内科学教学课件：11 IBD（Inflammatory Bowel Disease）

InflammatoryBowelDiseaseInflammatoryBowelDisease(IBD)Crohn’sDisease(CD)UlcerativeColitis(UC)UncertainColitisEpidemiologyRatehigherinnorthernclimatesandthedevelopedworldEqualincidencebetweenmenandwomenPeakincidence

CD15-35yearsbyfarthecommonest

UCusuallydiagnosedpriorto30years

Aggregationinfamilies25%ofpatientswithCD20%ofpatientswithUC

SmokingreducesriskofUCbutincreasesriskofCDEtiologyandPathogenesisEtiologyandPathogenesisGeneticeasytoinfectEnvironmentalfactorsFungusinintestinesImmuneandnon-immunesystemofintestinesImmunologicalreactionandinflammationEnvironmentalfactorsIBDismoreprevalentindevelopedcountriesandmorecommoninwhite-collarworkersRiskofUCNegative:Breastfeeding,appendectomy,smokingPositive:“Westerndiet”,left-handedness,depressionRiskofCDSmoking,second-handsmokeGeneticfactorsHighFamilyincidence,butlowwithspouse

ConcordanceforCDintwinsMutationsofGenePolygenediseaseandheterogeneticaldisease

InfectedfactorsMycobacteriumparatuberculosisParamyxovirusMeaslesvirusHelicobacterspeciesImmunefactorsAbnormalimmuneresponsetoauto-intestinalnormalfungusAbnormalfunctionofTcells

CDTypicalT-helper1(Th1)(cell-mediated)reaction

UCAtypicalT-helper2(Th2)(humoral)reactionNon-immunologicalcells:epithelialcell,vascularendothelialcellImmunecytokinesandmediumROMs,NO

Ulcerativecolitisisacontinuousinflammationandulcerationofthecolonandrectumandtypicallyinvolvesonlytheinnermostliningormucosa,withnosegmentsofnormaltissue.Crohn’sdisease

isachronic,relapsing,focal,asymmetric,transmuralinflammationofthegutanywherebetweenthemouthandtheanus,butispredominantlyseenintheterminalileumand/orcolon.DefinitionsPathologyHistopathologyofUCBeginwithintherectumandextendavariableadjacentlevel25%rectum25~50%rectumandsigmoidordescendingcolonOnethirdextendadjacenttosplenicflexureorinvolvetheentirecolonAfewinvolvetheterminalileumDiffuse,continuous,superficialandnot-focalinflammationSubmucosaormucosaHistopathologyofUCActivephaseofinflammation:AcuteinflammationcellsaccumulateandinvadethecryptsProgressivechanges:DegenerationornecrosisofthecryptepitheliumCryptabscessesShallowulcerationsextendingtothelaminapropriusRarelyandseverechanges:ToxicmegacolonandspontaneousperforationHistopathologyofUCChronicchanges:DistortedcryptarchitectureofcolonTransformed,disorganized,andlossofglandLossofcuppedcellsLossanddisappearanceofhaustrations,somuchasstraitnessThickingofthesmoothmuscleMalignanttumorPathologyofUCHistopathologyofCDInvolvesanysegmentorcombinationofsegmentsfromthemouthtoanus.Mostcommonlyterminalileumandrightcolon20perinvolveexclusivelythecolon15~20perlimitedtothesmallbowel50perBoth<10perinvolvethestomachandduodenumandusuallywithmoredistaldiseasefocal,discontinuous,asymmetric,transmuralinflammationAlllayerofmucosa,submucosa,muscle,serosaHistopathologyofCDMinuteaphthoidLinearulcerationIsolatingnormalislandsofmucosaCobblestoneappearanceExtenddeepthroughoutthelayersofthebowelwallFissula,andfistulaintothemesenteryororganHistopathologyofCDAcuteandchronicinflammatorycellsinvadesisolatedorcontiguoussinglecrypts(includingproducingcryptabscess)withnormaladjacentglandsTransmuralInflammatorychanges:thickeningofthebowelwallandnarrowingofthelumenFibroticchanges(healing):PermanentfocalstrictureNon-caseatinggranulomas(<20%)CrohnileitisClinicalmanifestationsClinicalmanifestationsofUCGastroenterology:Diarrhea:mostcommonly,rectalbleedingandpassageofmucopusAbdominalpain:locatedinleftloweranddownabdomenOthersymptom:anorexia,nausea,vomitPhysicalexamination:abdominaltenderness,reboundtendernessSystemicsymptom:ModerateandseverepatientsFever,fatigue,anemia,dehydrationClinicalclassificationofUCClinicaltypes:FirstoutbreakChronicrelapseChroniccontinuanceAcuteout-breakSeverityofdisease:MildModerateSeverePathologicalrange:Stagesofdisease:ActivestageandcatabaticstageMildModerateSevereBowelmovement<4perday4-6perday>6perdayBloodinstoolsmallmoderatesevereFevernone<37.5℃mean>37.5℃meanTachycardianone<90meanpulse>90meanpulseAnemiamild>100≤100ESR<30mm>30mmEndoscopicappearenceErythema,decreasedvascularpattern,finegranularityMarkederythema,coarsegranularity,absentvascularmarkings,contactbleedingnoulcerationSpontaneousbleeding,ulcerationsUlcerativeColitis:DiseasePresentationExperimentalinvestigationofUCBlood:HBWBCESRCRP

