DiseasesofCardiovascularSystem心血管系统Keypointsforstudyingsystemicpathology1.MorphologyMarcopathologicchanges:Microscopicpathologicchanges:histopathology2.ClinicalcourseorfeaturesFunctionalalterationsoftissuesandorgansSymptoms,signslaboratoryanalysisComplicationsOutcomeandsequences3.Etiology:pathogenicagents,riskorassociatedfactorsCategoriesofCardiovascularDiseases1.Inflammatorydiseases：infectious:endocarditis,myocarditis,pericarditisnon-infectious:rheumaticfever,vasculitis2.Arteriosclerosis动脉硬化动脉硬化:atherosclerosis动脉粥样硬化动脉粥样硬化,Medialcalcificsclerosis动脉中层钙化动脉中层钙化,arteriolosclerosis细细动脉硬化症动脉硬化症(hypertension)3.Valvulardiseases:congenitaloracquired4.Cardiomyopathy:primarycardiomyopathy5.Congenitalheartdiseases:6.Corpulmonale（肺心病）（肺心病）:7.Cardiactumor:CardiovasculardiseasesandagedistributionChildren,youth:CongenitalheartdiseasesInflammatorydiseases:rheumaticfever,myocarditisAdults:valvulardiseases,cardiomyopathy,vasculitisElderly:arteriosclerosis,corpulmonaleDiseasesindiscussionArteriosclerosis:Atherosclerosis:coronaryheartdiseaseHypertension:hypertensiveheartdiseaseRheumaticdisease：rheumaticheartdiseaseInfectiousendocarditisValvulardiseasesmyocarditisCardiomyopathy HistologicalstructureBloodvesselHeartIntima:endotheliumEndocardium:endotheliumMedia:internalelasticlamina,elastin,SMCMyocardia:myocyteAdventitia:externalelasticlaminaAdventitia:CT,neurofiber Atherosclerosis动脉粥样硬化DefinitionEpidemiologyBasicpathologicchangesSecondarychangesLesionsinvolvedorgansandmanifestationsAtherosclerosis动脉粥样硬化 Definition 广泛累及大 、中动脉，以脂质 (主要是胆固醇)在动脉内膜沉积、平滑肌细胞和胶原纤维增生，继发坏死，形成粥样斑块，常造成血管腔不同程度狭窄及血管壁硬化的疾病，相应器官可出现缺血性改变。1.Systemicinvolvementoflarge,medium-sizedarteries(aorta,coronary,cerebral,renalandiliac).2.Lipids(cholesterol)depositioninintima,hyperplasiaofsmoothmusclecells,fibrosisandnecrosis,formationofcharacteristicatheroplaque(atheroma，粥瘤),narrowingofarteriallumenandlossofelasticity.3.Ischemiaoforgans:atrophy,fibrosis,infarction Epidemiologypopulation：elderlymalefemaleIndustrialized:developedcountriesorregionsurbanruralBasicpathologicchanges:3stagesPreferablesites:aortaanditsmainbranchesAbdominalaorta,coronary,carotid,renalandiliacbranchostia,protrudingsurfaceofcurve1.Fattystreak（脂纹）:lipidsdepositGross：yellowstreaksorspotsflattenorslightlyelevatedCautions:1.Reversiblelesion2.Progresstofibro-plaqueinonlysomepatientsfatty streaks formationFattystreak:foamcellsaggregateandthickeningofintimaL/M：depositedlipidsandaggregatedfoamcellsSudanIIIstainingoflipids Foamcells:smallnucleiandvacuouscytoplasmfoamcellsderivingfrom:macrophagesofbloodSMCmigratefrommediaTrans-differentiationofSMCandcollagenproduction:fibrosisEarlier fibrous plaqueIntimaL/M:superficialfibrouscap:SMCsandextracellularmatrix(collagen,elastin,proteoglicans,externallipids).UnderlyingproliferatedSMCs,macophages,foamcells,freelipidsandextracellularmatrix.2.Fibrousplaque（纤维斑块）（纤维斑块）Gross：elevated,gray-yellowplaques3.Atheromatousplaque(atheroma)粥样斑块（粥瘤）Gross：markedelevated,gray-yellowplaques.EccentricplaqueandnarrowingoflumenAtheromatousplaque:fibrosis,necrosis(cleftsofcholesterol)andnarrowingoflumenL/M:hyalinefibrouscap,centralamorphousmaterials(necrosis)containingcellulardebris,lipids,cholesterolcrystals(orclefts),foamcells,andgranulationtissueatedgeandinflammatorycells:lymphocytes.Atheromatousplaque:mediaatrophyAtheromatousplaque:necrosis,cholesterolcrystals,foamcellssecondarychangesHemorrhage:intraplaquehemorrhage,hematoma（血肿）secondarychangesFocalrupture,ulceration:embolism:cholesterolemboli,Thrombosis：infarctionCalcification：mineraldepositionincap,necroticarealeadingtohardening,rigidity,fragilityofarterialwallAneurysm(动脉瘤）:segmentaldilationinsaccularorfusiformduetomediaatrophy.Trueaneurysm:segmentaldilationinsaccularorfusiformduetomediaatrophy.Dissectinganeurysm(夹层动脉瘤）:dissectionofmedia,accumulationofbloodcomingfromruptureofcaporvasavasorumsecondarychangesAneurysm1-4：trueaneurysm5：dissectinganeurysm（夹层动脉瘤）（夹层动脉瘤）6：falseaneurysmdissectinganeurysmofabdominalaortaLesionsinvolvedorgansandmanifestations1.Narrowingoflumenischemicatrophy2.Obstructionoflumeninfarctionhemorrhageofintra-plaquethrombosis3.Mediaatrophyaneurysmatherosclerosis of aortas with ulceration苏丹苏丹III染色染色1.Aorta:1.Aorta:aneurysm:abdominalaorta,fatalhemorrhageDissectinganeurysmofaorta:thrombus,doublelumenandatherosclerosis2.AtherosclerosisofcoronaryarteriesAtherosclerosisofcoronaryarteriesischemiaofmyocardiacoronaryheartdiseaseAnginapectorisMyocardialinfarctionChronicischemicheartdiseaseSuddencardiacdeath3.AtherosclerosisofcerebralarteriesPreferablesites:carotid,basilarartery,circlesofWillis,middlecerebralarteryInternalcarotid:carotidartery-onemiddle cerebral artery and one anteriorcerebralarteryVertebral: two vertebral arteries -one basilar artery - two posteriorcerebralarteries.20%ofcardiacoutputgoestothebrain,and80%ofcarotidflowgoestotheipsilateralmiddlecerebralartery.Anatomyofcerebralcirculation AtherosclerosisofcerebralarteriesChronicischemiacerebralatrophydementia,encephalopathyVasculardementiaisthesecondmostcommoncauseofdementiaintheUSAandEurope,butitisthemostcommonforminsomepartsofAsia.Acuteischemia:cerebralinfarction4.AtherosclerosisofrenalarteriesSegment:renalarteryandmainbranchesChronicischemia-repeatedinfarctionandscaring-atrophyandfibrosisGross:atheroscleroticatrophyofkidney:bilateral,asymmetric,de-conformation.atheroscleroticatrophyofkidney动脉粥样硬化固缩肾5.AtheroscleroticarteriesofextremitiesSites：iliacarteriesLowerextremities：atrophyofmusclesstumble:gangrene:ischemicinfarctionAtherosclerosisandaffectiononvariousorgansPathogenesisPathogenicagents:riskfactorsPathogenesis:Hardriskfactors(Largecontributiontoincidence;potentiallyavoidableortreatable)1.Hyperlipidemia:ParticularlyhypercholesterolemiaLDL,VLDL,HDL,apo-A1Thelevelofbloodlipids(cholesterol)correlatewithASExperiment：high-lipidintakeinducingASMetabolicalterationsoflipidsinducingAS：endocrinedisease,geneticdefects:prematuredASlipidsdepositionistheinitialandcriticaleventinpathogenesisofASHardriskfactors2.Hypertension:especiallyaftertheageof45veryimportantpromotingfactor3.Smoking:predominantatherogeniceffectsintheaortaandcoronaryvessels4.Diabetesmellitus:particularlyincoronary,cerebral,andperipheralarteriesinducinghypercholesterolemiaAge:age-relateddisease,incidenceofseverediseaseriseswitheachdecade.degenerationofarterialwall:declineinpotentialoflipids-cleaningSex:estrogenlevel-related.beforemenopause:male female;menopause:male=femaleGenetics:SomefamilieshaveincreasedmutationingenesofLDLreceptor,apoprotein,lipoproteinesterasemultiplegenes:predispositionConstitutionalriskfactorsSoftriskfactors(Smallcontributiontoincidenceinstatisticalstudies)LackofregularexerciseObesityStressfullifestyleHighcarbohydrateintakeHardenedunsaturatedfatintakePathogenesishypothesis1.Lipidhypothesis脂源性学说2.Injuryandresponsehypothesis损伤应答学说Endothelialdysfunction3.SMCproliferationorMutagenesishypothesis4.Chronicinflammationhypothesis5.MacrophageeffecthypothesisMedicine,Volume 42, Issue 9,September 2014,Pages 480-484MonocytesandmacrophagesTcellsMediatorsofInlammationVolume2013Keyprocess1.Endotheliainjuryandlipidsdeposition2.Endotheliadysfunction3.Macrophageinfiltration4.EmigrationandproliferationofSMC5.FibrosisandnecrosisCoronaryHeartDisease冠心病冠状动脉狭窄引起心肌缺血、缺氧，造成缺血性心脏病 (IschemicHeartDisease，IHD)。