病理學(xué)課件 心血管英 2014

Departmentofpathology

yangshaomin

2014.4DiseasesofCardiovascularsystemKeypointsforstudyingsystemicpathology

1.Morphology:

macropathologicchangesmicroscopicpathologicchanges:histopathology2.Clinicalcourseorfeatures:Functionalalterationsoftissuesandorgans

Symptoms:Signs:Laboratoryanalysis:Complications:Outcomeandsequelae:3.Etiology:pathogenicagents,riskorassociatedfactors

4.Pathogenesis:inflammatory,tumorous,metabolic,degenerative，immunologic,genetic,developmentalCategoriesofCardiovascularDiseases1.Arteriosclerosis:atherosclerosis,hypertension2.Inflammatorydiseases：infectious:endocarditis,myocarditis,pericarditisnon-infectious:rheumaticfever,vasculitis3.

Valvulardiseases:congenitaloracquired4.Cardiomyopathy:primarycardiomyopathy5.

Congenitalheartdiseases:6.

Corpulmonale:

7.

Cardiactumor:DiseasesindiscussionArteriosclerosis:AtherosclerosisHypertensionRheumaticdisease：rheumaticheartdiseaseInfectiousendocarditis:MyocarditisValvulardiseasesCardiomyopathyAgedistributionofCardiovasculardiseasesChildren,Youth：

Congenitalheartdiseases

Inflammatorydiseases:rheumaticfever,myocarditisAdults：

Valvulardiseases

Cardiomyopathy

VasculitisElderly：

Arteriosclerosis

CorpulmonaleNormalstructureofbloodvesselandheart

BloodvessleHeartIntima:endotheliumEndocardium:endothelium

Media:internalelasticlamina,elastin,SMCMyocardia:myocyte

Adventitia:externalelasticlaminaAdventitia:CT,neurofiber

彈性動(dòng)脈肌性動(dòng)脈Atherosclerosis

動(dòng)脈粥樣硬化Systemicinvolvementoflarge,medium-sizedarteries(aorta,coronary,cerebral,renalandiliac…).Lipids(cholesterol)depositioninintima,hyperplasiaofsmoothmusclecells,fibrosisandnecrosis,formationofcharacteristicatheroplaque(atheroma，粥瘤),narrowingofarteriallumenandlossofelasticity.Ischemiaoforgans:atrophy,fibrosis,infarction.Distribution：

abdominalaorta>coronaryarteries>

poplitealarteries>internalcarotidarteries>circlesofWillis

Preferablesites:aortaanditsoriginsofmajorbranchesBasicPathologicalChanges:4stages1.fattystreak

Gross：flattenormildlyraised,yellowdotsorstreaks

Microscopy：depositedlipidsandaggregatedfoamcells. sourcesoffoamcells：--bloodmonocytestissuemacrophages--medialSMCCautions:1.forminadolescence,reversible

lesion2.Progresstofibro-plaqueonlyinsomepatientsAortawithfattystreakAortawithfattystreakAortawithfattystreakSudanIIIstainingFattystreak:foamcellsaggregateandthickeningofintimaFoamcell：SudanIIIstainingoflipids

Foamcells:smallnucleiandvacuouscytoplasmfoamcellLipidsdepositionandformationoffoamcellsTrans-differentiationofSMCandcollagenproduction:fibrosis2.fibrousplaque

Gross：elevated,gray-yellowplaques

Microscopy：surface：fibrouscaps（collagenandextracellularmatrix,SMC）beneath：proliferatedSMCs,macrophages,foamcells,extracellouslipid,extracellularmatrix,leukocytes.EarlierfibrousplaqueIntimafibrousplaque3.atheromatousplaqueorathroma

Gross：obviouslyraised,whitetowhitishyellow,eccentricorpathylesions.Cutsurface，alotofyellowgrumouscore,coveredbyawhitefibrouscap。

Microscopy：

fibrouscap

necroticcore：containgadisorganizedmassoflipid,cholesteralclefts,debrisofdeadcells.

