消化道病理二ppt课件.ppt

炎症性肠病的临床病理THECLINICO PATHOLOGYOFINFLAMMATORYBOWELDISEASE IBD 2015 11 24 1 2 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 3 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 克罗恩病 CrohnDisease 5 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 2020 1 25 6 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 2020 1 25 7 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 2020 1 25 8 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 2020 1 25 9 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 2020 1 25 10 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 2020 1 25 11 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 2020 1 25 12 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 2020 1 25 克罗恩病肠切除标本大体观 13 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 2020 1 25 14 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 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 2020 1 25 15 正常的结肠粘膜组织结构 16 Figure13 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 2020 1 25 17 克罗恩病的肉芽肿病变 18 克罗恩病肉芽肿的高倍镜下观 19 大肠腺上皮隐窝结构变形 20 克罗恩病回肠炎下图见裂缝状溃疡 逆流性回肠炎 21 克罗恩病肠道活检H E染色切片组织学观察 22 23 箭头所示克罗恩病的透壁性炎症 24 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 最常见症状 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 2020 1 25 25 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 2020 1 25 26 克罗恩病小肠节段性病变特征模式图 2020 1 25 27 溃疡性结肠炎 UlcerativeColitis 28 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 2020 1 25 29 流行病学 Epidemiology InEuropeandNorthAmerica theincidenceofulcerativecolitisis4to7per100 000population anditsprevalenceis40to80per100 000 Itusuallybeginsinearlyadultlife withapeakincidenceinthethirddecade However italsooccursinchildhoodandoldage IntheUnitedStates whitesareaffectedmorecommonlythanblacks 2020 1 25 30 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 2020 1 25 31 病理变化 Pathology Ulcerativecolitisisadiffusedisease Itusuallyextendsfromthemostdistalpartoftherectum 远端直肠 foravariabledistanceproximally Fig 13 26 Sparingoftherectumorinvolvementoftherightsideofthecolonaloneisrareandsuggeststhepossibilityofanotherdisorder suchasCrohndisease Inflammationinulcerativecolitisisgenerallylimitedtothecolonandrectum Itrarelyinvolvesthesmallintestine stomach oresophagus Ulcerativecolitisisessentiallyamucosaldisease Deeperlayersareuncommonlyinvolved mainlyinfulminantcasesandusuallyinassociationwithtoxicmegacolon 2020 1 25 三大主要病变Threemajorpathologicfeaturescharacterizeulcerativecolitisandhelptodifferentiateitfromotherinflammatoryconditions 32 Figure13 26 Ulcerativecolitis Prominenterythemaandulcerationofthecolonbeginintheascendingcolonandaremostsevereintherectosigmoidarea 2020 1 25 33 Thefollowingmorphologicsequencemaydeveloprapidlyoroveracourseofyears 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 2020 1 25 34 Figure13 27 Ulcerativecolitis A Afull thicknesssectionofcolonresectedforulcerativecolitisshowsinflammationaffectingthemucosawithsparingofthesubmucosaandmuscularispropria B Sectionsofamucosalbiopsyfromapatientwithactiveulcerativecolitisshowexpansionofthelaminapropriaandseveralcryptabscesses arrows C Chroniculcerativecolitisshowssignificantcryptdistortionandatrophy 2020 1 25 35 PROGRESSIVECOLITIS Asthediseasecontinues mucosalfoldsarelost Lateralextensionandcoalescenceofcryptabscessescanunderminethemucosa leavingareasofulcerationadjacenttohangingfragmentsofmucosa Suchmucosalexcrescencesaretermedinflammatorypolyps Granulationtissuedevelopsindenudedareas Importantly thestricturescharacteristicofCrohndiseaseareabsent Microscopically colorectalcryptsmayappeartortuous branched andshortenedinthelatestages andthemucosamaybediffuselyatrophic 2020 1 25 36 ADVANCEDCOLITIS Inlong standingcases thelargebowelisoftenshortened especiallyintheleftside Mucosalfoldsareindistinctandarereplacedbyagranularorsmoothmucosalpattern Microscopically advancedulcerativecolitisischaracterizedbymucosalatrophyandachronicinflammatoryinfiltrateinthemucosaandsuperficialsubmucosa