Thenarrowingofcoronaryarteryresultsinhypoperfusion,hypoxia(ischemia)ofmyocardium.Pathogenesis1.Atherosclerosisofcoronaryarteries：95%theinitialandproximalsegments,mainbranchesofleftorrightcoronaryartery,especiallyleftanteriordescendingbranchseverity:I75%thrombosis,rupture,intraplaquehemorrhage2.Coronaryarteryvasospasm（冠状动脉痉挛）：3.Inflammatorydiseasesofcoronaryartery:syphilis,someofarteritisTypesandfeatures1.Anginapectoris心绞痛2.Myocardialinfarction心肌梗死3.Chronicischemicheartdisease慢性缺血性心脏病4.Suddencardiacdeath急性心源性死亡Anginapectoris心绞痛Thisisasymptomcomplex.Symptomscausedbytransientmyocardialischaemiathatfallsshortofinducingthecellularnecrosisthatdefinesmyocardialinfarction.Intermittentchestpain,transient,reversiblemyocardialsqueezing,crushingsubsternalsensation,radiatingtoleftarmMechanism:ischemiamyocytesinjury,metabolicproductsaccumulationnervesystemAngina PectorisSubtypesandfeatures1.Stable：Mostcommonform.stress-inducing,relievingbyrestorvasodilatorcause:fixednarrowing(75%)2.Unstable：increasingfrequencyandintense,longerlastingpreinfarctionanginacause:thrombosis,distalembolization,spasm3.Variant/Prinzmetal：Uncommonpattern,occursatrest;unrelatedtophysicalactivity,heartrateorbloodpressure;generallyrespondstovasodilators.cause:vasospasmMyocardialinfarction:心肌梗死PersistentandcompleteischemiaoflocalmyocardiumnecrosisofmyocytesPathogenesis:1.Thrombosis2.Spasm3.Hypoperfusion-increasingdemandTypes:left-sideheart1.Transmural:2.Subendocardial:SubendocardialMI心内膜下心肌梗死Features:1.Inner1/3ofmyocardium,includingtrabecula,papillarymuscles2.Disseminatedfociofinfarcts,involvingentireendocardium(circularMI),notlimitedtoareaofonearterysupply3.Severenarrowingofarteriesinlargepartsofarteries4.VasospasmrelatedRegionalmyocardial(ortransmural)infarctionMI区域性（或透壁性）心肌梗死Involvingareaandfrequency:leftright50%：leftanteriordescendingCA:anterior,apical,2/3anteriorinterventricularseptum25%：rightCA:leftposteriorventricle,1/3posteriorinterventricularseptum,rightventricleOthers：leftcircumflex:lateralleftventricleMorphologyCoagulativenecrosisinflammatoryresponsefibroushealingGross:post-infarctionIrregularshapedareasofinfarcts6hr:pallor8-9hr：yellow,dry,firm3-7d：yellow,soft,hyperemicandhemorrhageborder10d:softer,obvioushemorrhageborder2-3wk：red:granulationtissue,5wk：gray,firm,shrunk:scaring(organization)InfarctinleftanteriorwallInfarctinleftanterior,interventricularseptumL/M:coagulativenecrosis:Nochangesinearlyphase1-2hr:wavyfiberchange9hr：neutrophilsappear18-24hr:cytoplasmiccondensation(increasingeosinophilia,contractionbands);Nuclearchange:pyknosis,karyorrhexis24-72hr:neutrophilsinfiltration4d：hyperemicandhemorrhageinsurrounding7d:macrophages,granulationtissueatedge10d:granulationtissueinsurrounding2-8wk:scaring(organization)WavyfiberchangeCytoplasmic:condensation(increasingeosinophilia)Nuclearchange:pyknosiskaryorrhexisCytoplasmiccondensation(increasingeosinophilia,contractionbands),karyorrhexis,hyperemiaCytoplasmiccondensation(increasingeosinophilia),karyorrhexis,infiltratingneutrophilsInfiltratingneutrophils,myocytolysisMacrophages:1-2weekMacrophagesphagocytizingnecroticmyocytesOrganizationbygranulationtissueScaring,hypertrophyofremainingmyocytesRepairofmyocardialinfarctionInjuryandrepair1.Inflammation2.Fibrosis:scarformationHyperplasiaoffibroblastandmyofibroblastAngiogenesisExtracellularmatrixproteinStemcelltransplantationEmbryonicstemcellsSomaticstemcells:bonemarrowmesenchymalneonatalcardiomyocytesothersourcesiPS:inducedpluripotentcellBiochemicaldetectionProtein: