelowerdigestivetractresultinsignsandsymptomsofmalnutrition.

diSeaSeS of the SMall inteStine

The duodenum is often involved in the diseases of itsneighbours, in particular the pancreas and the biliarytract.Primarycanceroftheduodenumisaninfrequentdisease.Benigntumours,particularlypolypsandcarci-noids,aremorefrequent.Cancersofthecommonbileductorofthepancreasmaymaketheirpresenceknownbyobstructionoftheduodenumandpain.Thesecan-cers often are diagnosed by upper intestinal X-raystudies,endoscopy,ultrasound,orCTscanning.Benignanomaliesoftheorgansofthisarea, likeanencirclingring of pancreas, may also encroach upon theduodenum.

IncountriesoftheMiddleandFarEast,whereparasitesare endemic, roundworms and tapeworms in particular

CHAPTER 7

179

7 Diseases of the Intestines 7

areoftenfoundanchoredintheduodenum.Ininflamma-tions of the pancreas, the motility of the neighbouringduodenumisoftenimpaired,andoccasionallyulcerationwith hemorrhage occurs. A protozoal parasite, Giardia lamblia,cancontaminatedrinkingwaterandisacommoncauseofdiarrheaand,ifunrecognized,malabsorption.

Alackofcoordinationoftheinnercircularandouterlongitudinalmuscularlayersoftheintestinalwallusuallyresults in an accumulation of excess contents in theintestinal lumen, with consequent distension.This dis-tensionmaycausepainandusuallyresultsinhyperactivecontractions of the normal segment next to the dis-tendedarea.Suchcontractionsmaybestrenuousenoughto produce severe, cramping pain. The most commoncauseofdisturbedmotilityinthesmallintestineisfoodthat contains an unsuitable additive, organism, orcomponent.

Traveler’s Diarrhea

Traveler’s diarrhea is the abnormally swift passage ofwaterywastematerialthroughtheintestines,withconse-quent discharge of loose feces. Traveler’s diarrhea isaccompaniedbycrampingandlastsafewdays.Itisalmostalwayscausedbytoxin-generatingEscherichia coli.Shigellainfectionmayoccursimultaneously,however,andvisitorsto countries where giardiasis is endemic may sufferinfection.

Contaminatedsaladsremainthemostcommoncauseoftraveler’sdiarrheaincountrieswheretheclimateishot.Such diarrhea generally disappears spontaneously withabstentionfromfoodaccompaniedbydrinkingofnon-alcoholic fluids. Mixtures of sodium and potassiumchloride, sodium bicarbonate, and glucose reconstitutedwithwaterareonemethodoftreatment.

180


Intestinal Obstruction

Intestinal obstruction is the functional or mechanicalblockage of the alimentary canal. Functional blockageoccurswhenthemusclesoftheintestinalwallfailtocon-tractnormallyinthewavelikesequence(peristalsis)thatpropelstheintestinalcontents.Mechanicalobstructionsincludeanarrowingofthechannel(stricture),adhesions,tumours,thepresenceofaforeignobject,pressurefromoutside,hernia,volvulus,andintussusception.Inaherniaaloopofintestineprotrudingfromtheabdomenmaybecompressed at the point where it passes through theabdominal wall.A volvulus is a twisting of the intestineuponitself,andanintussusceptionisthetelescopingofasectionofintestineintoanadjacentportion.

Thelossoffluidsandchemicalsthroughvomitingisfrequentwithobstructionsthatarelocatedhighintheintestinal canal. Obstructions of the lower reaches ofthesmallintestine(ileum)andofthelargeintestineareinaccessibletoevacuationbyvomiting.Insuchcases,theintestine above the obstruction becomes distended byaccumulatedmaterialandswallowedair.Thepressureintheintestinalchannelmaycompromisethebloodsupplyandcausedeathoftissueinthewallsoftheintestine.Thewallsmaybecomeabnormallypermeable,allowingnoxiousagentstoescapeintotheabdominalcavityandtheblood-stream. The symptoms and treatment of intestinalobstructiondependonthenatureoftheobstructionanditslocation.Surgeryisoftennecessary.

Irritable Bowel Syndrome

Thecommondisorderknownasirritablebowelsyndrome(IBS) isprobablyduetoadisturbanceofthemotilityof

181


thewholeintestinaltractortoincreasedsensitivityofthelargeintestine.Thesymptomsvaryfromwaterydiarrheatoconstipationandthepassageof stoolswithdifficulty.Whenthecolonisinvolved,anexcessofmucusisoftenobserved in the stools. Pain and cramping are mostoftenfeltinthelowerabdomen.Generalizedabdominaldiscomfort,sometimeswithnausea,mayfollowdefecationandmaylast15to30minutes.Manysufferersexperiencehigh levels of stress, and some have periods of anxietydepression.

Occasionallyirritablebowelsyndromemaybeduetoanallergytospecificfoods.IBSmaydevelopfollowinganinfectionsuchasbacillarydysentery,afterwhichthesmallintestineremainsirritableformanymonths.TreatmentofIBSincludeseliminationofstress,psychologicalsupport,change in lifestyle, and exercise. Possible aggravatingitemssuchaslactose-containingfoods,coffee,anddeep-fried dishes should be eliminated from the diet, anddietaryfibreshouldbeaddedtohelpinresolvingconsti-pation. When discomfort is prominent, antispasmodicagents that relax smooth muscle, such as dicyclominehydrochlorideormebeverine,maybeprescribed.Ifdiarrheadoes not respond to dietary measures, diphenoxylate orloperamidemayslowthemovementoftheintestinalcon-tents,therebyincreasingthepotentialforthereabsorptionofwater.

Malabsorption

Malabsorptionoccurswhenthesmallintestineisunabletotransportbroken-downproductsofdigestivematerialsfrom the lumen of the intestine into the lymphatics ormesentericveins,wheretheyaredistributedtotherestofthe body. Defects in transport occur either because the

182


absorptive cells of the intestine lack certain enzymes—whetherbycongenitaldefectorbyacquireddisease—orbecausethecellsarehinderedintheirworkbyotherdiseaseprocesses that infiltrate the tissues, disturb motility,permitbacteriatooverpopulatethebowel,orblockthepathways over which transport normally proceeds.Malabsorption also may result from pancreatitis, cysticfibrosis,obstructionofthebileductsorlymphaticvessels,orsurgicalremovalofasectionofthesmallintestine.

Diagnosis of malabsorption is determined primarilyfrom the patient’s history, physical examination, X-rayfilmsoftheabdomen,andstudyofthestoolsundercon-trolleddietaryconditions.Motoraspectsoftheintestinecanbestudiedusingavarietyoftechniques.Abiopsyofthe small intestine may also be performed to detectabnormalities.

Congenital Malformations

Meckeldiverticulumisacommoncongenitalmalformationthatoccurswhentheductleadingfromthenaveltothesmallintestineinthefetusfailstoatrophyandclose.Theductservesastheprincipalchannelfornourishmentfromthe mother.The diverticulum in the child or adult mayrangefromasmallopeningtoatubethatisafootormoreinlength.Itmaycontaincellsderivedfromthestomachglandsthatsecreteacidandpepsin.Ifsuchsecretionsspillonto intestinal mucosa, the mucosa ulcerates and oftenbleeds.Thus,apepticulcercandevelopatasitefarfromthestomachorduodenum.Thepepticulcergivesrisetopain,bleeding,orobstruction,anditisthemostcommoncause of bleeding from the lower intestine in children.Meckeldiverticulummustbetreatedsurgicallyifcompli-cationsdevelop.

183


Anothercongenitalprobleminthesmall intestine isthe presence of multiple diverticula, or outpouchings ofmucosaandserosa.Multiplediverticulaareseenusuallyinelderlypersons,althoughoccasionallyonemaybethesiteofacuteinflammationinayoungadult.Bacteriaflourishin these diverticula because the outpouchings have nomotoractivityandcannotemptythemselves.Thebacteriadeprivethebodyofnutrientsandmaycausediarrheaandserious malabsorption. The overgrowth of bacteria alsoupsetsthemotoractivityofthesmallintestine.Antibioticsmay control the condition in the elderly, but surgicalresectionofdiverticulaisnecessaryinyoungerpersons.

Bacterial Infections

Manybacterialorganismscaninfectthehumanbodyandcausedisease.SpeciesofSalmonellathatcausetyphoidandparatyphoidremainendemicscourgesintropicalcountriesand, together with Shigella, are occasional causes of epi-demics in health care institutions, especially among theelderly. Diagnosis is confirmed by the presence of theorganismsinastoolculture.Antibioticsandsolutionsrichin electrolytes are effective therapy. Treatment is withantibiotics. Periodic vaccination is advisable for theprotectionofindividualsexposedtoareaswheretyphoidandparatyphoidareendemic.

Cholera, caused by Vibrio cholerae, is endemic toSoutheastAsiaandperiodicallybecomespandemic(widelydistributedinmorethanonecountry).Theoralorintrave-nous administration of electrolyte solutions rich inpotassium has revolutionized the treatment of cholera,becausedeathsareduetoamassivedepletionofelectro-lytesandwater.ThetoxinproducedbyV. choleraeattachestotheintestinalcells,theenterocytes,whereitstimulates

184


themembraneenzymeadenylatecyclase.Thisinturninter-feres with the intracellular enzyme 3',5'-cyclic adenosinemonophosphate synthetase (cyclic AMP), disrupting thesodiumpumpsystemformovementofwaterandallowingpotassiumandbicarbonatetoseepoutofthecell.

Parasitic Infections

Intropicalcountries,parasitismisendemic.Roundworms,tapeworms,amoebae,hookworms,strongyloides,thread-worms, and blood flukes (schistosomiasis) are the maintypes of parasites. Consequently it is commonplace inthese areas for multiple parasite infestation to occur inaddition to other disorders. This common occurrence,reflectingpoverty,lackofhealtheducation,malnutrition,contaminateddrinkingwater,andinadequatesanitation,isamajorfactorinchronicillnessandearlydeath.

Roundworms

Roundworms,particularlyAscaris lumbricoides,maycauseintestinalobstructionifpresentinsufficientnumbers.Asthey mature from the larval state to the adult worm,roundwormsmigratethroughthebody,causingascariasis,an infection characterized by fever; pneumonitis (lunginflammation); cholangitis (inflammation of the bileducts);andpancreatitis.Roundwormsinterferewiththeabsorption of fat and protein in the intestine, causingdiarrhea.Theyareeliminatedwiththeadministrationofpiperazineorotheranthelmintics,butoccasionallysurgeryisrequiredforobstruction.

Hookworms

Hookworm, or Ancylostoma duodenale, infection beginswhenthewormisinthelarvalstage.Itpenetratestheskin,usuallyofthefeet,migratesduringitslifecyclethroughthe

185


liverandthelungs,andattachestothemucosaof the small intestinewhere it matures.Hookworms depletethe body of nutrients,andonemajoreffectissevere chronic iron-deficiencyanemia.Thiseffectcanbecorrectedwith the oral adminis-trationofiron,andthenumber of worms canbe controlled with tet-rachloroethylene orotheranthelmintics.

Pinworms

Pinworms, or Enterobius vermicularis, live mainly in thececum.Theadultfemalemigratesatnighttotheanusandlays eggs on the perianal skin, which cause anal itching.Transmissionofthepinwormoccursviaafecal-oralroute,anditcanaffectanentirefamily.Pinwormscanbeeradi-catedwithpiperazineorvypriniumembonate.

Tapeworms

The common tapeworms are Taenia saginata, found inbeef,andT. solium, foundinpork.LarvaeofEchinococcus granulosus, mature worms of the genus Diphyllobothrium,andsomedwarftapewormsalsocausedisease.

Fertilizedovaarepassedinfecesandareingestedbyanintermediaryhostanimal,suchasacow.Theembryosmigrate to the bloodstream and on reaching muscle orvisceradevelopintolarvae.Whenthefleshisconsumedbyhumans,thelarvaepassintotheintestine,wherethey

This image shows two curled up parasitic roundworm. Kim Taylor/Dorling Kindersley/GettyImages

186


attach and mature into adult worms. Thus, the mostcommonsourceofinfectionisinadequatelycookedmeat.Tapeworms found in beef and pork only give rise tosymptoms if their number and size cause intestinalobstruction.Diphyllobothrium latum,afishtapeworm,maycause a severe anemia similar to pernicious anemia,becauseitconsumesmostofthevitaminB12inthedietofthehost.

Appendicitis

Appendicitisisaninflammationofthevermiformappendixthat may be caused by infection or partial or total

This is an illustration of the life cycle of Taeniasaginata (tapeworm found in beef ) and Taeniasolium (tapeworm found in pork). CDC/AlexanderJ.daSilva,PhD/MelanieMoser

187


obstruction. The primary symptom of appendicitis isabdominalpain.Inapersonwithanormallysitedappendix,thepainofappendicitisissituatedatapointbetweenthenavelandthefrontedgeoftherighthipbone.Butmanypeople have the appendix lying in an abnormal positionandmayfeelthepainofanappendicitisattackinadifferentormisleadinglocation,whichmakestheirsymptomsdif-ficulttodistinguishfromtheabdominalpaincausedbyavarietyofotherdiseases.

The early pain associated with appendicitis is usuallynotverysevere,andafteronetosixhoursormore,thepainmaybecomelocalizedtotherightlowerabdomen.Nauseaandvomitingmaydevelop,andfeverisusuallypresentbutisseldomhighintheearlyphasesoftheattack.Thepatient’sleukocytes(whitebloodcells)areusuallyincreasedfromanormalcountof5,000–10,000inanadulttoanabnormalcountof12,000–20,000.Thisphenomenoncanbecausedbymanyotheracuteinflammatoryconditionsthatoccurintheabdomen.

Careful diagnostic examination by a physician canusuallydetermineifacuteappendicitisisindeedcausingapatient’sabdominalpain.UltrasoundorCTscansmayalsobeusefulindiagnosingthecondition.Insomecasesadoctormaywaitandobservethepatient’ssymptomsforaperiodof10to24hourssothatadefinitivediagnosiscanbemade.Thiswaitdoesslightlyincreasetheriskthattheappendixwill ruptureandperitonitisset in, sothepatient iskeptundercarefulmedicalsurveillanceatthistime.Thebasictreatment of appendicitis is the surgical removal of theappendix in a minor operation called an appendectomy.Theoperationitselfrequireslittlemorethanahalfhourunderanesthesiaandproducesrelativelylittlepostoperativediscomfort.

Widespread use of antibiotics for upper-respiratoryand other diseases may have lessened the incidence of

188


acuteappendicitis,sothatmorecasesoflate-developingappendiceal abscess are being reported. Parasitic wormsalsocancontributetoitsincidence.Appendicitisprincipallyoccurs in persons younger than age 35; however, it doesoccasionallyoccurinelderlypeople.

Chronic Inflammations

Chronicinflammationsofthesmallintestineincludetuber-culosis and regional enteritis (Crohn disease). Thesedisturbancesaredifficult todiagnose intheirearlystagesbecause their initial symptoms are often vague. Generalsymptomsincludelow-gradefever,atendencytowardloose

A surgeon removes an inflamed appendix in Pretoria, South Africa. Doctors can use either a classic laparotomy involving an incision into the abdomen, or less-invasive laparoscopic surgery to remove these diseased organs. In laparo-scopic surgery, surgeons are guided by a laparoscope, a lit, telescope-like device introduced into the body through a tiny cut. GalloImages/GettyImages

189


stools, weight loss, and episodes of cramping abdominalpaincausedbyobstructionofthelumenandinterferencewithnormalmuscularactivitybyinflammationoftheintes-tinal wall. Diagnosis is usually determined by X-ray orcolonoscopy.Abiopsymayalsobeperformedtoexaminetheliningofthesmallintestine.

Celiac Disease

Celiacdisease,alsocallednontropicalsprueorceliacsprue,is an inherited autoimmune digestive disorder in whichpeople cannot tolerate gluten, a protein constituent ofwheat, barley, malt, and rye flours. General symptomsofthediseaseincludethepassageoffoul,pale-colouredstools (steatorrhea), progressive malnutrition, diarrhea,decreasedappetiteandweightloss,multiplevitamindefi-ciencies,stuntingofgrowth,abdominalpain,skinrash,anddefectsintoothenamel.Advanceddiseasemaybecharac-terized by anemia, osteoporosis, vision disturbances, oramenorrhea(absenceofmenstruationinwomen).

