病理学教学课件：消化系统疾病

Diseasesof

theGastrointestinalTractThedigestivesystemThegastrointestinaltractTheliverandthebiliarytractThepancreasDiseasesoftheGITractEsophagusStomachSmallandlargeintestinesAppendixBarrettesophagusPepticulcerIBDEsophagealCa

GastricCaColorectalCaAnatomic/Development/motorDisordersInflammatoryDiseases

Esophagitis

GastritisEnterocolitisAppendicitisTumorsAdenomaReflux~

Chronic~Carciod(NETs)NormalanatomyandhistologyoftheesophagusNormalanatomyandhistologyoftheesophagusEsophagogastricjunction≠Squamous-ColumnarjunctionEsophagitisInflammationoftheesophagealmucosaCausedbyavarietyofagentsPhysicalChemicalBiologicRefluxofgastriccontentsisthemostimportantcauseofesophagitis(refluxesophagitis)

Refluxesophagitis(返流性食管炎)ElongationofthelaminapropriapapillaeExtendingintothetopthirdoftheepitheliumBasalcellhyperplasia>1/5oftheepithelialthicknessIntraepithelialinflammatorycellsEosinophils,neutrophilsandlymphocytes

Refluxesophagitis

ClinicalfeaturesAgeOver40yOccasionallyseenininfantsandchildrenThedominantmanifestationHeartburn(烧心)Regurgitationofasourbrash(返酸)ThepotentialconsequencesBleeding,ulceration,strictureAtendencytodevelopBarrettesophagusBarrettesophagus(巴雷特食管)Definintion

Thereplacementofthenormaldistalstratifiedsquamousmucosabymetaplasticcolumnarepithelium,usuallycontaininggobletcellsAcomplicationoflong-standinggastroesophagealrefluxThemostimportantriskfactorforesophagealadenocarcinomaDiagnosticcriteriaEndoscopicevidenceofcolumnarepithelialliningabovethegastroesophagealjunctionHistologicevidenceofintestinalmetaplasiainthebiopsyspecimensfromthecolumnarepithelium.CarcinomasoftheesophagusWorldwide,squamouscellcarcinomasconstitute90%ofesophagealcancersMainlyinnorthChinaandMiddleEastAsiaAccountfor20%ofcancerdeathsButinmostofthewesterncountries……AdenocarcinomaSCCCarcinogenesisofesophagealCaLowgradedysplasiaSquamousepitheliumEsophagitisSCCHyperplasiaMetaplasia(barrett)HighgradedysplasiaAdenoCaCarcinomainsituCaoftheesophagusClinicalfeaturesofesophagealCa

Age:middletoelderageGender:Male>Female(4-5:1)Insidiousinonset,dysphagia(吞咽困难),obstruction,progressiveweightloss,…RoutinescreeningproceduresarerequiredforpatientswithchronicesophagitisandBarrettesophagus

LocationSCC:Upperthird20%Middlethird50%Lowerthird30%Adenocarcinoma:lowerthirdCarcinomasoftheesophagusMacroscopicappearanceMicroscopyEarlyCaAcarcinomaconfinedtothemucosaormucosaandsubmucosaThefive-yearsurvivalrate:75%AdvancedCaThefive-yearsurvivalrate:10%-20%NormalanatomyandhistologyofthestomachLoweresophagealsphincterGastritisDefinition:InflammationofthegastricmucosaAcutegastritisFocaldamagetothegastricmucosa,withacuteinflammation,erosionandhemorrhage,usuallytransientClinicalmanifestation:rangefromentirelyasymptomatictofatalEtiology:drugs(aspirin),smoking,alcohol,severestress,infection……Chronicgastritis

ThepresenceofchronicmucosalinflammatorychangesleadeventuallytomucosalatrophyandintestinalmetaplasiaEtiology

Helicobacterpylori(幽门螺杆菌)Autoimmune

GastroduodenalrefluxHotfoodsorbeveragesAlcoholMalnutritionNoninvasiveNon-sporeformingSea-gullorS-shapedGramnegativeSliverstainMotilityElaborationofureaseExpressionofbacterialadhesinsExpressionofbacterialtoxinsMacroscopicappearance