Myohemoglobulin（肌红蛋白）Enzymes：Creatinekinase(CK)肌酸激酶:2-4hr,24hpeak,72hnormalLDH(乳酸脱氢酶）:LDH1,LDH295%patientsLDH1/LDH21Troponins（肌钙蛋白）:2-4hr,24peak,last4-7dindicatorofmyocyteinjury心内膜下心肌梗死心内膜下心肌梗死透壁性心肌梗死透壁性心肌梗死深度深度累及心室壁内侧1/3的心肌，波及肉柱及乳头肌。累及心室壁全层或达室壁2/3范围范围多发性、小灶性坏死，分布不规则。严重者引起环状梗死梗死部位与冠状动脉分支供血区一致,病灶大,最大直径在2.5厘米以上原因原因严重、弥漫的冠状动脉AS性狭窄 + 诱因一支冠状动脉病变突出,并常附有动脉痉挛或血栓形成Complicationsandsequelae1.rupture：within1-2weeksapical:1/3tamponade（心包填塞）septum:heartfailurepapillarymusclesmitralinsufficiencyleftheartfailureAmJCardiol.2015Jan1;115(1):125-1402.Ventricularaneurysm：acuteorhealingphaseapicalheartfailure,muralthrombosisLeftventricularaneurysm3.Muralthrombi：infarctorVentricularaneurysm4.Pericarditis：fibrinsexudates5.CardiogenicshockTheinfarctareaofleftventricle40%，outputshock6.Cardiacarrhythmias：involveconductsystem7.ScarformationOrganization：small：2weekslarge：4-6weeksMyocardialfibrosis(心肌纤维化）Suddencardiacdeath(心源性猝死）Chronicischemicheartdisease(慢性缺血性心脏病） Hypertension高血压病Essentialorprimaryhypertension:idiopathic，arteriolosclerosisType：benignormalignant(accelerate)Secondaryhypertension:asapartofdiseases(kidney,endocrinetumor）Benignhypertension良性高血压病onsetatmiddleorelderly，progressslowlyClinicalcourse：1.Functionalderegulation:intervalvasospasmofarterioleorsmallarteries，hypertensioninfluctuation;asymptomatic2.Arteriolosclerosis:persistenthypertension3.Organs:compensatory（代偿期）:hypertrophyofheart,nephrosclerosis,cerebralarteriosclerosis,decompensatory（失代偿期）:cardiacfailure,cerebralhemorrhage,renalfailurePathologicchanges1.Arteriole2.Heart:leftventricle3.Kidney:4.Cerebralarteriole:5.Retinal:1.Arteriole:generalizedCharacteristicchange:hyalinearteriolosclerosisrenalafferentarteriole,spleniccentralarteriole,retinalcentralarteryPathology:Subendothelialproteindepositionhyalinedegenerationthickeningofwall,rigidity,luminalnarrowingandocclusionarteriolosclerosishyalinedegenerationofspleniccentralarteriolehyalinedegenerationofrenalafferentarteriolehyalinedegenerationofrenalarteriole2.Smallerarteries(musculararteries)Intimalthickening:hyperplasticSMC,fibrosis,matrixdepositionDuplicateinternalelasticlaminaMediahyperplastic：SMCsproliferationResult:narrowingoflumenSclerosisofsmallerarteriesinhypertension3.Organslesionsandmanifestations1)Hypertensiveheartdisease:leftventriclehypertrophymechanism：highpressure-increasingsystolicloadofleftventricleGross：hypertrophyofleftventriclewall，papillaryandtrabecularmusclesover2cminthicknessconcentrichypertrophy:withoutchamberdilation(compensation)eccentrichypertrophy：chamberdilationcardiacfailure(decompensation)Normalconcentric hypertrophyThickeningofleftventriclewall2cm L/M:hypertrophicmusclefibersNormalConcentric hypertrophyNormalEccentric hypertrophyDilated