albuminStool:MucopurulentbleedingstoolExcludedysentery,salmonella,ameba,schistosomeAutoantibodyexaminationP-ANCA(+)anti-Saccharomycescerevisiae(ASCA)(-)ColonoscopyinvestigationofUCColonoscopyDistributeddiffuselyandcontinuouslyAbsenceofthemucosalvascularpattern,Finegranularityofthemucosa,hemorrhage,exudationofmucopusDiffusederosionandsuperficialulcerationPseudopolyps,bridgedmucosa,lossanddisappearanceofhaustrations,somuchasstraitnessMicroscopymucosa,submucosainflammationcellsinvadeAcutestage:erosion,ulceration,cryptitisandcryptabscessChronicstage:disorganizedstructureofcryptandlossofcuppedcellsUCbyEndoscopyRadiographyinvestigationofUCRadiographyDisorderand(or)finegranularityofthemucosamulti-superficialulcerationCoarseedgeofmucosaandbur,nicheRoundandovi-roundthumb-printing(pseudopolyps)Lossanddisapperanceofhaustrations,somuchasstraitness,tubular-appearing“leadpipe”Severeandout-breakpatientsareforbiddenUCbybariumenemaClinicalmanifestationsofUCComplication:ToxicmegacolonMalignanttumorOthercomplication:bleeding,perforation,ileusToxicmegacolonClinicalmanifestationsofCDGastroenterology:Abdominalpain:mostcommonly,locatedindown-rightandaroundbellybutton,aggravatedafterdinnerDiarrhea:commonly,usuallywithoutrectalbleedingandpassageofmucopusMass:10~20%,usuallylocatedinrightlowerandaroundbellybuttonFistulaformation:inner-andouter-fistulaPathologicalchangesaroundrectumandanus:fistula,abscess,splitSystemicsymptom:(moreandobvious)Fever:common,mildandmoderatefeverInnutrition:fatigue,anemia,hypoalbuminExperimentalinvestigationofCDBlood:HBWBCESRCRP

albuminStool:OB(+)Autoantibodyexaminationanti-Saccharomycescerevisiae(ASCA)(+)ColonoscopyinvestigationofCDColonoscopyDistributedfocally,discontinuously,asymmetricallyLinearulceration,IsolatingnormalislandsofmucosaCobblestoneappearanceFissula,andfistulaintothemesenteryororganPseudopolyps,focalstricture,straitnessofbowlMicroscopyAlllayerofmucosa,submucosa,muscle,serosaLymphocyteinvadeandlinearulcerationNon-caseatinggranulomasorganizedstructureofcryptandcuppedcellsCrohn’soncolonoscopyLinearulcer Moderately Severely ulcerated ulceratedRadiographyinvestigationofCDRadiography(GIandBE) Distributedfocally,discontinuouslyDisorderofthemucosaLinearulcerationCobblestoneappearancePseudopolypsStraitnessandfistula“Jumpingsign”and“Liningsign”Crohn’sbybariumenemaCrohn’scolitis&stricture Close-upofstricture**ClinicalmanifestationsofCDComplication:Ileus:mostcommonlyCeliacabscessAbsorbingbadnessPerforationandbleedingToxicmegacolon,rarelyMalignanttumorOthercomplication:gall-stone,urine-stone,fattyliverDiagnosisandDifferentialdiagnosis