Panethmetaplasiaiscommon 2020 1 25 37 ClinicalFeatures Theclinicalcourseandmanifestationsareveryvariable Mostpatients 70 haveintermittentattacks withpartialorcompleteremissionbetweenattacks Asmallnumber 10 haveaverylongremission severalyears aftertheirfirstattack Theremaining20 havecontinuoussymptomswithoutremission 2020 1 25 38 MILDCOLITIS Halfofpatientswithulcerativecolitishavemilddisease Theirmajorsymptomisrectalbleeding sometimesaccompaniedbytenesmus rectalpressureanddiscomfort Thediseaseinthesepatientsisusuallylimitedtotherectumbutmayextendtothedistalsigmoidcolon Extraintestinalcomplicationsareuncommon andinmostpatientsinthiscategory diseaseremainsmildthroughouttheirlives 2020 1 25 39 MODERATECOLITIS About40 ofpatientshavemoderateulcerativecolitis Theyusuallyhaverecurrentepisodesofloosebloodystools crampyabdominalpain andfrequentlylow gradefever lastingdaysorweeks Moderateanemiaisacommonresultofchronicfecalbloodloss 2020 1 25 40 SEVERECOLITIS About10 ofpatientshavesevereorfulminantulcerativecolitis oftenduringaflareofactivity Theymayhavemorethan6andsometimesmorethan20bloodybowelmovementsdaily oftenwithfeverandothersystemicmanifestations Bloodandfluidlossrapidlyleadstoanemia dehydration andelectrolytedepletion Massivehemorrhagemaybelife threatening Aparticularlydangerouscomplicationistoxicmegacolon whichischaracterizedbyextremedilationofthecolonandanassociatedhighriskforperforation Fulminantulcerativecolitisisamedicalemergencyrequiringimmediate intensivemedicaltherapy and insomecases promptcolectomy About15 ofpatientswithfulminantulcerativecolitisdieofthedisease 2020 1 25 41 ThedistinctionbetweenulcerativecolitisandCrohncolitisisbasedondifferentanatomicallocalizationandhistopathology Table13 1 Themedicaltreatmentofulcerativecolitisdependsonthesitesinvolvedandtheseverityoftheinflammation The5 aminosalicylate鈥揵asedcompoundsarethemainstaysoftreatmentforpatientswithmild to moderateulcerativecolitis Corticosteroidsandimmunosuppressiveandimmunoregulatoryagents azathioprineormercaptopurine areusedinpatientswhohavesevereandrefractorydisease 2020 1 25 42 ExtraintestinalManifestations Arthritisisseenin25 ofpatientswithulcerativecolitis Eyeinflammation mostlyuveitis andskinlesionsdevelopinabout10 Themostcommoncutaneouslesionsareerythemanodosumandpyodermagangrenosum thelatterisaserious noninfectivedisordercharacterizedbydeep purulent necroticulcersintheskin Liverdiseaseoccursinabout4 ofpatients mostcommonlyprimarysclerosingcholangitis Thromboembolicphenomena usuallydeepveinthrombosesofthelowerextremities occurin6 ofulcerativecolitispatients 2020 1 25 43 UlcerativeColitisandColorectalCancer Peoplewithlong standingulcerativecolitishaveahigherriskofcolorectalcancerthanthegeneralpopulation Colorectalepithelialdysplasiaisaneoplasticepithelialproliferationandprecursortocolorectalcarcinomainpatientswithlong termulcerativecolitis High gradeepithelialdysplasiareflectsasignificantriskforthedevelopmentofcolorectalcancer andwhenidentifiedinabiopsy itisastrongindicationforcolectomy 2020 1 25 44 TABLE13 1ComparisonofthePathologicFeaturesintheColonofCrohnDiseaseandUlcerativeColitis 2020 1 25 Lesion CrohnDisease UlcerativeColitis MacroscopIc Thickenedbowelwall Typical Uncommon Luminalnarrowing Typical Uncommon 透壁性lesions Common Absent Rightcolonpredominance Typical Absent Fissuresandfistulas Common Absent Circumscribedulcers Common Absent Confluentlinearulcers Common Absent Pseudopolyps Absent Common MICROSCOPIc Transmuralinflammation Typical Uncommon Submucosalfibrosis Typical Absent Fissures Typical Rare Granulomas Common Absent Cryptabscesses Uncommon Typical 45 SUMMARY Crohndiseaseandulcerativecolitisareidiopathicinflammatoryboweldiseasesbelievedtoresultfromabnormallocalimmuneresponsesagainstunknownmicrobesand orselfantigensintheCrohndiseaseAssociatedwithHLA DR7and DQ4alleles andwithmutationsintheNOD2gene whichencodesanintracellularsensorofmicrobesResultsfroma