Thewayinwhichthediseasemanifestsvarieswidely.Forexample,somepeopleexperienceseveregastrointes-tinal symptoms, whereas others are asymptomatic, areirritableanddepressed,ordevelopanitchyskinrashwithblisters,knownasdermatitisherpetiformis.Ifleftundiag-nosedoruncontrolled,celiacdiseasemayleadtointestinaladenocarcinoma(malignanttumourofglandulartissue)orintestinallymphomaortomiscarriageinpregnantwomen.Pregnantwomenaffectedbythediseaseandthussufferingfromvitamindeficienciesarealsoatanincreasedriskforgivingbirthtoinfantswithcongenitaldisorders.

Inchildren,celiacdiseasebeginswithinseveralmonthsof adding gluten-containing foods such as cereal to thediet.However,theonsetofthediseaseisalsoinfluenced

190


by the length of time the child was breast-fed and bythe amountofglutenthatthechild ingests.Thediseasefrequently is first noticed following an infection and ischronic, with periods of intestinal upset, diarrhea, andfailuretogrowandgainweight,interspersedwithperiodsof apparent normality. Adult celiac disease commonlybeginspasttheageof30,butitmayappearatanearlieragefollowingseverestress,surgery,orchildbirth.

Severalgenemutationshavebeenidentifiedinceliacdisease. However, genetic mutations themselves do notgiverisetothedisease.Instead,itistriggeredbythecom-binationofgeneticandenvironmentalfactors;i.e.,whenagenetically predisposed individual eats foods containinggluten.Inpeoplewithceliacdisease,glutenstimulatestheimmune system to produce autoantibodies that damagethemucosalliningofthesmallintestine.

In most cases, celiac disease can be diagnosed bybloodtestsforanti-tissuetransglutaminaseantibodyandanti-endomysialantibody.Diagnosisisusuallyconfirmedbyendoscopicexaminationandbiopsyofthesmallintes-tine. Endoscopy provides visual evidence of intestinaldamage,markedbyflatteningofthevilliinthemucosallining,whichnormallyprojectintotheintestinalcavityand increase the surface area available for nutrientabsorption.Biopsiedtissueisexaminedforthepresenceof certain lymphocytes that indicate inflammationcausedbygluten.

Celiacdiseaseisestimatedtooccur,onaverage,inabout1inevery266peopleworldwide.However,onlyaboutthreepercentofthesepeopleareactuallydiagnosedwithceliacdisease.Thisisinpartbecausesomepeopleareasymptom-atic, but it is also attributed to misdiagnosis, since manysymptoms of the disease are similar to other conditions,including irritable bowel syndrome, Crohn disease, and

191


chronic fatigue syndrome. Several autoimmune diseaseshavemutationsinthesamechromosomalregionasceliacdisease, and although the underlying mechanisms remainunclear, these diseases often develop in association withceliacdisease.Asaresult, the longerapersonwithceliacdiseaseremainsundiagnosedormisdiagnosed,themorelikelyheorsheistodevelopanassociatedautoimmunedisease, such as a thyroid disorder, type I diabetes, orautoimmunehepatitis.

Thesymptomsofmostpatientsarerelievedbystrictadherencetoagluten-freediet.Inchildrentheintestinalmucosaisusuallyhealedwithinseveralmonthstooneyearof initiating the diet, and in adults, it is usually healedwithintwoyears.Inrarecases,symptomsanddestructionof themucosal liningmayprogressdespiteagluten-freediet;theseindividualsgenerallyreceiveintravenousvitamintherapy.

Tropical Sprue

Tropicalsprueisanacquireddiseasecharacterizedbythesmallintestine’simpairedabsorptionoffats,vitamins,andminerals.Whileitscauseisunknown,infection,parasiteinfestation, vitamin deficiency, and food toxins havebeensuggestedaspossiblecauses.ItisfoundprimarilyintheCaribbean,SoutheastAsia,India,andareasinwhichpolishedriceisastaplefood.Sprueoftenattacksmiddle-aged adults and is commonly caused by bacterialcontamination of the small intestine, which in turn isresponsibleforinadequatefatdigestionandabsorption.

The onset of the disease is insidious. In the initialphase,complaintsincludefatigue,weakness,lossofappetite,severevomiting,dehydration,andnumerousbulky,frothy,greasy, light-coloured stools. In infants and children,

192


sometimesweeksormonthselapsebeforeatypicalpatternisrevealed.Oftenprofoundbehavioralchangesoccur,astemper and irritability alternate with timidity and with-drawalsigns.Notableisthesad,fretfulfacialexpressionofyoungsterssoafflicted.

Thesecondstageoftropicalspruefollowsinthreetosixmonthswithprominentweightloss,inflamedandpain-fully fissured tongue, fissures of the mouth lining, andswellingandscalingofthelipsaccompaniedbychangesinthe cornea (hyperkeratosis). If the disease progresses tothe third stage, severe anemia and imbalance of protein(e.g., albumins, globulins) and electrolytes (e.g., sodium,potassium,andchlorineinsolution)mayprecipitatetotaldebilitation.Dramaticimprovementoccursafteradmin-istering folic acid, a chemical of the vitamin B complexfound in leafy vegetables and liver and also producedsynthetically.

diSeaSeS of the large inteStine

Awidevarietyofdiseasesanddisordersoccurinthelargeintestine.Abnormalrotationofthecolonisfairlyfrequentandoccasionallyleadstodisorders.Unusuallylongmesen-teries (the supporting tissues of the large intestine) maypermitrecurrenttwisting,cuttingoffthebloodsupplytothe involved loop. The loop itself may be completelyobstructed by rotation. Such complications are usuallyseen in elderly patients and particularly in those with alonghistoryofconstipation.

Constipation

Constipationisthedelayedpassageofwastethroughthelower portion of the large intestine, with the possible

193


dischargeofrelativelydry,hardenedfecesfromtheanus.Amongthecausescitedforthedisorderarelackofregu-larityinone’seatinghabits;spasmsofthelargeintestine;metabolic diseases such as hypothyroidism or diabetesmellitus;neurologicaldisorderssuchasastroke;certainmedications including morphine, codeine, antidepres-sants,andantispasmodics;lackofsufficientfibreinone’sfood;andexcessiveuseoflaxatives.

Constipationmayalsobecausedbyintestinalobstruc-tionbytumoursorpolypsorbyweaknessoftheabdominalmuscles. Temporary constipation most often occurs inconjunctionwithachangeor interruptioninone’susualactivities,asintravel,temporaryconfinementtobed,orachangeineatingorsleepinghabits.Inmostcases,dietaryandlifestylechangescanhelprelieveconstipation.

Megacolon

Aganglionic megacolon, or Hirschsprung disease, is aconditionofunknowncausethatischaracterizedbytheabsenceofganglioncellsandnormalnervefibresfromthedistal (or lower) 3 to 40 cm (1 to 16 inches) of the largeintestine.Neuromusculartransmissionisabsentfromthissegment, and peristalsis cannot occur. It is thus a func-tionalobstruction.In10percentofcases,alargersegmentis involvedand,onrareoccasions,thewholecolon.Thearea of normal intestine above the obstruction workshardertopushonthefecalcontents,andeventuallythemuscleofthenormalsegmentthickens.Theentirecolonthusslowlybecomesmoreandmoredistendedandthick-walled. Diagnosis is made by the examination of themicroscopicappearanceofadeepbiopsyofthelowerrec-tum.Varioussurgicalproceduresareusedtocorrect thecondition.

194


Acquiredmegacoloniscommonlycausedbyacombi-nation of faulty toilet training and emotional disordersduringchildhood,inwhichthechildwithholdsdefecation.The administration of increasing amounts of laxativesfailstosolvetheproblempermanently,andovertimetheintrinsic innervationintheintestinalwall isdamaged.Adilatedrectumfulloffecesdevelopsovertheyears.Theimpacted feces act as an obstruction, and further fecalmaterialpilesupbehind,withvoluminusdilatationofthewholecoloninsomecases.

Evacuationofthecontentsofthebowelpriortosurgery,ifitisrequired,mayrequirehospitalizationforuptothreemonths.Acquiredmegacolonisoccasionallyencounteredinthosewithschizophreniaandseveredepression.Itmayberelatedtoneurologicaldisorderssuchasparaplegia,tounrecognizedrectalstrictures,andtosomemetabolicdis-orders. Severe degrees of constipation, often running infamilies and leading to megacolon, occur, but the causehasnotbeendiscovered.Resectionofthecolonandunit-ingtheileumtotherectumiseffectivetreatment.

Diarrhea

Diarrheaistheabnormallyswiftpassageofwastematerialthroughthelargeintestine,withconsequentdischargeofloose feces from the anus. Because water is normallyabsorbed from the colonic content, principally in theascending,orright,colon,diarrheacanbecausedbyanyinflammatory,neoplastic,orvasculardisturbanceofthatpartofthecolon.Diarrheacanalsobecausedbybacterial,viral,orparasiticinfection.Mostcasesofdiarrheaarenotseriousanddonotrequiretreatment.

Diarrheaiscommoninthosewhoaredeficientinlac-tase, the enzyme that splits lactose (milk sugar) into itscomponent parts, glucose and galactose. Shortly after

195


drinkingmilk,suchpersonsusuallyhavesevereintestinalcramping,followedlaterbywaterydiarrhea.Thelactoseinthemilkisnotbrokendown,anditstaysinthelumenofthe small intestine, drawing water to it. The increasedbulkoffluidandsugardistendstheintestine,whichthencontractsactively.Therapidcontractionsdrivethemate-rialalongtheintestineintothecolon,whichcannotabsorbthewaterrapidlyenough.Theresultantwatery,unformedstoolsarefrequentlyacidic.

Intestinal Gas

Intestinal gas consists principally of swallowed air andpartlyofby-productsofdigestion.Whenapersonisinanuprightposition,gasdiffusestotheuppermostportionsofthecolon.Thereitiscompressedbythecontractionofadjacent segments, giving rise to pain that is localizedeither near the liver and gallbladder or under the dia-phragmandheart.Thispaincanbeincorrectlythoughttobeassociatedwithdiseasesoftheseorgans,whereasitisactuallycausedbyincreasedgasinthecolon.Eatingslowertoreducetheamountofairingested,decreasingtheintakeofcarbonatedbeveragesandwhippedfoodsthatcontainair bubbles, and avoiding certain gas-producing foods,such as most beans, onions, sprouts, nuts, and raisins,usuallyhelptoreduceflatulence.

Diverticula of the Large Intestine

Diverticulaofthelargeintestineariseinthewallassmallpouchesorsacs.Arteriespenetratethemuscularwallsofthe colon from its outside covering, the serosa, and dis-tribute themselves in the submucosa. With aging, andperhapsinpersonspredisposedtothedisorder,thechannelsinwhichthesearteriesliebecomelarger.Iftheperistaltic

196


activityofthecolonmaintainsahighpressurewithinitslumen, as in persons straining to defecate, the mucousmembrane of the colon may be driven slowly into thesechannels and eventually may follow the arteries back totheirsiteofcolonicentranceintheserosa.Atthistime,the outward-pushing mucosa becomes a budding sac, ordiverticulum,ontheantimesentericborderofthecolonwithaconnectiontothelumen.

In the Western world, multiple colonic diverticulaoccur in as many as 30 percent of persons over age 50.Diverticulaareparticularlycommoninthosewhosedietsare deficient in fibre. Hypertrophy (increase in size andmass) of the muscle fibre of the colon, especially in thesigmoid region, precedes or accompanies diverticulosis.Thisisespeciallyapparentinthediverticulosisinmiddle-agedpersonsasopposedtothatintheelderly.

The principal dangers of diverticulosis are hemor-rhage and inflammation. Hemorrhage results from theactionofhardstoolsagainstthesmallarteriesofthecolonthatareexposedandunsupportedbecauseofdiverticula.Asthearteriesage,theybecomelesselastic, lessabletocontract after bleeding begins, and more susceptible todamage. Diverticulitis occurs when the narrow necks ofthediverticulabecomepluggedwithdebrisorundigestiblefoodstuff and when bacteria—uninhibited by the usualmotoractivitythatkeepstheintestineclean—proliferatein the blind sacs. When the sacs enlarge, the adjacentintestinal wall becomes inflamed and irritable, musclespasmsoccur,andthepatientexperiencesabdominalpainandfever.Ifthesacscontinuetoenlarge,theymayruptureintotheperitoneum,givingrisetoperitonitis,aninflam-mation of the peritoneum. More commonly they fixthemselvestoneighbouringorgansandproducelocalizedabscesses, which may prove difficult to treat surgically.

197


Mild diverticulitis responds well to antibiotics. Massivehemorrhagesoftenrequireemergencysurgery.Recurrentdiverticulitis requires resection of the affected area ofthecolon.

Abscesses of the Large Intestine

Abscesses(cavitiesofpusformedfromdisintegratingtissue)intheperianalareaarecommoncomplicatingfeaturesofmanydiseasesanddisordersofthelargeintestine.Fungalinfections of the moist and sometimes poorly cleansedareaaroundtheanusarecommonandpermitthemacera-tion(orgradualbreakingdown)oftissueandinvasionbybacteria from the skin and colon. In diabetics, who aresusceptible to skin infection, perianal hygiene is veryimportant.

Bacterial Infections of the Colon

Thecolonmaybecome inflamedbecauseof invasionbypathogenic, or disease-causing, bacteria or parasites. Avariety of species of Shigella, for example, attack themucous membrane of the colon and produce an intensebut rather superficial hemorrhage. In infants and in theelderly,theamountoffluidandproteinlostbytheintenseinflammatory response may be fatal, but ordinarily suchsymptoms are less serious in otherwise healthy persons.Salmonella species, responsible for severe generalizedinfectionsoriginatingfrominvasionofthesmallintestine,maydamagethe lymphfolliclesofthecolon,buttheydo notproduceageneralizedinflammationofthecolon(colitis). The cytomegalic virus, on the other hand, cancauseaseverecolitis,producingulcerations.Lymphopathia venereumcausesamoregeneralizedandsuperficialcolitis.

198


Foodresiduesprovideanexcellentculturemediumforbacteria,andtheinteriorofthecolonisanearlyidealenvi-ronment for their growth. The most widely distributedparasiteproducingdisease inthecolon istheprotozoanEntamoeba histolytica. This parasite enters the digestivetractviathemouthandlodgesinthececumandascendingcolon.Thisusuallyresultsinirritabilityoftheascendingcolonandfailuretoabsorbwaterproperly,sothat inter-mittent,waterydiarrheaensues.Theamoebasunderminethe mucosal coat and may create large ulcerations thatbleedexcessively.Stoolscontainblood,butthereislittlepus or other evidence of reaction by the colon to theinvadingorganism.

Inmoregeneralizedamoebiccolitis, the rectumandsigmoidcolonareinvadedbyE. histolytica,whichmanifesttheirpresencebynumerousdiscreteulcerationsseparatedfromeachotherbyarelativelynormal-appearingmucousmembrane.Theamoebasmayentertheportalcirculationandbecarriedtotheliver,whereabscessesformandsome-times rupture into the chest or the abdominal cavity.Immunologic tests of the blood may help in diagnosis.Afteridentificationoftheparasitesbydirectsmeartestsfromthemarginoftheulcersorfromthestools,acombi-nation of amoebicidal drugs and a broad-spectrumantibiotic—i.e.,anantibioticthatistoxictoawidevarietyof parasites, usually metronidazole and tetracycline—isadministered.

Inflammatory Bowel Disease

Inflammatoryboweldisease(IBD)isachronicinflamma-tionoftheintestinesthatresultsinimpairedabsorptionofnutrients.IBDencompassestwodisorders:Crohndisease(regional ileitis)andulcerativecolitis.TheonsetofIBD

199


typically occurs between the ages of 15 and 35, and thediseasetendstoruninfamilies.

The factors that trigger intestinal inflammation andonset of IBD remain unknown. Symptoms of IBD maydevelop suddenly or gradually and include constipation,diarrhea,fever,rectalbleeding,andabdominaldiscomfort.InbothCrohndiseaseandulcerativecolitis,patientsmayexperience periods of symptom remission and relapse.IBDisparticularlydifficult todiagnose inchildren,andaffectedchildrenmayfailtogrowproperly.Inadditiontophysicalexamination,bloodtests,andstoolanalysis,IBDmay be diagnosed by colonoscopy, in which the entirecolonisinvestigated,orsigmoidoscopy,inwhichonlytherectum and sigmoid colon are investigated. IndividualswithafamilyhistoryofIBDmayundergogenetictestingforspecificgenemutationstodeterminetheirsusceptibilitytothedisease.

