ChapterVI

DiseasesofCardiovascularSystem(心血管系統(tǒng)疾病)Cardio

vascularsystemHeart

Blood

vessels“Pump”Moremorbidity&mortality

-Approximatelyhalfofalldeathcausedbydisordersofcirculatorysystem-InUS,myocardialinfarctionaloneisresponsiblefor20-25%ofalldeathSystemicPathology·

Etiology,Pathogenesis

·

Pathologicmorphology

·

Clinico-pathologicalcorrelation

·

ConsequenceGeneralpathology

?SystemicpathologyExample:MyocardialinfarctionCoagulativenecrosis

GranulationtissueScarArrhythmiasmyocardialruptureVentricularaneurysm

……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(動(dòng)脈硬化)

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）Essentialhypertension,diabetesmellitusHardeningDefinition---hard,thicken,lostelasticityofarterywallAtherosclerosis(動(dòng)脈粥樣硬化,AS)

Intimallesionscalledatheromas

(粥樣瘤),oratheromatousoratherosclerotic

plaques(動(dòng)脈粥樣硬化斑塊)

→luminalnarrow→WallweakeningseriouscomplicationsTheconstitutional(immutable)riskfactors(無法改變的因素)●AgedominantinfluenceIHDrisewitheachdecade/middleageorlater●Gender●Genetics

polygenic hypertension,diabetes,hereditarygeneticderangementinlipoproteinmetabolismEpidemiologyThemajormodifiableriskfactors(可變的因素)●

HyperlipidemiaH-LDL-C,H-Lp(a),H-TG,L-HDL-C

LDL:“badcholesterol”deliveringcholesteroltoperipheraltissue

highdietarycholesterol,saturatedfats:eggyolk,animalfats

HDL：“goodcholesterol”transportingcholesteroltotheliver

exercise,moderateconsumptionofethanol↑;obesity,smoking↓

Omega-3fattyacidsabundantinfishoil,beneficialtodecreaseLDL-C,TG●

Cigarettesmoking

●

Hypertension●DiabetesmellitusAdditionalriskfactors

●

InflammationasmarkedbyC-reactiveprotein(CRP)●

Hyperhomocystinemia(高半胱氨酸血癥）

●

Factorsaffectinghemostasis

●

Otherfactors:obesity,physicalinactivity,stress“typeA”personalitybehaviorMultipleriskfactorshaveamultiplicativeeffectPathogenesisAchronicinflammatoryresponseofthearterialwalltoendothelialinjuryModifiedlipoproteinsInflammatorycells:Monocyte-derivedmacrophages,TlymphocytesThenormalconstituentsofthearterialwallsThreecomponentsNormalEndothelialinjurywithmonocyteandplateletadhesion

Monocyteandsmoothmusclecellmigrationintotheintima,withmacrophageactivationMacrophageandsmoothmusclecelluptakeofmodifiedlipidsandfurtheractivation

IntimalsmoothmusclecellproliferationwithECMelaboration,formingawell-developedplaque

MORPHOLOGYIntimalthickening&lipidaccumulationgivingrisetofattystreak&thenatheromaFattystreak（脂紋or脂斑）

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

Ostiaofbranches

--Fattystreak:foamcells--Mayevolveintoadvancedlesionsordisappear

Microscopy2.Fibrousplaqueandatheroscleroticplaque(纖維斑塊和粥樣斑塊)Gross:whitetoyellow,red-brownwiththrombosisoverthesurface

ф0.3~1.5cmcancoalescetoformlargermassesThebasicstructureofanatheromatousplaqueMicroscopy

MassontrichromestainF:fibrouscapC:acentralnecrotic(lipid)coreL:lumenTheinternalandexternalelasticmembranesaredestroyedThemediaisthinnedunderthemostadvancedplaqueScatteredinflammatorycells,calcification,andneovascularizationatthejunctionofthecapandcoreClinicallyimportantchangesofatheroscleroticplaques

