消化道病理二

炎症性肠病的临床病理

THECLINICO-PATHOLOGYOFINFLAMMATORYBOWELDISEASE(IBD)

1整理ppt2整理ppt溃疡性结肠炎〔Ulcerativecolitis〕克罗思病〔Crohn’sdisease〕未定型结肠炎〔Indeterminatecolitis〕IBM一词主要是指两种肠病：克罗思病和溃疡性结肠炎。两者临床病程与病史不同，病变有别，但某些特点相同，而治疗原那么不同。Inflammatoryboweldiseaseisatermthatdescribestwodiseases:Crohndiseaseandulcerativecolitis.Althoughthesetwodisordershavedifferentclinicalcoursesaswellasnaturalhistoriesandareusuallyclearlydistinguishable,theyhavecertaincommonfeatures.IBD的类型3整理ppt无特异性实验室检测指标〔Nospecificlaboratorytests〕抗中性粒细胞胞质抗体pANCA(anti-neutrophilcytoplasmicantibody)60-75%的溃疡性结肠炎病例〔Ulcerativecolitis:60-75%〕10-40%的克罗思病病例〔Crohn’sdisease:10-40%〕抗酿酒酵母菌抗体ASCA(anti-Saccharomycescerevisiaeantibody)40-80%的溃疡性结肠炎病例〔Crohn’sdisease:40-80%〕<10%的克罗思病病例〔Ulcerativecolitis:<10%〕基因检测：NOD2和其他的IBD基因〔GenetictestingforNOD2andotherIBDgenes〕

IBD的实验室检测4整理ppt克罗恩病

〔CrohnDisease〕5整理ppt克罗恩病〔CROHNDISEASE〕肠炎特点〔FeaturesofInflammationoftheIntestine〕

慢性，节段性，透壁性〔Chronic,Segmental,Transmural〕病变以小肠远端为主，右半结肠可受累，可有消化道甚至肠外组织受累〔Crohndiseaseoccursprincipallyinthedistalsmallintestinebutmayinvolveanypartofthedigestivetractandevenextraintestinaltissues.Thecolon,particularlytherightcolon,maybeaffected.〕2023/12/266整理ppt克罗恩病的流行病学〔EPIDEMIOLOGY〕全球发生克罗思病，每年发病率为0.5-5人/每10万人群。过去30年来，来自各国的报道说明，全球的克罗思发病率急剧增加。〔Crohndiseaseoccursworldwide,withanannualincidenceof0.5to5per100,000.Reportsfromvariouscountriesindicatethattheincidencehasincreaseddramaticallyoverthepast30years.〕欧洲的该病病例最常见于青少年或年轻成人,犹太人群呈高发病率，女性较男性稍微多见(1.6:1).ThediseaseusuallyappearsinadolescentsoryoungadultsandismostcommonamongpersonsofEuropeanorigin,withaconsiderablyhigherfrequencyintheJewishpopulation.Thereisaslightfemalepredominance(1.6:1).2023/12/267整理ppt发病机制〔PATHOGENESIS〕家族性遗传性体质ConcordanceratesintwinpairsandsiblingsstronglyimplicateageneticpredispositiontoCrohndisease.AfamilyhistoryofinflammatoryboweldiseaseismorecommonforCrohndiseasethanforulcerativecolitis.AputativesusceptibilitylocusforCrohndiseasehasbeenassignedtothecentromericregionofchromosome16whereitisassociatedwiththeNOD2/CARD15locus,whichcodesforanintracellularreceptorforbacterialproductsinvolvedininnateimmunity.自身免疫机制ThepossibilitythatCrohndiseasereflectsimmunologicallymediateddamagetotheintestineissuggestedby(1)thechronicandrecurrentnature〔慢性反复发作〕oftheinflammationand(2)itsassociationwithsystemicmanifestations〔全身损害〕thataresuggestiveofautoimmunedisease.Mostrecentimmunologicstudiesfocusonthepossibleroleofcell-mediatedcytotoxicity.2023/12/268整理ppt肠道粪便流的作用ThefecalstreamappearstobeofprimeimportanceinthepathogenesisofCrohndisease,asevidencedby：(1)thebeneficialeffectsofsurgicalbypass〔肠旁路吻合的好处〕(2)thepatternofpreanastomoticrecurrenceinpatientswithside-to-endanastomoticsites〔侧-端吻合处前段复发〕,and(3)thefrequencyofearlyinflammatorylesions(aphthoiderosions)intheepitheliuminassociationwithmucosallymphoidtissue〔淋巴组织增生之上皮处早期炎症-口疮样糜烂〕.2023/12/269整理ppt病理变化〔PATHOLOGY〕

克罗思病有两大病变特征，以此与其他的炎症性肠病相鉴别：

TwomajorcharacteristicsofCrohndiseasedifferentiateitfromotherGIinflammatorydiseases.