ResearchhasindicatedthatIBDispolygenic,meaningthatvariations inmultiplegenescombinetogiverisetothe disease. While the exact combinations of geneticvariantsthatcauseIBDhavenotbeenidentified,individualgenetic variations associated with the disease have beendiscovered. For example, mutation of a gene calledTNFRSF6B(tumournecrosisfactorreceptorsuperfamily,member 6b, decoy), which is involved in suppressinginflammationinthegastrointestinaltract,hasbeenlinkedwiththeonsetofIBDinchildhood.Inaddition,variationof a gene called GLI1 (glioma-associated oncogenehomolog 1), identified in patients in northern Europe,resultsinreducedactivityoftheanti-inflammatoryGLI1protein, and dampened activity of this protein has beenassociatedwithincreasedinflammationintheintestines.

Furthermore, some genetic variations are associatedwithincreasedriskforbothulcerativecolitisandCrohn

200


disease,whereasothervariationsaredisorder-specific.Forexample, variation of a gene called ECM1 (extracellularmatrix protein 1) has been linked to ulcerative colitis,whereas variation of a gene called NOD2 (nucleotide-binding oligomerization domain containing 2) has beenlinkedtoCrohndisease.Thediscoveryofgeneticmuta-tions that lead to specific abnormalities in immunefunctioninIBDhasfacilitatedresearchintothedevelop-mentofuniquetreatmentstrategies.Forexample,thereispotentialforthedevelopmentofanagentthattargetstheGLI1 protein to restore the protein’s activity to normallevels, thereby reducing intestinal inflammation andrelievingsymptoms.

Treatmentgenerallyincludesadietlowinfat,highinprotein and easily digestible carbohydrates, and free oflactose (milk sugar). Increased intakes of certain nutri-ents, such as iron, calcium, and magnesium, andsupplementation with fat-soluble vitamins may also berecommended, along with additional fluid and electro-lytestoreplacelossesduetodiarrhea.Anti-inflammatoryagents, such as corticosteroids (e.g., prednisone) andmesalamine, and immunosuppressive agents, such ascyclosporine and methotrexate, may be prescribed forpatientswithmoderatetosevereIBD.

Ulcerative Colitis

Themostcommonformofchroniccolitis(inflammationof the colon) in the Western world is ulcerative colitis.This condition varies from a mild inflammation of themucosaoftherectum—givingrisetoexcessivemucusandsomespottingofbloodinthestools—toasevere,suddenillness, with destruction of a large part of the colonicmucosa, considerable blood loss, toxemia and, less com-monly,perforation.Themostcommonvarietyaffectsonlythe rectum and sigmoid colon and is characterized by

201


diarrheaandthepassageofmucus.Ulcerativecolitistendstofollowaremitting-relapsingcourse.Diagnosisisdeter-minedbyperformingacolonoscopyorabiopsy.

Another type of colitis arises when antibiotic usecausestheabnormalproliferationofcertaintypesofbac-teriainthecolon,leadingtoinflammation.Thisdisorderistreatedbystoppingtheuseofthecausalantibioticandadministering others such as vancomycin or mexronida-zole. About 15 percent of all cases of colitis involveextensionofthediseasebeyondtheareainitiallyaffected,with an increase in severity.Where the destruction hasbeenextensive,thereisariskofmalignancy10to20yearsaftertheonsetofthedisease.

Crohn Disease

Crohn disease, also called regional enteritis or regionalileitis, is characterized by chronic inflammation of thedigestivetract,usuallyoccurringintheterminalportionoftheileum.Crohndiseasewasfirstdescribedin1904byPolishsurgeonAntoniLeśniowski.ItwaslaternamedforAmericangastroenterologistBurrillBernardCrohn,whoin 1932, in collaboration with fellow physicians LeonGinzburg and Gordon D. Oppenheimer, published athoroughdescriptionofathen-unknownintestinaldisordertheycalledregionalileitis.

Today, Crohn disease is characterized as a type ofinflammatory bowel disease (IBD) and has been associ-atedwithabnormal functionof the immunesystemandgenetic variations. The disease also has been linked toabnormal changes in populations of intestinal bacteria.Forexample,Faecalibacterium prausnitzii,anormalinhabit-ant of the human intestinal tract, is found in decreasedlevelsinpeoplewithCrohndisease.Mycobacterium avium paratuberculosis,foundintheintestinaltractsofruminantsaffected by Johne disease, which is similar to Crohn

202


This medical exhibit portrays Crohn disease. It shows the healthy gastrointestinal tract and the gastrointestinal tract with Crohn disease. NucleusMedicalArt,Inc./GettyImages

203


disease in humans, has been isolated from the blood ofsome patients. However, despite these associations, thecauseofCrohndiseaseremainsunknown.

ThemostcommonsymptomsofCrohndiseaseincludediarrhea and abdominal pain. Rectal bleeding, fever,weightloss,arthritis,andanemiaareindicationsofmoderateto severe disease. Some patients develop fistulas, orabnormalpassagesconnectingtheboweltootherorgans,such as the bladder or the vagina. These often lead toabscesses(pus-filledcavitieswithintissues).Theformationoffistulasandthethickeningoftheintestinalwall—tothepointofobstruction—aretheonlymicroscopicfindingsthatdistinguishCrohndiseasefromulcerativecolitis,theothertypeofIBD.

InCrohndiseasethemaximumdamagetotheintes-tine occurs beneath the mucosa, and lymphoidconglomerations, known as granulomata, are formed inthe submucosa. In addition, Crohn disease attacks theperianal tissues more often than does ulcerative colitis.Crohndiseaseisdiagnosedbyacombinationofmethods,including blood and stool analysis and colonoscopy.Diagnosis may be confirmed by other methods, such asbariumenema,whichusesX-raystoexaminetheintestinefollowing rectal insertion of a liquid barium contrastagent.Anothermethod,capsuleendoscopy,examinestheintestinesviaapill-sizedvideocamerathat isswallowedbythepatientandtransmitsimagestosensorsattachedtothepatient’sbodyasitpassesthroughthedigestivetract.

A combination of immunosuppressive and anti-inflammatory drugs, including corticosteroids andaminosalicylic acid compounds, are used to treat Crohndisease.The drugs are effective both in treating acuteepisodesandinsuppressingthediseaseoverthelongterm.Depending on the circumstances, hematinics, vitamins,

204


high-protein diets, and blood transfusions are also used.Surgical resection of the portion of the large bowelaffectedisoftenperformed.Theentirecolonmayneedtobe removed and the small intestine brought out to theskinasanileostomy,anopeningtoserveasasubstitutefortheanus.

Colorectal Cancer

Colorectalcancerisadiseasecharacterizedbyuncontrolledgrowthofcellswithinthelargeintestine(colon)orrectum(terminalportionofthelargeintestine).Coloncancer(orbowelcancer)andrectalcanceraresometimesreferredtoseparately.Colorectalcancerdevelopsslowlybutcanspreadtosurroundinganddistanttissuesofthebody.

Causes and Symptoms of Colorectal Cancer

Likemostcancers,colorectalcancershavemultiplecauses,manyofwhichremainunknown.Somecasesappear tobeinherited,whereasothersseemtooccurrandomlyortohavenongeneticcauses.Approximately95percentofcolorectalcancersinvolvetheglandularcellsinthewallof the colon and are called adenocarcinomas. Othercolorectal cancers may begin among hormone-producingcells,immunecells,orunderlyingconnectivetissue.

Several factors increase the risk of developing thedisease. Colorectal cancer becomes more common withincreasingage.Ninetypercentofcasesarediagnosedinpeople age 50 or older. A family history of colorectalcancer—specifically forms such as familial adenomatouspolyposis(FAP),Gardnersyndrome,andhereditarynon-polyposis colon cancer (HNPCC)—can predispose anindividualtodevelopingcolorectalcancer.Eachoftheseconditionsiscausedinpartbyaknowngeneticmutation.In addition, Ashkenazi Jews have a slightly higher

205


incidenceofcolorectalcancerduetoamutatedgene,andthereexistsagenemutationthatincreasesriskofcolorectalcancer in people of European descent but does notincrease risk in people of Japanese descent. This lattermutation, discovered in 2008, was the first to provideevidenceofethnicdifferencesingeneticsusceptibilitytocolorectalcancer.

Chronic inflammatory bowel diseases such as Crohndiseaseorulcerativecolitisareassociatedwithcolorectalcancer,asisthepresenceofalargenumberofnoncancerouspolypsalongthewallofthecolonorrectum.Otherriskfactorsincludephysicalinactivityandadiethighinfats.Those who have previously been treated for colorectalcancerarealsoatincreasedriskofrecurrence.

Becausecolorectalcancerisadiseaseofthedigestivetract,manyofthesymptomsareassociatedwithabnormaldigestionandelimination.Symptomsincludeepisodesofdiarrheaorconstipationthatextendfordays,bloodinthestool, rectal bleeding, jaundice, abdominal pain, loss ofappetite, and fatigue. Because these symptoms accom-panyavarietyofdifferentillnesses,aphysicianshouldbeconsultedtodeterminetheircause.

Diagnosis of Colorectal Cancer

Diagnosesofcolonandrectalcancersaremadebymeansof several techniques. During a digital rectal exam, thephysicianinsertsaglovedfingerintotherectumandfeelsitssurfaceforabnormalities.Afecaltestmayalsobeusedtodetectthepresenceofbloodinthestool.Inordertoexaminetherectummorecarefully,aphysicianmayuseanarrow,flexibletubecalledasigmoidoscopetolookattheliningoftherectumandtheendofthecolon.Colonoscopyusesasimilardevicetoexaminetheentirecolon.Abiopsymay also be conducted in which abnormal tissue isremoved by using the colonoscope and then examined

206


underamicroscopeforsignsofcancer.AnX-rayprocedurecalled a double-contrast barium enema may be used.Bariumsulfateisusedtocoatthecolon,andthecolonisfilledwithair.AseriesofX-raysarethentaken,andtheresultinghigh-contrastimagesindicateanyabnormalitiespresent.

If cancer is found, the degree to which it has spread(metastasized) from the colon or rectum is determined.Biopsiesmaybeconductedofsurroundingtissues,oroneof several imaging techniques may be used to detectmetastasis. Techniques include rectal ultrasound, MRI,andX-rayorCTscans.

Oncecolorectalcancerhasbeendiagnosed,itsstageisthen determined to indicate how far the cancer has pro-gressed.Stage0colorectalcancerisalsocalledcarcinomainsituandisconfinedtotheliningofthecolonorrectum.Stage I cancers have spread into the connective tissuebeneaththeliningorintotheunderlyingmusclelayer.StageIIcancershavespreadcompletelythroughthewallofthecolonorrectumbuthavenotinvadednearbylymphnodes.Stage III colorectal cancer has reached nearby lymphnodes,andstageIVcancershavespreadtodistantstruc-turessuchasthelungs,liver,bones,orreproductiveorgans.

Colorectalcancerpatientshaveanexcellentfive-yearsurvivalratewhenthediseaseisdetectedearly,andthosewhoreachthisstageoftengoontolivelong,healthylives.Approximatelytwo-thirdsofpatientswithlocalmetastasessurviveforfiveormoreyears,butincaseswherecancerisdetectedlateandhasspreadtodistantregionsofthebody,thefive-yearsurvivalrateisverylow.

Treatment and Prevention of Colorectal Cancer

Colorectalcanceristreatedbysurgery,chemotherapy,orradiation.The method used depends on the site of thecancerandthedegreetowhichithasspread.Forcancers

207


localizedtothecolonorrectum,surgeryisusuallyallthatis required. For early-stage colon cancer, a colonoscopemaybeusedtoremovethecanceroustissue.Otherearlycancersrequireasurgicalresection,wherebytheportionof the colon containing the cancerous tissue is removedalong with surrounding tissue and nearby lymph nodesandtheremainderofthecolonisrepaired.

Rectal cancers may be treated by removing only thecancerous polyp or polyps, the cancer plus surroundingtissues,orlargersectionsoftherectum.Somecancersmayberemovedbyburningtheminaprocedurecalledelec-trofulguration. In cases where the lower portion of therectumisinvolved,acolostomymayberequired,wherebythesurgeoncreatesanartificialopeningfortheremovalofwaste.Ifcolorectalcancerhasspreadtosurroundingtissuessuch as those of the uterus, prostate, liver, kidneys, orbladder,moreextensivesurgerymayberequiredtoremoveallorpartoftheseorgans.

Both colon and rectal cancers may be treated withradiation, using either external beams or surgicallyimplantedradioactivepellets.Radiationisusuallyusedinconjunction with surgery—either before the surgery toshrink tumours or following surgery to destroy smallamounts of remaining cancerous tissue. Chemotherapymayalsobeindicatedfortreatmentofcolorectalcancers,especially when cancer has spread to other parts of thebody but also as an adjuvant therapy to primary surgeryandradiation.Sideeffectsofbothradiationandchemo-therapymayincludevomiting,diarrhea,andfatigue.

Alifestylethatincludesregularexerciseandadietlowinfatsandhighinfruitsandvegetableshelpstopreventcolorectalcancer.Earlydetectionisimportantinpreventingthe development of advanced colorectal cancer. Somemedicalsocietiesrecommendregularscreeningbyaphy-sicianafterage50.

208


Hemorrhoids

Ahemorrhoid,orpile,isformedbydistensionofthenet-workofveinsunderthemucousmembranethatlinestheanalchannelorundertheskinliningtheexternalportionof the anus.A form of varicose vein, a hemorrhoid maydevelop from anal infection or from increase in intra-abdominal pressure, such as occurs during pregnancy,whileliftingaheavyobject,orwhilestrainingatstool.Itmaybeacomplicationofchronicliverdiseaseortumours.

Theweaknessinthevesselwallthatpermitsthedefectto develop may be inherited. Mild hemorrhoids may betreatedbysuchmethodsastheuseofsuppositories,non-irritatinglaxatives,andbaths.Ifclotshaveformed,orinthe presence of other complications, the hemorrhoidsmayrequiresurgicalremoval.

209

DISEASES OF THE LIVER AND PANCREAS

Avariety of agents, including viruses, drugs, environ-mental pollutants, genetic disorders, and systemic

diseases,canaffecttheliverandthepancreas.Inthelivertheresultingdisordersusuallyaffectoneofthethreefunc-tional components: the hepatocyte (liver cell), the bilesecretory (cholangiolar)apparatus,or thebloodvascularsystem. Diseases of the pancreas typically affect one ofthe organ’s two primary glandular tissues: the exocrinetissueortheendocrinetissue.Boththeliverandthepancreascanalsobeaffectedbyinflammationordysfunctionofthegallbladderorothercomponentsofthebiliarytract.

diSeaSeS of the liver

Diseases of the liver—though generally limited to thehepatocytes, the bile secretory apparatus, or the bloodvascularsystem—mayintimealso involveothercompo-nents.Thus,althoughviralhepatitis(inflammationoftheliver) predominantly affects hepatocytes, it commonlyleadstodamagedcanaliculi,smallchannelsthattransportbilefromhepatocytes.

Most acute liver diseases are self-limiting, and liverfunctionreturnstonormaloncethecausesareremovedoreliminated.Insomecases,however,theacutediseasepro-cessdestroysmassiveareasoflivertissueinashorttime,leadingtoextensivedeath(necrosis)ofhepaticcells.Forexample, when acute hepatitis lasts for six months ormore, a slow but progressive destruction of the

CHAPTER 8

210


surroundinglivercellsandbileductsoccurs,astagecalledchronicactivehepatitis.Ifhepatocellulardamageissevereenoughtodestroyentireacini(clustersoflobules),healthytissueisoftenreplacedwithfibrousscartissue.Bilecana-liculi and hepatocytes regenerate in an irregular fashionadjacenttothescartissueandresultinachronicconditioncalledcirrhosisoftheliver.Whereinflammatoryactivitycontinuesaftertheonsetofcirrhosis,thedisorderlyregen-eration of hepatocytes and cholangioles may lead to thedevelopmentofhepatocellularorcholangiolarcancer.

