消化道病理二

炎癥性腸病的臨床病理

THECLINICO-PATHOLOGYOFINFLAMMATORYBOWELDISEASE(IBD)

1整理ppt2整理ppt潰瘍性結(jié)腸炎〔Ulcerativecolitis〕克羅思病〔Crohn’sdisease〕未定型結(jié)腸炎〔Indeterminatecolitis〕IBM一詞主要是指兩種腸?。嚎肆_思病和潰瘍性結(jié)腸炎。兩者臨床病程與病史不同，病變有別，但某些特點相同，而治療原那么不同。Inflammatoryboweldiseaseisatermthatdescribestwodiseases:Crohndiseaseandulcerativecolitis.Althoughthesetwodisordershavedifferentclinicalcoursesaswellasnaturalhistoriesandareusuallyclearlydistinguishable,theyhavecertaincommonfeatures.IBD的類型3整理ppt無特異性實驗室檢測指標(biāo)〔Nospecificlaboratorytests〕抗中性粒細胞胞質(zhì)抗體pANCA(anti-neutrophilcytoplasmicantibody)60-75%的潰瘍性結(jié)腸炎病例〔Ulcerativecolitis:60-75%〕10-40%的克羅思病病例〔Crohn’sdisease:10-40%〕抗釀酒酵母菌抗體ASCA(anti-Saccharomycescerevisiaeantibody)40-80%的潰瘍性結(jié)腸炎病例〔Crohn’sdisease:40-80%〕<10%的克羅思病病例〔Ulcerativecolitis:<10%〕基因檢測：NOD2和其他的IBD基因〔GenetictestingforNOD2andotherIBDgenes〕

IBD的實驗室檢測4整理ppt克羅恩病

〔CrohnDisease〕5整理ppt克羅恩病〔CROHNDISEASE〕腸炎特點〔FeaturesofInflammationoftheIntestine〕

慢性，節(jié)段性，透壁性〔Chronic,Segmental,Transmural〕病變以小腸遠端為主，右半結(jié)腸可受累，可有消化道甚至腸外組織受累〔Crohndiseaseoccursprincipallyinthedistalsmallintestinebutmayinvolveanypartofthedigestivetractandevenextraintestinaltissues.Thecolon,particularlytherightcolon,maybeaffected.〕2023/12/266整理ppt克羅恩病的流行病學(xué)〔EPIDEMIOLOGY〕全球發(fā)生克羅思病，每年發(fā)病率為0.5-5人/每10萬人群。過去30年來，來自各國的報道說明，全球的克羅思發(fā)病率急劇增加?！睠rohndiseaseoccursworldwide,withanannualincidenceof0.5to5per100,000.Reportsfromvariouscountriesindicatethattheincidencehasincreaseddramaticallyoverthepast30years.〕歐洲的該病病例最常見于青少年或年輕成人,猶太人群呈高發(fā)病率，女性較男性稍微多見(1.6:1).ThediseaseusuallyappearsinadolescentsoryoungadultsandismostcommonamongpersonsofEuropeanorigin,withaconsiderablyhigherfrequencyintheJewishpopulation.Thereisaslightfemalepredominance(1.6:1).2023/12/267整理ppt發(fā)病機制〔PATHOGENESIS〕家族性遺傳性體質(zhì)ConcordanceratesintwinpairsandsiblingsstronglyimplicateageneticpredispositiontoCrohndisease.AfamilyhistoryofinflammatoryboweldiseaseismorecommonforCrohndiseasethanforulcerativecolitis.AputativesusceptibilitylocusforCrohndiseasehasbeenassignedtothecentromericregionofchromosome16whereitisassociatedwiththeNOD2/CARD15locus,whichcodesforanintracellularreceptorforbacterialproductsinvolvedininnateimmunity.自身免疫機制ThepossibilitythatCrohndiseasereflectsimmunologicallymediateddamagetotheintestineissuggestedby(1)thechronicandrecurrentnature〔慢性反復(fù)發(fā)作〕oftheinflammationand(2)itsassociationwithsystemicmanifestations〔全身損害〕thataresuggestiveofautoimmunedisease.Mostrecentimmunologicstudiesfocusonthepossibleroleofcell-mediatedcytotoxicity.2023/12/268整理ppt腸道糞便流的作用ThefecalstreamappearstobeofprimeimportanceinthepathogenesisofCrohndisease,asevidencedby：(1)thebeneficialeffectsofsurgicalbypass〔腸旁路吻合的好處〕(2)thepatternofpreanastomoticrecurrenceinpatientswithside-to-endanastomoticsites〔側(cè)-端吻合處前段復(fù)發(fā)〕,and(3)thefrequencyofearlyinflammatorylesions(aphthoiderosions)intheepitheliuminassociationwithmucosallymphoidtissue〔淋巴組織增生之上皮處早期炎癥-口瘡樣糜爛〕.2023/12/269整理ppt病理變化〔PATHOLOGY〕