periphery：granulationtissue,neovascularization,somefoamcellandlymphocytes.atheromatousplaque:EccentricplaqueandnarrowingoflumenatheromatousplaqueAtheromatousplaque:mediaatrophyAtheromatousplaque:necrosis,cholesterolcrystals,plicatedplaqueorsecondarychanges

1)hemmorrhage:hematoma 2)rupture,ulceration,orerosion:cholesterolemboli,atheroemboli3)thrombusformation4)calcification,ossification5)aneurysm：localizedabnormaldialtionofabloodvesselortheheart.ulcerationHemorrhagehematomaThrombosis1-4：trueaneurysm；5：arterialdissection；6：pseudoaneurysmAneurysm（動(dòng)脈瘤）Localizedabnormaldialtionofabloodvesselortheheart.

?atherosclerosis,siphilis……

?“true”aneurysm（真性動(dòng)脈瘤）pseudoaneurysm（假性動(dòng)脈瘤）arterialdissection（動(dòng)脈夾層）:Marfansyndromearterialdissection（動(dòng)脈夾層）Lesionsofinvolvedorgansandmanifestations1.Narrowingoflumenischemicatrophy2.Obstructionoflumeninfarction

hemorrhageofintra-plaquethrombosis

3.Mediaatrophy

aneurysm1.aortic2.coronaryarteries3.cerebralarteries4.renalarteries5.arteriesofextremities1.Atherosclerosisinaorticaneurysm:abdominalaortafatalhemorrhage,aorticvalves:insufficiencyatherosclerosisofaortaswithulcerationElastinstainingDissectinganeurysmofaorta:thrombus,doublelumenandatherosclerosisMicroscopicappearanceofdissectinganeurysm:dissectionofaorticmedia2.Atherosclerosisincoronaryarteries--coronaryheartdisease（冠狀動(dòng)脈性心臟?。?-Anginapectoris--Myocardialinfarction--Chronicischemicheartdisease--Suddencardiacdeath3.Atherosclerosiscerebralarteries：carotid,basilarartery,circlesofWillis,middlecerebralartery--Atrophy:VasculardementiaisthesecondmostcommoncauseofdementiaintheUSAandEurope,butitisthemostcommonforminsomepartsofAsia.--Infarction:acuteischemia--HemorrhageAnatomyofcerebralcirculation

20%ofcardiacoutputgoestothebrain,and80%ofcarotidflowgoestotheipsilateralmiddlecerebralartery.

Internalcarotid:carotidartery--onemiddlecerebralarteryandoneanteriorcerebralarteryVertebral:twovertebralarteries-onebasilarartery--twoposteriorcerebralarteries.

ThecircleofWillis:theanteriorcommunicatingarterythatjoinsthetwoanteriorcerebralarteries,andthetwoposteriorcommunicatingarteries,eachofwhichjoinsaposteriorcerebralarterywithanipsilateralcarotidartery.4.Atherosclerosisofrenalarteriessegment：renalarteryandmainbranchesChronicischemia-repeatedinfarctionandscaring-atrophyandfibrosisGross：atheroscleroticatrophyofkidney:

bilateral,asymmetric,deconformation.atheroscleroticatrophyofkidneyHypertension,primarygranulo-contractedkidney5.AtheroscleroticarteriesofextremitiesSites：iliacarteries,poplitealarteries

Clinicalfeatures:--muscleatrophyoflowerextremity--intermittentclaudication--gangrene:ischemicinfarctionEpidemiologyandriskfactorsMiddle-agedoroldmanMale>femaleDevelopeddistricturban>>ruralConstitutionalriskfactorsAge:age-relateddisease,

incidenceofseverediseaseriseswitheachdecade.

degenerationofarterialwall:declineinpotentialoflipids-cleaningSex

:estrogenlevel-related.

beforemenopause:malefemale;menopause:male=femaleGenetics:

Somefamilieshaveincreasedrisk:SinglegenemutationinLDLreceptor,apoprotein,lipoproteinesterasemultiplegenes:predispositionHardriskfactorsLargecontributiontoincidence;potentiallyavoidableortreatable