Benigncysts(tissueswellingsfilledwithfluid)inthelivermayoccurascongenitaldefectsorastheresultofinfections from infestation of the dog tapeworm(Echinococcus granulosus). Abscesses on the liver resultfrom the spread of infection from the biliary tract orfromotherpartsofthebody,especiallytheappendixandthepelvicorgans.SpecificliverabscessesalsoresultfrominfectionswiththeintestinalparasiteEntamoeba histolytica.Abscessesusuallyrespondwelltotreatmentwithspecificantibiotics, although surgical drainage is required insomecases.

Acute Hepatocellular Hepatitis

Althoughanumberofvirusesaffecttheliver—includingcytomegalovirus and Epstein-Barr virus, which causesinfectious mononucleosis—there are three distinctivetransmissiblevirusesthatarespecificallyknowntocauseacutedamagetolivercells.ThesevirusesarehepatitisAvirus (HAV), hepatitis B virus (HBV), and hepatitis Cvirus(HCV).ThehepatitisAvirusistransmittedalmostexclusivelyviathefecal–oralroute,anditthrivesinareaswhere sanitation and food handling are poor and handwashingisinfrequent.HAVproliferatesintheintestinaltractduringthetwoweeksfollowingtheonsetofsymptoms,

211

7 Diseases of the Liver and Pancreas 7

butitthendisappears.Manyinfectedpersonsareunawareofbeingill,sincetheirdiseaseremainsasymptomaticorquitemild.

TheincubationperiodofHAVinfections,fromviralingestiontotheonsetofsymptoms,averagesfourtofiveweeks. Acute illness in an otherwise healthy pregnantwomandoesnotappeartohaveadverseeffectsuponthefetus.PersonscanbecomepassivelyimmunizedagainstHAVforseveralmonthswitheitherthehepatitisAvaccineorasingleinjectionofimmunoglobulin.PersonscanbeactivelyimmunizedtoHAVbyacquiringthevirussubse-quent to becoming passively immunized, but suchinfectionsareeitherinapparentorverymild.

Hepatitis B virus is present throughout the world inasymptomatichumancarrierswhomayormaynothaveongoing liver disease. Formerly, the disease was widelyspreadbythetransfusionofwholebloodorbloodproducts,suchasthecryoprecipitateusedinthetreatmentofhemo-philia.Sincethesignsofinfectionhavebecomesoreadilyidentifiable, this mode of transmission is much lesscommon,comprisingonlyabout10percentofcases,com-pared with 60 percent in the past. Virus particles incarriers are found in bodily secretions, especially salivaandsexualemissions,aswellasinblood.TheincidenceofBantigensishighamongpersonsengaginginpromiscu-oussexualactivity,drugaddictswhosharesyringes,healthcare workers, and infants of mothers who are carriers.Many newly infected persons develop the acute diseasewithin three weeks to six months after exposure, whilesomedevelopanasymptomaticformofhepatitisthatmayappear only as chronic disease years later. Others elimi-natetheviruscompletelywithoutanysymptomsbeyondtheappearanceofantibodiestosurfaceantigen,whilestillothers become carriers of surface antigen and thus pre-sumablyareinfectivetoothers.

212


There are two methods of preventing hepatitis B:passiveimmunization,throughtheuseofaspecificimmu-noglobulin derived from patients who have successfullyovercomeanacuteHBVinfection;andactiveimmuniza-tion,throughtheinjectionofnoninfective,purifiedHBVsurfaceantigen.Thefirstmethodisusedfollowingspecificexposuresthatcarryahighriskofinfection,suchasusingneedlescontaminatedwithHBVparticles,theingestionofbodysecretionslikelytobeinfected,orthebirthofaninfant to a surface-antigen-positive mother.The secondmethod, active immunization, is used for those whobelongtogroupswithahighriskofHBVinfection,suchaschildrenlivinginendemicareas,medicalpersonnelinhigh-risk specialties, drug addicts, sexually promiscuouspersons,andfamilygroupslivingclosetoknowncarriers.Activeimmunization,involvingaseriesofthreeinjectionsofvaccineoveraperiodofthreetosixmonths,hasbeenshowntoconferahighdegreeofresistancetoinfection.

Hepatitis C appears to be transmitted in a mannersimilar to HBV transmission.The incidence for HCV ishigh among persons engaging in promiscuous sexualactivity, intravenous drug users, homosexual males, chil-dren living in endemic areas, infants born to infectedmothers, health care workers, and hemodialysis patients.Theaverageincubationperiodofthediseaseisaboutsevenweeks, and an acute attack of hepatitis C is usually lessseverethanacutehepatitisB.HepatitisC,however,ismorelikely to become chronic than is hepatitis B, and it mayrecur episodically with acute flares. The two approvedtreatmentsforhepatitisCarealphainterferonandriba-virin, but only about half of those receiving the drugsrespondtothem.

ThesymptomscharacteristicofacutehepatitiscausedbyHAV,HBV,andHCVareessentiallysimilar.Patientsoften complain of a flulike illness for several days, with

213


chills,fever,headache,cough,nausea,occasionaldiarrhea,and malaise. Abdominal pain caused by swelling of theliver is a common complaint. As many as half of theinfectedpatientsdeveloponlymildsymptomsornoneatall.Asmallpercentageofpatients,especially thosewithHBVinfections,maydevelophives,painfulskinnodules,acutearthritis,orurinarybleedingcausedbythedeposi-tionoflargeimmuneantigen-antibodycomplexesinthesmallbloodvesselsofadjacentorgans.Afterseveraldaysofsuchsymptoms,jaundicecommonlydevelops.Attimesthejaundiceissomildthatitisnotnoticedbypatients,although they often do note that the urine has becomedarkamberincolourbecauseofthehighlevelsofwater-soluble bilirubin transmitted to the kidneys by thebloodstream.

Theonsetofjaundiceusuallybringswithitamarkedimprovement in other symptoms. Jaundice lasts abouttwoweeksbutmaycontinueforseveralmonths,eveninthose who have complete recovery. Some patients com-plain of itching during this period, and they notice thelight colour of their stools. These symptoms probablyresult fromthecompressionofbilecanaliculiand intra-lobular bile ducts by the swelling of hepatocytes andKupffercells.Thechangesresultinthereducedsecretionofbilepigmentsintothebiliarysystem,theirrefluxintothebloodstream,andthedepositionofbilesaltsandotherbiliaryconstituentsintheskinandsubcutaneoustissues—aconditioncalledobstructivejaundice.Afterthephaseofjaundicesubsides,almostallpatientswithhepatitisA,andat least 90 percent of those with hepatitis B, recovercompletely.

Aside from jaundice, the physical examination ofpatients with acute viral hepatitis may reveal nothingmorethanadetectableenlargementand,attimes,tender-nessoftheliver.Somealsoshowanenlargedspleen.Signs

214


ofconfusionordisorientationindicateseveredamagetotheliver.Thediagnosisofhepatitisisconfirmedbybloodtests that show marked elevations of enzymes (amino-transferases)releasedfromdamagedlivercellsandbythepresenceofviralantigensoracuteviralantibodies(IgM).

A small number, perhaps 1 percent, of patients withviral hepatitis, especially the elderly, develop a sudden,severe(fulminant)formofhepaticnecrosisthatcanleadtodeath.Inthisformofthedisease,jaundiceincreasestohighlevelsduringthefirst7to10days;spontaneousbleedingoccurs because of reductions of blood-clotting proteins;andirrationalbehaviour,confusion,orcomafollow,causedbytheaccumulationinthecentralnervoussystemofthebreakdownproductsofproteinnormallymetabolizedbytheliver.Beyondsupportivemeasuresthereisnoeffectivetreatment of fulminant hepatic failure except livertransplantation.

Acute hepatitis also may be caused by the overcon-sumptionofalcoholorotherpoisons,suchascommercialsolvents(e.g.,carbontetrachloride),acetaminophen,andcertainfungi.Suchagentsarebelievedtocausehepatitiswhentheformationoftheirtoxic intermediatemetabo-litesinthelivercellisbeyondthecapacityofthehepatocyteto conjugate, or join them with another substance fordetoxificationandexcretion.

Acute Canalicular (Cholestatic) Hepatitis

Acutecanalicular(cholestatic)hepatitisismostcommonlycaused by certain drugs, such as psychopharmacologics,antibiotics,andanabolicsteroidsor,attimes,byhepatitisviruses. The symptoms are generally those of biliaryobstruction and include itching, jaundice, and light-colouredstools.Drug-inducedcholestasisalmostinvariably

215


disappearswithindaysorweeksafterexposuretotheagentisdiscontinued.

Acutecongestiveliverdiseaseusuallyresultsfromthesuddenengorgementoftheliverbyfluidsaftercongestiveheart failure.The liver may enlarge and become tender.Thelevelsofhepatocyticenzymesinthebloodareoftengreatlyincreased,andrecoveryisrapidoncetheheartfailureimproves. Jaundice is uncommon in acute hepaticcongestion.

Chronic Active Hepatitis

Chronichepatitisistheresultofunresolvedacuteinjuryandisassociatedwithongoingliverdamage.Thecourseofthedisease isusuallyslowbutrelentlesslyprogressive.Amilderformofchronicdisease,calledpersistenthepatitis,doesnotappeartoleadtoprogressiveliverdamagedespiteevidenceofacontinuingmildinflammation.Thesecondi-tions may result from viral hepatitis, drug-inducedhepatitis,autoimmuneliverdiseases(lupoidhepatitis),orcongenitalabnormalities.Aprominentautoimmuneliverdisease is Wilson disease, which is caused by abnormaldeposits of large amounts of copper in the liver.Granulomatoushepatitis—aconditioninwhichlocalizedareasofinflammation(granulomas)appearinaportionoftheliverlobule—isatypeofinflammatorydisorderasso-ciatedwithmanysystemicdiseases,includingtuberculosis,sarcoidosis, schistosomiasis, and certain drug reactions.Granulomatous hepatitis rarely leads to serious interfer-encewithhepaticfunction,althoughitisoftenchronic.

ChronicviralhepatitisBandCcanbetreatedwithinterferon. Cirrhosis of the liver, and occasionally livercancer, usually result from a gradual loss of liver func-tion.Chronichepatitisthatistheresultofautoimmune

216


disorders usually responds to the administration ofimmunosuppressivemedicationsandadrenalcorticoste-roids,whichmoderatetheinflammatoryreaction.

Cirrhosis

The end result of many forms of chronic liver injury iscirrhosis,orscarringoflivertissueinresponsetopreviousacinarnecrosisandirregularregenerationoflivernodulesandbileducts.Amongthecongenitaldisordersproducingcirrhosis are Wilson disease, hemochromatosis (over-depositionofironpigment),cysticfibrosis,biliaryatresia(congenitalabsenceofapartofthebileducts),andalpha1-antitrypsin deficiency, or the congenital absence of aproteolyticenzymeinhibitorthatresultsintheaccumula-tionofabnormalformsofcarbohydrateinhepatocytes.

A close-up of a human liver. The right lobe displays severe cirrhosis.3D4Medical.com/GettyImages

217


IntheWesternworld,cirrhosisofthelivermostcom-monlyresultsfromchronicheavyintakeofalcohol.ThistypeofcirrhosisisknownasLaënnec,orportal,cirrhosis.Chronicviralhepatitisisprobablytheleadingcauseofcir-rhosis in underdeveloped countries. Primary biliarycirrhosis—ageographicallywidespread,thoughuncommon,autoimmune inflammatory disease of bile ducts—is adisorder primarily affecting middle-aged and olderwomen.The inflammation leads to necrosis and gradualdisappearanceofbileductsoveraperiodofoneormoredecades.Secondarybiliarycirrhosisresultsfromchronicobstructionorrecurrentinfectionintheextrahepaticbileducts caused by strictures, gallstones, or tumours.Infestationofthebiliarytractwithaliverfluke,Clonorchis sinensis, is a cause of secondary biliary cirrhosis inAsia.Cirrhosis occasionally is the result of chronic vascularcongestion of the liver in persons with prolonged heartfailureandinthosewithchronicobstructionofthehepaticveinscausedbybenignbloodclotsormetastaticcancer.

Symptomsofcirrhosisareusuallyabsentduringtheearly stages of the disease. Occasionally, cirrhosis isdetectedduringaphysicalexaminationwhenanenlarge-mentoftheliver,spleen,orveinsintheupperabdominalwall is found. More often, patients develop symptomsrelated either to the failure of the liver to perform itsfunctionsortocomplicationscausedbythecirculatorychanges that a cirrhotic liver imposes on the venousblood flow from the intestinal tract (portal hyperten-sion). Thus, common symptoms of cirrhosis includejaundice, resulting from reduced passage of conjugatedbilirubinintothebiliarytract;increasedbleeding,fromsequestrationofbloodplateletsinacongestedspleen;ordeficientproductionofshort-livedcoagulationproteinsby the liver.There may be certain changes in the skin,suchastheappearanceofsmallspiderlikevascularlesions

218


onthehands,arms,orface,amarkedreddeningofportionsofthepalms,orenlargementofthebreastinfemalesorreduction in testicular size in males.These symptomsarebelievedtooccurbecauseoftheliver’s inabilitytometabolize the female sex hormones normally pro-ducedbythebody.

The gradual accumulation of fluid in the abdominalcavity (ascites), sometimes accompanied by swelling ofthe ankles, is attributable to portal hypertension and toreduced hepatic production of albumin. Failure of theliver to metabolize amino acids and other products ofproteindigestionmayleadtothestateofconfusioncalledhepatic encephalopathy. Loss of appetite, reduction ofmuscle mass, nausea, vomiting, abdominal pain, andweakness are other symptoms of hepatic cirrhosis.Diabetesinapatientwithcirrhosisisfrequentlycausedbyhemochromatosis(excessivedepositionofironintis-sues, especially in the liver and pancreas), since irondeposits compromise the production of insulin by theisletsofLangerhansinthepancreas.Severespasticdisordersof the muscles in the limbs, head, and face suggest thepresenceofWilsondisease,especiallyifthereisafamilyhistory,sincethecopperdepositscharacteristicofthatdisorderaretoxictotheliverandtostructuresinthebaseofthebrain.Ahistoryofchroniclunginfectionsorofpro-gressiveobstructivelungdiseasemaybepresentinpatientswithcysticfibrosisoradeficiencyofalpha1-antitrypsin.

Adiagnosisofcirrhosisisconfirmedbybloodteststhatshow an elevated concentration of hepatocytic enzymes,reduced levels of coagulation proteins, elevated levels ofbilirubin,and,mostimportantly,reducedamountsofserumalbumin (a major protein of human blood plasma) andincreases in serum globulin (a specific group of proteinsfound in blood plasma and including immunoglobulins).Althoughothertestsmayalsobeabnormalinpatientswith

219


acute liver disease, serum albumin levels are usually notreducedintheacutestageofthediseasebecausethatpro-teinisratherlong-lived(uptoonemonth)andlevelsdonotdecreaseuntiltheliverdiseasebecomeschronic.

Elevatedlevelsofserumironorcoppersupportadiag-nosisofhemochromatosisorWilsondisease,respectively,whileapositivetestforserumantibodiestocellularmito-chondria isassociatedalmostsolelywithprimarybiliarycirrhosis.ThepresenceofHBVsurfaceantigenorofdeltaagentsuggestsviralcirrhosis.Abiopsyoftheliveristhemostvaluablediagnostictest,sincethisproceduremakesavailableanactualspecimenoflivertissueformicroscopicexamination. Treatment of cirrhosis of the liver neverresultsinacompletelynormalorgan,sincetheprocessofscarringandnodularregenerationispermanent.Thepro-cessitself,however,canbepreventedoritsprogresshaltedbymanagingtheprecipitatingfactorsofthedisease.

Hepatic Encephalopathy

Hepatic encephalopathy refers to changes in the brainthat occur in patients with advanced acute or chronicliverdisease.Iflivercellsaredamaged,certainsubstancesthatarenormallycleansedfromthebloodbythehealthyliverarenotremoved.Theseproductsofcellmetabolismareprimarilynitrogenoussubstancesderivedfromprotein,especiallyammonia,orpossiblycertainshort-chainfattyacids.Theypasstothebrainwheretheydamagefunctioningnervoustissueorsubverttheactionsofneurotransmitters—chemicalmessengersthatcarryimpulsesfromonebraincelltoanother.

Inacutecases,thebrainbecomesswollentothepointwhere normal breathing may cease. Chronic exposurecanleadtodestructionofnervecellswithreplacementby scar tissue (gliosis). A patient with chronic hepatic

220


encephalopathymaydevelopprogressivelossofmemory,disorientation,andmusculartremors,leadingtoaformofchronicdementia.Theingestionofproteininvariablyaggravatesthesesymptoms.Patientswithgastrointestinalbleeding,infection,kidneyfailure,andconstipationandthosewhoaretakingcertainmedicationsareallatriskofworsenedepisodesofhepaticencephalopathy.