chamber2)kidney:benignnephrosclerosismechanism：afferentarteriolehyalinosisandluminalnarrowing-atrophyandfibrosisofnephronaccompanyingcompensatoryhypertrophyofnephron.Pathologicchanges：symmetric,granularatrophyHyalinearteriosclerosisandsmallarterysclerosisdiffuseatrophyofnephrons,interstitialfibrosis.Hypertrophyofglomerulianddilatedtubules(compensation).Benignnephrosclerosis:characteristicgranularappearanceMicroscopicfeaturesofbenignnephrosclerosisRenaldysfunctionandclinicalmanifestationsProteinuria,hematuria：glomerulidamageGlomerularfiltrationrate:atrophyofglomeruliandtubulesRenalfailure：azotimia,uremia3)Brain：headache,nauseaCerebralvessels：hyaline,orfibrinoidnecrosisarterioles;atherosclerosisofsmallarteries,thrombosis,microaneurysms:infarctionandhemorrhage.A.Arteriolosclerosis:hyalinewallthickeningandmildlumennarrowing.B.MediamineralisationA.fibrinoidnecrosis.B.fibrosis.C.thrombosedlesionLacunes:smallfociofinfarctsCerebralhemorrhagedestructionofbraintissue,elevatedIntracranialpressureherniationBasalgangliaarea(Putamen):hemiparesis(paralysisofhalfthebody),hemianopsia,oraphasia.Cerebrallobes:Thalamus:Cerebellum：nausea,vomiting,dizziness,ataxia.Pons：HemorrhageofbasalgangliaareawithmidlineshiftBasalgangliahemorrhageinvolvingventriclePontinehemorrhage SubarachnoidhemorrhageandhyalinedegenerationofsmallarteriesHypertensiveencephalopathy（高血压脑病）:bloodpressureoverthelimitsofcerebralautoregulation,dysfunctionofcentralnervesystem.hypertensiveemergency（高血压危象）:markedelevatedbloodpressureandmultipleorgansdysfunction.4)Hypertensiveretinopathy:Sclerosisofcentralretinalartery:white,silverypapilledemaretinalexudation:flame-shapedhemorrhagefocalinfarction:spot(softcotton-wool)retinaldetachmentEyesvesselchangescouldpredictseverehypertensionriskTheeyesmaybethewindowtothesoulandfuturehypertensionThemostcommonfindings:inter-retinalhemorrhages,bothflame-shapedanddotandblothemorrhagesMalignanthypertension恶性高血压病Primary,orbenignhypertensionderivingElevatedlevelofplasmareninClinicalfeatures：Severehypertension:230/130mmHgHypertensiveencephalopathyRenaldysfunction:persistentproteinuria,hematuriaDeathwithinoneyear:uremia,cerebralhemorrhage,cardiacfailurePathologicchanges1.Arteriole：fibrinoidnecrosis-necrotizingarteriolitis2.Smallerarteries：hyperplasticarteriosclerosisthickeningintima:hyperplasticSMC，“onion-skin”3.kidney：malignantnephrosclerosisNecrotizingarteriolitis:Necrotizingglomerulolitis:micro-hemorrhagesThrombosis:micro-infarctions4.Brain：ischemia,infarction,hemorrhageFlea-bitten kidneyEtiologyandPathogenesisBenignHypertensionRiskfactorsofhypertension1.Genetic:familial,geneticpredispositionpolygenetic2.Dietaryhabit:intakes:highsodium,lowpotassiumandcalcium3.Psychologic：stress4.Occupation:5.Obesity:PathogenesisKeyprocess1.Bloodvolume：Na+-fluidsaccumulation2.Peripheralresistanceofbloodvessels：increasedvasaconstrictionrepressedvasadilationSomeofthefactorsinvolvedinthecontrolofbloodpressurethataffectthebasicequation:bloodpressure-cardiacoutputxperipheralresistanceTherenin-angiotensinsystem:themajorregulatorsofreninrelease,thebiochemicalcascadeandeffectsofangiotensinII（血管紧张素II）.CNS:centralnervoussystem,ECFV:extracellularfluidvolumeIncreasedsympatheticoutflowinprimaryhypertensionBioMedResearchInternationalVolume2014Rheumatism（风湿病）GroupA-betahaemolyticstreptococcus（A组溶血性链球菌）relatedhypersensitivedisease.Systemicinvolvementofconnectivetissues,acuteorchronicinflammation.Fibrinoidnecrosisofcollagen,formationofrheumaticgranuloma(Aschoffbody).Heart,joints,artery,especiallytheendocardiumofheartClinicalfeaturesAcutephase：RheumaticFever(RF)feverpancarditispolyarthritisskinrashes(erythemamarginatumandsubcutaneousnodules)neurologicalsymptoms(Sydenhamschorea)小舞蹈症Laboratoryfindings：raisedESRandC-reactiveprotein,groupAstreptococcalinfections(ie,positivethroatcultureandanelevatedstreptococcalantibodytiter).chronicphase:RecurrentepisodechronicvalvulardiseaseEpidemiology1.Post-infectionofstreptococcus：1-5weeksafterstreptococcalinfectionandrecurrentacuteRFalwaysprecededbyinfectionElevatedserumtitersofASOandantihyaluronidaseantibodies(抗透明质酸酶抗体）Tissuelesionsaresterile(i.e.containnostreptococci)2.Regions:consistentwithepidemicofstreptococcus3.Initialattackinchildren:615yrs，Recurrentattacksinyouth：chronicheartdisease4.Effectiveinpreventionwithusageofantibiotics5.Decreasingincidenceinlatestdecades: I Improved socioeconomic status: poverty, undernutrition, poorhousing,overcrowdingdevelopmentinsurgicalrepairandvalvereplacementPathogenetichypothesis1.Cross-reaction:Streptococci：humantissueshyaluronidasecapsuleheartvalveglycoproteinsmembraneantigensmyocardialsarcolemmaMproteincardiacmyosinVirulentstrainsas“rheumatogenic”:heavilyencapsulated,possesslargeMprotein,highlyvirulent,extremelyresistanttophagocytosis.HomologybetweenMproteinandhumanskeletalproteins*2.Tlymphocytemediatedautoimmuedisease:streptococcalsuperantigenandcardiacmyosininfectionheart injuryantibodymyocarditisendocarditisRheumaticheartdiseasepericarditisMorphologySystemicinvolvementofconnectivetissues1.Rheumaticgranuloma:Aschoffbodyapathonosticlesionforrheumatisminmyocardium,endocardium,vascularwall,subcutaneous,periarticulartissue2.Sero-fibrinousexudates:inserousmembrane:pericardium,articularcavity,pleuraRheumaticgranuloma：threephases1.Alterativeorexudativephase:connectivetissue:Interstitialsubstance:mucinoiddegeneration:edema,accumulatedacidmucopolysacharide,Collagen:swelling,fragmentationofcollagenfibrinoidnecrosisInfiltrationoflymphocytes,plasmacellsandmacrophageslastingaboutonemonthmucinoiddegeneration,edema,swelling,fragmentationofcollagenfibrinoidnecrosis:inendocardium2.proliferative/granulomatousphaseAschoffbody：acharacteristiclesionforrheumatismNodulesinround,ovary,orfusiform,distributeinmyocardium,subcutaneous,nearbyarteriesorjoints1)focioffibrinoidnecrosisincentral2)surroundedbyAschoffcells：activatedhistiocytes-plumpabundantcytoplasm,vesicularnucleiwithcentralchromatinmass:owl-eyedincross,andcaterpillar-likeinlongitudinal(caterpillarcells)-Anitschkowcells.Aschoffgiantcells：multinucleated2-4nuclei3)lymphocytes:Tlymphocyteslastingfor2-3monthsAschoffbodyRheumaticgranuloma:AschoffbodyAschoffbodyinendocardium3.Fibrosis(healingphase)Clearingoffibrinoidnecrosis,decreasingofAshoffcells，hyperplasticfibroblast,collagendepositiontinyscarformationinfusiformlasting2-3monthsEntirecourse：4-6months.DifferentchangesmaybeseeninsamesitesRheumaticlesionin serousmembrane(pericardium,articularcavity,pleura)：sero-fibrinousexudatesCompletelysubsideoradhesioninsomecasesbyfibrosisOrgansinvolvedandmanifestationsHeartJointsSkinArteryCentralnervoussystemRheumaticheartdisease40%ofpatientsRheumaticpancarditis:affectspericardium,myocardium,endocardium1.Endocarditis：valves:mitralmitral+aorticaortictricuspidpulmonarymural：endocardiuminleftatriumMorphologyGross：swellingorthickeningofvalvesandchordaetendinea1-2mmwart-likevegetations（赘生物）alonglinesofclosureofvalves:atrialsurfaceinmitralorventricularinaorticverrucous（疣状）endocarditisMechanism:valvularedema,necrosisdetachmentofendotheliainlinesofclosureplateletsaggregatethrombosis:fibrindepositionwhitethrombuswart-likevegetationsVegetationsAtrialsurfacePapillarymusclesChordaetendineaMitralverrucousendocarditis:swellingorthickeningofvalvesandchordaetendineaL/M：edema,inflammation,fibrinoidnecrosis,proliferationofAschoffcells,plateletsaggregatefibrindeposition-thrombuswart-likevegetationsConsequenceandclinicalmanifestations1.Fibrosisofvalvularlesionsandorganizationofvegetations-leaflets:thickened,shrunken,fusion,rigidity,calcification;fibrosisofchordaetendinae:regurgitation（回流）2.Endocardia:thickened,shrunken;leftatrium:McCallumspatch3.Clinical：murmur：bloodflowthroughabnormalvalvesComplicationsandconsequences1.Dysfunctionofvalvesalesserstenosisorinsufficiency2.Chronicrheumaticvalvedisease:Stenosisorinsufficiency:cardiachypertrophyordilationcardiacdysfunction3.Infectiveendocarditis:Subacutebacterialendocarditis(SBE)2.Myocarditis：Pathology：AschoffnodulesinmyocardiuminterstitialedemaandmildinflammationClinic：asymptomorprolongedP-RintervalonECG，cardiacfailure3.Pericarditis:Serousexudate:pericardialeffusion：enlargecardiacborderFibrinousexudate:shaggyheart：frictionalsoundsorganization,adhesionRestrictivepericarditisRheumaticarthritisoccursin75%ofcasesFeatures:MigratorypolyarthritislargejointsNosequelaePathology：articularcavity：Sero-fibrinousexudatesPeriarticulartissue:fibrinoidnecrosis,AschoffnodulesCompletelysubsideDifferingfromRheumatoidarthritisRheumaticsynositisSkinrashes1.Exudative-Erythemamarginatum:inabout5%ofcases.Therashisserpiginousandlonglasting.2.Hyperplastic-Subcutaneousnodules(ie,Aschoffbodies):in10%ofpatientsandareedematous,fragmentedcollagenfibers.Theyarefirm,painlessnodulesontheextensorsurfacesofthewrists,elbows,andknees.CentralnervoussystemChorea(Sydenhamschorea):Thischaracteristicmovementdisorderoccursin5-10%ofcases.Sydenhamschoreaconsistsofrapid,purposelessmovementsofthefaceandupperextremities.Onsetmaybedelayedforseveralmonths.Rheumaticarteritislargeormedium-sizedarteries:narrowingoflumenRheumaticarteritisInfective(bacterial)EndocarditisEndocarditis:bacteriadirectlyinvadetheendothelium:heartvalves,theringsofconnectivetissuethatsurroundthevalves,andtheinnerliningsoftheheartchambers.Localinfectionofbacterialessvirulentmouth,GUorGIinfectionstrongvirulent(pyogenic)woundinfectionBlood:bacteremia,septicemia,pyemiaCardiacabnormalityornormalvalvessuppurative:vegetation，ulcerationdysfunctionofvalvesSubacuteoracuteinfectiveendocarditis(SBEorABE) Subacuteinfectiveendocarditis(SBE)overweekstoseveralmonths1.Lessvirulentbacteria：especiallyviridansstreptococci2.Septicemia:developafterasymptomaticbacteremiasfrominfectedgumsortheGUorGItract3.Cardiacabnormality:Rheumaticvalvedisease,Congenitalheartdisease:mitral,aortic,tricuspid4.morphologyGross：vegetation:large,polypoid,L/M：vegetationcontainsplatelets,fibrins,bacteriaHealing:vegetationsfibrosisandscared5.Complications：curableEvidenceofendocardialinvolvement:functionalvalvulardysfunction，changingmurmur,tachycardiaBacteremia(septicemia):positivebloodcultures,splenomegalySystemicembolism：dislodgmentofvegetations,sterileinfarctsImmunologicalphenomena:glomerulonephritisOslersnodesinskinRothsspotsinretinalAcuteinfectiveendocarditis(ABE)afewdays1.Pyogenicbacteria:Staphylococcusaureus,groupAhemolyticstreptococci2.trauma,woundinfectionpyemia3.Developonnormalvalves：aortic,mitral4.Morphology:Gross：ulceration,abscess:valvulardestruction;vegetation:large,softABEinmitral:vegetationsandulcersABEinmitral:necrosisandbacteria*L/M：necrosis,lotsofneutrophils,vegetationwithplentyofbacteria*Healing:vegetationsfibrosisandscaredABE:bacteriainvegetationSBEABEVegetationLessbacteriaAbundantbacteria5.Clinicalfeatures:highfever,toxicappearance,rapidvalvulardestruction,andsepticshock6.Complications:Valvularpenetrate,disruptofcordeatendinae:deathEmbolism：infarctionPyemia:embolicabscessesValvulardiseaseValvulardysfunctionresultingfromdamageorcongenitaldeformationMainconsequenceofchronicrheumaticheartdiseaseStenosis：incompleteopen,obstructionInsufficiency：incompleteclose,regurgitationincreasingburdenofheartSymptomandsign:murmur,hypertrophyofheart,heartfailure1.Mitralstenosis:murmurindiastolicLeftatriumhypertrophy,dilationdecompensationpulmonarycongestion:edema,hemorrhagehypertensionofpulmonaryarteryrightventriclehypertrophyrightatriumdilationtricuspidinsufficiencyrightatriumfailuresystemiccongestion*Littlechangesinleftventriclep 多由风湿性心内膜炎p 正常二尖瓣口面积为5cmp 瓣膜口狭窄可缩小到1.0cm-2.0cm，严重时可达0.5cmp 瓣膜轻度增厚，呈隔膜状p 后期使瓣膜呈“鱼口状” 左心房左心房 肺静脉肺静脉 肺组织肺组织 肺动脉肺动脉 右心室右心室 心心 衰衰2.Mitralinsufficiency:murmurinsystolicLeftatriumandventriclehypertrophy,dilationdecompensationpulmonarycongestion:edema,hemorrhagehypertensionofpulmonaryartery. 左心房左心房 左心室左心室 肺静脉肺静脉 肺组织肺组织 肺动脉肺动脉 右心室右心室 心心 衰衰p 多由风湿性心内膜炎引起p 临床表现：听诊心尖区可闻及收缩期吹风样杂音p X-线：显示左心室肥大，呈“球形心”3.Aorticinsufficiency:murmurindiastolicResults：RF,AS,Syphilis,MarfanssyndromeLeftventriclehypertrophy,dilationdecompensationpulmonarycongestion:edema,hemorrhagehypertensionofpulmonaryartery.4.Aorticstenosis:murmurinsystolicLeftventriclehypertrophy,dilation. 左心室左心室 左心衰左心衰 肺病变肺病变 右心衰右心衰 MyocarditislocalordiffuseinflammationofmyocardiumPathogenicclassification:1.Virus2.Bacteria3.Parasites4.Immunogenic5.IdiopathicViralMyocarditis1.Typesofviruses:Coxsackievirus,ECHOvirus,malasiavirus,influenzavirus,adenovirus,etc.2.Pathogenesis:directcytotoxicimmune-mediated3.Pathology:NecrosisInterstitialinfiltrationoflympho-macrophagesFibrosisCardiomyopathy心肌病Primary：idiopathicSecondary：chemicaltoxicandotherdiseasesPrimarycardiomyopathy:Congestive(Dilated)：扩张性Hypertrophic：肥厚性Restrictive：限制性Arrhythmogenicrightventricular:ARVC致心律失常性右室心肌病1.DilatedorCongestiveCardiomyopathy：Gross:dilationofchambersL/M：degenerationofmyocytes,fibrosisFigure3.Cardiomyocyte.Differentcellularcompartmentscontainingtheprincipaldilatedcardiomyopathy-relatedproteinsareshown.BiomarkMed.2013;7(4):517-33Table1.Majordilatedcardiomyopathy-causinggenes.GeneProteinEstimatedfractionofdilatedcardiomyopathy(%)InheritancepatternTTNTitin1525ADLMNALaminA/C48ADMYH7-myosinheavychain48ADTNNT2CardiactroponinT36ADRBM20RNA-bindingprotein2036ADBAG3BCL2-associatedathanogene324ADTPM1-tropomyosin24ADDSPDesmoplakin13ADandARSCN5ASodiumchannel12ADACTC1Cardiacactin12ADMYBPC3Myosin-bindingproteinC1ADDMDDystrophin1XLTAZTafazzin1XLPLNPhospholamban1ADPKP2Plakophilin1ADDESDesmin1ADandARDSG2Desmoglein1ADLDB3Cypher/ZASP1ADTNNI3CardiactroponinI1ADandARTNNC1CardiactroponinC1ADAD: Autosomal dominant; AR: Autosomal recessive; XL: X-linked. 2.Hypertrophiccardiomyopathy:Gross:asymmetrichypertrophyofseptumL/M:hypertrophicandirregulararrangedmyocardia3.RestrictivecardiomyopathyorEndomyocardialfibrosis:Progressivefibrosisofendo-orsubendocardianarrowingofchambersalterativeinfillingofchambersSecondary,Specificcardiomyopathy克山病（KeshanDisease)地方性心肌病1935年发现于黑龙江克山县流行于东北、华北、西北及西南山地或丘陵地带病理：心肌变性、坏死及修复后瘢痕，病变弥漫分布，新旧交替临床：急性或慢性心功能不全DiseasesindiscussionArteriosclerosis:Atherosclerosis:coronaryheartdiseaseHypertension:hypertensiveheartdiseaseRheumaticdiseaserheumaticheartdiseaseInfectiousendocarditisValvulardiseasesCardiomyopathymyocarditis