HyperlipidemiaParticularlyhypercholesterolaemia,LDL,VLDL,HDL,apo-AI,Lp-aThelevelofbloodlipids(cholesterol)correlatewithASExperiment：high-lipidintakeinducingASMetabolicalterationsoflipidsinducingAS：endocrinedisease,geneticdefects:prematuredASlipidsdepositionistheinitialandcriticaleventinpathogenesisofASHypertension

Especiallyaftertheageof45

veryimportantpromotingfactorSmoking

PredominantatherogeniceffectsintheaortaandcoronaryvesselsDiabetes

Particularlyincoronary,cerebral,andperipheralarteries

inducinghypercholesterolemiaLDL:OX-LDL:lipidsorapo-BiNOS,MPO

RolesofOX-LDL：ingestedbymacrophagesthroughthescavengerreceptor–formingfoamcellsIncreasesmonocyteaccumulationStimulatereleaseofgrowthfactorsandcytokinesCytotoxictoECsandSMCsExamplesofGenesthatInfluenceDevelopmentofAtherosclerosisinHypercholesterolemiaMiceCell,Vol.104,503–516,February23,2001SoftriskfactorsSmallcontributiontoincidenceinstatisticalstudiesLackofregularexerciseObesityStressfullifestyleHighcarbohydrateintakeHardenedunsaturatedfatintakePathogenesis:4hypotheses1.Lipidhypothesis2.Mutagenesishypothesis3.Injuryandresponsehypothesis4.Receptordefecthypothesis：

germlinemutationofLDLreceptorKeyprocessofinjuryandresponsehypothesis1.Endotheliainjuryandlipidsdeposition2.Endotheliadysfunction3.Macrophageinfiltration4.EmigrationandproliferationofSMC5.FibrosisandnecrosisThecomponentsofplaque

lipids:LDLTheroleofOX-LDL：Chemotaxis：Inducingexpressionofadhesionmoleculesofendothelia：ICAM-1，VCAM-1Scavengerreceptor:foamcellsformationCytotoxicInitiatingimmunereaction

PossibleMechanismsbywhichoxLDLComponentsCanExertProatherogenicEffectsCell,Vol.104,503–516,February23,2001Thecomponentsofplaque

EndothelialcellsInjuryfactors：hyperlipidemia,hypertension,smoking,homocysteine,hemodynamicfactors,toxins…..necrosis,apoptosis

Production:Adhesionmolecules:

ICAM-1，VCAM-1,selectins---monocytemigration

Cytokines:monocytes/SMCproliferationThecomponentsofplaqueMacrophages:-infiltrating,scavengerreceptor(SR-A/cd36),cytokines-producingSmoothmusclecells:Migration:Proliferation:PDGF,FGF,etc.Collagensynthesis:TGF-βSmad-pathwayPotentialTargetsforDevelopmentofSmallMoleculeInhibitorsofAtherosclerosisCell,Vol.104,503–516,February23,2001CoronaryHeartDisease，CHD

冠心病

Definition：

Thenarrowingofcoronaryarteryresultsinhypoperfusion,hypoxia(ischemia)ofmyocardium.

IschemicHeartDisease:IHDPathogenesis：1.Atherosclerosisofcoronaryarteries：>95%severity:I:<25%,II=25–50%,III=51-75%,IV>75%

theinitialandproximalsegments,mainbranchesofleftorrightcoronaryartery,especiallyleftanteriordescendingbranchthrombosis,rupture,intraplaquehemorrhage2.Coronaryarteryvasospasm：3.Inflammatorydiseasesofcoronaryartery:-syphilis,rheumatism,someofarteritisTypesandfeatures1.Anginapectoris心絞痛2.Myocardialinfarction心肌梗死3.Chronicischemicheartdisease慢性缺血性心臟病4.Suddencardiacdeath心源性猝死1.anginapectoris心絞痛：Intermittentchestpaincausedbytransient,reversiblemyocardialischemia.

squeezing,crushingsubsternalsensation,radiatingtoleftarmMechanism:severetransientischemiametabolicproductsaccumulationsympatheticnervesystemSubtypesandfeatures1.Stable：-exertionorstress-inducing,relievedbyrestorvasodilator-cause:coronaryarteriesnarrowing(>75%)2.Unstable：