The treatment of hepatic encephalopathy involves,first,theremovalofalldrugsthatrequiredetoxificationinthe liver and, second, the reduction of protein intake.Ammonia is a potentially harmful by-product of diges-tion,anditsconcentrationinthebloodcanbeloweredinone of two ways. The first is through the reduction ofintestinalbacteriabyadministrationofentericantibiotics,which reduce the production of ammonia in the colon.Theotherisbyadministrationoflactulose,anonabsorb-ablecarbohydratewhoseby-productsmakethecontentsof the colon more acidic, creating an environment thatreduces the diffusion of ammonia from the intestinallumentotheportalbloodvessels.

Portal Hypertension

Portalhypertensionistheincreasedpressureintheportalveinanditstributaries.Itistheresultofimpedimentstovenous flow into the liver, and is brought about by thescarring characteristic of the cirrhotic process. Theincreased pressure causes feeders of the portal vein todistend markedly, producing varices, or dilations of theveins.Whenvaricesarelocatedinsuperficialtissues,theymayruptureandbleedprofusely.Varicesmostcommonlyoccurintheloweresophagus,thestomach,andtheperi-anal region. Esophageal varices are likely to bleed mostheavily,and,becauseofthereducedbloodflowintheliverthatresultsandthelargeamountofproteincontainedin

221


thebloodthatisshedintotheintestines,profusebleedingfromesophagealvaricesisfrequentlyassociatedwiththeonsetofhepaticencephalopathyorcoma.Becauseoftheirlocationatthe lowerendoftheesophagusortheupperportion of the stomach, bleeding from varices is oftendifficult tocontrol. Itmaystopspontaneously,but it islikelytorecur.

Considerable success in stemming such hemorrhageandpreventingitsrecurrencehasbeenachievedbyusingrubberbandstoblockthebloodsupplytoeachvarixorbytheinjectionofsclerosing(hardening)agentsintovaricesduring endoscopic visualization. If variceal bleedingpersistsandifthepatientcanwithstandalongandcomplexoperativeprocedure,surgicalformationofashunt,orarti-ficial passageway, may be performed.The shunt may gofrom the portal vein or one of its feeders to a systemicabdominalvein,suchasthevenacavaortheleftrenalvein,orfromthehepaticveintotheportalvein.

Ascites

Theaccumulationoffluidintheabdominalcavity,orascites,isrelatedtoportalhypertension,significantreductioninserum albumin, and renal retention of sodium. Whenalbuminlevelsinthebloodarelowerthannormal,thereisamarkedreductionintheforcethatholdsplasmawaterwithinthebloodvesselsandnormallyresiststheeffectsoftheintravascularpressure.Theresultingincreaseinintra-vascular pressure, coupled with the increased internalpressure caused by the portal venous obstruction in theliver, leads to massive losses of plasma water into theabdominalcavity.Theassociatedreductionofbloodflowtothekidneyscausesincreasedelaborationofthehormonealdosterone,which,inturn,causestheretentionofsodiumandwaterandareductioninurinaryoutput.Inaddition,

222


becausethemovementofintestinallymphintotheliverisblockedbythecirrhoticprocessintheliver,thebackflowofthisfluidintotheabdominalcavityisgreatlyincreased.

Thevolumeofabdominalascitesinadultswithcirrhosismayreachlevelsasgreatas10to12litres(11to13quarts).Asciticfluidmayaccumulateinthescrotumandinthechestcavity, where its presence, combined with the upwardpressureonthediaphragmfromtheabdominalfluid,mayseverely affect breathing.Appetite also is often reducedbytheabdominaldistention.

The treatment of cirrhotic ascites begins with theremoval of enough fluid directly from the abdomen byneedle puncture to ease discomfort and breathing.Patientsareplacedondietslowinsalt(sodiumchloride),andtheyaregivendiureticdrugstoincreasetheoutputofwater by the kidneys. If these measures do not controlmassiveascites,ascitescanbedrainedinternallyintothegeneralvenousbloodsystembyrunningaplastictubefromtheabdominalcavity,undertheskinofthechest,intotheright internal jugular vein of the neck (peritoneovenousshuntofLeVeen)orfromthehepaticveintotheportalvein.

Hepatorenal Syndrome

Hepatorenalsyndrome,aprogressivereductioninkidneyfunctionthatoftenoccursinpersonswithadvancedacuteor chronic liver disease, probably results from an inade-quateflowofbloodthroughthecortical(outer)portionsof the kidneys, where most removal of waste productsoccurs.Insomeinstances,hepatorenalsyndromeiscausedbymarkedreductionsinbloodvolumethatresultfromalow concentration of water in the blood. Hemorrhagesalsocanreducekidneyfunctionbyleadingtodamageofrenaltubules.

223


With advanced hepatocytic dysfunction, a spasm ofbloodvesselsintherenalcortexcanoccur,whichresultsinprogressivefailureinkidneyfunctionandoftenleadstodeath.Thekidneysthemselvesarefrequentlyundamagedstructurally.Treatmentofpatientswithvolumedepletionandtubulardamageoftenmayleadtosignificantimprove-ment in kidney function. Dialysis may improvesymptoms.

Liver Cancer

Livercancerreferstoanyofseveralformsofdiseasethatare characterized by tumours in the liver. Benign livertumoursremain inthe liver,whereasmalignanttumoursare,bydefinition,cancerousandthuscapableofinvadingtissuesoutsidetheliver.Mostmalignantlivertumoursarehepatomas,alsocalledhepatocellularcarcinomas(HCCs).HCCsaccountforfewerthan1percentofU.S.cancersbutarecommoninAfrica,SoutheastAsia,andChina.Thesetumours begin in the functional cells of the liver andaccountfor85percentofalllivercancers.Theremainingcancersdevelopfrombloodvessels(hemangiosarcomas),smallbileducts,(cholangiocarcinomas),orimmaturelivercells (hepatoblastomas). Hepatoblastomas occur primar-ilyinchildren.Treatmentandprognosisforlivercancersvary, depending on the type and stage, or degree, ofadvancement.

Causes and Symptoms of Liver Cancer

Thecausesoflivercancervaryandinmanycasesremainunknown, but several factors have been identified thatincrease the risk of developing the disease. PreviousinfectionwithhepatitisBorhepatitisCvirusesisclearlylinkedtolivercancer,asiscirrhosisoftheliver.Exposure

224


to several chemicals also increases cancer risk. Thesechemicalsincludevinylchloride(commonlyusedinplasticsmanufacturing),thoriumdioxide(onceusedwithcertainX-rayprocedures),aflatoxin(apoisonproducedbyafungusofspoiledpeanutsandcertaingrainproducts),andarsenic.Use of anabolic steroids and oral contraceptives mayincreasetheriskofcertaintypesof livercancer.Otherillnesses suchasgallstones,chronic inflammationof thecolon or gallbladder, and certain parasitic infections arealsoriskfactors.

Symptoms of liver cancer often remain undetecteduntil the disease has progressed to an advanced stage.Symptoms include abdominal pain or swelling, loss ofappetite, unexplained weight loss, an early sense of full-ness during meals, or jaundice. Individuals with chronicliverdiseasesmayexperienceasuddenworseningoftheiroverall condition. Laboratory tests may reveal elevatedlevelsofcalciumintheblood, lowbloodsugar,orothersignsofliverdysfunction.

Diagnosis and Prognosis of Liver Cancer

Earlydiagnosisofliverdisordersusuallyinvolvesabloodtest for abnormal liver function. Special tests for twospecificantigensinthebloodmayalsoindicatelivercancer.Ifcancerissuspected,abiopsywillbedoneeitherduringexploratory surgery or by inserting a thin needle intotheliver.

Thecancerisfurtherdiagnosedbymeansofimagingtechniques such as CT scans, MRI, and ultrasound. InsomecasesanX-rayprocedurecalledangiographywillbeusedtoexaminebloodvessels inandaroundthe liver.Aphysiciancanalsodirectlyexaminetheliverwithalaparo-scope,aflexibletubewithalensontheendthatisinsertedthroughanincisionintheabdomen.

225


Oncelivercancerhasbeendiagnosed,itsstageisthendeterminedtoindicatehowfarthecancerhasprogressed.Some tumours that are localized, or found in a confinedarea of the liver, may be completely removed. Otherlocalized cancers cannot be completely removed, as theresultant loss of remaining liver function would be fatal.Advancedcancerhaseitherinvadedalargeportionoftheliverorspread(metastasized)todistanttissuesinthebody.

Whereassurvivabilityofmostcancersisexpressedintermsofafive-yearsurvivalrate,therapidcourseofthisdisease following appearance of symptoms has resultedinuseofathree-yearsurvivalrate.Thisrateisfairlyhighifthecancerislocalizedandcanbecompletelyremovedbysurgery.Ifthecancerislocalizedbutinoperable,therateislower,andinmoreadvancedstagesoflivercancerthe three-year survival is low. Unfortunately, overall sur-vivalfromlivercancerislowerthanthatformanyothertypesofcancerbecause it isnotusuallydetected in itsearlystages.

Treatment and Prevention of Liver Cancer

Surgerycancurelivercancer,butonlywhenthecancerislimited to a region small enough to permit its removalwhileleavingenoughoftheliverbehindtoperformnormalfunctions. Surgery is not curative for cancers that havespreadbeyondtheliverandisnotusuallyrecommendedforpatientswithcirrhosis.Whensurgeryisnotanoption,somelocaltumourscanbedestroyedeitherbybeingfrozenorbybeinginjectedwithalcohol.Othercancersmaybestarvedbyblockingnearbybloodvessels.Thisprocedure,however, carries inherent risks because it also blocksbloodflowtohealthylivertissue.

Radiation therapy is rarely used to treat liver cancerowing to the high sensitivity of healthy liver cells to

226


radiation. Chemotherapy may be used, especially if thecancer has spread to distant tissues, to seek out anddestroy as many cancer cells as possible.A chemothera-peuticagentmay,insomecases,beadministereddirectlyintothemainarterythatfeedstheliver.Thisallowsdirectdelivery of cancer-destroying drugs to the liver whileminimizingsystemicexposure.

Theriskoflivercancercanbegreatlyreducedbytakingstepstoeliminatekeyriskfactors.HepatitisBinfectioncanbe prevented by vaccination against the virus and byavoidingunprotectedsexualcontactorcontactwithhumanblood.HepatitisCcanalsobeavoidedbyeliminatingdirectexposuretoblood.Alcoholconsumptionshouldbelimited;anabolicsteroidsshouldneverbeusedwithouttheadviceof a physician; and guidelines regarding vinyl chlorideexposureshouldbefollowed.

diSeaSeS of the biliary tract

There are several important diseases of the biliary tractthataffectthefunctionnotonlyofthebiliarysystembutalsooftheorgansandtissuesassociatedwithit.Disordersofthebiliarytractcanleadtoanexcessaccumulationofbilepigmentsinthebloodstream,givingrisetojaundice,inwhichtheskin,thewhitesoftheeyes,andthemucousmembranes acquire a yellow to orange and sometimesevengreenishdiscoloration.Examplesofbiliarydiseasesincludegallstonesandcancer.

Gallstones

Cholelithiasis,ortheformationofgallstonesinthegall-bladder,isthemostcommondiseaseofthebiliarytract.Gallstonesareofthreetypes:stonescontainingprimarilycalcium bilirubinate (pigment stones); stones containing

227


25percentormoreofcholesterol(cholesterolstones);andstones composed of variable mixtures of both bilirubinandcholesterol(mixedgallstones).

PigmentstonesaremorecommonincertainpartsofAsiathanintheWesternworld,andtheyusuallyoccurinpersons who have forms of anemia caused by the rapiddestruction of red blood cells (hemolysis). Hemolyticdiseaseresultsfromthehereditaryoracquiredacquisitionofabnormalformsofhemoglobinorfromabnormalitiesoftheredbloodcellmembraneindisorderssuchassicklecellanemia, thalassemia, or acquired hemolytic anemias.Increased destruction of red blood cells leads to abnor-mally large amounts of bilirubin, the hemoglobinderivative,intheliverandtheconsequentsecretionintothebiliarytractofincreasedamountsofthewater-solubleconjugate, bilirubin diglucuronide, a pigment that isnormallysecretedintheurine.Inthebiliarytract,particu-larlyinthegallbladder,someofthisbilirubindiglucuronideisbrokendownbyenzymesintowater-insolublebilirubin,whichthentendstoformstones.

There are two types of pigment stones, black andbrown.Blackstonestendtoformmainlyinthegallbladderandoccurinsterilebile,whilebrownstonesmayoccurinanypartofthebiliarytractinpatientswithchronicbiliaryinfectionsandstasis(stagnationofblood).Thereasonsfortheincreasedincidenceofpigmentstonesamongpersonswith cirrhosis of the liver and the elderly are not clear,althoughincreasedredbloodcelldestructionmayplayapart.The occurrence of pigment stones is slightly morecommoninwomen.

Cholesterol and mixed stones occur when the pro-portionofcholesterolinbileexceedsthecapacityofbileacidsandthephospholipidlecithintocontainthetotalamount of cholesterol in micellar colloidal solution.When this critical micellar concentration is surpassed

228


andthesolutionissaturated,crystallineparticlesofcho-lesterol are formed. The resulting gallstones containlarge amounts of crystalline cholesterol and smallerquantitiesofcalciumbilirubinate.Purecholesterolgall-stonesarerare.

Cholesterolgallstonesoccurabouttwiceasfrequentlyinwomenastheydoinmen,andatyoungerages.Thoseatincreasedriskofcholesterolgallstonesincludepersonswhoareobese,ondietshighincaloriccontentorincholesterol,diabetic,ortakingfemalesexhormones.Eachofthesefac-torsfavoursincreasedconcentrationsofcholesterolinbile.Inaddition,somepersonsareunable,forgeneticreasons,toconvertsufficientamountsofcholesteroltobileacids,thusfavouringtheincreasedformationofstones.

Some illnesses, such as Crohn disease, reduce thecapacityofthelowersmallintestinetoreabsorbbileacids,leadingtodeficitsofbileacidsthatcannotbeovercomebyhepaticsynthesisalone.Duringpregnancy,theratioofchenodeoxycholic acid to cholic acid in hepatic bile isreduced,thusmakingbilemorepronetoproducestones.Decreasedflowofbileinthegallbladder,aconditionthatoccurslateinpregnancy,inpersonsondietslowinfat,andamongdiabetics,alsoappearstofavourtheformationofcholesterol stones. Occasionally, some persons producelithogenic bile, which results from reduced concentra-tionsofphospholipids.

Symptomsare likely tobeabsent inabouthalfofallpatients who have gallstones. When they do appear,symptomsarecausedbyobstructionofaportionofthebiliarytract,mostcommonlythecysticductatthepointwhere itemerges fromthegallbladder.Thisobstructionleadstopainfulcontractionofthegallbladder,swellingofitswall,andacuteinflammation(cholecystitis).Duringanattack of cholecystitis, patients are often found to have

229


fever,sharppainintheupperabdomen(whichalsomaybefelt in the right shoulder region), tenderness over theregionofthegallbladder,andelevationsofthewhitebloodcellcount.Iftheobstructionoftheneckofthegallbladderisprolonged,bacterialinfectionsmayappear,leadingtoformationofanabscess.

Patientswithbacterialinfectionsinthegallbladderorbileductscommonlyhavesevereshakingchills,withhigh,spiking fevers. Jaundice does not occur with gallstonecomplications unless the stones become impacted andobstructthecommonbileduct,thusslowingorinterrupt-ingthefreepassageofbilefromthelivertotheintestine.This jaundice is associated with a marked lightening ofstoolcolour,causedbytheabsenceofbilepigmentsintheintestine, and a change in the colour of urine to a darkamber,causedbylargequantitiesofconjugatedbilirubin.