第一，严重通常累及肠壁全层，故称之为透壁性炎症。

First,theinflammationusuallyinvolvesalllayersofthebowelwallandis,therefore,referredtoastransmuralinflammatorydisease.第二，肠壁病变是间断性的，即节段性肠炎病变，间有未受累及的正常肠组织

Second,theinvolvementoftheintestineisdiscontinuous;thatis,segmentsofinflamedtissueareseparatedbyapparentlynormalintestine.2023/12/2610整理ppt克罗恩病病变分布的四大部位特征回盲部病变为主，占50%

mainlytheileumandcecuminabout50%ofcases仅有小肠病变，占15%

onlythesmallintestinein15%仅有大肠病变，占20%

onlythecolonin20%肛门直肠区病变为主，占15%

女性肛门直肠区克罗恩病可蔓延到外阴部

mainlytheanorectalregionin15%.InwomenwithanorectalCrohndisease,theinflammationmayspreadtoinvolvetheexternalgenitalia.2023/12/2611整理ppt大体观(GROSSLY)肠壁与邻近肠系膜增厚，水肿，肠系膜脂肪环绕肠周〔爬行脂肪〕Thebowelandadjacentmesenteryarethickenedaswellasedematous,andmesentericfatoftenwrapsaroundthebowel(Creepingfat).肠系膜淋巴结常常肿大，变硬，相互融合Mesentericlymphnodesarefrequentlyenlarged,firm,andmattedtogether.肠腔狭窄〔水肿与纤维化共同作用所致〕，可见鹅卵石状外观〔因结节状肿胀、肠壁纤维化和粘膜溃疡所致〕Theintestinallumenisnarrowedbyacombinationofedemaandfibrosis.Nodularswelling,fibrosis,andmucosalulcerationleadtoacobblestoneappearance.溃疡特点：早期的溃疡呈口疮状或葡行状；晚期的溃疡变深呈线状裂缝或裂纹状Inearlycases,ulcershaveeitheranaphthousoraserpiginousappearance;later,theybecomedeeperandappearaslinearcleftsorfissures(seeFig.13-23B).2023/12/2612整理ppt图片A.末端回肠远端肠壁明显增厚，伴有回盲瓣变形。可见一纵向溃疡(箭头所示)图片B.该回肠节段另一纵向溃疡。受损粘膜水肿，形成圆形/卵圆形结节状隆起，使病变肠段粘膜呈鹅卵石样外观。右下侧局部粘膜局部未受累2023/12/26

克罗恩病肠切除标本大体观13整理ppt大体切面观Thecutsurfaceofthebowelwallshowsthetransmural〔透壁性〕natureofthedisease,withthickening〔增厚〕,edema〔水肿〕,andfibrosis〔纤维化〕ofalllayers.Involvedloopsofbowelareoftenadherent〔粘连〕,andfistulas〔瘘管〕betweensuchsegmentsarefrequent.Thesefistulasmayalsopenetratefromthebowelintootherorgans〔肠壁瘘管穿入其它器官〕,includingthebladder,uterus,vagina,andskin.Lesionsinthedistalrectumandanusmaycreateperianalfistulas〔肛旁瘘〕,awell-knownpresentingfeature.2023/12/2614整理pptMicroscopically,Crohndiseaseappearsasachronicinflammatoryprocess.Duringearlyphasesofthedisease,theinflammationmaybeconfinedto〔局限于〕themucosaandsubmucosa.Small,superficialmucosalulcerations(aphthousulcers口疮样溃疡)areseen.Later,long,deep,fissure-like〔裂隙状〕ulcersareseen,andvascularhyalinizationandfibrosisbecomeapparent.ThemicroscopichallmarkofCrohndiseaseistransmural,nodular,lymphoidaggregates(Fig.13-24).Discrete〔散在的〕,noncaseating〔非干酪样〕granulomas〔肉芽肿〕,mostlyinthesubmucosa,maybepresent.AlthoughthepresenceofgranulomasisstrongevidenceinfavorofCrohndisease,lessthanhalfofthecasesshowtheselesions.ThepathologicfeaturesofCrohndiseasearesummarizedinFigure13-25.2023/12/2615整理ppt正常的结肠粘膜组织结构16整理pptFigure13-24.克罗恩病.图片A显示溃疡至粘膜下层；淋巴组织聚集在粘膜下、邻近肌层和浆膜下。图片B显示粘膜活检，可见小灶上皮样肉芽肿位于两个无损的腺隐窝之间。