克羅思病有兩大病變特征，以此與其他的炎癥性腸病相鑒別：

TwomajorcharacteristicsofCrohndiseasedifferentiateitfromotherGIinflammatorydiseases.

第一，嚴(yán)重通常累及腸壁全層，故稱之為透壁性炎癥。

First,theinflammationusuallyinvolvesalllayersofthebowelwallandis,therefore,referredtoastransmuralinflammatorydisease.第二，腸壁病變是間斷性的，即節(jié)段性腸炎病變，間有未受累及的正常腸組織

Second,theinvolvementoftheintestineisdiscontinuous;thatis,segmentsofinflamedtissueareseparatedbyapparentlynormalintestine.2023/12/2610整理ppt克羅恩病病變分布的四大部位特征回盲部病變?yōu)橹鳎?0%

mainlytheileumandcecuminabout50%ofcases僅有小腸病變，占15%

onlythesmallintestinein15%僅有大腸病變，占20%

onlythecolonin20%肛門直腸區(qū)病變?yōu)橹?，?5%

女性肛門直腸區(qū)克羅恩病可蔓延到外陰部

mainlytheanorectalregionin15%.InwomenwithanorectalCrohndisease,theinflammationmayspreadtoinvolvetheexternalgenitalia.2023/12/2611整理ppt大體觀(GROSSLY)腸壁與鄰近腸系膜增厚，水腫，腸系膜脂肪環(huán)繞腸周〔爬行脂肪〕Thebowelandadjacentmesenteryarethickenedaswellasedematous,andmesentericfatoftenwrapsaroundthebowel(Creepingfat).腸系膜淋巴結(jié)常常腫大，變硬，相互融合Mesentericlymphnodesarefrequentlyenlarged,firm,andmattedtogether.腸腔狹窄〔水腫與纖維化共同作用所致〕，可見鵝卵石狀外觀〔因結(jié)節(jié)狀腫脹、腸壁纖維化和粘膜潰瘍所致〕Theintestinallumenisnarrowedbyacombinationofedemaandfibrosis.Nodularswelling,fibrosis,andmucosalulcerationleadtoacobblestoneappearance.潰瘍特點：早期的潰瘍呈口瘡狀或葡行狀；晚期的潰瘍變深呈線狀裂縫或裂紋狀I(lǐng)nearlycases,ulcershaveeitheranaphthousoraserpiginousappearance;later,theybecomedeeperandappearaslinearcleftsorfissures(seeFig.13-23B).2023/12/2612整理ppt圖片A.末端回腸遠端腸壁明顯增厚，伴有回盲瓣變形?？梢娨豢v向潰瘍(箭頭所示)圖片B.該回腸節(jié)段另一縱向潰瘍。受損粘膜水腫，形成圓形/卵圓形結(jié)節(jié)狀隆起，使病變腸段粘膜呈鵝卵石樣外觀。右下側(cè)局部粘膜局部未受累2023/12/26