UsuallyreddenedandcoarseSometimesthickenedWithlong-standingatrophicdisease,themucosamaybecomethinnedandflattenedChronicgastritisChronicgastritis

Chronicsuperficial/non-atrophicgastritis(慢性浅表性/非萎缩性胃炎)Inflammatoryinfiltrate:lymphocytesandplasmacellsinthelaminapropriaNoevidentofglandlossandmucosalatrophy

TypeAAutoimmune-relatedPerniciousanemia(恶性贫血)APCA+IFA+Body/fundusDiffusedlesionTypeBH.PyloriassociatedNoanemiaAPCA-IFA–Antrum/pangastritisFocaldistributionChronicatrophicgastritisInflammatoryinfiltrateAtrophyMetaplasiaIntestinal~(肠上皮化生)Pyloricgland~(幽门腺化生)DysplasiaMicroscopyClinicalfeaturesUpperabdominaldiscomfortNauseaandvomitingPerniciousanemia----autoimmunegastritisComplicationsPepticulcersCarcinomaLymphoma-MALToma

Pepticulcer(消化性溃疡)AbreachinthemucosaofthealimentarytractthatextendsthroughthemuscularismucosaintothesubmucosaordeeperMostcommonlyintheduodenumandstomachUlcervsErosionEpithelialdisruptionwithinthemucosabutnobreachofthemuscularismucosaPathogenesisofpepticulcers

TherolesofH.pyloriinthepathogenesisofpepticulcersBacterialgeneproductscauseepithelialinjuryandinductionofinflammationEnhancesgastricacidsecretionandimpairsduodenalbicarbonateproductionBacterialplatelet-activatingfactorpromotesthromboticocclusioninthesurfacecapillariesImmunogenicproteinsevokerobustimmuneresponseinthemucosaMorphologyofpepticulcersLocationsAnteriorandposteriorwallofthefirstportionoftheduodenumLessercurvatureofthestomach

Macroscopicappearance

1-2cmindiameterRoundtooval,sharplypunched-outNoelevatedmarginsSmoothandcleanbaseMicroscopyMicroscopy

DefectsinthemucosapenetrateatleastintothesubmucosaNecroticfibrinoiddebrisNon-specificinflammatoryinfiltrate,predominatelyneutrophilsActivegranulationtissueinfiltratedwithmononuclearleukocytesFibroustissueorscarClinicalfeaturesSymptomsEpigastricgnawingBurningBoringpainComplicationsBleeding:15%-20%,1/4ofulcerdeathPerforation:5%,2/3ofulcerdeathObstruction:2%GastriccarcinomasEpidemiologyThesecondmostcommontumorintheworld:verycommoninChinaMale:Female=2:1Asteadydeclineinboththeincidenceandthemortalityoverthepastsixdecades

RiskfactorsH.pyloriinfectionDietBilereflux

MorphologyofgastriccarcinomasLocationThelessercurvatureoftheantropyloricregionMacroscopicappearanceDiffusetypegastricAdenocarcinomaLinitisplastica(皮革胃)----"leatherbottle"appearanceUlcerativeCavsbenignulcerBordersRoundtoovalwithstraightwallsLeveledwiththesurroundingmucosaBase:smoothandcleanGastricfolder:radiatingBordersIll-definedIrregular,heaped-upBase:shaggy,necroticGastricfolder:disappearorinterruptedHistologicclassificationofgastriccarcinomasTheWHOclassification

PapillaryadenocarcinomaTubularadenocarcinomaMucinousCaSignetringcellCaanditsvariantsAdenosquamousCaSquamousCaUndifferentiatedCaOthersLaurénclassificationIntestinaltype

BecomposedofglandularstructuresElderlypatientsThroughthesequenceofchronicgastririsIMDysCaH.pyloriassociatedDiffusetypeBecomposedof

poorlydifferentiateddyscohesivemalignantcellsYoungerpatientsEtiologyandprecancerouslesionsunknownClinicalfeaturesWeightlossAnorexia,dyspepsia,earlysatietyAnemia(irondeficiency),hematemesisLeftsupraclavicular(锁骨上)lymphnode(Virchownode,