A.ThecoloninvolvedwithCrohndiseaseshowsanareaofmucosalulceration,anexpandedsubmucosawithlymphoidaggregates,andnumerouslymphoidaggregatesinthesubserosaltissuesimmediatelyadjacenttothemuscularisexterna.B.ThismucosalbiopsyinCrohndiseaseshowsasmallepithelioidgranuloma(arrows)betweentwointactcrypts.2023/12/2617整理ppt克罗恩病的肉芽肿病变18整理ppt克罗恩病肉芽肿的高倍镜下观19整理ppt大肠腺上皮隐窝结构变形20整理ppt克罗恩病回肠炎以下图见裂缝状溃疡逆流性回肠炎21整理ppt克罗恩病肠道活检H-E染色切片组织学观察22整理ppt23整理ppt箭头所示克罗恩病的透壁性炎症24整理ppt临床特点(CLINICALFEATURES)克罗恩病的临床表现与病史各自不同，与发病部位相关TheclinicalmanifestationsandnaturalhistoryofCrohndiseasearehighlyvariableandrelatetotheanatomicalsitesinvolvedbythedisease.最常见病症：75%病人腹痛腹泻；50%病人回归热Themostfrequentsymptomsareabdominalpainanddiarrhea,whichareseeninmorethan75%ofpatients,andrecurrentfever,evidentin50%.吸收不良和营养不良；腹泻和肠出血；以直肠肛门病变为主的可反复发生肛瘘Whenthesmallintestineisdiffuselyinvolved,malabsorptionandmalnutritionmaybemajorfeatures.Crohndiseaseofthecolonleadstodiarrheaandsometimescolonicbleeding.Inafewpatients,themajorsiteofinvolvementistheanorectalregion,andrecurrentanorectalfistulasmaybethepresentingsign.2023/12/2625整理ppt克罗恩病的继发病变肠道阻塞、瘘管和肠穿孔IntestinalobstructionandfistulasarethemostcommonintestinalcomplicationsofCrohndisease.Occasionally,freeperforationoftheboweloccurs.发生肠癌

SmallbowelcancerisatleastthreefoldmorecommoninpatientswithCrohndisease,andthediseasealsopredisposestocolorectalcancer.NocureforCrohndiseaseisavailable.Severalmedicationssuppresstheinflammatoryreaction,includingcorticosteroids,sulfasalazine,metronidazole,6-mercaptopurine,cyclosporine,andanti-TNFantibodies.Surgicalresectionofobstructedareasorofseverelyinvolvedportionsofintestineanddrainageofabscessescausedbyfistulasareoftenrequired.2023/12/2626整理ppt克罗恩病小肠节段性病变特征模式图2023/12/2627整理ppt溃疡性结肠炎

〔UlcerativeColitis〕28整理ppt溃疡性结肠炎〔ULCERATIVECOLITIS〕是结直肠发生的慢性浅表性炎症UlcerativeColitisisaChronicSuperficialInflammationoftheColonandRectum临床表现慢性腹泻，直肠出血。是有加重和缓解，可伴有局部和全身并发症Ulcerativecolitisischaracterizedbychronicdiarrheaandrectalbleeding,withapatternofexacerbationsandremissionsandwiththepossibilityofseriouslocalandsystemiccomplications.2023/12/2629整理ppt流行病学〔EPIDEMIOLOGY〕InEuropeandNorthAmerica,theincidenceofulcerativecolitisis4to7per100,000population,anditsprevalenceis40to80per100,000.Itusuallybeginsinearlyadultlife,withapeakincidenceinthethirddecade.However,italsooccursinchildhoodandoldage.IntheUnitedStates,whitesareaffectedmorecommonlythanblacks.2023/12/2630整理ppt发病机制〔PATHOGENESIS〕原因不清，可能与遗传相关Thecauseofulcerativecolitisisunknown.Insomefamiliesasmanyassixpatientswiththisdiseasehavebeendescribed,andconcordancehasbeenreportedinmonozygotictwins.However,availablefamilystudiesdonotsuggestanydistinctmodeofgenetictransmission.自身免疫病机制

