消化道病理二潰瘍性結腸炎（Ulcerativecolitis）克羅思病（Crohn’sdisease）未定型結腸炎（Indeterminatecolitis）IBM一詞主要是指兩種腸?。嚎肆_思病和潰瘍性結腸炎。兩者臨床病程與病史不同，病變有別，但某些特點相同，而治療原則不同。

Inflammatoryboweldiseaseisatermthatdescribestwodiseases:Crohndiseaseandulcerativecolitis.Althoughthesetwodisordershavedifferentclinicalcoursesaswellasnaturalhistoriesandareusuallyclearlydistinguishable,theyhavecertaincommonfeatures.IBD的類型無特異性實驗室檢測指標（Nospecificlaboratorytests）抗中性粒細胞胞質抗體

pANCA(anti-neutrophilcytoplasmicantibody)60-75%的潰瘍性結腸炎病例（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的實驗室檢測克羅恩病

（CrohnDisease）

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，右半結腸可受累，可有消化道甚至腸外組織受累

（Crohndiseaseoccursprincipallyinthedistalsmallintestinebutmayinvolveanypartofthedigestivetractandevenextraintestinaltissues.Thecolon,particularlytherightcolon,maybeaffected.）2023/12/29克羅恩病的流行病學（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，來自各國的報道表明，全球的克羅思發(fā)病率急劇增加。

（Crohndiseaseoccursworldwide,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).2023/12/29發(fā)病機制（Pathogenesis）家族性遺傳性體質

ConcordanceratesintwinpairsandsiblingsstronglyimplicateageneticpredispositiontoCrohndisease.AfamilyhistoryofinflammatoryboweldiseaseismorecommonforCrohndiseasethanforulcerativecolitis.AputativesusceptibilitylocusforCrohndiseasehasbeenassignedtothecentromericregionofchromosome16whereitisassociatedwiththeNOD2/CARD15locus,whichcodesforanintracellularreceptorforbacterialproductsinvolvedininnateimmunity.自身免疫機制

ThepossibilitythatCrohndiseasereflectsimmunologicallymediateddamage

totheintestineissuggestedby(1)thechronicandrecurrentnature（慢性反復發(fā)作）

oftheinflammationand(2)itsassociationwithsystemicmanifestations（全身損害）

thataresuggestiveofautoimmunedisease.Mostrecentimmunologicstudiesfocusonthepossibleroleofcell-mediatedcytotoxicity.2023/12/29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-端吻合處前段復發(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）.2023/12/29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.2023/12/29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.2023/12/29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

Inearlycases,ulcershaveeitheranaphthousoraserpiginousappearance;later,theybecomedeeperandappearaslinearcleftsorfissures(seeFig.13-23B).2023/12/29圖片A.末端回腸遠端腸壁明顯增厚，伴有回盲瓣變形。可見一縱向潰瘍(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/卵圓形結節(jié)狀隆起，使病變腸段粘膜呈鵝卵石樣外觀。右下側局部粘膜部分未受累2023/12/29

克羅恩病腸切除標本大體觀大體切面觀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.2023/12/29Microscopically,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.ThepathologicfeaturesofCrohndiseasearesummarizedinFigure13-25.2023/12/29正常的結腸粘膜組織結構Figure13-24.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.2023/12/29克羅恩病的肉芽腫病變克羅恩病肉芽腫的高倍鏡下觀大腸腺上皮隱窩結構變形克羅恩病回腸炎下圖見裂縫狀潰瘍逆流性回腸炎克羅恩病腸道活檢H-E染色切片組織學觀察箭頭所示克羅恩病的透壁性炎癥臨床特點(ClinicalFeatures)克羅恩病的臨床表現與病史各自不同，與發(fā)病部位相關TheclinicalmanifestationsandnaturalhistoryofCrohndiseasearehighlyvariableandrelatetotheanatomicalsitesinvolvedbythedisease.