克羅恩病腸切除標(biāo)本大體觀13整理ppt大體切面觀Thecutsurfaceofthebowelwallshowsthetransmural〔透壁性〕natureofthedisease,withthickening〔增厚〕,edema〔水腫〕,andfibrosis〔纖維化〕ofalllayers.Involvedloopsofbowelareoftenadherent〔粘連〕,andfistulas〔瘺管〕betweensuchsegmentsarefrequent.Thesefistulasmayalsopenetratefromthebowelintootherorgans〔腸壁瘺管穿入其它器官〕,includingthebladder,uterus,vagina,andskin.Lesionsinthedistalrectumandanusmaycreateperianalfistulas〔肛旁瘺〕,awell-knownpresentingfeature.2023/12/2614整理pptMicroscopically,Crohndiseaseappearsasachronicinflammatoryprocess.Duringearlyphasesofthedisease,theinflammationmaybeconfinedto〔局限于〕themucosaandsubmucosa.Small,superficialmucosalulcerations(aphthousulcers口瘡樣潰瘍)areseen.Later,long,deep,fissure-like〔裂隙狀〕ulcersareseen,andvascularhyalinizationandfibrosisbecomeapparent.ThemicroscopichallmarkofCrohndiseaseistransmural,nodular,lymphoidaggregates(Fig.13-24).Discrete〔散在的〕,noncaseating〔非干酪樣〕granulomas〔肉芽腫〕,mostlyinthesubmucosa,maybepresent.AlthoughthepresenceofgranulomasisstrongevidenceinfavorofCrohndisease,lessthanhalfofthecasesshowtheselesions.ThepathologicfeaturesofCrohndiseasearesummarizedinFigure13-25.2023/12/2615整理ppt正常的結(jié)腸粘膜組織結(jié)構(gòu)16整理pptFigure13-24.克羅恩病.圖片A顯示潰瘍至粘膜下層；淋巴組織聚集在粘膜下、鄰近肌層和漿膜下。圖片B顯示粘膜活檢，可見小灶上皮樣肉芽腫位于兩個無損的腺隱窩之間。

A.ThecoloninvolvedwithCrohndiseaseshowsanareaofmucosalulceration,anexpandedsubmucosawithlymphoidaggregates,andnumerouslymphoidaggregatesinthesubserosaltissuesimmediatelyadjacenttothemuscularisexterna.B.ThismucosalbiopsyinCrohndiseaseshowsasmallepithelioidgranuloma(arrows)betweentwointactcrypts.2023/12/2617整理ppt克羅恩病的肉芽腫病變18整理ppt克羅恩病肉芽腫的高倍鏡下觀19整理ppt大腸腺上皮隱窩結(jié)構(gòu)變形20整理ppt克羅恩病回腸炎以下圖見裂縫狀潰瘍逆流性回腸炎21整理ppt克羅恩病腸道活檢H-E染色切片組織學(xué)觀察22整理ppt23整理ppt箭頭所示克羅恩病的透壁性炎癥24整理ppt臨床特點(CLINICALFEATURES)克羅恩病的臨床表現(xiàn)與病史各自不同，與發(fā)病部位相關(guān)TheclinicalmanifestationsandnaturalhistoryofCrohndiseasearehighlyvariableandrelatetotheanatomicalsitesinvolvedbythedisease.最常見病癥：75%病人腹痛腹瀉；50%病人回歸熱Themostfrequentsymptomsareabdominalpainanddiarrhea,whichareseeninmorethan75%ofpatients,andrecurrentfever,evidentin50%.吸收不良和營養(yǎng)不良；腹瀉和腸出血；以直腸肛門病變?yōu)橹鞯目煞磸?fù)發(fā)生肛瘺Whenthesmallintestineisdiffuselyinvolved,malabsorptionandmalnutritionmaybemajorfeatures.Crohndiseaseofthecolonleadstodiarrheaandsometimescolonicbleeding.Inafewpatients,themajorsiteofinvolvementistheanorectalregion,andrecurrentanorectalfistulasmaybethepresentingsign.2023/12/2625整理ppt克羅恩病的繼發(fā)病變腸道阻塞、瘺管和腸穿孔IntestinalobstructionandfistulasarethemostcommonintestinalcomplicationsofCrohndisease.Occasionally,freeperforationoftheboweloccurs.發(fā)生腸癌