Illustration of a gallbladder that has been sectioned to reveal the gallstones contained within it. 3D4Medical.com/GettyImages

230


Gallstones are easy to diagnose since canaliculi, smallchannelsinthegallbladder,canbeeasilydetectedbyultra-sonography.Enlargementofthegallbladderandbileducts(resulting from obstruction) also can be detected by thismethod. If gallstones are discovered on routine examina-tionorduringabdominalsurgeryforotherreasons,andifthepatienthasnohistoryofgallstonesymptoms,nothingprobablyneedstobedone.Thesituationisdifferent,how-ever, in persons who are clearly symptomatic or who aresuffering acute complications, such as cholecystitis orabscesses.Thetraditionaltreatmentinthesecasesissurgi-calremovalofthediseasedgallbladderandexplorationofthebileductsbyX-raysatthetimeofsurgeryforstones.Oncethegallbladderandductalstonesareremoved,thereislittlelikelihoodthatcholesterolorblackpigmentstoneswillrecur,althoughbrownpigmentstonesmayoccasionallyrecurinthebileductsaftercholecystectomy.

Cholesterolgallstonescanbedissolvedwithoutsurgeryaslongasthegallbladderhasretaineditsabilitytoconcen-trate bile and the cystic duct is unobstructed. This isaccomplished by regular oral administration of drugsmadefrombileacidscalledurosodiolandchenodiol.Theingestion of these medications increases the amount ofbile acids in hepatic bile and increases the ratio of bileacids to cholesterol, thus changing the bile from litho-genic to nonlithogenic. This medication must becontinuedformorethanoneyearforthecholesterolgall-stones to be completely dissolved and then continuedpermanently at reduced doses to prevent the reappear-ance of stones. Only a small percentage of patients arewillingtoundergothispermanenttreatment,andtheuseof bile acids is confined either to those who stronglyopposesurgeryorthoseforwhomsurgeryimposesgreatrisk.Pigmentstonesdonotrespondtobileacidtherapy.

231


Other Biliary Tract Disorders

Cancerofthebiliarytractisrarebutmayoccurinalmostanystructure,includingthegallbladder,thehepaticducts,the common bile duct, or the hepatopancreatic ampulla(ampullaofVater).About90percentofpersonswithprimarycancerofthegallbladderalsohavegallstones.Theriskofcancer in persons with gallstones, however, is very low(about1percentorless).

Congenitalcystsandparasiticinfections,suchasliverflukes,seemtoleadtoincreasedriskofcancerofthebileduct.Personswithextensivechroniculcerativecolitisorprimary sclerosing cholangitis also show a greater thannormal incidence of bile duct carcinoma. Obstructivejaundice is usually the first sign of biliary tract cancer.Surgery is the only treatment, and the cure rate is low.Becausemostbiliaryductcancersgrowveryslowly,physi-cians often try to relieve the obstructive jaundice bypassing tubular stents (supporting devices) through theobstruction,usingendoscopicorradiologictechniques.

Postcholecystectomy syndrome is characterized bypainfulattacks,oftenresemblingpreoperativesymptoms,thatoccasionallyoccurfollowingthesurgicalremovalofgallstones and the gallbladder. These attacks may berelated to biliary stricture, gallstones, or intermittentmuscularspasmsofthesphincterofOddi(hepatopancre-aticsphincter).Drugsareusedtohelppreventorreducesymptoms.

Jaundice

Jaundice,oryellowingoftheskin,sclera(outerlayeroftheeyeball), and mucous membranes, occurs whenever thelevel of bilirubin in the blood is significantly above

232


normal.Thisconditionisevidentinthreedifferenttypesof disorders, more than one of which may be presentsimultaneouslyinasingleperson.

Thefirsttype,unconjugated,orhemolytic,jaundice,appears when the amount of bilirubin produced fromhemoglobinbythedestructionofredbloodcellsormus-cletissue(myoglobin)exceedsthenormalcapacityofthelivertotransportit.Thiscanalsohappenwhentheabil-ityofthelivertoconjugatenormalamountsofbilirubininto bilirubin diglucuronide is significantly reduced byinadequate intracellular transport or enzyme systems.The second type, hepatocellular jaundice, arises whenliver cells are damaged so severely that their ability totransportbilirubindiglucuronideintothebiliarysystemis reduced, allowing some of this yellow pigment toregurgitateintothebloodstream.Thethirdtype,chole-static, or obstructive jaundice, occurs when essentiallynormallivercellsareunabletotransportbilirubineitherthroughthecapillarymembraneoftheliver,becauseofdamageinthatarea,orthroughthebiliarytract,becauseof anatomical obstructions (closure or absence of anopening,gallstones,cancer).

Unconjugated Jaundice

Unconjugated,orhemolytic,jaundiceischaracterizedbytheabsenceofbilepigmentsintheurineandbynormalstoolcolor.Thecolouroftheurineisnormalbecausethebilirubininthebloodisunconjugatedtoglucuronicacidandthereforeboundtobloodalbuminandinsoluble inwater.Thusthebilirubin isnotfilteredbythekidneys.The color of stools remains normal because muchof thebilirubin intheblood isfilterednormallybytheliverandenterstheintestinepromptlybywayofthebili-arysystem.

233


Hemolytic diseases in newborns may lead to seriousbraindamage (kernicterus) if theunconjugatedbilirubincrosses into the brain stem and destroys vital nuclei.Exposinginfantsatriskforkernicterustobluelightcon-vertsthebilirubintoharmlessandcolourlessdegradationproducts.Unconjugatedhyperbilirubinemiaalsooccursinmany newborns, especially if they are premature, whenthebilirubintransportenzymesystemsarenotfullydevel-oped.Thisdisorderisself-limited,mayrequireoccasionalexposurestobluelight,andusuallydisappearswithinthefirsttwoweeksofextrauterinelife.Gilbertdisease,afairlycommon hereditary deficiency in the hepatic transportprotein ligandin and the conjugating enzyme glucuronyltransferase,resultsinaharmlesslifelongtendencytomilddegreesofunconjugatedjaundice,especiallyduringperiodsoffastingorfatigue.

This newborn baby is being treated for jaundice by being placed under bili lights. RoderickChen/FirstLight/GettyImages

234


Hepatocellular Jaundice

Hepatocellular jaundice,present inall typesofhepatitisandcirrhosisandincongestiveliverdisease,ischaracter-izedbydarkamberurineandnormalorslightlypalerthannormalstools.Becausemuchofthebilirubininthebloodalreadyhasbeenconjugatedbytheendoplasmicreticulumofthehepatocyte,itiswater-solubleandcanbefilteredbythekidneys.Stoolsareusuallynormalbecausesomebilepigmentalsomanagestobeexcretedintothebiliarytractandintestine.

Cholestatic Jaundice

Cholestatic jaundice is also distinguished by amber-colouredurine,butthecolourofthestoolsislikelytobeverypale(clay-coloured)duetothefailureofbilepigmentstopassintotheintestine.Itchingoftheskiniscommonlyassociatedwiththiscondition.Cholestasisoccursinmanytypesofhepatitis,especiallythosecausedbycertaindrugs,andindiseasesthatprimarilydamagesmallbilepassagesintheliver(intrahepticcholestasis).Cholestaticjaundicealsooccurs inpatientswithobstructivedisordersof thebiliarytractoutsideoftheliver(extrahepaticcholestasis).It is often impossible to determine the level of obstruc-tion by means of examination alone, and moresophisticated imaging techniques are required to locatethesiteofdamage.

diSeaSeS of the pancreaS

Diseasesofthepancreascanhavesevereimpactsondiges-tionandontheutilizationofcarbohydratesbythebody.Examples of common conditions affecting the digestivefunctionsofthisorganarepancreatitis,inwhichinflam-mation causes the digestive enzymes produced by the

235


organtobreakdownthetissuesofthepancreasitself,andpancreaticcancer,inwhichtheabnormalgrowthofcellscausesseveredysregulationintheproductionandsecre-tion of pancreatic hormones and enzymes. Pancreaticdiseasealsooccursasacomplicationofcysticfibrosis,inwhichthickmucusplugsblockthenormalsecretoryfunc-tionsoftheorgan.

Pancreatitis

Inflammationofthepancreas,orpancreatitis,isprobablythemostcommondiseaseofthisorgan.Thedisordermaybeconfinedtoeithersingularorrepeatedacuteepisodes,oritmaybecomeachronicdisease.Therearemanyfactorsassociatedwiththeonsetofpancreatitis,includingdirectinjury to the pancreas, certain drugs, viral infections,heredity, hyperlipidemia (increased levels of blood fats),andcongenitaldeformitiesoftheductalsystem.

IntheWesternworld,mostcasesarerelatedeithertoalcoholism or to gallstones, especially when stones passspontaneouslyintothehepatopancreaticampulla(ampullaofVater).Althoughtheimmediatecauseofacutepancre-atitisisnotalwaysclear,itseemstoinvolveoneormoreofthe following factors: heavy stimulation of pancreaticacini;increasedpressurewithintheductbecauseofpartialobstruction (gallstones) or edema (alcohol); and damagetothefineductalnetworkinthepancreas,whichallowstheescapeofactivatedanddestructivedigestiveenzymesinto the substance of the pancreas itself and into sur-roundingtissues.

Overstimulation of secretory enzyme productionmechanismsintheacinarcellmayalsoleadtotheactiva-tionofintracellular(lysosomal)enzymesystems,resultingin the conversion of proenzymes to active forms thatbegintodigestcellularorganelles.Theglandthusbegins

236


to self-destruct. Similar damage may appear in otherorgans,suchasthelungs,kidneys,andbloodvessels,whichreceive these activated enzymes by way of the blood-stream.Itisnotclearhowtheproenzymetrypsinogenisconvertedtotrypsininthedamagedacinarcell,butitisknownthattheactivationoftheotherproenzymespro-ceeds from this conversion. The extent of acinardestruction appears to depend on the strength of thecausativefactors.

Localized,severeabdominalandmidbackpainresult-ing from enzyme leakage, tissue damage, and nerveirritationisthemostcommonsymptomofacutepancre-atitis.Inseverecases,respiratoryfailure,shock,andevendeathmayoccur.Theseverityofthesymptomsgenerallydependsontheextentofthedamagetothepancreas.Thediagnosisisconfirmedbythedetectionofelevatedlevelsof pancreatic enzymes (amylase and lipase) in the bloodand,ifisletcellfunctionisdisturbedbytheinflammatoryprocess, elevated blood glucose levels. Ultrasonographicor CT scans of the upper abdomen usually reveal anenlargedandswollenpancreas.Sustainedpain,oftenwithfever, suggests the presence of a pseudocyst or abscesscausedbylocalizedareasofdestructionandinfectionsinthepancreas.

Acutepancreatitisistreatedprimarilybysupportivetherapy,withreplacementoffluidandsodiumandcontrolof pain. In severe cases, washing necrotic material andactiveenzymesfromtheabdominalcavityduringsurgerymay be beneficial. Following recovery from an acuteattack, thepreventionof furtherattacksshouldbe theprimarygoal.Thus,theremovalofgallstones,cessationofalcoholconsumption,alow-fatdiet,anddiscontinuationof toxic drugs (thiazide diuretics, immunosuppressives,and corticosteroids, for example) can be helpful mea-sures. In instances where repeated attacks of acute

237


pancreatitishaveresultedinstrictures(scars)ofthemainpancreaticduct,surgicalrepairmaydecreasethenumberoffurtherattacks.

Chronic Pancreatitis

Chronicpancreatitisrarelyfollowsrepeatedacuteattacks.Itseemsinsteadtobeaseparatedisorderthatcanresultfrommucusplugsandprecipitationofcalciumsaltsinthesmaller pancreatic ducts. The progressive loss of acinarand islet cell function follows, presumably as a conse-quence of continuous inflammation resulting from theductalblockage.Progressivecalcification,whichattimesresultsintheformationofstonesinthemajorpancreaticducts,hasbeenattributedtodiminishedproductionofanacinarproteinthatnormallyholdscalciuminsolution.

AlcoholismandcertainhereditaryfactorsaccountforalmostallofthecasesofchronicpancreatitisseenintheWesternworld.Chronicproteinmalnutritionisaprimarycauseinunderdevelopedcountries.Recurrentabdominalpain, diabetes, and intestinal malabsorption of dietarynutrientsarethemainsymptomsofchronicpancreatitis.Weightlossanddeficienciesoffat-solublevitamins(A,D,E, and K) are common. Treatment includes abstinencefrom alcohol, management of diabetes with insulin, andingestionoforalpancreaticenzymesupplementstocorrectdietarymalabsorption.

Cystic Fibrosis

Cysticfibrosisisinherited,butitisnotexpressedunlessbothmembersofapairofhomologous,orcorresponding,chromosomescarrythetrait.Themajorfunctionalabnor-mality in persons with the disease appears to be theelaboration by mucous glands throughout the body of

238


secretionscontaininggreaterthannormalconcentrationsofproteinandcalcium.Thisimbalanceleadstoincreasedviscosityofthesecretionsofmucusandorganicconstitu-entsinglandducts.Theresultingpluggingprocessinthepancreas almost invariably causes destruction and scar-ring of the acinar tissue, usually without damaging theisletsofLangerhans.Asimilarprocessinthehepaticbiliarysystemproducesaformofcirrhosis.Incysticfibrosis,theresultingpancreaticinsufficiencyusuallycanbetreatedbytheoralreplacementofpancreaticenzymes.

Pancreatic Cancer

Pancreaticcancerisadiseasecharacterizedbyabnormalgrowthofcellsinthepancreas.Thepancreasisprimarilymadeupoftwodifferenttissueswithseparatefunctions.Thefirsttissue,theexocrinepancreas,secretesenzymesintothedigestivetract,aidingthebreakdownoffatsandproteins. The other is the endocrine pancreas, whichsecretesglucagonandinsulinintothebloodstreamtocon-trolbloodsugarlevels.Ninety-fivepercentofpancreaticcancersdevelopfromtheexocrinepancreas.Theremaining5percentareoftencalledneuroendocrinetumoursorisletcellcancers;thesedevelopfromendocrinecells.

Causes and Symptoms of Pancreatic Cancer

Asisthecasewithmanycancers,symptomsofpancreaticcancer are shared with those of many other illnesses.Symptoms often do not appear until the cancer hasadvanced to a late stage. They include abdominal pain,unexplainedweightloss,problemswithsugarmetabolism,anddifficultydigestingfattyfoods.Asapancreatictumourgrows,itmayblockthecommonbileduct,whichleadstoabuildupofbilirubininthebloodandcausesjaundice(a

239


yellowingoftheskinandeyes).Blockageofthebileductmayalsocausethegallbladdertobecomeenlarged.

Thecausesofpancreaticcancervaryandinmanycasesremain unknown. However, several factors have beenidentifiedthatincreasetheriskofdevelopingpancreaticcancer.Thetwomostimportantofthesefactorsaresmok-ing,whichisassociatedwithabout30percentofpancreatictumours,andcentralobesity(accumulationoffatprimarilyaroundtheabdomen),whichcanincreaseriskofpancreaticcancerbyasmuchas70percentinsomepostmenopausalwomen.Inbothmenandwomen,centralobesityisassoci-atedwithincreasedlevelsofinsulinandwithdisruptionofnormalendocrineandmetabolicfunctions.However,themechanism by which abnormally high insulin levels anddysfunctional metabolism in centrally obese individualsgive rise to pancreatic cancer is unclear. Furthermore, adiethighinanimalproducts,particularlyanimalfat,alsoincreasescancerrisk.

Environmental factors, such as exposure to certaindyes, pesticides, and petroleum products, may increasethe probability of developing pancreatic cancer.Uncontrollableriskfactorsincludeage,sex—malesare30percent more likely to develop cancers of the pancreasthanarefemales—andillnessessuchasdiabetesmellitusandchronicpancreatitis.Anestimated10percentofcasesof pancreatic cancer are the result of inherited defects.Some of these cases arise in association with knowngenetic syndromes, such as Peutz-Jeghers syndrome andhereditary nonpolyposis colon cancer. Other cases areassociated with familial pancreatic cancer, generallydefinedastheoccurrenceofpancreaticcancerinatleastonepairoffirst-degreerelatives.Mutationsinagenedes-ignated PALLD (palladin, or cytoskeletal associatedprotein)havebeenlinkedtofamilialpancreaticcancer.

240


Diagnosis of Pancreatic Cancer

Bloodteststhatassessvariouspancreaticandliverfunc-tionsmaysuggestpancreaticcancer.Ifcancerissuspected,aneedlebiopsyoranendoscopyprocedureisusuallycon-ductedtoexaminepancreaticcellsorthepancreasitselfforsignsofcancer.However,theseproceduresareinvasiveandareassociatedwithanincreasedriskforseriouscom-plications,includingpancreatitis.