●Hemorrhageintoaplaque●Rupture,ulceration,orerosion→thrombusformation

Atheroembolism●Calcification●Aneurysmformation：動(dòng)脈瘤、夾層動(dòng)脈瘤PlaqueruptureAcutecoronarythrombosisonaplaquewithfocalrupture,triggeringfatalmyocardialinfarctionHemorrhageintoplaqueAneurysmAbdominalaortaClinicalconsequencesofatherosclerosisAorta AneurysmCoronaryA.CoronaryHeartDiseaseCerebralA. Thrombosis,Aneurysm,Hemorrhage,AtrophyRenalA. Infarction,Nephrosclerosis,HypertensionFemoral,Popliteal,TibialA.Intermittentcramp,GangreneIschemicHeartDisease(缺血性心臟病)(CoronaryArteryDisease)Atherosclerosis→NarroworOcclusionofLumenofCoronaryA.

Coronaryperfusion↓Myocardialdemand↑

Ischemia,FunctionDisturbance,InfarctionofHeartEpidemiology

●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:coronaryarteriesCoronaryarteries(冠狀動(dòng)脈)ThefrequenciesofocclusionofvariouscoronaryarteriesandthedistributionoftheresultantinfarctsLeftanteriordescendingcoronaryartery40%~50%Anteriorandapicalleftventricle;anteriortwothirdsoftheinterventricularseptumRightcoronaryartery30%~40%Posteriorwalloftheleftventricle;posterioronethirdoftheinterventricularseptum；rightventricleLeftcircumflexcoronaryartery15%~20%lateralwalloftheleftventricleLesionsofCoronaryAtherosclerosis

Plaquechanges:thrombosis,hemorrhage,vasospasm

Criticalstenosis:>=75%GradeofOcclusion:I級(jí)<25%；II級(jí)26-50%；III級(jí)51-75%；IV級(jí)>76%PlaqueruptureAcutecoronarythrombosisonaplaquewithfocalrupture,triggeringfatalmyocardialinfarctionMassiveplaquerupturewiththrombus,triggeringafatalmyocardialinfarctionClinicalPresentations

1.Anginapectoris2.Myocardialinfarction3.Chroniccoronaryheartdisease4.Suddencoronarydeath

Anginapectoris(心絞痛)

Anintermittentchestpaincausedbytransient,reversiblemyocardialischemia(1)Stable

---Afixedatheroscleroticnarrowing(usually>75%)---Occurinthesettingofincreaseddemands---Relievedbyrest(reducingdemand)orbyadministrationofnitroglycerin(vasodilator)

(2)

Unstable

---Afixedatheroscleroticnarrowing(usually≥90%)---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

irreversiblePromptinterventionThrombolysis(溶栓)Angioplasty(血管成形術(shù))Coronaryarterialbypassgraft(血管搭橋)MORPHOLOGY

MItypicallybeginsinthesubendocardialregionMIusuallyreachesitsfullsizewithin3to6hoursPatternsofinfarctionDependingon…

TheinvolvedvesselThedurationoftheocclusionMetabolicdemandsofthemyocardiumExtentofcollateralsupply

1.

Transmuralinfarctions2.Subendocardialinfarctions3.MicroscopicinfarctsGross

●

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

Coagulationnecrosis/inflammationFormationofgranulationtissueOrganization&scar-AcuteMIRupture

Scar(remoteinfarction，陳舊性梗死)“Irregular”map-likeAreasofnecrosis(arrow);Theanteriorscar(arrowhead);Hemorrhage(asterisk)duetoventricularrupture<1day---coagulationnecrosisedemawavyfibers3-4daysCompletecoagulationnecrosisofmyofibersHeavyneutrophilicinfiltrate7-10daysWell-developedphagocytosis

3wkGranulationtissueCollagenfibersScar-Richcollagenfibers-ResiduemyofibersReperfusioninjury

Restorationofbloodflow→greaterdamageMitochondrialdysfunction;Myocytehypercontracture(高度攣縮);Freeradicals;Leukocyteaggregation;PlateletandcomplementactivationClinicalFeatures

●

Thechestpaincannotberelieved“Silent”infarctsarecommonindiabeticpatients&elderlypersons