SmallbowelcancerisatleastthreefoldmorecommoninpatientswithCrohndisease,andthediseasealsopredisposestocolorectalcancer.NocureforCrohndiseaseisavailable.Severalmedicationssuppresstheinflammatoryreaction,includingcorticosteroids,sulfasalazine,metronidazole,6-mercaptopurine,cyclosporine,andanti-TNFantibodies.Surgicalresectionofobstructedareasorofseverelyinvolvedportionsofintestineanddrainageofabscessescausedbyfistulasareoftenrequired.2023/12/2626整理ppt克羅恩病小腸節(jié)段性病變特征模式圖2023/12/2627整理ppt潰瘍性結(jié)腸炎

〔UlcerativeColitis〕28整理ppt潰瘍性結(jié)腸炎〔ULCERATIVECOLITIS〕是結(jié)直腸發(fā)生的慢性淺表性炎癥UlcerativeColitisisaChronicSuperficialInflammationoftheColonandRectum臨床表現(xiàn)慢性腹瀉，直腸出血。是有加重和緩解，可伴有局部和全身并發(fā)癥Ulcerativecolitisischaracterizedbychronicdiarrheaandrectalbleeding,withapatternofexacerbationsandremissionsandwiththepossibilityofseriouslocalandsystemiccomplications.2023/12/2629整理ppt流行病學(xué)〔EPIDEMIOLOGY〕InEuropeandNorthAmerica,theincidenceofulcerativecolitisis4to7per100,000population,anditsprevalenceis40to80per100,000.Itusuallybeginsinearlyadultlife,withapeakincidenceinthethirddecade.However,italsooccursinchildhoodandoldage.IntheUnitedStates,whitesareaffectedmorecommonlythanblacks.2023/12/2630整理ppt發(fā)病機制〔PATHOGENESIS〕原因不清，可能與遺傳相關(guān)Thecauseofulcerativecolitisisunknown.Insomefamiliesasmanyassixpatientswiththisdiseasehavebeendescribed,andconcordancehasbeenreportedinmonozygotictwins.However,availablefamilystudiesdonotsuggestanydistinctmodeofgenetictransmission.自身免疫病機制

Thepossibilitythatanabnormalimmuneresponsemaybeinvolvedhasbeenstudiedextensively.Thereisabundantlymphoidtissuethroughoutthecolon,andulcerativecolitismayoccurwithautoimmune-likeconditions,suchasuveitis,erythemanodosum,andvasculitis.Increasedcirculatingantibodiesagainstantigensincolonicepithelialcellsandagainstcross-reactingantigensinenterobacteriamayoccur.Antineutrophilcytoplasmicantibodiesarefoundin80%ofpatientswithulcerativecolitis.However,theseabnormalitiesareneitheruniqueforulcerativecolitis,noraretheyaprerequisiteforthedevelopmentofthedisease.2023/12/2631整理ppt病理變化〔PATHOLOGY〕Ulcerativecolitisisadiffusedisease.Itusuallyextendsfromthemostdistalpartoftherectum〔遠端直腸〕foravariabledistanceproximally(Fig.13-26).Sparingoftherectumorinvolvementoftherightsideofthecolonaloneisrareandsuggeststhepossibilityofanotherdisorder,suchasCrohndisease.Inflammationinulcerativecolitisisgenerallylimitedtothecolonandrectum.Itrarelyinvolvesthesmallintestine,stomach,oresophagus.Ulcerativecolitisisessentiallyamucosaldisease.Deeperlayersareuncommonlyinvolved,mainlyinfulminantcasesandusuallyinassociationwithtoxicmegacolon.2023/12/26三大主要病變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