Inordertomakeacorrectdiagnosisandtodeterminethestageofthecancer,multipleimagingtechniquesmaybe employed that allow doctors to see the pancreas,despite its location deep within the abdominal cavity.Imaging techniques commonly used include CT scans,MRI,anddifferenttypesofultrasound,includingtrans-abdominalultrasound(imagingperformedontheexternalsurfaceoftheabdomen)andendoscopicultrasound(EUS;anultrasounddeviceissentthroughanendoscopetotakeimagesofinternaltissues).Varioustechniquesthatcom-bine contrast agents (dyes) with X-ray imaging are alsoused to determine whether the bile duct or other ductswithin the pancreas are blocked. One example is calledpercutaneous transhepatic cholangiography (PTC), inwhichaneedleisusedtoinjectadyedirectlyintotheliver,followed by X-ray imaging. Other X-ray imaging tech-niques include angiography, in whichX-rays are used toviewbloodvesselstodetermineifthecancerhasspreadthroughthewallsofthevesselsfeedingintothepancreas.

Becauseearlydetectionofpancreaticcanceriscriticalfor patient survival, research is becoming increasinglyfocused on specific markers (subtle, identifiable cellularchanges) that are detectable in precancerous pancreaticlesions. One method of early detection employs speciallight-scattering spectroscopy techniques in combinationwithexistingendoscopetechnology.Thislight-scattering

241


imagingtechnologyisextremelysensitiveandisaimedatdetectingspecificmarkersincellsinthefirstpartofthesmallintestine(theduodenum)thatareindicativeofveryearlyprecancerouspancreaticlesions.Itisalsomuchlessinvasive than needle biopsy and traditional endoscopyproceduresforpancreaticlesiondetectionbecausedoctorsneedonlyexamineaneasilyaccessibleregioninthesmallintestine.

Oncepancreaticcancerhasbeendiagnosed,itsstageis then determined to indicate how far the cancer hasprogressed.StageIcancersareconfinedtothepancreasand have not spread to nearby lymph nodes. Stage IIcancershavespreadlocallytothebileductorsmallintes-tine but have not reached the lymph nodes, whereasstage III tumours have reached these nodes. Stage IVcancers have spread to other organs such as the lungs,liver,spleen,orcolon.

Thesurvivalratefrompancreaticcancerislowerthanthatseenwithmanyothercancersbecausethesymptomsof pancreatic cancer often do not become obvious untilthelaterstagesofthedisease.Theaveragefive-yearsurvivalratefromallstagesofpancreaticcancerisextremelylow,asistheone-yearsurvivalrate.However,survivalratesarehigherforpatientswhohavetheircancerdiagnosedearlyinthecourseofthedisease.

Treatment and Prevention of Pancreatic Cancer

Surgerycanbeusedtotreatpancreaticcancer,but,giventhepoorprognosisofthediseaseandtheunusuallyhighnumber of complications associated with pancreatic sur-gery,surgeryisusuallyreservedforcasesinwhichthereisareasonablepossibilityofcuringthedisease.Ifthecancerisconsideredtobeincurable,majorsurgeryisdonemainlyto relieve symptoms or digestive problems. Islet celltumoursareoftenlocalizedtothetailofthepancreas,and

242


adistalpancreatectomymaybeconductedtoremovethisportionofthepancreasalongwiththespleen.

ExocrinecancersareoftentreatedwiththeWhippleprocedure,acomplicatedsurgicalapproachthatremovesall or part of the pancreas and nearby lymph nodes, thegallbladder,andportionsofthestomach,smallintestine,andbileduct.Seriouscomplicationsoftenarisefollowingthisprocedure,whichrequiresanextensivehospitalstayandconsiderableexperienceonthepartof thesurgeon.Other exocrine tumours are sometimes treated by com-plete removal of the pancreas (total pancreatectomy).Surgerycanalsobeusedtorelievecomplicationsofpan-creaticcancers,suchasobstructionofthebileduct.Thebileductmayberedirectedaroundthetumour,oratubemaybeplacedinthebileducttokeepitopen.

Radiation therapy is sometimes used in conjunctionwithsurgery—oftenpriortosurgerytoreduceatumourtoamoremanageablesizebutalsoaftersurgerytodestroyanyremainingcancercells.Thepositionofthepancreasin the abdominal cavity makes it a difficult target forfocusedradiotherapy,butaprocedureusingradiotherapysimultaneouslywithsurgerypermitsthesurgeontofocusradiationdirectlyontothepancreasbymovingobstruct-ingorgansaside.Sideeffectsofthisradiationtherapymayinclude vomiting, diarrhea, fatigue, or skin irritationsresemblingasunburn.

Chemotherapy is generally used when pancreaticcancershavespreadtodistantorgansandmayberequiredsothatasmanycancercellsaspossiblecanbesoughtoutand destroyed. Endocrine or islet cell tumours may betreatedwithhormonetherapy,inwhichspecifichormonesareusedtostoporslowthegrowthofthecancer intheendocrinecells.Targeteddrugtherapiesthatblockcellularprocessesdrivingcancercellproliferationhavebeenusedin combination with chemotherapy in some pancreatic

243


cancer patients. For example, a drug called erlotinib(Tarceva)blockstheactivityofakinase(atypeofenzyme)associated with the epidermal growth factor receptor(EGFR),whichstimulatesunregulatedcelldivisionwhenmutatedincancercells.Whenerlotinibisgivenincombi-nation with the chemotherapeutic agent gemcitabine(Gemzar),anantimetabolitethatinhibitsthesynthesisofgenetic material in dividing cells, patient survival isimproved,althoughonlymodestly.Severalothertargeteddrugssuchascetuximab(Erbitux),amonoclonalantibodythatbindstoEGFRandthuspreventskinaseactivationandcelldivision,arebeingdevelopedandtestedinclinicaltrialsforpancreaticcancer.

Inmostcases,pancreaticcancercannotbecompletelyprevented,butriskcanbedecreasedbyreducingorelimi-natingcigarettesmokingandfollowingadietlowinanimalproducts and high in fruits and vegetables. Researchersare also investigating anti-inflammatory therapeuticagents that inhibit an enzyme called cyclooxygenase-2(COX-2).BecauseCOX-2playsaroleininflammationandmediatestumourgrowthanddevelopment,itisavaluabletarget for thedevelopmentofdrugsused inthepreven-tion and treatment of several cancers, including breastcancer,colorectalcancer,andpancreaticcancer.Inpeopleat risk for familial pancreatic cancer, routine endoscopycanbeusedtomonitorchangesinpancreatictissue.Iftissueabnormalitiesarise,thepancreascanberemovedbeforecancerdevelops.

244

CONCLUSION

The digestive system is relatively simple in anatomicterms—itisatubethroughwhichfoodpassesandis

broken down into useful components.The physical andchemicalprocessesthatunderliethepassageoffoodandthe extraction and absorption of nutrients are relativelyrecentdiscoveries,havingbeenmadeprimarilyinthe20thcentury.Asaresult,thereremainsmuchtobeunderstoodabout the digestive system—especially concerning thefunctionofcertaindigestivesubstancessuchashormonesand the characterization of diseases of the digestivetissues.

Onemajorareaofmodernresearchintothedigestivesystem involves understanding how the stomach andintestinesrelaysignalsconveyinginformationaboutsatiety,hunger, and cravings to the brain. Many animals areknowntoseekoutandeatspecifictypesoffoodstofulfilltheirnutrientneeds.Humanslivinginthemodernworld,however, have access to a large variety of foods, andunderstandingwhatcompelsapersontochoosetoeatanappleratherthanabananawhengiventheopportunityto have either, combines information about humanbehaviour as well as about the basic physiology of thehumandigestivesystem.

Advancementsinmolecularbiology,biochemistry,andgeneticshaveproveninvaluabletoexpandinguponexistingknowledgeofthedigestivesystem.In2009,forexample,scientistsoverturnedtheoncelong-heldtheorythatthehumantonguecontainsdistinctareasoftastereception.Scientistsstudyingthemolecularandbiochemicalprop-ertiesoftastereceptorsonthetonguefoundthatindividual

245

7 Conclusion 7

receptorscapableofdetectingsensationsofsalty,sweet,bitter,sour,andumami(meaty)areactuallywidelydistrib-uted and intermingled with one another, rather thanisolated as populations of one receptor type in separateareasofthetongue.

Investigationsintothecausesofdigestivesystemdis-ease have focused primarily on identifying geneticabnormalitiesthateithercausediseasedirectlyorplaceaperson at increased risk for disease. In many instances,scientistshavediscoveredthatgeneticvariationsassoci-ated with complex conditions such as Crohn diseaseappear to predispose an individual to disease, meaningthat having a particular genetic variation cannot alonecause the disorder. Thus, scientists are also working toidentifytheenvironmentalfactorsthatinteractwiththesegeneticvariationsandtherebycontributetothedevelop-mentofdisease.Adeeperunderstandingofthecausesandprocessesunderlyingdigestivediseasepromisestofacili-tatethedevelopmentofnewpreventative,diagnostic,andtherapeuticapproachesfortheseconditions.

246

GLOSSARY alveolar mucosaThelooselyattachedmucousmem-

branecoveringthebasalpartofthejawandcontinuingintothefloorofthemouthinwardlyandintothecheekvestibuleoutwardly.

benign Noncancerous.bicarbonateLiquidsecretedbytheepithelialcellslining

ductsinthepancreas.Bicarbonatehelpsneutralizetheacidgoingfromthestomachtothesmallintestine.

bolusFoodthathasbeenchewedandmixedinthemouthwithsaliva.

canaliculi Smallchannelsthattransportbilefromhepatocytes.

cecum Pouchorlargetubelikestructureinthelowerabdominalcavitythatreceivesundigestedfoodmate-rialfromthesmallintestineandisconsideredthefirstregionofthelargeintestine.

cellulose Acomplexcarbohydrate,orpolysaccharide,consistingof3,000ormoreglucoseunits.

cementum Thinlayerofbonelikematerialcoveringtherootsandsometimesotherpartsoftheteeth.

chylomicrons Lipoproteinsthattransportdietarylipidsfromtheintestinestootherlocationsinthebody.

chyme Athicksemifluidmassofpartiallydigestedfoodanddigestivesecretionsthatisformedinthestomachandintestineduringdigestion.

diuretic Asubstancethatdecreasestheamountoffluidreabsorbedbythetubulesofthekidneyswhenthefluidpassesbackintotheblood,increasingurineflow.

247

7 Glossary 7

epidermis Theoutermostprotectiveportionoftheskin.epilepsyChronicneurologicaldisordercharacterizedby

suddenandrecurrentseizuresthatarecausedbyexcessivesignalingofnervecellsinthebrain.

folic acid Water-solublevitaminoftheBcomplexthatisessentialinanimalsandplantsforthesynthesisofnucleicacids.

frenulum linguae Elevatedfoldofmucousmembranethatbindseachliptothegums.

gastric mucosaMucousmembraneliningtheinsideofthestomachthatworkstolubricatethefoodmassesinordertofacilitatemovementandtoprovideapro-tectivelayerovertheliningepitheliumofthestomachcavity.

gastritisAcuteorchronicinflammationofthemucosallayersofthestomach.

gingivaeMorecommonlyknownas“gums,”connectivetissuecoveredwithmucousmembrane,attachedtoandsurroundingthenecksoftheteethandadjacentalveolarbone.

Golgi apparatus Membrane-boundorganelleofeukary-oticcellsresponsiblefortransporting,modifying,andpackagingproteinsandlipidsintovesiclesfordeliverytotargeteddestinations.

halitosis Badbreath,mostcommonlycausedbybacteria.ileumThefinalandlongestsegmentofthesmallintestine

specificallyresponsiblefortheabsorptionofvitaminB12andthereabsorptionofconjugatedbilesalts.

jaundiceExcessaccumulationofbilepigmentsinthebloodstreamandbodilytissuesthatcausesayellowtoorangeandsometimesevengreenishdiscolorationoftheskin,thewhitesoftheeyes,andthemucousmembranes.

lactealsThelymphaticvesselsthatservethesmallintestine.

248


leukoplakiaPrecanceroustumourofthemucousmem-branes,mostcommoninoldermenandusuallyseenonthelipsortongue.

lymphocytes Typeofwhitebloodcellthatdeterminesthespecificityoftheimmuneresponsetoinfectiousmicroorganismsandotherforeignsubstances.

lysosomeSubcellularorganellethatisfoundinalleukaryoticcellsandisresponsibleforthecell’sdiges-tionofmacromolecules,oldcellparts,andmicroorganisms.

malignant Cancerous.mastication Up-and-downandside-to-sidemovements

ofthelowerjawthatassistinreducingparticlesofsolidfood,makingthemmoreeasilyswallowed;chewing.

papillaeProjectionsontheuppersurfaceofthetonguethatcontaintastebuds.

sigmoidoscopeFlexiblefibre-opticendoscopetoexaminetherectumandtheterminalsectionofthelargeintestine,knownasthesigmoidcolon.

triglycerides Anyoneofanimportantgroupofnaturallyoccurringlipidsthatcanbebrokendownforenergy.

249

BIBLIOGRAPHY Textbooks on the digestive system include Tadataka

Yamadaetal.(eds.),Textbook of Gastroenterology,3rded.,2vol. (1999); Leonard R. Johnson (ed.), Physiology of the Gastrointestinal Tract,3rded.,2vol.(1994);andMarvin H.Sleisenger and John S. Fordtran, Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management, 6th ed., ed. by Mark Feldman, Marvin H.Sleisenger,andBruceF.Scharschmidt,2vol.(1998).

JamesL.Gould,WilliamT.Keeton,andCarolGrantGould,Biological Science,6thed.(1996),isacomprehensivestudy that includes an examination of digestion.SpecializedstudiesincludeH.J.VonkandJ.R.H.Western,Comparative Biochemistry and Physiology of Enzymatic Digestion(1984);LeonardR.Johnson(ed.),Physiology of the Gastrointestinal Tract, 3rd ed., 2 vol. (1994); Horace W.Davenport,Physiology of the Digestive Tract: An Introductory Text,5thed.(1982);CharlesF.Code(ed.),Alimentary Canal,5vol.(1967–68);JohnMorton,Guts: The Form and Function of the Digestive System,2nded.(1979);J.B.Jennings,Feeding, Digestion, and Assimilation in Animals, 2nd ed. (1972); andB.I.BalinskyandB.C.Fabian,An Introduction to Embryology,5thed.(1981).

AnatomicaldescriptionandillustrationcanbefoundinsuchcomprehensivetextsasHenryGray,Anatomy of the Human Body, 30th American ed., ed. by Carmine D.Clemente (1985); Leslie Brainerd Arey, Developmental Anatomy: A Textbook and Laboratory Manual of Embryology,rev. 7th ed. (1974); Frank H. Netter, A Compilation of Paintings on the Normal and Pathologic Anatomy of the Digestive System, ed. by Ernst Oppenheimer, 3 vol. in 1

250


(1957–62; reissued 1997), vol. 3 of The Ciba Collection of Medical Illustrations;R.J.Last,Last’s Anatomy: Regional and Applied,8thed.,ed.byR.M.H.McMinn(1990);andAlfredSherwood Romer andThomas S. Parsons, The Vertebrate Body,6thed.(1986).

Gastrointestinaldiseasesarediscussedinsuchworksas Eugene R. Schiff, Michael F. Sorrell, and Willis C.Maddrey(eds.),Schiff ’s Diseases of the Liver,8thed.,2vol.(1999); Robert F. Service, “Stalking the Start of ColonCancer,” Science, 263(5153):1559–60 (March 18, 1994);Martin J. Blaser, “The Bacteria behind Ulcers,” Scientific American, 274(2):104–107 (February 1996); Joseph Alper,“UlcersasanInfectiousDisease,”Science,260(5105):159–160 (April 9, 1993); Charles Herbert Best and NormanBurkeTaylor,Best and Taylor’s Physiological Basis of Medical Practice, 12thed.,editedbyJohnB.West (1991);andE.J.HolborowandW.G.Reeves(eds.),Immunology in Medicine: A Comprehensive Guide to Clinical Immunology, 2nd ed.(1983). Specialized studies include Harvey J. Dworken,Gastroenterology: Pathophysiology and Clinical Applications(1982); Marvin H. Sleisenger and John S. Fordtran,Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management, 6th ed., edited byMark Feldman, Marvin H. Sleisenger, and Bruce F.Scharschmidt, 2 vol. (1998); David J.C. Shearman, Niall Finlayson, and Michael Camilleri (eds.), Diseases of the Gastrointestinal Tract and Liver,3rded.(1997);H.L. Duthie(ed.), Gastrointestinal Motility in Health and Disease (1978);William S. Haubrich and Fenton Schaffner, Bockus Gastroenterology,5thed.,editedbyJ. Edward Berk,4vol.(1994);andFranklin Bicknell,Vitamins in Medicine,4thed.,edited by Brian M. Barker and David A. Bender, 2 vol.(1980–82).InformationoncurrentresearchisavailableinFredKernandA.L.Blum(eds.),Gastroenterology Annual.