-increasingfrequencyandintense,longerlastingpreinfarctionangina -cause:superimposedthrombosis,distalembolization,spasm3.Variant(Prinzmetal)：

-

non-inducingstress-cause:vasospasm2.myocardialinfarction，MI

Persistentandcompleteischemiaoflocalmyocardium—necrosisofmyocytes,persistentchestpainPathogenesis:AtherosclerosisThrombosisSpasmHypoperfusion-increasingdemandTypes:1.Transmural:2.Subendocardial:SubendocardialMI心內(nèi)膜下心肌梗死

Features:1.Inner1/3ofmyocardium,includingpapillarymuscles2.Disseminatedfociofinfarcts,involvingentireendocardium(circumferentialMI),notlimitedtoareaofonearterysupply3.Severenarrowingofarteriesinlargepartsofarteries4.VasospasmrelatedtransmuralorregionalMI透壁性或區(qū)域性心肌梗死InvolvingmostofthethicknessoftheventricularwallInvolvingareaandfrequency:left>right-50%：leftanteriordescendingCA:anterior,apical,anterior2/3interventricularseptum -25%：rightCA:posteriorleftventricle,posterior1/3interventricularseptum,rightventricle -15~20%:leftcircumflexCA:lateralwallandbasalportionofleftventricle,leftatriumMorphologyCoagulativenecrosis→

inflammatoryresponse→fibroushealingGross:post-infarctionIrregularshapedareasofinfarcts6hr:pallor 8-9hr：yellow,dry,firm,mute 4d：hyperemicandhemorrhageborder 10d:yellow,soft2-3wk：red,granulationtissue 5wk：gray,firm,shrunk:scaring(organization)InfarctinleftventricleanteriorwallInfarctinposteriorleftventricleandposterior1/3interventricularseptumScarformationofinfarctMicroscopy:coagulativenecrosis:--Nochangesinearly1-2hr:wavyfiberchange9hr：neutrophilsappear18-24hr:cytoplasmiccondensation(increasingeosinophilia,contractionbands);Nuclearchange:pyknosis,karyorrhexis24-72hr:neutrophilsinfiltration4d~7d：hyperemicandhemorrhageborder,macrophages,granulationtissueatedge10d:prominentgranulationtissueinsurrounding.2-8wk:scaring(organization)WavyfiberchangeCytoplasmic:condensation,increasingeosinophiliaNuclearchange:pyknosiskaryorrhexisCytoplasmiccondensation(increasingeosinophilia,contractionbands),pyknosisCytoplasmiccondensation(increasingeosinophilia),pyknosis,

infiltratingneutrophilsInfiltratingneutrophils,myocytolysisMacrophages:1-2weekMacrophagesphagocytizingnecroticmyocytesOrganizationbygranulationtissue

Fibrosis,hypertrophyofremainingmyocytesSequencesofchangesinmyocardialinfarctionTimeGrossMicroscopy0-30minNochangeNochange1-2hrNochangefew“wavy”fibersatmarginofinfarct4-12hrNochangeearlycoagulationnecrosis,edema,occasionalneutrophils,mininalhemorrhage18-24hrslightpallorormottlingcontinuingcoagulationnecrosis(nuclearpyknosis,cytoplasmiceosinophilia);“contractionband”necrosisatperiphery,neutrophilicinfiltrate24-72hrpallorcompletecoagulationnecrosis,heavyneutrophilicinfiltrate4-7dcentralpallorwithhyperemicbordermacrophagesappear,phagocytosisofnecroticfibers,granulationtissuevisibleatedgeofinfarct10dyellow,soft,shrunken,purpleborderwelldevelopedphagocytosis,prominentgranulationtissueinperipheralarea7-8wkfirm,grayfibrosisRepairofmyocardialinfarctionInjuryandrepair1.Inflammation2.Fibrosis:scarformationHyperplasiaoffibroblastandmyofibroblastAngiogenesisExtracellularmatrixStemcelltransplantationEmbryonicstemcellsSomaticstemcells:bonemarrowmesenchymalneonatalcardiomyocytesothersourcesLaboratoryevaluationofMIProtein: MyohemoglobulinEnzymes：indicatorofmyocyteinjury