●Rapid&weakpulseDiaphoretic（出汗）&nauseous（惡心）,particularlywithposteriorwallMIs

●Electrocardiographicabnormalities

Qwaves,STsegmentchanges,&TwaveinversionslethalArrhythmias

●Laboratoryevaluation

Troponins（肌鈣蛋白）andCK-MB（肌酸激酶同工酶）havehighspecificityandsensitivityformyocardialdamageConsequences&ComplicationsofMI

Dependingon--infarctsize--site--fractionalthicknessofthemyocardialwallthatisdamaged1.Contractiledysfunction

Cardiogenicshock:massiveMIs,involving≥40%oftheleftventricle2.Arrhythmias

(心律失常)

Myocardialirritability&conductiondisturbancesSuddendeath3.Myocardialrupture

Mostcommonbetweendays3-7afterMIsParticularlyinpapillarymuscleandventricularwallofleftventricle,andventricularseptum4.Pericarditis5.Chamberdilation6.Muralthrombus→thromboembolism7.Ventricularaneurysm

---AlatecomplicationoflargetransmuralMIs---Thebulgingofthenoncontractilefibrousmyocardiumduringsystole---Athin-walled,fibrousoutpouchingoftheventricularwall---OftenwithamuralthrombusChronicIschemicHeartDisease

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(sustained）>=140and/or>=90Borderline130–13985-89ClassificationofHypertension

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

Achronicdiseasewithspasmandsclerosisofarterioleandsmallartery

causedbydifferentfactors,andeventuallyresultinginthelesionsoforgansPathogenesis

TheBPlevelisdeterminedbytheinteractionofmultiplegenetic,environmental,anddemographicfactorsthatinfluence2hemodynamicvariables:cardiacoutputandtotalperipheralresistance

MORPHOLOGYHyalinearteriolosclerosis(benignhypertension)HyperplasticarteriolosclerosisNecrotizingarteriolitis(malignanthypertension)ThickeningofthewallswithnarrowingofthelumenProcessesofbenignhypertension

Stage1:Functionaldisturbance（功能障礙期）SpasmofarterioleandsmallarteriesStage2:Changesofvascularsystem（動(dòng)脈病變期） Smallartery&Arteriole–hyalinedegeneration Large&medialartery–atherosclerosis

Stage3:Lesionsoforgans（器官病變期）

Heart---HypertensiveheartdiseaseLeftventricularhypertrophy

Earlystage

ConcentrichypertrophyLater

Acentrichypertrophydilationofcardiacchambers

LM:Myocyteshypertrophy,withprominentnuclearenlargementandhyperchromasia(“boxcarnuclei”)InterstitialfibrosisKidney–Arterionephrosclerosis

Grosssymmetricallyatrophicdiffuse,finegranularityofsurface

Microscopyhyalinearteriolosclerosisischemicatrophycompensatedhypertrophy&dilation

Arrangedatintervals

Brain

HypertensiveencephalopathyEdema,softening(microinfarct),microaneurysmsHemorrhage:basalganglia

基底核（內(nèi)囊）

lenticulostriateartery

(豆紋動(dòng)脈branchingsquarefromarteriaecerebrimedia)

Malignanthypertension

Necrotizingarteriolitis:fibrinoidnecrosisHyperplasticarteriolosclerosisonion-skin,concentric,laminatedthickeningofthewallsBenignvsMalignantHypertensionBenign

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

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

Rheumaticfeverisanacute,immunologicallymediated,multisystem

inflammatorydisease.

FollowinganepisodeofgroupAβ-hemolyticstreptococcalinfections(usuallypharyngitis)afteranintervalofafewweeks

Occuringinheart,synovium,joints,bloodvessels,skin,etc.AcuterheumaticcarditisChronicvalvulardeformitiesAfteraninitialattack,thereisincreasedvulnerabilitytoreactivationofthedisease.Justlikeacrazydog,lickingalloverthebodyandfinallybitingtheheartEtiologyandPathogenesis

ImprovedsocioeconomicconditionsRapiddiagnosisandtreatment

AhypersensitivityreactioninducedbygroupAstreptococci

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

AntibodiesdirectedagainsttheMproteinsofgroupAstreptococcicross-reactwithnormalproteinspresentintheheart,joints,andothertissues.Theincidenceandmortality↓