Thepossibilitythatanabnormalimmuneresponsemaybeinvolvedhasbeenstudiedextensively.Thereisabundantlymphoidtissuethroughoutthecolon,andulcerativecolitismayoccurwithautoimmune-likeconditions,suchasuveitis,erythemanodosum,andvasculitis.Increasedcirculatingantibodiesagainstantigensincolonicepithelialcellsandagainstcross-reactingantigensinenterobacteriamayoccur.Antineutrophilcytoplasmicantibodiesarefoundin80%ofpatientswithulcerativecolitis.However,theseabnormalitiesareneitheruniqueforulcerativecolitis,noraretheyaprerequisiteforthedevelopmentofthedisease.2023/12/2631整理ppt病理变化〔PATHOLOGY〕Ulcerativecolitisisadiffusedisease.Itusuallyextendsfromthemostdistalpartoftherectum〔远端直肠〕foravariabledistanceproximally(Fig.13-26).Sparingoftherectumorinvolvementoftherightsideofthecolonaloneisrareandsuggeststhepossibilityofanotherdisorder,suchasCrohndisease.Inflammationinulcerativecolitisisgenerallylimitedtothecolonandrectum.Itrarelyinvolvesthesmallintestine,stomach,oresophagus.Ulcerativecolitisisessentiallyamucosaldisease.Deeperlayersareuncommonlyinvolved,mainlyinfulminantcasesandusuallyinassociationwithtoxicmegacolon.2023/12/26三大主要病变Threemajorpathologicfeaturescharacterizeulcerativecolitisandhelptodifferentiateitfromotherinflammatoryconditions:32整理pptFigure13-26.Ulcerativecolitis.Prominenterythemaandulcerationofthecolonbeginintheascendingcolonandaremostsevereintherectosigmoidarea.2023/12/2633整理pptTHEFOLLOWINGMORPHOLOGICSEQUENCEMAYDEVELOPRAPIDLYOROVERACOURSEOFYEARS.EARLYCOLITIS:Earlyintheevolutionofthedisease,themucosalsurfaceisraw,red,andgranular.Itisfrequentlycoveredwithayellowishexudateandbleedseasily.Latersmall,superficialerosionsorulcersmayappear.Theseoccasionallycoalescetoformirregular,shallow,ulceratedareasthatappeartosurroundislandsofintactmucosa.Themicroscopicfeaturesofearlyulcerativecolitisinclude(1)mucosalcongestion,edema,andmicroscopichemorrhages;(2)adiffusechronicinflammatoryinfiltrateinthelaminapropria;and(3)damageanddistortionofthecolorectalcrypts,whichareoftensurroundedandinfiltratedbyneutrophils.Suppurativenecrosisofthecryptepitheliumgivesrisetothecharacteristiccryptabscess,whichappearsasadilatedcryptfilledwithneutrophils(Fig.13-27).2023/12/2634整理pptFigure13-27.Ulcerativecolitis.A.Afull-thicknesssectionofcolonresectedforulcerativecolitisshowsinflammationaffectingthemucosawithsparingofthesubmucosaandmuscularispropria.B.Sectionsofamucosalbiopsyfromapatientwithactiveulcerativecolitisshowexpansionofthelaminapropriaandseveralcryptabscesses(arrows).C.Chroniculcerativecolitisshowssignificantcryptdistortionandatrophy.2023/12/2635整理pptPROGRESSIVECOLITIS:Asthediseasecontinues,mucosalfoldsarelost.Lateralextensionandcoalescenceofcryptabscessescanunderminethemucosa,leavingareasofulcerationadjacenttohangingfragmentsofmucosa.Suchmucosalexcrescencesaretermedinflammatorypolyps.Granulationtissuedevelopsindenudedareas.Importantly,thestricturescharacteristicofCrohndiseaseareabsent.Microscopically,colorectalcryptsmayappeartortuous,branched,andshortenedinthelatestages,andthemucosamaybediffuselyatrophic.2023/12/2636整理pptADVANCEDCOLITIS:Inlong-standingcases,thelargebowelisoftenshortened,especiallyintheleftside.Mucosalfoldsareindistinctandarereplacedbyagranularorsmoothmucosalpattern.Microscopically,advancedulcerativecolitisischaracterizedbymucosalatrophyandachronicinflammatoryinfiltrateinthemucosaandsuperficialsubmucosa.Panethmetaplasiaiscommon.2023/12/2637整理pptCLINICALFEATURESTheclinicalcourseandmanifestationsareveryvariable.Mostpatients(70%)haveintermittentattacks,withpartialorcompleteremissionbetweenattacks.Asmallnumber(<10%)haveaverylongremission(severalyears)aftertheirfirstattack.Theremaining20%havecontinuoussymptomswithoutremission.2023/12/2638整理pptMILDCOLITIS:Halfofpatientswithulcerativecolitishavemilddisease.Theirmajorsymptomisrectalbleeding,sometimesaccompaniedbytenesmus(rectalpressureanddiscomfort).Thediseaseinthesepatientsisusuallylimitedtotherectumbutmayextendtothedistalsigmoidcolon.Extraintestinalcomplicationsareuncommon,andinmostpatientsinthiscategory,diseaseremainsmildthroughouttheirlives.2023/12/2639整理pptMODERATECOLITIS:About40%ofpatientshavemoderateulcerativecolitis.Theyusuallyhaverecurrentepisodesofloosebloodystools,crampyabdominalpain,andfrequentlylow-gradefever,lastingdaysorweeks.Moderateanemiaisacommonresultofchronicfecalbloodloss.2023/12/2640整理pptSEVERECOLITIS:About10%ofpatientshavesevereorfulminantulcerativecolitis,oftenduringaflareofactivity.Theymayhavemorethan6andsometimesmorethan20bloodybowelmovementsdaily,oftenwithfeverandothersystemicmanifestations.Bloodandfluidlossrapidlyleadstoanemia,dehydration,andelectrolytedepletion.Massivehemorrhagemaybelife-threatening.Aparticularlydangerouscomplicationistoxicmegacolon,whichischaracterizedbyextremedilationofthecolonandanassociatedhighriskforperforation.Fulminantulcerativecolitisisamedicalemergencyrequiringimmediate,intensivemedicaltherapy,and,insomecases,promptcolectomy.About15%ofpatientswithfulminantulcerativecolitisdieofthedisease.2023/12/2641整理pptThedistinctionbetweenulcerativecolitisandCrohncolitisisbasedondifferentanatomicallocalizationandhistopathology(Table13-1).Themedicaltreatmentofulcerativecolitisdependsonthesitesinvolvedandtheseverityoftheinflammation.The5-aminosalicylate鈥揵asedcompoundsarethemainstaysoftreatmentforpatientswithmild-to-moderateulcerativecolitis.Corticosteroidsandimmunosuppressiveandimmunoregulatoryagents(azathioprineormercaptopurine)areusedinpatientswhohavesevereandrefractorydisease.2023/12/2642整理pptEXTRAINTESTINALMANIFESTATIONSArthritisisseenin25%ofpatientswithulcerativecolitis.Eyeinflammation(mostlyuveitis)andskinlesionsdevelopinabout10%.Themostcommoncutaneouslesionsareerythemanodosumandpyodermagangrenosum;thelatterisaserious,noninfectivedisordercharacterizedbydeep,purulent,necroticulcersintheskin.Liverdiseaseoccursinabout4%ofpatients,mostcommonlyprimarysclerosingcholangitis.Thromboembolicphenomena,usuallydeepveinthrombosesofthelowerextremities,occurin6%ofulcerativecolitispatients.2023/12/2643整理pptULCERATIVECOLITISANDCOLORECTALCANCERPeoplewithlong-standingulcerativecolitishaveahigherriskofcolorectalcancerthanthegeneralpopulation.Colorectalepithelialdysplasiaisaneoplasticepithelialproliferationandprecursortocolorectalcarcinomainpatientswithlong-termulcerativecolitis.High-gradeepithelialdysplasiareflectsasignificantriskforthedevelopmentofcolorectalcancer,andwhenidentifiedinabiopsy,itisastrongindicationforcolectomy.2023/12/2644整理pptTABLE13-1COMPARISONOFTHEPATHOLOGICFEATURESINTHECOLONOFCROHNDISEASEANDULCERATIVECOLITIS2023/12/26LesionCrohnDiseaseUlcerativeColitisMacroscopIcThickenedbowelwallTypicalUncommonLuminalnarrowingTypicalUncommon透壁性lesionsCommonAbsentRightcolonpredominanceTypicalAbsentFissuresandfistulasCommonAbsentCircumscribedulcersCommonAbsentConfluentlinearulcersCommonAbsentPseudopolypsAbsentCommonMICROSCOPIcTransmuralinflammationTypicalUncommonSubmucosalfibrosisTypicalAbsentFissuresTypicalRareGranulomasCommonAbsentCryptabscessesUncommonTypical45整理pptSUMMARYCrohndiseaseandulcerativecolitisareidiopathicinflammatoryboweldiseasesbelievedtoresultfromabnormallocalimmuneresponsesagainstunknownmicrobesand/orselfantigensintheCrohndiseaseAssociatedwithHLA-DR7and-DQ4alleles,andwithmutationsintheNOD2gene,whichencodesanintracellularsensorofmicrobesResultsfromachronicTcell-mediatedinflammatoryreactioninvolvingIFN-γ-producingTH1cellsand,perhaps,IL-17-producingTH17cellsManifestedbychronicinflammationwithgranulomas,ulcers,andstricturescausedbyfibrosis,involvingthetermi