DiagnosisofUCChronicdiarrhea,rectalbleedingandpassageofmucopus,abdominalpain,diverseextentsofsystemicsymptomAtleastoneimportantchangesofcoloscopyorBEandbiopsyExcludeotherdiseasesAtypicalclinicalpresentationbuthavetypicalchangesofcoloscopyorBEandbiopsyalsocanbediagnosisedTypicalclinicalpresentationbuthaveatypicalchangesofcoloscopyorBEandbiopsyshouldbedoubtedDifferentialdiagnosisofUCCrohn’sdiseaseChronicdysentery:cultureofstool,anti-inflammationisusefulAmebiasis:rightcolon,collarbuttonulceration,amebiccystsortrophozoitesSchistosome:historyofcontact,wormeggColoncancer:colonoscopyandBEIBS:functionalchangesOthersDiagnosisofCDSynthetizedanalysis:clinic,radiography,endoscopyExcludeinflammatoryornon-inflammatorycolondiseases,MTSurgeryexplorationitemclinicradiographyendoscopybiopsyspecimentresectedFocalanddiscontinuouschanges＋＋＋CobblestoneappearanceandLinearulceration＋＋＋Inflammationalllayers＋腹块＋狭窄＋狭窄＋Non-caseatinggranulomas＋＋Fistula＋＋＋Changesofanus123123+456/34+2/3*123＋DoubtDiagnosedDiagnosed＋＋DifferentialdiagnosisofCDIntestineTB:secondary,ileocecum,non-focalchanges,PPD(+),caseationUCIntestinallymphoma:requiringsurgicaldiagnosedAcuteappendicitisOthers:chronicdysentery,amebiasis,schistosomeUCCDClinicalGrossbloodinstoolYesOccasionallyMucopusYesOccasionallySystemicsymptomsOccasionallyFrequentlyPainOccasionallyFrequentlyAbdominalmassRarelyYesSignificantperinealdiseaseNoFrequentlyFistulasNoYesSmall-intestinalobstructionNoFrequentlyColonicobstructionRarelyFrequentlyResponsetoantibioticsNoYesRecurrenceaftersurgeryNoYesANCA-positiveFrequentlyRarelyASCA-positiveRarelyFrequentlyUCCDEndoscopicLocationRectumTerminalileumRectalsparingRarelyFrequentlyContinuousdiseaseYesOccasionally“Cobblestoning”NoYesBiopsyLayerofinflammationMucosaandsubmucosaAlllossofcuppedcellsYesNoNon-caseatinggranulomaNoOccasionallyRadiographicSmallbowelsignificantlyabnormalNoYesAbnormalterminalileumOccasionallyYesSegmentalcolitisNoYesAsymmetriccolitisNoYesStrictureOccasionallyFrequentlyUveitis-inflammationoftheeyeDigitalclubbingErythemanodoumPyodermagangrenosumArthritisofthebackArthritisofthejointsinthelimbsSclerosingcholangitisExtraintestinalmanifestationsAphthousstomatitis（口疮）Pyodermagangrenosum（坏疽脓皮病）ErythemanodosumSclerosingcholangitisTreatmentTreatmentofIBDSymptomcontrolBowelrestDrugsSurgerySymptomaticreliefRest,food,nutritionAnti-diarrhealagents,egloperamide(Lomotil)maybeusedinchronic,stableIBD.BowelrestNothingtoeatordrinkforafewdaysElementaldiet-carbohydrates,short-chainfattyacidsandveryshortpeptidesoraminoacids;tastespoorlyTotalparenteralnutrition-allnutrientsandcaloriesadministeredintravenously;mostexpensiveandsmallriskoffatalcomplicationsMedicalTreatmentofIBDSulfasalazineor5-ASASteroidAntibiotics,e.g.,ciprofloxacin,metronidazoleetc.Azathioprineand6mercapto-purineCyclosporinAnti-tumournecrosisfactorantibodySulfasalazineAffectthemetabolismofarachidonicacidandinhibitthesynthesisofprostaglandinCleanuptheoxygenfreeradicalandrelievetheinflammationInhibittheimmunologicalreactionMechanismofactionSulfasalazineor5-ASATheactiveanti-inflammatorymoietyisthe5-ASA.5-ASA:mesalazine、olsalazine、balsalazideBesidessulfasalazine:AsacolandPentasaCanbeadministeredorallyortopicallyintheformofenemaorsuppository.Mostoftheadverseeffectsduetothesulfapyridine:headache,fever,rash,nausea,infertilityinmalesandrarelyagranulocytosis.UsageanddosageofSulfasalazineMildandmoderateUCorCD:4g/d,qidMaintenancedose:2g/d,1～2yearsP.OandalsoinjenemRecheckhemogramregularly

GlucocorticoidsAcuteout-break,mild-moderateandsevereandfulminatingIBDwhichwithbadtherapeuticeffect40mg/d,po（decrement）、or/andinjenemSevere:ivgttLocalizedinrectumandsigmoidcolon:injenemBudesonide:injenemSide-effectsaremany….

Moodchanges,diabetes,hypertension,thinskin,cushingoidphenotype,immunosuppression,osteoporosisetc.AnnouncementsofCDExcludeabdominalabscessbeforeuseInitialdosageshouldbesufficientDecrementshouldbeslowHormonedependentLonguseshouldsupplyCaandVitDAntibiotics(mainlyinCD)ExactmechanismofactioninCrohn’sisunknown.Clinicaltrialshaveestablishedefficacyofmetronidazole,ciprofloxacin.Azathioprineand6MPAzathioprineismetabolizedto6-mercaptopurine,apurineanaloguethatinhibitsDNAsynthesis.BadtherapeuticeffecttoSteroidandhormoned