魏尔啸淋巴结)enlargementKrukenbergtumor:intraperitonealspreadtobothovariesPrognosis:largelydependsonthedepthofinvasionandtheconditionsofmetastasisEarlygastriccarcinoma:Caconfinedtothemucosaorsubmucosawith/withoutLNmetastasis5ysurvivalrate90%-95%Advancedgastriccarcinoma:5ysurvivalrate15%GastriclymphomaMostlyMALT(mucosaassociatedlymphoidtissue)lymphomaLow-gradeB-celllymphomaIndolentH.pyloriassociatedLymphoma(MALToma)AdenocarcinomaLymphoidaggregatesIntestinalmetaplasiaH.pyloriinfectionChronicgastritisUlcerPC=PlicaecircularesV=VilliTC=TaeniaecoliH=HaustraOA=OmentalappendicesHNormalanatomyandhistologyoftheintestinesPCCellsinVilli&cryptsAbsorptivecellsGobletcellsPanethcellsEndocrinecellsUndifferentiatedcellsDiseasesofsmallandlargeintestinesInfectiousenterocolitisTyphoidfever(肠伤寒)Bacillarydysentery(菌痢)Amebiasis(阿米巴病)Schistosomiasis(血吸虫病)Idiopathicinflammatoryboweldisease(特发性炎症性肠病，IBD)Crohndisease(克罗恩病)Ulcerativecolitis(溃疡性结肠炎)ColorectalneoplasmsAdenomaCarcinomaIdiopathicInflammatoryBowelDiseaseAheterogeneousgroupofdiseasescharacterizedbyanexaggeratedanddestructivemucosalimmuneresponseTwomaindisorders

Crohndisease(CD):affectsanyportionofthegastrointestinaltract,butmostofteninvolvesthedistalsmallintestineandcolonUlcerativecolitis(UC):

limitedtothecolonandrectumPathogenesisunexplainedGeneticpredisposition:CD>UCImmunologicfactors:abnormalTcellresponseMicrobialfactors:providetheantigenictriggertoadysregulatedimmunesystemInflammationisthecommonfinalpathwayforthepathogenesisofIBDPrimarilyoccurinWesterndevelopedpopulationsOccuratanyage,peakagesarethe2ndand3rddecadesoflife.Whites>nonwhitesSystemicinflammatorydiseaseswithpredominantGIinvolvementCommonfeaturesofCD&UCDistinctivefeaturesRubberyandthickenedintestinalwallwithnarrowingoflumenCobblestoneappearanceAphthousulcers(阿弗他溃疡),linearulcers(线状溃疡),fissures(裂隙溃疡),andfistula(瘘管)“Creepingfat”(蔓生脂肪):SerosalextensionofmesentricfatBeginsintherectumandextendsproximallyRed,granularappearanceofthemucosawithonlyislandsofsurvivingmucosaPseudopolyps(假息肉)MacroscopicappearanceCDUCTransmuralinflammationUlceration,penetrationNoncaseatinggranulomas(非干酪样坏死性肉芽肿)MicroscopyDiffuse,predominantlymononuclearinflammatoryinfiltrateinthelaminapropria

Cryptabscesses(隐窝脓肿)Submucosalfibrosisandatrophy

CDUCClinicalfeaturesCDManifestationsRecurrentepisodesofdiarrheaFeverAbdominalpainComplicationsFistulaformationAbdominalabscessesorperitonitisIntestinalstrictureorobstructionUCManifestationsRelapsingbloodymucoiddiarrheaExtraintestinalmanifestationsaremorecommonComplicationsToxicmegacolonwithpotentialofruptureRiskofCaishigherthanCDColorectalNeoplasms

AdenomaAnintraepithelialneoplasm,characterizedbyhypercellularitywithenlarged,hyperchromaticnuclei,varyingdegreesofnuclearstratificationandlossofpolarity

