ChapterVI

DiseasesofCardiovascularSystem心血管系統(tǒng)疾病

DepartmentofPathology

Cardio

vascularsystemHeart

Blood

vessels“Pump”

Moremorbidity&mortality

-Approximatelyhalfofalldeathcausedbydisordersofcirculatorysystem-InUS,myocardialinfarctionaloneisresponsiblefor20-25%ofalldeathSystemicPathology·

Etiology,Pathogenesis

·

Pathologicmorphology

·

Clinico-pathologicalcorrelation

·

ConsequenceGeneralpathology

?SystemicpathologyExample:MyocardialinfarctionCoagulativenecrosis

GranulationtissueScarmyocardialruptureArrhythmiasVentricularaneurysm

……ContractiledysfunctionHeartfailureshock,deathMorphologyConsequencesCardio

vasculardiseasesHeart

Blood

vesselsIschemicheartdisease←AtherosclerosisHypertensionRheumaticHeartDiseaseValvularheartdisease(InfectiveEndocarditis) MyocarditisCardiomyopathy

Large

(Elastic):Aorta&largebranches,pulmonaryarteries

Medial(Muscular):Coronary,renalarteries

Small(ф<2mm):Arteriole(ф20~100μm)

ArteryBasicconstituents:-Endothelialcells(ECs)-Smoothmusclecells(SMCs)-Extracellularmatrix(ECM)Vascularwallcells’responsetoinjury

ECs---dysfunction:contraction,proliferationSMCs---migratory&proliferativeactivityECM---↑ThickeningofthewallluminalnarrowElasticity↓TwoprincipalmechanismsofvasculardiseasesNarrowingorcompletelyobstructingtheluminaWeakeningofthewalls,leadingtodilationorrupture

Arteriosclerosis

Classification

Atherosclerosis（動(dòng)脈粥樣硬化）

Large&medium-sizedarteries

M?nckebergmedialcalcificsclerosis（動(dòng)脈中層鈣化）

Arteriolosclerosis（細(xì)動(dòng)脈硬化）

Smallarteries&arterioles

Essentialhypertension,diabetesmellitusHardeningAtherosclerosis(AS)

Intimallesionscalledatheromas

(粥樣瘤),oratheromatousoratherosclerotic

plaques(動(dòng)脈粥樣硬化斑塊)

→luminalnarrow→WallweakeningseriouscomplicationsTheconstitutional(immutable)riskfactors●AgedominantinfluenceIHDrisewitheachdecade/middleageorlater●Gender●Genetics

polygenic hypertension,diabetes,hereditarygeneticderangementinlipoproteinmetabolismEpidemiologyThemajormodifiableriskfactors●

Hyperlipidemia

especiallyHypercholesterolemia

LDL:“badcholesterol”deliveringcholesteroltoperipheraltissue

highdietarycholesterol,saturatedfats:eggyolk,animalfats

HDL：“goodcholesterol”transportingcholesteroltotheliver

exercise,moderateconsumptionofethanol↑;obesity,smoking↓

Omega-3fattyacidsabundantinfishoil,beneficial●

Cigarettesmoking

●

Hypertension●DiabetesmellitusAdditionalriskfactors

●

InflammationasmarkedbyC-reactiveprotein(CRP)●

Hyperhomocystinemia(高半胱氨酸血癥）●

Lipoproteina

●

Factorsaffectinghemostasis

●

Otherfactors:obesity,physicalinactivitystress“typeA”personalitybehaviorMultipleriskfactorshaveamultiplicativeeffectPathogenesis

Response-to-injuryhypothesis---AchronicinflammatoryresponseofthearterialwalltoendothelialinjuryModifiedlipoproteinsInflammatorycells:Monocyte-derivedmacrophages,TlymphocytesThenormalconstituentsofthearterialwallsThreecomponentsNormalEndothelialinjurywithmonocyteandplateletadhesion

Monocyteandsmoothmusclecellmigrationintotheintima,withmacrophageactivationMacrophageandsmoothmusclecelluptakeofmodifiedlipidsandfurtheractivation

IntimalsmoothmusclecellproliferationwithECMelaboration,formingawell-developedplaque*MinisummaryAtherogenesisisdrivenbyaninterplayofvesselwallinjuryandinflammation.Themultipleriskfactorsforatherosclerosisallcauseendothelialcelldysfunctionandinfluencesmoothmusclecellrecruitmentandstimulation.