Creatinekinase(CK):2-4hr,24hpeak,72hnormal,CK-MBTroponins:2-4hr,24hpeak,last4-7d,cTnILDH:

Complications1.Heartfailureandarrhythmias:majorcauseofdeath

Theinfarctareaofleftventricle>40%，outputshockinvolveconductsystemlethalarrhythmia2.rupture：within1-2weeks

-apical:1/3tamponade-septum:heartfailure-papillarymusclesdysfunctionmitralinsufficiencyleftheartfailure3.Pericarditis：serumand

fibrinsexudates

4.Ventricularaneurysm：acuteorhealingphasemuralthrombusoftenpresent,heartfailure,arrhythmias 5.Muralthrombi：infarctorventricularaneurysm6.Organization,Scarformation：

small：2weeks,large：4-6weeksLeftventricularaneurysmHypertension

高血壓

systolic

diastolicNormal： 140mmHg 90mmHgBorderline： 140~160 90~95Hypertention： 160 95Bloodpressure=Na+ReninvasoconstrictionAngiotensinogenaldosteroneAngiotensinIAngiotensinIIpH,hypoxia,neuralVascularwallthicknessACEperipheralresistancebloodvolume×PathogenesisNa+channelcatecholamines(-)(+)(+)KininsPGNO(+)Renalarterystenosis,renin-secretingtumorkidney： 1)renin-angiotensinsystem2)Na+balance:bloodvolume,atrialnatriureticpeptide,3)antihypertensivesubstances(PG,NO)2.Neural-endocrine：1)arteriolesympatheticnerve：

αreceptor:vasoconstrictionβreceptor:vasodialation

2)atrialnatriureticpeptide3)renin-angiotensin–aldosteronesystemPathogenesisTypesofhypertentionessentialorprimary:90-95%chronic（benign）:95%accelerated（malignant）:5%secondaryorsymptomatic:5%-10%asapartofdiseases-renal:renalarterystenosis,chronicrenaldisease-endocrine:adrenalhyperfunction,hyperthyroidism,renin-producingtumors-neurologic:acutestressMechanismofprimaryhypertensionMulti-factordisorder:1.geneticpredisposition:familial,polygenetic2.dietetic：Na+、K+、Ca++3.stressGenemutationandhypertentionBenignhypertension良性高血壓onsetatmiddleorelderly，progressslowly

Clinicalcourse：1.Functionalderegulation:intervalvasospasmofarterioleorsmallarteries，hypertensioninfluctuation;2.Arteriosclerosis:persistenthypertension3.Organs:compensatory:hypertrophyofheart,nephrosclerosis,cerebralarteriosclerosisdecompensatory:cardiacfailure,cerebralhemorrhage,renalfailurePathologicchanges1.Arterioleandsmallerarteries2.Organslesionsandmanifestations：

Heart

Kidney

Cerebral

Retinal1.Arteriole:(<1mm,1-2layersmusculararteries)

-Generalized：renalafferentarteriole,spleniccentralarteriole,retinalcentralartery-Characteristicchange:hyalinearteriolosclerosis-Pathology:

Subendothelialproteindepositionhyalinedegenerationthickeningofwall,rigidity,luminalnarrowingandocclusionarteriolosclerosisBasicpathologicalchangeshyalinedegenerationofspleniccentralarteriolehyalinedegenerationofrenalafferentarteriolehyalinedegenerationofrenalarteriole2.Smallerarteriesonion-skin,concentric,laminatedthickeningofthewallsIntimalthickening:SMCsproliferation,fibrosis,matrixdepositionDuplicateinternalelasticlaminaMediahyperplastic：SMCsproliferationSclerosisofsmallerarteriesinhypertension3.Hypertensiveheartdisease-Leftventriclehypertrophy