IncidenceAgerelated:<40y20%-30%;>40y40%-50%Familialpredisposition:a4-foldgreaterriskamongfirstdegreerelativesLocation:66%-77%inrectosigmoidCorrelationswithCRC80%sporadicCRCarisefromadenomasFour-foldgreaterriskforCRCAdenoma

vs

PolypMacroscopicappearanceFlatPedunculatedNon-pedunculatedSessileMicroscopyFormationofglandortubule----tubular~Formationoffinefingerletsorformationofvilli----villous~Mixtureoftheabove----tubulovillous~ColorectalAdenocarcinomaOneofthemostcommonneoplasmsPeakageofincidence:sixthtoseventhdecadesPredisposingfactorsAdenomatouspolypsDietandlifestyleMeatAlcoholconsumptionSmoking“amongtherewardsofthewesternizedlifestyle”Long-standingUCorCDIrradiation:rareClinicalfeaturesHematochezia(便血),anaemia(贫血),constipation(便秘),fever,weightloss,abdominalpainMacroscopicappearanceMicroscopy

(WHOclassification)AdenocarcinomaMedullarycarcinomaMucinousadenocarcinomaSerratedadenocarcinomaSignetringcarcinomaAdenosquamouscarcinomaSquamouscarcinomaSpindlecellcarcinomaMedullarycarcinomaUndifferentiatedcarcinomaT=PrimaryTumorTisCarcinomainsitu,invasionoflaminapropriaT1 TumorinvadessubmucosaT2TumorinvadesmuscularispropriaT3TumorinvadesthroughthemuscularispropriaintopericolorectaltissuesT4aTumorpenetratesthevisceralperitoneumT4bTumordirectlyinvadesorisadherenttootherorgansorstructuresN=RegionalLymphNodesN0NoregionallymphnodemetastasisN1Metastasisin1-3lymphnodesN2aMetastasisin4-6lymphnodesN2bMetastasisinmorethan7lymphnodesM=DistantMetastasisM0NodistantmetastasisM1aMetastasisconfinedtooneorganorsiteM1bMetastasesinmorethanoneorgan/siteortheperitoneumTNMStagingTNMstagingand5-yrsurvivalrateStageTNM0TisN0M0IT1-2N0M0IIAT3N0M0IIBT4aN0M0IICT4bN0M0IIIAT1-2T1N1N2aM0IIIBT3-T4aT2-3T1-2N1N2aN2bM0IIICT4aT3-4aT4bN2aN2bN1-2M0IVAnyTAnyNM1TwomainpathwaysforthecarcinogenesisofCRCChromosomalinstabilitypathway(染色体不稳定途径)(Wnt/β-cateninpathway)Involvedin80%ofsporadicCRCFamilialadenomatouspolyposis(FAP)Microsatelliteinstabilitypathway(微卫星不稳定途径)Involvedin10%-15%ofsporadicCRCHereditarynonpolyposiscolorectalcancer(HNPCC)Familialadenomatouspolyposis

(家族性腺瘤性息肉病,FAP)AnautosomaldominantdisorderRelativelyrare(1in8000individuals)Numerousadenomatouscolorectalpolyps,moreinthedistalcolonHaveanintrinsictendencytoprogresstoCa(<40y),accountfor1%ofCRCExtra-IntestinalManifestationsofFamilialAdenomatousPolyposisGastric:FundicGlandPolyps(胃底腺息肉)Liver:Hepatoblastoma(肝母细胞瘤)Pancreas:Pancreatoblastoma(胰母细胞瘤)Eye:CongenitalHyperpigmentationofRetina(先天性视网膜色素沉着)Nasopharynx:JuvenileNasalAngiofibroma(幼年性鼻血管纤维瘤)Thyroid:PapillaryCarcinoma(乳头状癌)Brain:Medulloblastoma(髓母细胞瘤)Skin:EpidermalCyst(表皮样囊肿)SoftTissue:Fibromatosis(纤维瘤病)Bone:Osteoma(骨瘤)Causedbyagermlinemutation(胚系突变)

inAdenomatousPolyposisColi(APC)geneon5q21-22ServeasthemodelfortheWnt/β-cateninpathwayofcarcinogenesisinthelargebowelAdenoma-carcinomasequenceGerm-lineorsomaticmutationProoncogenesmutationLOHofadditionalcancersuppressorgeneAdditionalmutationGrosschromosomalalterations(aneuploid)Wnt/β-cateninpathwayHereditarynonpolyposiscolorectalcancer(HNPCC,Lynchsyndrome)AnautosomaldominantdisorderCharacterizedbythedevelopmentofcolorectalcarcinomaandcancersofotherorgans

