消化道病理(二)

炎症性肠病的临床病理THECLINICO-PATHOLOGYOFINFLAMMATORYBOWELDISEASE(IBD)王军臣2015-11-24•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，而治疗原则不同。Inflammatoryboweldiseaseisatermthatdescribestwodiseases:Crohndiseaseandulcerativecolitis.Althoughthesetwodisordershavedifferentclinicalcoursesaswellasnaturalhistoriesandareusuallyclearlydistinguishable,theyhavecertaincommonfeatures.IBD的类型•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的实验室检测克罗恩病（CrohnDisease）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.）2019/12/23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，来自各国的报道表明，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).2019/12/23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.2019/12/23•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）.2019/12/23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.2019/12/23克罗恩病病变分布的四大部位特征(1)回盲部病变为主，占50%mainlytheileumandcecuminabout50%ofcases(2)仅有小肠病变，占15%onlythesmallintestinein15%(3)仅有大肠病变，占20%onlythecolonin20%(4)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.2019/12/23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).2019/12/23•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。右下侧局部粘膜部分未受累2019/12/23克罗恩病肠切除标本大体观大体切面观•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.2019/12/23•Microscopically,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.•Th