-

Mechanism：highpressure--increasingsystolicloadofleftventricle-Gross：

thickeningofleftventriclewallover2cminthickness，hypertrophyofpapillarymuscles

concentrichypertrophy:withoutchamberdilation(compensation)

eccentrichypertrophy：chamberdilationcardiacfailure(decompensation)-L/M:hypertrophicmusclefibersNormalconcentrichypertrophyConcentrichypertrophyNormalThickeningofleftventriclewall

>2cm

EccentrichypertrophyDilatedchamberNormal4.kidney:arteriolarnephrosclerosis/primarygranulo-contractedkidneyMechanism：afferentarteriolehyalinosisandluminalnarrowing-atrophyandfibrosisofnephroneunitsaccompanyingcompensatoryhypertrophyofglomeruliortubulesPathologicchanges：Gross:symmetric,granularatrophyL/M:HyalinearteriosclerosisandsmallarterysclerosisDiffuseatrophyofglomeruliandtubulesHypertrophyofglomerulianddilatedtubulesInterstitialfibrosisMicroscopicfeaturesofbenignnephrosclerosisClinicalmanifestations:Glomerularfiltrationrate?Renaldysfunction:Proteinuria,hematuria：glomerulidamage

Renalfailure：azotimia,uremia5.Brain：Cerebralvessels：

hyaline,orfibrinoidnecrosis;atherosclerosisofsmallarteries,thrombosis,microaneurysms—infarctionandhemorrhage.Cerebraledema:headache,nauseaHypertensiveencephalopathy:bloodpressureoverthelimitsofcerebralautoregulation,dysfunctionofcentralnervesystem.

Hypertensiveemergency:markedelevatedbloodpressureandmultipleorgansdysfunction.microinfarctofbrain:

Lacunarinfarction（腔隙性腦梗死）:smallfociofinfarcts,thrombosis.Cerebralhemorrhage：destructionofbraintissue,elevatedintracranialpressure—herniation

Basalgangliaarea(Putamen):

hemiparesis,hemianopsia,oraphasia.

Cerebrallobes:Thalamus:Cerebellum：nausea,vomiting,dizziness,ataxia.Pons：

Arteriolosclerosis

A.Arteriolosclerosis:hyalinewallthickeningandmildlumennarrowing.

B.Mediamineralisation

Arteriolosclerosis

A.fibrinoidnecrosis.B.fibrosis.C.thrombosedlesion.Smallvesselatherosclerosis

Lacunes:smallfociofinfarctsHemorrhageofbasalgangliaareawithmidlineshiftBasalgangliahemorrhageinvolvingventriclePontinehemorrhage

Subarachnoidhemorrhageandhyalinedegenerationofsmallarteries6.Hypertensiveretinopathy:Sclerosisofcentralretinalartery：white,silverypapilledemaretinalexudation,hemorrhage:flame-shapedfocalinfarction:spot(softcotton-wool)retinaldetachmentEyes'vesselchangescouldpredictseverehypertensionrisk

–Theeyesmaybethewindowtothesoul–andfuturehypertensionMalignant(accelerated)hypertension

惡性高血壓PrimaryorfrombenignhypertensionelevatedlevelofplasmareninClinicalfeatures：

Severehypertension:230/130mmHg

HypertensiveencephalopathyRenaldysfunction:persistentproteinuria,hematuria

Deathwithinoneyear:uremia,cerebralhemorrhage,cardiacfailurePathologicchanges1.Arteriole：fibrinoidnecrosis-necrotizingarteriolitis2.Smallerarteries：hyperplasticarteriosclerosisthickeningintima,hyperplasticSMC，“onion-skin”3.kidney：malignantnephrosclerosis

Necrotizingarteriolitis:Necrotizingglomerititis:micro-hemorrhagesThrombosis:micro-infarctions