↓↓Anautoimmuneresponseagainstself-antigens

GeneticsusceptibilityRheumaticfeveroccursinonlyabout3%ofpatientswithgroupAstreptococcalpharyngitisMORPHOLOGYBasicpathologicchanges3phases

Necrotic&exudativephase

Fibrinoidnecrosis,inflammatoryinfiltrates

Regeneration(proliferativephase)

Rheumaticgranuloma(rheumaticbody,Aschoffbody)

FibrosisreoccurFibrinoidnecrosis（纖維素樣壞死）Rheumaticbody(Aschoffbody)---Oftenlieincloseproximitytoasmallvessel---Acentralfocusoffibrinoidnecrosissurroundedbyachronicmononuclearinflammatoryinfiltrate---AschoffcellsAschoffcellsRheumaticHeartDisease

1.Acute“Pancarditis”（全心炎）

(1)Rheumaticendocarditis

Mitral(二尖瓣)50%;Mitral+Aortic(二尖瓣+主動(dòng)脈瓣)50% Edematous,thickened,fibrinoidnecrosis,verrucae(疣狀物)

(vegetation(贅生物),mayresolveorprogress)(2)Rheumaticmyocarditis:Aschoffbodies(3)Rheumatic

pericarditis:

Fibrinousexudate(corvillosum(絨毛心),generallyresolvewithoutsequelae)

Rheumaticendocarditis主動(dòng)脈瓣二尖瓣Rheumaticmyocarditis風(fēng)濕小體Rheumaticpericarditis纖維蛋白性滲出漿液性滲出2.Chronic

Characterizedbyorganizationoftheacuteinflammation&subsequentscarring

Fibrousscar

Themitralvalvesexhibitleafletthickening,commissuralfusionandshortening,andthickeningandfusionofthechordaetendineae.Valvularstenosis,regurgitationMicroscopy:neovascularization,diffusefibrosisthickening,commissuralfusionandshorteningofvalvesFishmouth(mitralvalve)InflammatoryneovascularizationPathologicChangesinOtherOrgans

Rheumaticarthritis

(風(fēng)濕性關(guān)節(jié)炎)

Largerjoints,migratorypolyarthritis

Withoutsequelae

Skin

Erythemaannularecentrifugum(離心性環(huán)形紅斑)subcutaneousnodules(皮下結(jié)節(jié))

Rheumaticarteritis(風(fēng)濕性動(dòng)脈炎)

Brain

Neurondegeneration,gliacellproliferation

extrapyramidal(椎體外系)involved,choreaminor(小舞蹈病)ClinicalFeatures

AntibodiestooneormorestreptococcalenzymesAnti-StreptolysinO↑

SignsPericardialfrictionrubsWeakheartsoundsTachycardia(心動(dòng)過速)orotherarrhythmiasCongestiveheartfailure<5%deathInfectiveEndocarditis

Definition

Infectionofthecardiacvalvesormuralsurfaceoftheendocardium,resultingintheformationofbulky,friable

vegetationCause

Anytypeofmicroorganism,mostbybacteria

Antibiotictherapyblursthedistinction.

Aparticularlydifficultinfectiontoeradicatebecauseoftheavascularnatureoftheheartvalves.

ClassificationFormsOrganismValvesAcuteHighvirulencePreviouslynormalSubacuteLowvirulencePreviouslyabnormalPathogenesis

Conditionsthatincreasetherisk(1)Preexistingcardiacabnormalities:rheumaticheartdisease(2)Prostheticheartvalves(瓣膜修復(fù)后):nodifferencebetweenmechanicalandbio-prostheticvalves(3)Hostfactors:DM,immunodeficiency,intravenousdrugabuse

Bacteremia

AninfectionelsewhereApreviousdental,surgicalorotherinterventionalprocedure,e.g.urinarycatheterization(導(dǎo)尿管插入)IntravenousdrugabusersMORPHOLOGY

Thehallmarkisthepresenceofvalvularvegetationscontainingbacteriaorotherorganisms.