Astrongfamilyhistoryofdevelopingcolorectalcanceratanearlyage(average46years)Accountfor1%-2%ofcolorectalcarcinomasRapidprogressionfromadenomatocarcinomaPredominantlyright-sidedIncreasedproportionofmucinousorpoorlydifferentiatedtumorsWithmarkedhost-lymphocyticinfiltrationBetterprognosis

CausedbygermlinemutationsinDNAmismatchrepairgenesleadingtoahighfrequencyofMSIHNPCCMismatchrepairandMicrosatelliteTheMSIpathwayofcarcinogenesisinthelargebowelNoclearlyidentifiablemorphologiccorrelatesMSIDiploidThanksforyourattention！DiseasesoftheliverandthebiliarytractDept.ofPathologySchoolofBasicMedicalSciencesPekingUniversityTheliverandthebiliarytractViralhepatitisAlcoholicliverdiseaseCirrhosisPortalhypertensionPrimarycarcinomaoftheliverCholecystitisCholelithiasis(gallstones)AnatomyandfunctionsRightlobeFalciformligamentLeftlobeThelargestparenchymalorganinthebodyProcessesdietarynutrientsSynthesisofserumproteinsDetoxification&excretionofendogenouswasteproductsandpollutantxenobioticsNormalhistologyHepaticAcinusItocellGeneralresponsesoflivertoinjuriesCelldegeneration&celldeathInflammationRegenerationFibrosis&cirrhosisDegenerationBallooning~:edemaFeathery~:retainedbiliarymaterialSteatosis:accumulationoffatdropletsMicrovesicularsteatosisMacrovesicularsteatosisNecrosis&ApoptosisAccordingtothenatureofcelldeathCoagulativenecrosisApoptoticcelldeath:CouncilmanbodyLyticnecrosisAccordingtodistributionCentrilobularnecrosisSpotty/focalnecrosis“Piecemeal"necrosis----interfacehepatitisBridgingnecrosisSubmassivenecrosisMassivenecrosisNecrosis&ApoptosisInflammationNecrosisincitesinflammatoryreactionCytotoxiclymphocytesattackantigen-expressinglivercellsLymphocytescollectintheportaltractKupffercellsengulfapoptoticcellsGranulomatousreactionRegenerationHepatocellularproliferationDuctalreaction

Whenhepatocelluarnecrosisoccursandleavestheconnectivetissueframeworkintact,almostperfectrestitutionoftheliverstructurecanoccurFibrosisandcirrhosisResponsetoinflammationordirecttoxicinsulttotheliverDepositionofcollagenGenerallyirreversibleViralHepatitisInfectionofthelivercausedbyagroupofviruseshavingaparticularaffinityfortheliverHepatitisAHepatitisBHepatitisCHepatitisDHepatitisEDoublestrandedDNAvirusHepatitisBvirusNon-protectiveProtectiveX-proteinTranscriptionaltransactivatorofhostgenesTwophasesofHBVinfectionsProliferativephaseHBV-DNAinepisomalformwithformationofcompletevirionsandallassociatedantigensHBsAgandHBcAgleadtoactivationofCD8+TlympocyteswhichthencausehepatocytesdamageIntegrativephaseHBV-DNAmaybeincorporatedintothehostgenomeViralreplicationisstoppedandliverdamagesubsidedbuttheriskofhepatocellularCapersistsTransmission:bloodandbodyfluidsVertical:mothertoneonateHorizontal:transfusion,dialysis,drugabuse,sexIncubationperiod:4-26wks0.5-1%/