4.Brain：ischemia,infarction,hemorrhageNecrotizingarteriolitis:fibrinoidnecrosisofarteriolesEMHyperplasticarteriolosclerosis:onion-skin,luminalobliterationIMalignanthypertensionFlea-bittenkidneyAtherosclerosisBenignhypertensionLocationLargeandmediumarteriesArterioleandsmallerarterialBasicpathologyatheromaHyalineandhyperplasticarteriolosclerosisDepositmateriallipidplasmaproteinAterialwallEccentricthickeningConcentricthickeningAteriallumanEccentricnarrowingConcentricnarrowingInfluencetoorganischemiaHypertension,ischemiarelationAccelerateATHCommonfeaturesAge-relatedRheumatism風(fēng)濕病Definition：RelatedwithgroupAβhaemolyticstreptococcalpharyngitisHypersensitiveinflammationMainlyinvolveconnectivetissuesHeart,joints,artery,especiallytheendocardiumofheartFibrinoidnecrosisofcollagen,Charactericrheumaticgranuloma(Aschoffbody).Clinicalfeatures-Acutephase：RheumaticFever(RF)

fever

pancarditispolyarthritisskinrashes(erythemamarginatum環(huán)形紅斑andsubcutaneousnodules)neurologicalsymptoms(Sydenham'schorea)Laboratoryfindings：raisedESRandC-reactiveprotein,groupAstreptococcalinfections(ie,positivethroatcultureandanelevatedstreptococcalantibodytiter).-chronicphaseofrheumatism:Recurrentepisode

chronicvalvulardeformities

Epidemiology1.Post-infectionofstreptococcus：1-5wksafterstreptococcalinfectionandrecurrentacuteRFalwaysprecededbyinfectionElevatedserumtitersofASOandantihyaluronidaseantibodesTissuelesionsaresterile(i.e.containnostreptococci)2.

Regions:

streptococciprevailingregion3.Initialattachinchildren:

6-15yRecurrentattacksinyouth：chronicheartdisease4.Effectiveinusageofantibiotics

5.Decreasingincidenceinlatestdecades:

improvedsocioeconomicstatus:poverty,undernutrition,poorhousing,overcrowding

Pathogenesis1.Associatedpathogen:GroupAstreptococcuswasestablishedasthesoleetiologicagentofthedisease.Thevirulencefactors:（1）Hemolysin,streptolysinS,isoneofthemosttoxicproteinsknown.Itcausesrapiddestructionofcellmembranesandisverycardiotoxic.（2）Hemolysin,StreptolysinO,isalsoapowerfulcardiactoxin.（3）Streptokinaseanddesoxyribonuclease:liquefyfibrinandnucleicproteins.（4）Streptococcalhyaluronidasepromotesrapidspreadoftheorganismsthroughtissues.（5）Erythrogenictoxins:responsiblefortherashoffeverandshock.（6）Mprotein:containsmoietiesthatbehaveassuperantigens.Manyofthesesecretedtoxinshavethepropertiesofsuperantigens.

Virulentstrainsas“rheumatogenic”:heavilyencapsulated,possesslargeMprotein,highlyvirulent,extremelyresistanttophagocytosis.Pathogenesis2.Theimmuneresponse:

1)Exaggeratedimmuneresponse:

largeloadofsuperantigenicpropertiesofMproteinandthevariousstreptococcaltoxins2)Similarepitopes:hostantigensidenticaltosomestreptococcalepitopeshavebeenidentifiedinsynovia,heart,brain,andrelatedtopolyarthritis,nodules/erythema,chorea.Evidences:SomeofHLADRsBcellalloantigenlabeledD8/173)Mimeticautoimmunityisaveryattractivepathogenetichypothesisbutevidenceforitsrelevanceisstillindirect.

Pathogenetichypothesis1.Cross-reaction：Streptococcihumantissueshyaluronidasecapsule

heartvalveglycoproteins

membraneantigens

myocardialsarcolemmaMproteincardiacmyosin

2.Tlymphocytemediatedautoimmuedisease:superantigencardiacmyosin

betahaemolyticstreptococcalAcuterheumaticheartdiseaseImmuneresponsemyocarditispericarditisendocarditisBasicpathologicchanges：3phases1.Alterativeandexudativephase:connectivetissue:Interstitialsubstance:mucinoiddegeneration:edema,accumulatedacidmucopolysacharide,

Collagen:swelling,fr