MORPHOLOGYIntimalthickening&lipidaccumulationgivingrisetofattystreak&thenatheromaFattystreak（脂紋or脂斑）

Gross:yellow,flatspots,or>=1.0cmstreaks,oilredstaining(+)

orificesofbranches

--Fattystreak:foamcells--Mayevolveintoadvancedlesionsordisappear

Microscopy2.AtheroscleroticplaqueGross:whitetoyellow,red-brownwiththrombosisoverthesurface

ф0.3~1.5cmcancoalescetoformlargermassesThebasicstructureofanatheromatousplaqueMicroscopy

MassontrichromestainF:fibrouscapC:acentralnecrotic(lipid)coreL:lumenTheinternalandexternalelasticmembranesaredestroyedThemediaisthinnedunderthemostadvancedplaqueScatteredinflammatorycells,calcification,andneovascularizationatthejunctionofthecapandcore*MinisummaryAtherosclerosisisanintima-basedlesioncomposedofafibrouscapandanatheromatous(literally,“gruel-like”)core;theconstituentsoftheplaqueincludeSMCs,ECMs,inflammatorycells,lipids,andnecroticdebris.

Naturalhistory,morphologicfeatures&mainpathogenicevents

Clinicallyimportantchangesofatheroscleroticplaques

●Rupture,ulceration,orerosion→thrombusformation●Hemorrhageintoaplaque●Atheroembolism●Aneurysmformation●CalcificationPlaqueruptureAcutecoronarythrombosisonaplaquewithfocalrupture,triggeringfatalmyocardialinfarctionHemorrhageintoplaqueAneurysmAcuteplaquechange

Rupture/fissuringErosion/ulcerationHemorrhageintotheatheroma

Thin

Fibrouscap

DenseLarge

Lipidcores

Small

Dense

Inflammation

LittleClinicalconsequencesofatherosclerosis*Atheroscleroticplaquesdevelopandgrowslowlyoverdecades.

*Stableplaquescanproducesymptomsrelatedtochronicischemia

bynarrowingvessels,whereasunstableplaquescancausedramaticandpotentiallyfatalischemiccomplicationsrelatedtoacuteplaquerupture,thrombosis,orembolization.

Aorta AneurysmCoronaryA.CoronaryHeartDiseaseCerebralA. Thrombosis,Aneurysm,Hemorrhage,AtrophyRenalA. Infarction,Nephrosclerosis,HypertensionFemoral,Popliteal,TibialA.Intermittentcramp,GangreneIschemicHeartDisease(IHD)CoronaryArteryDiseaseNarroworOcclusionofLumenofCoronaryA↓Coronaryperfusion↓Myocardialdemand↑

Ischemia,FunctionDisturbance,InfarctionofHeartInthevastmajorityofcases,cardiacischemiaisduetocoronaryarteryatherosclerosisvasospasm,vasculitis,andembolismarelesscommoncausesEpidemiology

●Leadingcauseofmorbidityandmortalityinindustrializednations

●Annually,ahalf-millionAmericansdieofIHD

●↓Cardiacriskfactors:smokingcessationprogramhypertension&diabetictreatmentcholesterol-loweringagentsNormalheart

“Pump”

Weight:♂250～270g,♀240～260gWallthickness:leftventricle0.9~1.0cmrightventricle0.3~0.4cmatrium0.1~0.2cmValves：asingledirectionofbloodflowMyocardium：nearlyinexhaustibleBloodsupply:coronaryarteriesCoronaryarteriesLesionsofCoronaryAtherosclerosis