251

A

abscesses,84,93,151,154,157,188,196,197,198,203,210,229,230,236

accessorypancreaticduct,73achalasia,46,159,160,165acinarcells,35,99–101,114,235,

236,237activetransport,explanation

of,121acutecanalicular(cholestatic)

hepatitis,214–215acutehepatocellularhepatitis,

210–214alveolararteries,26alveolarbone,25,28alveolidentales(toothsockets),26amoebae,184,198amylase,34,36,73,99,123,

124,236analcanal,82,83–85Ancylostoma duodenale,184–185anemia,irondeficiency,146,

174,185anemia,pernicious,146,174,

175,186antrum,49,50,51,52,54,56,60,

103,104,116,171,174anus/analopening,19,81,82,84,

85,185,193,194,208appendicesepiploicae,77appendicitis,79,93,186–188

appendix,71,79–81,138,186–188,210

argentaffincells,71–72Ascaris lumbricoides,184ascendingcolon,19,74,76,77,78,

194,198ascites,221–222Auerbachplexus(myenteric

plexus),64,65–66,104,115,116,160

BBanting,SirFrederickG.,107Barrettesophagus,162,165Bayliss,SirWilliamM.,113–114Behçetsyndrome,143Best,CharlesH.,107bile,63,78,86,89,91,92,94,

95–97,112,115,126,128,129,131,132,133,209,210,213,226,227,228,229,230,232,234

biliarytract,89,91,131,178,209,210,213,214,217

diseasesof,226–234overviewof,93–97

bilirubin,86,92,93,97,213,217,218,227,229,231,232,233,234,238

bloodflukes(schistosomiasis),184,215

body(ofstomach),49

INDEX

252

Boerhaavesyndrome,163–164bolus,21,42,45,155,157bombesin,116Brunnerglands,70,73brushborder,69,70,124,127,

129,131,132,133,134

Ccalcium,55,65,70,99,133–134,

200,224,237,238canaliculi,91,92,209,210,

213,230cancer

ofthebiliarytract,226,231colorectal/colon,175,204–208,

239,241,243esophageal,148,164–168liver,24,93,215,223–226oral,144,147–151pancreatic,235,238–243stomach,168,174–177

carbohydrates,digestionof,123–124

cardia,49cavities(dentalcaries),142,144,

151–152,155cecum,19,74,76,79,185,198celiacdisease,143,189–191celiac(solar)plexus,51,64celiactrunk,50Chagasdisease,160cheeks,21,23,24,31,148,149cholecystokinin,78,95,96,100,

111,112–113,116,126cholera,183–184chronicactivehepatitis,215–216chyme,38,47,55,57–58,61,66,

73,74,122cirrhosis,210,215,216–219,222,

223,225,227,234,238

cleftlip,154commonbileduct,73,94–95,96,

99,178,229,231,238conditionedsalivaryreflex,35congenitaldefects/disorders,33,

154,156,175,182–183,189,210,215,216,231,235

constipation,explanationof,192–193

corrosiveesophagitis,157Crohndisease(regionalenteri-

tis/ileitis),188,190,198,199–200,201–204,205,228,245

cysticduct,94–95,228,230cysticfibrosis,182,216,218,235,

237–238

DDavidoffcells(Panethcells/cells

ofPaneth),68,71dentalcaries(cavities),142,144,

151–152,155descendingcolon,19,74,76,77,

78,82diabetesmellitus,102,109,134,

169,193,239diarrhea

explanationof,194–195traveler’s,178,179

dietaryfibre,digestionof,124–125

Diphyllobothrium,185,186Diphyllobothrium latum,186distalcolon,83diverticula

oftheesophagus,163–164ofthelargeintestine,195–197

duodenalbulb,60,63,67,171,172duodenalpacemaker,65


253

7 Index 7

duodenalpapilla(papillaofVater),63,73,94

duodenojejunalflexure,63duodenum,19,49,50,52,60,63,

65,66,67,69,70,73,92,94,95,96,99,100,103,105,111,112,113,114,121–122,123,126,133,136,169,170–171,172,173,174,178,179,182,241

dysphagia,156,157–158,159,163,165

EEchinococcus granulosus,185,210endocrinehormones,explanation

of,102–103endocytosis,explanationof,121endorphins,115enkephalins,66,115Entamoeba histolytica,198,210Enterobius vermicularis,185enterochromaffin-likecells,

55,112enterohepaticcirculation,97,132enzymatichydrolysis,36epiglottis,31,42Escherichia coli,179esophagus,19,38,39,40,41,

42–43,49,51,89,142,148,169,220,221


externalanalsphincter,82,84–85externalhemorrhoidalvein,82

Ffacilitateddiffusion,explanation

of,121fats,digestionof,128–130

feces/fecalmatter,58,61,74,79,82,84–85,88,134,172,179,185,193,194,205,210

fistulas,203folicacid,131–132,192Fordycedisease,142foveolaegastricae,53frenulumlinguae,24,25fundus,49,50,116,174fungusinfection,33

Ggallbladder,19,57,58,63,73,89,

92,94,95–97,112,113,116,122,195,209,224,226,227,228,229,230,231,239,242

gallstones,93,96,159,217,224,226–230,231,232,235,236

gas,intestinalexplanationof,195movementofthroughthe

digestivetract,136–138gastricatrophy,174gastricglands,19gastricinhibitorypolypeptide,113gastricjuices,38,39,46,47,

55–57,58,129,169–170gastrin,54,56,57,58–59,78,96,

103,104,105,111,114,116gastrincells,54gastritis,168,173–174gastroesophagealrefluxdisease,

142,158,160–163generalizedcandidiasis,157Giardia lamblia,179gingivitis,26glossitis,142,144,146–147glossopalatinearches,42glottis,24,39

254

glucagon,57,78,86,99,102,109–110,111,114,238

gobletcells,68,77Goldberger,Joseph,144granulomatoushepatitis,215gums(gingivae),24,25–26,28,35,

147,148,151,152

Hhalitosis,152,155haustra,77heartburn,46,160,162,169Heister,valveof

(valvulaspiralis),95Helicobacter pylori,170,172,173,

174,175,177hemochromatosis,216,218,219hemorrhoids,84,85,208hepaticartery,89hepaticducts,89,91,93–94,

95,231hepaticencephalopathy,218,

219–220,221hepaticflexure,76hepaticvein,132,217,

221,222hepatitis

acutecanalicular(cholestatic),214–215

acutehepatocellular,210–214chronicactive,215–216

hepatitisAvirus(HAV)/hepati-tisA,210–211,213

hepatitisBvirus(HBV)/hepatitisB,210,211–212,213,215,219,223,226

hepatitisCvirus(HCV)/hepatitisC,210,212,215,223,226

hepatopancreaticampulla(ampullaofVater),94,99,231,235

hepatopancreaticsphincter(sphincterofOddi),94,95,231

hepatorenalsyndrome,222–223herpessimplex,23hookworms,184–185hydrochloricacid,54,55,58,97,

100,104,112,113,114,132hypergastrinemia,58–59

Iileocecalvalve,63,74,76ileum,19,63–64,65,66,67,69,

70,71,74,76,132,133,134,180,194,201

iliaccolon,76immunity,digestivetractas

organof,138–141indigestion(dyspepsia),168–169inferiormesentericartery,77,82inferiormesentericvein,78inflammatoryboweldisease,

198–204insulin,86,99,101–102,105–109,

110,111,113,218,237,238,239interdentalpapillae,26internalanalsphincter,81,82,83,

84,85internalhemorrhoidalvein,82internaliliacartery,78,82intestinalglands(Lieberkühn

glands),68,70,71,72intestinalobstruction,180,184,

186,193iron,70,92,135–136,146,165,174,

185,200,216,218,219irondeficiencyanemia,146,174,185


255

7 Index 7

irritablebowelsyndrome,180–181,190

isletsofLangerhans,99,101–102,103,107,109,111,113,218,238

Jjaundice,93,131,205,213,214,

215,217,224,226,229,231–234,238

jejunum,19,63–64,67,69,70,71,103,111,121,122,123,126,133,137

joule,explanationof,119

KKerckring,valvesof(plicae

circulares),67–68,77kilocalorie,explanationof,119Kupffercells,91,213

Llargeintestine/colon,19,47,52,

57–58,61,63,64,89,97,114,125,132,137,138,167,178,180,181,220,224,239,241


larynx,31,39,40,42,45,148,150,163,165

leukoplakia,23,33,148,149Lieberkühnglands(intestinal

glands),68,70,71,72lips,19,21–23,24,25,142,144,

147,148,150,192liver,19,47,51,57,64,73,76,95,

96,97,102,107,108,109,124,128,130,131,132,133,136,

166,195,198,207,208,227,229,231,232,234,240,241

diseasesof,209–226overviewof,86-93

lobules,89–90,210,215loweresophagealsphincter,39,

45,46,116,159,160,161lymphocytes,138–141Lymphopathia venereum,197–198lysozyme,36,37,68,71

Mmagnesium,134–135,200major/mainpancreaticduct

(ductofWirsung),73,94,99,237

malabsorption,explanationof,181–182

Mallory-Weisslesion,164mastication/chewing,21,23,26,

27,31,35,78,100,154,155Meckeldiverticulum,182megacolon,193–194Meissnerplexus,64Menetrierdisease,175mesentery,63,64,139,140,161mesocolon,81microvilli/villi,68–70,72,77,90,

95,105,124,139,190motilin,52,114,116mouth,19,21,38,39,40,42,155,

156,192,198diseasesof,142–154overviewof,23–37

mucin,68mucoidcells,53multipleendocrineneoplasia

typeI,59mumps,156

256

musculuspuborectalis,83myentericplexus(Auerbach

plexus),64,65–66,104,115,116,160

Nneurotensin,116

OOddi,sphincterof(hepatopan-

creaticsphincter),94,95,231orbicularisorismuscle,23oxyntic(parietal)cells,54–55,173

Ppalate,hardandsoft,21,24–25,

31,39,42,148,151,153pancreas,19,47,57,63,73,86,89,

94,103,105,107,109,111,112,114,122,126,127,173,178,179,218

diseasesof,209,234–243overviewof,97–102

pancreaticpolypeptide,113pancreatitis,234–237,239,240Panethcells/cellsofPaneth

(Davidoffcells),68,71paracrinehormones,explanation

of,102–103paraesophagealhernia,162–163parietal(oxyntic)cells,54–55,173Parkinsondisease,155parotidduct,23passivediffusion,explanation

of,121Paterson-Kelly(Plummer-

Vinson)syndrome,165Pavlov,IvanPetrovich,56

pellagra,144–146pelviccolon,76,81,83pepsin,54,55,58,116,125,126,

170,182pepsinogen,54,58,171peptic/pepticrefluxesophagitis,

157,160,162periodontalmembrane,21,26,28peristalticrush,67peristalticwaves/contractions,

39,40,42–43,45,46,51–52,66–67,72,82,159,160,161,180,193,195–196

peritonsillarabscess(quinsy),154permanentteeth,28–29perniciousanemia,146,174,175,

186persistenthepatitis,215Peutz-Jegherssyndrome,142,239Peyerpatches,71,72,77,138,139,

140pharyngitis,152–154pharynx/throat,19,24,31,38,39,

45,46,142,147,148,150,156,158,160,163


pinworms,185plicaecirculares(valvesof

Kerckring),67–68,77Plummer-Vinson(Paterson-

Kelly)syndrome,165portahepatis,89,91,93portalhypertension,217,218,

220–221portalvein,51,64,78,89,107,

133,220,221,222Prevotella histicola,152primaryteeth,28–29prostaglandins,54–55,115proteins,digestionof,125–128


257

7 Index 7

pyloricsphincter,50,51,52pylorus,49,50,60,63

Rrectalampulla,81,82rectalvalves,82rectum,19,58,76,77,78,81–83,

84,85,89,194,198,199,200,203,204–207

regionalenteritis/ileitis(Crohndisease),188,190,198,199–200,201–204,205,228,245

rennin,56rickets,133,152roundworms,178–179,184rugae,49

Ssaliva,19,21,23,31,33,35–37,39,

40,147,154–156,163,168salivaryglands,19,21,23,24,25,

142,143,148,154diseasesof,154–156overviewof,33–35

Salmonella,183,197schistosomiasis(bloodflukes),

184,215scleroderma,46,157secretin,57,78,96,100,111,112,

113–114segmentingcontractions,66serotonin,55,66,72,112Shigella,179,183,197sigmoidcolon,19,58,74,76,78,

81,82,198,199,200sinusoids,90,91Sjögrendisease,155smallintestine,19,21,47,49,50,

55,57,58,59,74,76,77,78,79,89,92,95,96,97,99,103,110,112,114,116,121,122,123,128,129,132,133,136,137,138,142,195,197,204,228,241,242


solar(celiac)plexus,51,64somatostatin,66,96,99,102,

103,108,110–111,114speech,23,24,31,33,36,37,154spleen,47,76,89,92,97,139,140,

177,213,217,241,242splenicflexure,76splenicvein,64,78,89Starling,ErnestH.,113–114stomach,19,21,35,38,39,40,43,

45,46,61,63,70,76,89,97,103,104–105,107,111,112,113,114,122,125,126,129,132,133,135,136,142,156,157,161,162,163,164,166,167,182,220,221,242,244


streptococcalpharyngitis(strepthroat),153

strictures,157,162,180,194,217,231,237

strongyloides,184substanceP,116succusentericus,73suckingpad,23superiormesentericartery,64,77superiormesentericplexus,64superiormesentericvein,64,

78,89superiorpancreaticduodenal

artery,64swallowing,24,31,33,38–40,41,

258

42,43,45,100,148,149,153,154,155,156,157–158,162,165,168

syphilis,144,146,153systemiclupuserythematosus,155

Ttaeniae,77,81Taenia saginata,185tapeworms,178–179,184,

185–186,210tastebuds,24,31,32–33,35teeth,19,21,24,25,26–29,31,36,

142,147,148,149,151–152,154,189

threadworms,184tongue,19,21,24,25,29–33,35,

39,42,142,143–144,146–147,148,149,153,154,192

tonsils,31,42,138,147,148,153trachea/windpipe,41,43,156transversecolon,19,74,76,77traveler’sdiarrhea,178,179Treitz,ligamentof,63tropicalsprue,191–192trypanosomes,160T. solium,185tuberculosis,153,188,215tylosis,165

Uulcerativecolitis,198,199,

200–201,203,205,231ulcers/ulceration,23,46,55,57,

59,72,104,105,142,143,147,155,157,162,163,168,169–173,174,175,179,182,197,198

unconditionedsalivaryreflex,35

upperesophagealsphincter,39,42,45,158

uvula,25,153

Vvagusnerve,51,54,56,60,64,72,

95,96,115,116,158,169valvulaspiralis(valveof

Heister),95vasoactiveintestinalpolypep-

tide,99,100,104,111,114–115

Vater,ampullaof(hepatopancreaticampulla),94,99,231,235

Vater,papillaof(duodenalpapilla),63,73,94

vermilionborderofthelip,21,23Verner-Morrisonsyndrome,115vestibule,24Vibrio cholerae,183–184villi/microvilli,68–70,72,77,90,

95,105,124,139,190Vincentgingivitis,144,147vitaminA,129,131,148,151,237vitaminB12,55,70,132,174,186vitaminD,129,131,132–133,134,

152,237vitaminE,129,131,237vitaminK,74,129,131,237

WWilsondisease,215,216,218,219Wirsung,ductof(major/main

pancreaticduct),73,94,99,237

ZZollinger-Ellisonsyndrome,59zymogenic(chief)cells,54


THE DIGESTIVE SYSTEM SYSTEM, THE... · Diseases of the Mouth and Oral Cavity 142 Pellagra 144...

Documents

Transcript of THE DIGESTIVE SYSTEM SYSTEM, THE... · Diseases of the Mouth and Oral Cavity 142 Pellagra 144...