Aorticandmitralvalvesarethemostcommonsitesofinfection.SBE“repair”

ABE“damage”

Causativeorganismlowvirulencea-hemolyticstreptococcihighvirulencestaphylococcusaureusPathogenesisPreexistingabnormality

Nativevalves

Commonsitesmitral/aorticvalves

aorticvalves

Friable,bulkyvegetationscontainbacteria,single/multiple,≥1valveInfluence:typeoforganisms,degreeofhostreaction,previousantibiotictherapy

MicroscopicallyPlatelet,fibrin,inflammatoryinfiltrates,bacteriaGranulation,fibrosis,calcification,chronicinflammatoryinfiltratesdestructionofthevalves&vicinity,ringabscesses(inperivalvulartissue)Sequelaechronicvalvulardisease,regurgitationRupture,suddendeath,chronicvalvulardiseaseSBE“repair”ABE“damage”SitesotherthanheartSystemicemboli,anemicinfarcts,GNSystemicemboli,septicinfarcts(suppuration),ConsequenceHealing,chronicvalvulardiseaseDeath,SBEABEofaorticvalveTricuspidvalve,rightatriumOftennotedinintravenousdrugabusersABEofaorticvalve,multipleabscessesEmbolizationviacoronaryarterySterile&nomicroorgnisms

Smalltomedium-sized,bland,nondestructivevegetationsatthelineofvalveclosure

Usuallyfoundonpreviouslynormalvalves

Pathogenesis?

Subtleendothelialabnormalities;Hypercoagulablestates; malignanciesparticularadenocarcinoma, SLE,etc.

NonbacterialThromboticEndocarditis(NBTE,非細(xì)菌性栓塞性心內(nèi)膜炎)Gross:Singleormultiplenodules,alongthevalveclosure,ф<5mmMicroscopy:Platelet,fibrin&otherbloodcomponentsConsequences:ResolvespontaneouslyLambl’sexcrescences(delicatestrandsoffibroustissue)Clinicalfeatures:Asymptomatic,systemicemboli&infarctsApotentialnidusforbacterialendocarditisnon-bacterialthromboticendocarditisNBTEComparisonBetweenDiverseValvularVegetationsSmall,warty(疣狀),inflammatoryvegetations,alongthelinesofvalveclosureIrregular,large,briskdestructionofchordaetendineaeEmbolizeSmalltomedium,sterile,non-destructive,atthelineofvalveclosureEmbolizeRheumaticendocarditisInfectiveendocarditisValvularHeartDiseasesAdiversegroupofacquiredorcongenitallesions

Stenosis:thick,rigid,commissural

fusion

,obstruction

Incompetence(insufficiency):thick,rolling,shorteningcommissural

fusion

regurgitation

Combinedvalvulardisease(multivalvulardisease)StenosisandregurgitationcoexistAnatomyofheart&bloodflowMitralStenosis(二尖瓣狹窄)Cause:rheumaticheartdisease

Hemodynamicandheartchanges:

Earlystage：hypertrophy&dilationofleftatrium

Latestage：edemaandcongestionofpulmonaryhypertrophyanddilationoftherightheartrightHeartfailure

Clinicalfeatures:

DiastolicmurmurattheauscultationareaofmitralvalvePinkcoloredfoamysputumMuralthrombus,embolizeCongestionofmanyorgans二尖瓣狹窄附壁血栓形成“PyriformHeart”（梨形心）MitralRegurgitation(二尖瓣關(guān)閉不全)Cause:rheumaticheartdiseaseHemodynamicandheartchanges:

HypertrophyanddilationofthefourchambersLeftandRightHeartFailureEdemaandcongestionofpulmonaryPulmonaryhypertension

Clinicalfeatures:

Systolemurmurattheauscultationareaofmitralvalve

GlobalHeart（球形心）AorticStenosis(主動(dòng)脈瓣狹窄)Cause:rheumaticheartdiseaseHemodynamicandheartchanges:HypertrophyanddilationofthefourchambersLeftandrightHeartFailureEdemaandcongestionofpulmonaryPulmonaryhypertension

Clinicalfeatures:SystolemurmurattheauscultationareaofAorticValve;anginapectoris(心絞痛)AorticRegurgitation(主動(dòng)脈瓣關(guān)閉不全)Cause:rheumaticheartdisease,infectiveendocarditis;syphiliticarteritis