Acuteplaquechanges,vasospasm

Criticalstenosis:>=75%ThefrequenciesofocclusionofvariouscoronaryarteriesandthedistributionoftheresultantinfarctsLeftanteriordescendingcoronaryartery40%~50%Anteriorandapicalleftventricle;anteriortwothirdsoftheinterventricularseptumRightcoronaryartery30%~40%Posteriorwalloftheleftventricle;posterioronethirdoftheinterventricularseptumLeftcircumflexcoronaryartery15%~20%lateralwalloftheleftventricleRupture,fissuring,orulceration→rapidthrombosisHemorrhageintothecoreofplaquesVasospasmAcutePlaqueChangeAcutecoronarysyndromesPalpitations；Pain；Exertionaldyspnea（勞力性呼吸困難）；Diaphoresis（大汗）；Nausea（惡心）;DecreasedexercisetolerancePlaqueruptureAcutecoronarythrombosisonaplaquewithfocalrupture,triggeringfatalmyocardialinfarctionMassiveplaquerupturewiththrombus,triggeringafatalmyocardialinfarctionClinicalPresentations

1.Anginapectoris2.Myocardialinfarction3.Chroniccoronaryheartdisease4.Suddencoronarydeath

Anginapectoris

Anintermittentchestpaincausedbytransient,reversiblemyocardialischemia

(1)Stable

---Afixedatheroscleroticnarrowing(usually>70%)---Occurinthesettingofincreaseddemands---Relievedbyrest(reducingdemand)orbyadministrationofnitroglycerin(vasodilator)

(2)

Unstable

---Resultsfromasmallfissureorruptureofatheroscleroticplaquetriggeringplateletaggregation,vasoconstriction,andformationofamuralthrombus---Occurprogressivelyatlesslevelsofexertionorevenatrest(3)Variant---Causedbyvasospasm---OccuratrestAcrushingorsqueezingsubsternalsensation,mayradiatedowntheleftarmMyocardialInfarction(MI，心肌梗死)

NecrosisofheartmuscleresultingfromischemiaMostMIsarecausedbyacutecoronaryarterythrombosis

Plaquedisruption→Plateletaggregation&vasospasm→Thrombosis↓Occludingthecoronaryarterylumen↓IschemiaMyocardialResponsetoIschemia●Biochemistry:Withinsecondsaerobicglycolysis↓,ATP↓●Function&morphology:Withinaminuterapidlossofcontractility,ultrastructuralchanges

reversible20~40minutescoagulationnecrosis

irreversiblePromptinterventionThrombolysisAngioplastyCoronaryarterialbypassgraftMORPHOLOGY

MItypicallybeginsinthesubendocardialregionMIusuallyreachesitsfullsizewithin3to6hours

PatternsofinfarctionDependingon…

TheinvolvedvesselThedurationoftheocclusionMetabolicdemandsofthemyocardiumExtentofcollateralsupply

1.Transmuralinfarctions2.Subendocardialinfarctions3.MicroscopicinfarctsGross

●

MIslessthan12hoursoldusuallyarenotgrosslyapparent●By12to24hoursafterMI,aninfarctusuallycanbegrosslyidentifiedbyared-bluediscolorationcausedbystagnated,trappedblood●Map-likeMicroscopy

Coagulationnecrosis/inflammationFormationofgranulationtissueOrganization&scar-AcuteMI-Remoteinfarction(Scar)-Rupture(Deathcause)“Irregular”map-like1day---coagulationnecrosisedemawavyfibers3-4daysCompletecoagulationnecrosisofmyofibersHeavyneutrophilicinfiltrate7-10daysWell-developedphagocytosis

3wkCollagenfibersGranulationtissueScar-Richcollagenfibers-ResiduemyofibersReperfusioninjury

Restorationofbloodflow→greaterdamageMitochondrialdysfunction,myocytehypercontracture,freeradicals,leukocyteaggregation,&PlateletandcomplementactivationcontributingtomicrovascularinjuryClinicalFeatures