year0.02%/

year2.5%/

yearHepatitisCvirusAsmall,single-strandedRNAviruswithenvelopeTransmission:parenteral(transfusion,sexual,vertical)Themostfrequentcauseoftransfusion-mediatedhepatitisIncubationperiod:2to26wksNon-protectiveFrequentlyprogressestochronicliverdisease1-4%/yClinicalSyndromesAnumberofclinicalsyndromesmaydevelopfollowingexposuretohepatitisvirusesAsymptomaticinfection:serologicevidenceonlyCarrierstate:withoutapparentdisease/withsubclinicalchronichepatitisAcutehepatitis:anictericorictericChronichepatitis:withorwithoutprogressiontocirrhosisFulminanthepatitis:withmassivetosubmassivehepaticnecrosisThecarrierstateHarboroneofthevirusesbutsufferfewornoadverseeffectsHavenonprogressiveliverdamagebutareessentiallyfreeofsymptomsordisabilityHBVandHCVcanproducea~HDV:notclearHAVandHEV:noAcuteviralhepatitisAnyoneofthehepatotropicvirusescancausesymptomaticacuteviralhepatitis,althoughuncommonforacuteHCVinfectionThediseasecanbedividedintofourphases:AnincubationperiodAsymptomaticpreictericphaseAsymptomaticictericphaseConvalescenceClinicalfeaturesNausea,vomiting,fever,diarrhea,jaundiceMildlyenlargedtenderliverElevatedserumaminotransferaseClinicalcourse:<6mon

MorphologyofacuteviralhepatitisMacroscopicappearanceSlightlyenlargedandgreen,dependingonthedegreeofjaundiceandthestageofthediseaseIll-definedareasthatarepaleyellow,hemorrhagicandgranularonthecutsurfaceMicroscopyCelldegeneration(ballooning~)withspottynecrosis,piecemealnecrosis,andoccasionalbridgingnecrosisKupffercellhyperplasiaandhypertrophyHepatocyteregenerationduringtherecoveryphaseInflammatoryinfiltrationintheportaltracts,predominatelymononuclearcellsChronicviralhepatitisAsymptomatic,biochemical,orserologicevidenceofcontinuingorrelapsinghepaticdiseaseformorethan6m,withhistologicallydocumentedinflammationandnecrosis.MayresultfromanyoftheviralhepatitisesexceptHAVandHEVinfectionsEtiologyratherthanthehistologicpatternisthesinglemostimportantindicatorfordevelopingchronichepatitisClinicalfeatureFatigue,lossofappetite,mildjaundiceSpidernevi,palmarerythema,mildhepatomegalyPersistentelevationofserumaminotransferase…..HighlyvariableandnotpredictiveofoutcomeMorphologySharedwithacutehepatitisGround-glasshepatocytes----HBVSteatosis&lymphoidaggregates----HCVGrading:mild,moderateandsevereAccordingtotheseverityofnecrosisFulminanthepatitisFulminanthepaticfailure:clinicalinsufficiencyprogressesfromonsetofsymptomstohepaticencephalopathywithin2-3wkSubfulminanthepaticfailure:extendingupto3monViralhepatitisisthemostcommoncausesClinicalfeaturesJaundiceHypoalbuminemiaFetorhepaticus:formationofmercaptansEncephalopathy

Overallmortalityrangesfrom25%-90%intheabsenceoflivertransplantationMacroscopicappearance

Massive/submassivehepaticnecrosisTheentire/partoftheliverisaffectedSoftandshrunkenThecapsuleiswrinkled,andthecutsurfaceismuddywithbilestainingMicroscopyLyticnecrosiswithfewhepatocytesremainingRegenerationoflivercellsAlcoholicliverdiseaseLeadingcauseofliverdiseaseinWesterncountriesPathogenesisInterruptsthelipidmetabolismInductionofcytochromeP-450leadstoaugmentedtransformationofotherdrugstotoxicmetabolitesDirectlyaffectsmicrotubularandmitochondrialfunctionandmembranefluidityFreeradicalsgeneratedduringoxidationofethanolreactwithmembranesandproteinsActivatedneutrophilsinalcoholichepatitisreleasetoxicoxygenmetabolitesThreedistinctive,overlappingformsHepaticsteatosis(fattyliver)MacrovesicularCompletelyreversibleAlcoholichepatitisHepatocytesswellingandnecrosis,mallorybodiesNeutrophilicreactionFibrosis:sinusoidalandperivenularCirrhosisInitially,micronodular,<0.3cmAttheend-stage,mixedmicro-andmacronodularMallorybodyCirrhosisAdiffusenodulationoftheliverresultingfromfibrousbandssubdividingtheliverintoregenerativenodulesThearchitectureoftheentireliverisdisruptedAmongthetop10causesofdeathintheWesternworldEtiologyViralhepatitisAlcoholabuseBiliarydisease,ironoverload,etc.Theend-stageofchronicliverdiseasePathogenesisCentralpathogeneticprocessProgressivefibrosisReorganizationofthevascularmicroarchitectureStimuliofperisinusoidalstellatecells–ItocellsMacroscopicappearanceThelivermaybeenlargedorsmallandshrunkenFibrousbandsdividetheliverintovarioussizesofnodulesMicronodularforms:themajorityofnodules≤3mmMacronodularforms:mostofthenodules>3mmMixedmacromicronodularformsMicroscopyHepatocellulardeathRegenerationGeneralizedfibrosisresultinginanodularpatternDisruptionofthearchitectureoftheentireliver