最常見癥狀：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)橹鞯目煞磸桶l(fā)生肛瘺

Whenthesmallintestineisdiffuselyinvolved,malabsorptionandmalnutritionmaybemajorfeatures.Crohndiseaseofthecolonleadstodiarrheaandsometimescolonicbleeding.Inafewpatients,themajorsiteofinvolvementistheanorectalregion,andrecurrentanorectalfistulasmaybethepresentingsign.2023/12/29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.2023/12/29克羅恩病小腸節(jié)段性病變特征模式圖2023/12/29潰瘍性結腸炎

（UlcerativeColitis

）

潰瘍性結腸炎（UlcerativeColitis）是結直腸發(fā)生的慢性淺表性炎癥UlcerativeColitisisaChronicSuperficialInflammationoftheColonandRectum臨床表現慢性腹瀉，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.2023/12/29流行病學（Epidemiology）InEuropeandNorthAmerica,theincidenceofulcerativecolitisis4to7per100,000population,anditsprevalenceis40to80per100,000.Itusuallybeginsinearlyadultlife,withapeakincidenceinthethirddecade.However,italsooccursinchildhoodandoldage.IntheUnitedStates,whitesareaffectedmorecommonlythanblacks.2023/12/29發(fā)病機制（Pathogenesis）原因不清，可能與遺傳相關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.2023/12/29病理變化（Pathology）Ulcerativecolitisisadiffusedisease.Itusuallyextendsfromthemostdistalpartoftherectum（遠端直腸）foravariabledistanceproximally(Fig.13-26).Sparingoftherectumorinvolvementoftherightsideofthecolonaloneisrareandsuggeststhepossibilityofanotherdisorder,suchasCrohndisease.Inflammationinulcerativecolitisisgenerallylimitedtothecolonandrectum.Itrarelyinvolvesthesmallintestine,stomach,oresophagus.Ulcerativecolitisisessentiallyamucosaldisease.Deeperlayersareuncommonlyinvolved,mainlyinfulminantcasesandusuallyinassociationwithtoxicmegacolon.2023/12/29三大主要病變Threemajorpathologicfeaturescharacterizeulcerativecolitisandhelptodifferentiateitfromotherinflammatoryconditions:Figure13-26.Ulcerativecolitis.Prominenterythemaandulcerationofthecolonbeginintheascendingcolonandaremostsevereintherectosigmoidarea.2023/12/29Thefollowingmorphologicsequencemaydeveloprapidlyoroveracourseofyears.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).2023/12/29Figure13-27.Ulcerativecolitis.A.Afull-thicknesssectionofcolonresectedforulcerativecolitisshowsinflammationaffectingthemucosawithsparingofthesubmucosaandmuscularispropria.B.Sectionsofamucosalbiopsyfromapatientwithactiveulcerativecolitisshowexpansionofthelaminapropriaandseveralcryptabscesses(arrows).C.Chroniculcerativecolitisshowssignificantcryptdistortionandatrophy.2023/12/29PROGRESSIVECOLITIS:Asthediseasecontinues,mucosalfoldsarelost.Lateralextensionandcoalescenceofcryptabscessescanunderminethemucosa,leavingareasofulcerationadjacenttohangingfragmentsofmucosa.Suchmucosalexcrescencesaretermedinflammatorypolyps.Granulationtissuedevelopsindenudedareas.Importantly,thestricturescharacteristicofCrohndiseaseareabsent.Microscopically,colorectalcryptsmayappeartortuous,branched,andshortenedinthelatestages,andthemucosamaybediffuselyatrophic.2023/12/29ADVANCEDCOLITIS:Inlong-standingcases,thelargebowelisoftenshortened,especiallyintheleftside.Mucosalfoldsareindistinctandarereplacedbyagranularorsmoothmucosalpattern.Microscopically,advancedulcerativecolitisischaracterizedbymucosalatrophyandachronicinflammatoryinfiltrateinthemucosaandsuperficialsubmucosa.Panethmetaplasiaiscommon.2023/12/29ClinicalFeaturesTheclinicalcourseandmanifestationsareveryvariable.Mostpatients(70%)haveintermittentattacks,withpartialorcompleteremissionbetweenattacks.Asmallnumber(<10%)haveaverylongremission(severalyears)aftertheirfirstattack.Theremaining20%havecontinuoussymptomswithoutremission.2023/12/29MILDCOLITIS:Halfofpatientswithulcerativecolitishavemilddisease.Theirmajorsymptomisrectalbleeding,sometimesaccompaniedbytenesmus(rectalpressureanddiscomfort).Thediseaseinthesepatientsisusuallylimitedtotherectumbutmayextendtothedistalsigmoidcolon.Extraintestinalcomplicationsareuncommon,andinmostpatientsinthiscategory,diseaseremainsmildthroughouttheirlives.2023/12/29MODERATECOLITIS:About40%ofpatientshavemoderateulcerativecolitis.Theyusuallyhaverecurrentepisodesofloosebloodystools,crampyabdominalpain,andfrequentlylow-gradefever,lastingdaysorweeks.Moderateanemiaisacommonresultofchronicfecalbloodloss.2023/12/29SEVERECOLITIS:About10%ofpatientshavesevereorfulminantulcerativecolitis,oftenduringaflareofactivity.Theymayhavemorethan6andsometimesmorethan20bloodybowelmovementsdaily,oftenwithfeverandothersystemicmanifestations.Bloodandfluidlossrapidlyleadstoanemia,dehydration,andelectrolytedepletion.Massivehemorrhagemaybelife-threatening.Aparticularlydangerouscomplicationistoxicmegacolon,whichischaracterizedbyextremedilationofthecolonandanassociatedhighriskforperforation.Fulminantulcerativecolitisisamedicalemergencyrequiringimmediate,intensivemedicaltherapy,and,insomecases,promptcolectomy.About15%ofpatientswithfulminantulcerativecolitisdieofthedisease.2023/12/29ThedistinctionbetweenulcerativecolitisandCrohncolitisisbasedondifferentanatomicallocalizationandhistopathology(Table13-1).Themedicaltreatmentofulcerativecolitisdependsonthesitesinvolvedandtheseverityoftheinflammation.The5-aminosalicylate鈥揵asedcompoundsarethemainstaysoftreatmentforpatientswithmild-to-moderateulcerativecolitis.Corticosteroidsandimmunosuppressiveandimmunoregulatoryagents(azathioprineormercaptopurine)areusedinpatientswhohavesevereandrefractorydisease.2023/12/29ExtraintestinalManifestationsArthritisisseenin25%ofpatientswithulcerativecolitis.Eyeinflammation(mostlyuveitis)andskinlesionsdevelopinabout10%.Themostcommoncutaneouslesionsareerythemanodosumandpyodermagangrenosum;thelatterisaserious,noninfectivedisordercharacterizedbydeep,purulent,necroticulcersintheskin.Liverdiseaseoccursinabout4%ofpatients,mostcommonlyprimarysclerosingcholangitis.Thromboembolicphenomena,usuallydeepveinthrombosesofthelowerextremities,occurin6%ofulcerativecolitispatients.2023/12/29UlcerativeColitisandColorectalCancerPeoplewithlong-standingulcerativecolitishaveahigherriskofcolorectalcancerthanthegeneralpopulation.Colorectalepithelialdysplasiaisaneoplasticepithelialproliferationandprecursortocolorectalcarcinomainpatientswithlong-termulcerativecolitis.High-gradeepithelialdysplasiareflectsasignificantriskforthedevelopmentofcolorectalcancer,andwhenidentifiedinabiopsy,itisastrongindicationforcolectomy.2023/12/29TABLE13-1ComparisonofthePathologicFeaturesintheColonofCrohnDiseaseandUlcerativeColitis2023/12/29LesionCrohnDiseaseUlcerativeColitisMacroscopIcThickenedbowelwallTypicalUncommonLuminalnarrowingTypicalUncommon透壁性lesionsCommonAbsentRightcolonpredominanceTypicalAbsentFissuresandfistulasCommonAbsentCircumscribedulcersCommonAbsentConfluentlinearulcersCommonAbsentPseudopolypsAbsentCommonMICROSCOPIcTransmuralinflammationTypicalUncommonSubmucosalfibrosisTypicalAbsentFissuresTypicalRareGranulomasCommonAbsentCryptabscessesUncommonTypicalSUMMARYCrohndiseaseandulcerativecolitisareidiopathicinflammatoryboweldiseasesbelievedtoresultfromabnormallocalimmuneresponsesagainstunknownmicrobesand/orselfantigensintheCrohndiseaseAssociatedwithHLA-DR7and-DQ4alleles,andwithmutationsintheNOD2gene,whichencodesanintracellularsensorofmicrobesResultsfromachronicTcell-mediatedinflammatoryreactioninvolvingIFN-γ-producingTH1cellsand,perhaps,IL-17-producingTH17cellsManifestedbychronicinflammationwithgranulomas,ulcers,andstricturescausedbyfibrosis,involvingtheterminalile