●

Thechestpaincannotberelieved“silent”infarctsindiabeticpatients&elderlypersons

●Rapid&weakpulseDiaphoretic&nauseous,particularlywithposteriorwallMIs

●Electrocardiographicabnormalities

Qwaves,STsegmentchanges,TwaveinversionslethalArrhythmias

●Laboratoryevaluation

*MiniSummary1.Myocardialischemialeadstolossofmyocytefunctionwithin1to2minutesbutcausesnecrosisonlyafter20to40minutes.2.Myocardialinfarctionisdiagnosedonthebasisofsymptoms,electrocardiographicchanges,andmeasurementofserumCK-MBandtroponins.3.Grossandhistologicchangesofinfarctionrequirehourstodaystodevelop.4.Infarctioncanbemodifiedbytherapeuticintervention(e.g.,thrombolysisorstenting),whichsalvagesmyocardiumatriskbutmayalsoinducereperfusion-relatedinjury.Consequences&ComplicationsofMI

Dependingon--infarctsize--site--fractionalthicknessofthemyocardialwallthatisdamaged

1.Contractiledysfunction

Cardiogenicshock:massiveMIsinvolving≥40%oftheleftventricle2.Arrhythmias

Myocardialirritability&conductiondisturbancesSuddendeath3.Myocardialrupture

Mostcommonbetweendays3-7afterMIsVentricularwallfatalhemopericardium（心包積血）&cardiactamponade（心包填塞）

MostcommonPapillarymuscleseveremitralregurgitationVentricularseptumleft-to-rightshunting4.Pericarditis5.Chamberdilation6.Muralthrombus→thromboembolism7.Ventricularaneurysm

---AlatecomplicationoflargetransmuralMIs---Thebulgingofthenoncontractilefibrousmyocardiumduringsystole---Athin-walled,fibrousoutpouchingoftheventricularwall---Oftenwithamuralthrombus8.

Progressivelateheartfailure

*MiniSummary

Complicationsofinfarctionincludecontractiledysfunction,arrhythmia,myocardialrupture,pericarditis,chamberdilation,muralthrombus,aneurysmformation,andCHF.ChronicIschemicHeartDisease

Thedevelopmentofprogressivecongestiveheartfailureasaconsequenceoflong-termischemicmyocardialinjuryCoronaryarteries:moderatetosevereatherosclerosisHeart:Gross---enlarged,leftventriculardilationandhypertrophy,patchyscars,muralthrombiMicroscopy---myocardialhypertrophy,fibrosis,subendocardialmyocytevacuolizationClinicalfeatures:progressiveanginapectoris,MI,arrhythmiasSuddenCardiacDeath

Unexpecteddeathfromcardiaccauses,occurringwithin24hoftheonsetofsymptoms

CoronaryarterydiseasesinadultsNon-atheroscleroticcausesinyoungervictimsAlethalarrhythmia,eg.VentricularfibrillationHypertensionAdultbloodpressure

GradeSystolicpressure(mmHg)Diastolicpressure(mmHg)Normal<=130<=85Hypertension>=140and/or>=90Borderline130–13985-89ClassificationofHypertension

?Essential(idiopathic):90–95%Arterioles/smallarteries Benign:Malignant=9:1?Secondary:diseasesofadrenalglands,renaldiseases,renalarterystenosisEssential(Primary,Idiopathic)Hypertension

Achronicdiseasewithspasm&sclerosisofarterioleandsmallartery

causedbydifferentfactorsandincreaseofcardiacoutputinducesincreaseofbloodpressureandlesionsoforgansPathogenesis

TheBPlevelisdeterminedbytheinteractionofmultiplegenetic,environmental,anddemographicfactorsthatinfluence2hemodynamicvariables:cardiacoutputandtotalperipheralresistance

MORPHOLOGYHyalinearteriolosclerosis(benignhypertension)HyperplasticarteriolosclerosisNecrotizingarteriolitis(malignanthypertension)ThickeningofthewallswithnarrowingofthelumenProcessesofbenignhypertension

Stage1:FunctionaldisturbanceSpasmofarterioleandsmallarteriesStage2:Changesofvascularsystem Smallartery&Arteriole–hyalinedegeneration Large&medialartery–atherosclerosis

Stage3:Lesionsoforgans

Heart---HypertensiveheartdiseaseLeftventricularhypertrophy

EarlystageConcentrichypertrophyLater

Acentrichypertrophydilationofcardiacchambers

LM:Myocyteshypertrophy,withprominentnuclearenlargement&hyperchromasiaInterstitialfibrosisKidney–Arterionephrosclerosis

Grosslysymmetricallyatrophicdiffuse,finegranularityofsurface

Microscopicallyhyalinearteriolosclerosisischemicatrophycompensatedhypertrophy&dilation

Arrangedatintervals顆粒性固縮腎

Brain

HypertensiveencephalopathyEdema,softening(microinfarct),microaneurysmsHemorrhage:basalganglia

基底核（內(nèi)囊）

lenticulostriateartery

豆紋動(dòng)脈Malignanthypertension

Necrotizingarteriolitis:fibrinoidnecrosis

Hyperplasticarteriolosclerosisonion-skin,concentric,laminatedthickeningofthewallsBenignvsMalignantHypertensionBenign

MalignantIncidence high(90%) low(10%)Age middleorsenior youngerormiddleBP>140/90mmHg>200/120mmHg

Symptom light severeLesion hyalineofarteriole fibrinoidnecrosisofarteriole&smallarteriesCourse >10yr1–2yrCauseofdeath cerebralhemorrhage, renalfailure,heartfailure uremia(95%)Rheumatism(風(fēng)濕?。?/p>

Rheumaticfeverisanacute,immunologicallymediated,multisystem

inflammatorydisease.

FollowinganepisodeofgroupAβ-hemolyticstreptococcalinfections(usuallypharyngitis)afteranintervalofafewweeks

Occuringinheart,synovium,joints,bloodvessels,skin,etc.AcuterheumaticcarditisChronicvalvulardeformities

Afteraninitialattack,thereisincreasedvulnerabilitytoreactivationofthedisease.Justlikeacrazydog,lickingalloverthebodyandfinallybitingtheheartEtiologyandPathogenesis

ImprovedsocioeconomicconditionsRapiddiagnosisandtreatment

AhypersensitivityreactioninducedbygroupAstreptococci

(1)Symptomstypicallydevelopabout2~3weeksafterinfection.(2)Streptococciareabsentfromthelesions.

AntibodiesdirectedagainsttheMproteinsofgroupAstreptococcicross-reactwithnormalproteinspresentintheheart,joints,andothertissues.Theincidenceandmortality↓↓↓

Anautoimmuneresponseagainstself-antigens

GeneticsusceptibilityRheumaticfeveroccursinonlyabout3%ofpatientswithgroupAstreptococcalpharyngitisMORPHOLOGYBasicpathologicchanges3phases

Necrotic&exudativephase

Fibrinoidnecrosis,inflammatoryinfiltrates

Regeneration

Rheumaticgranuloma(rheumaticbody,Aschoffbody)

Fibrosis“Reoccur”Rheumaticbody(Aschoffbody)---Oftenlieincloseproximitytoasmallvessel---Acentralfocusoffibrinoidnecrosissurroundedbyachronicmononuclearinflammatoryinfiltrate---AschoffcellsRheumaticHeartDisease

1.AcutePancarditis

(1)Rheumaticendocarditis

Mitral50%Mitral+Aortic50% Edematous,thickened,fibrinoidnecrosis,verrucae(vegetation,mayresolveorprogress)(2)Rheumaticmyocarditis:Aschoffbodies(3)Rheumaticpericarditis:

Fibrinousexudate(corvillosum,generallyresolvewithoutsequelae)

2.Chronic

Characterizedbyorganizationoftheacuteinflammation&subsequentscarring

Fibrousscar

Themitralvalvesexhibitleafletthickening,commissuralfusionandshortening,andthickeningandfusionofthechordaetendineae.Valvularstenosis,regurgitation

Microscopy:neovascularization,diffusefibrosisAcutesuperimposedonchronicFishmouthButtonholeTreatment