ClinicalfeaturesofcirrhosisJaundice

mixedconjugated&unconjugatedbilirubinHepaticdysfunctionPortalhypertensionTheultimatemechanismofmostcirrhoticdeathsisProgressiveliverfailureComplicationsrelatedtoportalhypertensionHepatocellularcarcinomaClinicalfeaturesofcirrhosisHepaticdysfunctionHypoalbuminemia:causedbydecreasedalbuminsynthesisCoagulationfactordeficiencies:causedbydecreasedsynthesisofcoagulationfactorsHyperestrinism:palmarerythema;spidernevi;testicularatrophyandgynecomastiaHepaticencephalopathyPortalhypertensionIncreasedresistancetoportalbloodflowClassifiedbythesiteofportalvenousobstructionPrehepatic:portalandsplenicveinobstructionIntraheptic:intrahepaticvascularobstruction,mostoftenbycirrhosis,metastatictumororschistosomiasisPosthepatic:venouscongestioninthedistalhepaticvenouscirculation,mostoftenasaresultofconstrictivepericarditis,tricuspidinsufficiency,congestiveheartfailure,orhepaticveinocclusionMainmanifestationsAscitesSplenomegalyPortosystemicshuntsEsophagealvaricesRectalhemorrhoidsPeriumbilicalvenouscollaterals(caputmedusae)

caputmedusaeEsophagealvaricesHepatictumorsBenigntumorsHemangioma:themostcommonbenigntumorsoftheliverAdenoma:relatedtouseoforalcontraceptivesMalignanttumorsMetastatictumors:accountforthemajorityofhepaticmalignancies,topthree---colon,lung&breastPrimarycarcinomasoftheliverHepatocellularcarcinomas(HCC):70%Cholangiocarcinomas(ICC):15%Combinedhepatocellularandcholangiocarcinoma:haveaworseprognosisascomparedwithpatientswithHCCHepatocellularcarcinomaAmalignanttumorderivesfromhepatocytesThemostcommonprimarymalignancyoftheliverMostcommonetiologicalfactorsViralinfections(HBV,HCV)DietaryaflatoxinB1ingestionChronicalcoholabuseFrequentlymarkedbyincreasedserumconcentrationofalpha-feto-protein(AFP)HasapropensityforinvasionofvascularchannelswithhematogenousdisseminationMacroscopicappearanceUnifocal:massivetumorMultifocal:widelydistributednodulesofvariablesizeDiffuselyinfiltrativeMicroscopyRangingfromwell-differentiatedtopoorlydifferentiatedlesionsBileproductsorhyalinebodies(α-1-antitrypsin)maybefoundHepatocellularcarcinomaPrognosisFive-yearsurvivalrate:<5%Largelyresistanttoradio-orchemotherapyLong-termsurvivalislikelyonlyinpatientswithsmall(<3cm,≤

2nodules),asymptomaticHCCthatcanbetreatedbySurgicalresectionLivertransplantationPercutaneousethanoloraceticacidinjectionPercutaneousradiofrequencythermalablationCholangiocarcinomaAnintrahepaticmalignanttumorcomposedofcellsresemblingthoseofbileductsLesscommonthanhepatocellularcarcinomaOccursmostfrequentlyintheFarEastEtiology

Parasites:Opisthorchisviverrini,ClonorchissinensisHepatolithiasisThoriumdioxide(Thorotrast)Notassociatedwi