SurgicalreplacementofdiseasedvalvesBioprostheticvalvesMechanicalValvesPathologicChangesinOtherOrgans

Rheumaticarthritis

Largerjoints,migratorypolyarthritis

Withoutsequelae

Skin

Erythemaannulare,subcutaneousnodules

Rheumaticarteritis

Brain

Neurondegeneration,gliacellproliferation

extrapyramidalinvolvedchoreaminor

ClinicalFeatures

Antibodiestooneormorestreptococcalenzymes

StreptolysinO

SignsPericardialfrictionrubsWeakheartsoundsTachycardiaorotherarrhythmiasCongestiveheartfailure<5%deathMiniSummary

Rheumaticheartdiseaseresultsfromantistreptococcalantibodiesthatcross-reactwithcardiactissues.

Itmostcommonlyaffectsthemitralvalve.

RheumaticgranulomaInfectiveEndocarditis

Definition

Infectionofthecardiacvalvesormuralsurfaceoftheendocardium,resultingintheformationofbulky,friable

vegetationCause

Anytypeofmicroorganism,mostbybacteria

Antibiotictherapyblursthedistinction.

Aparticularlydifficultinfectiontoeradicatebecauseoftheavascularnatureoftheheartvalves.

ClassificationFormsOrganismValvesAcuteHighvirulencePreviouslynormalSubacuteLowvirulencePreviouslyabnormalPathogenesis

Conditionsthatincreasetherisk(1)Preexistingcardiacabnormalities:rheumaticheartdisease(2)Prostheticheartvalves:nodifferencebetweenmechanicalandbio-prostheticvalves(3)Hostfactors:DM,immunodeficiency,intravenousdrugabuse

Bacteremia

AninfectionelsewhereApreviousdental,surgicalorotherinterventionalprocedure,e.g.urinarycatheterizationIntravenousdrugabusersMORPHOLOGY

Thehallmarkisthepresenceofvalvularvegetationscontainingbacteriaorotherorganisms.

Aorticandmitralvalvesarethemostcommonsitesofinfection.SBE“repair”

ABE“damage”

Causativeorganismlowvirulencea-hemolyticstreptococcihighvirulencestaphylococcusaureusPathogenesisPreexistingabnormality

Nativevalves

Commonsitesmitral/aorticvalves

aorticvalves

GrosslyFriable,bulkyvegetationscontainbacteria,single/multiple,≥1valveInfluence:typeoforganisms,degreeofhostreaction,previousantibiotictherapyMicroscopicallyPlatelet,fibrin,inflammatoryinfiltrates,bacteriaGranulation,fibrosis,calcification,chronicinflammatoryinfiltratesdestructionofthevalves&vicinity,ringabscesses(inperivalvulartissue),Sequelaechronicvalvulardisease,regurgitationRupture,suddendeathchronicvalvulardiseaseSBE“repair”ABE“damage”SitesotherthanheartSystemicemboli,anemicinfarcts,GNSystemicemboli,septicinfarcts(suppuration),ConsequenceHealing,chronicvalvulardiseaseDeath,chronicvalvulardiseaseABEofaorticvalveTricuspidvalve,rightatriumOftennotedinintravenousdrugabusersABEofaorticvalve,multipleabscessesEmbolizationviacoronaryarterySterile&nomicroorgnisms

Smalltomedium-sized,bland,nondestructivevegetationsatthelineofvalveclosure

Usuallyfoundonpreviouslynormalvalves

Pathogenesis?

Subtleendothelialabnormalities;Hypercoagulablestates; Malignanciesparticularadenocarcinoma; SLE,etc.

NonbacterialThromboticEndocarditis(NBTE)

Microscopy:Singleormultiplenodules,alongthevalveclosure,ф<5mm

Gross:Platelet,fibrin&otherbloodcomponents

Consequences:ResolvespontaneouslyLamblexcrescences(delicatestrandsoffibroustissue)

Clinicalfeatures:Asymptomatic,systemicemboli&infarctsApotentialnidusforbacterialendocarditisNBTEComparisonBetweenDiverseVavularVegetationsSmall,warty,inflammatory