Classification of heart failure心力衰竭的分類

HeartFailureDepartmentofPathophysiologyZhangXiao-ming病史：患者，女，40歲，風(fēng)濕性心臟病史10余年。近3月來出現(xiàn)勞累后心慌、悶氣，伴浮腫、腹脹，不能平臥。體查：重病容,半坐臥位,頸靜脈怒張,呼吸36次/分,兩肺底可聞濕性羅音。心界向左右兩側(cè)擴(kuò)大,心率130次/分,血壓(110/80mmHg)

。Clinicalexample心尖部可聞IV級(jí)收縮期吹風(fēng)樣及舒張期雷鳴樣雜音。肝臟在右肋下6cm可觸及，有壓痛，腹部有移動(dòng)性濁音，骶部及下肢明顯凹陷性水腫。

1.BasicConcepts2.Causes3.Classificationofheartfailure4.Pathogenesisofheartfailure

5.Compensatorymechanismsinheartfailure6.Functionalandmetabolicalterations7.Treatmentprinciples1.BasicConcepts(1)Heartfailure(2)Cardiacinsufficiency(3)Congestiveheartfailure

Heartfailureisthepathologicalprocessinwhichthesystolicor/anddiastolicfunctionoftheheartisimpaired,andasaresult,cardiacoutputdecreasesandisunabletomeetthemetabolicdemandsofthebody.(2)cardiacinsufficiencyincludecompensatorystageanddecompensatorystage.

(3)CongestiveheartfailureisakindofchronicHFwithexpansionofbloodvolume.HFwithincreasedvolumeandfluidaccumulatedinthelungs,abdominalorgans(especiallytheliver)andperipheraltissues.Prevalance2to3million400,000newcases1996WHOsurvey:Incidencerate1.9%men>women2-yearmortalityrate37%6-yearmortalityrate82%American:2.CausesEtiologicalcauses

(2)

Theprecipitatingcauses

contractilityafterloadpreloadStrokeVolumeCardiacoutputHeartrateDeterminantsofcardiacfunction

Etiologicalcauses

1)Dysfunctionofmyocardium

(A)Myocardialdamage:myocardialinfarction;Cardiomyopathy;Myocarditis(B)Metabolicdisturbance

ischemiaandhypoxia;beriberi2)OverloadformyocardiumPressureoverload

(increasedafterload):

(Afterload

istheresistancetoshorteningthatthemusclemustovercomeduringcontraction.)

systemichypertensionaorticstenosis,pulmonaryhypertension,pulmonaryarterystenosis.Aorticsemilunarvalvestenosis

aorticnarrowPulmonarysemilunarvalvestenosis

pulmonaryarterystenosis(B)Volumeoverload(increasedpreload):

Preloadisthestretchexertedonthemuscleintherestingstate.(diastolicphase.)

Reasonsofincreasedvolumeoverloadforleftventricle:(a)mitralregurgitation(b)aorticregurgitationReasonsofthevolumeoverloadforrightventricle:(a)tricuspidregurgitation(b)pulmonaryregurgitation

(c)interatrialseptaldefect,ifthedirectionofbloodshuntinatrialseptalisfromlefttoright.(d)Interventricularseptaldefect,ifthedirectionofbloodshuntininterventricularseptalisfromlefttoright.(e)highcardiacoutputstatessecondarytohyperthyroidism,anemia,arterivenousfistula,andhepaticcirrhosismayalsoberesponsibleforvolumeoverloadoftheventricles.1)Infection

leftheartfailure↓pulmonaryvascularcongestionpulmonaryedema↓susceptibletopulmonaryinfection.

(2)TheprecipitatingcausesInfectionofairwayfevertachycardiahypoxia↙↓↘↑ATPconsumption↓ATPproduction↓↓↓↓↓needmorecardiacoutputaggravatemyocardialinjury↓↓aggravateheartfailure

2)Acid-BasedisturbanceAcidosisHyperkalemia3)Arrhythmias

(A)Tachycardiatachycardia→O2consumption↑↓shortdiastolicphase↙↘lessventricularfillinglesscoronaryfilling↓↓reducedCO/strokereducedO2supplytomyocardium↓reducedcontractileforce↙aggravateheartfailure

(B)Brachycardia

BrachycardialeadstothereductionofCO/min.CO/min=CO/stroke×heartrate(strokes/min)4)Pregnancy5)others

(1)Accordingtothecourseofdisease

1)AcuteHF

2)ChronicHF3.Classificationofheartfailure(2)Accordingtotheseverity1)mildHForcompletecompensation2)middleHForincompletecompensation3)severeHFordecompensationClassPatientSymptoms

ClassI(Mild)Nolimitationofphysicalactivity.Ordinaryphysicalactivitydoesnotcauseunduefatigue,palpitation,ordyspnea(shortnessofbreath).ClassII(Mild)Slightlimitationofphysicalactivity.Comfortableatrest,butordinaryphysicalactivityresultsinfatigue,palpitation,ordyspnea.ClassIII(Moderate)Markedlimitationofphysicalactivity.Comfortableatrest,butlessthanordinaryactivitycausesfatigue,palpitation,ordyspnea.ClassIV(Severe)Unabletocarryoutanyphysicalactivitywithoutdiscomfort.Symptomsofcardiacinsufficiencyatrest.Ifanyphysicalactivityisundertaken,discomfortisincreased.NYHAClassification

(3)Accordingtothecardiacoutput(CO)

1)

Low-outputHF

2)High-outputHF

Thecardiacoutputwilldecreasefrom“highoutputstate”,buttheabsolutevalueisstillgreaterthanthenormalvalueofhealthyperson.低輸出量型心衰高輸出量型心衰前高輸出量型心衰正常心輸出量正常人

Thesituationof“highoutputstate”occursinthepatientswith:hyperthyroidism,anemia,arterio-venousfistulas,beriberi.(5)Accordingtothefunctionimpaired

1)systolicfailure

2)Diastolicfailure(4)Accordingtothelocationofheartfailure

1)Left-sideheartfailure(LHF)2)Right-sideheartfailure(RHF)3)Biventricularfailure

(wholeheartfailure)CaseofHF

A60-year-oldmansustainedanextensiveacutemyocardialinfarctioninleftventricle4yearsbeforehisrecentadmission.Sincethattime,hehasbecomeprogressivelymorebreathlessonexertion.

Thequestionsare:(a)Whatistheetiologicalcause?(b)WhattypeofHFthepatientisaccordingtothediseaseprocess?(c)WhattypeofHFthepatientisaccordingtothepositionoflesion?(d)Washethehigh-outputHF?(e)WhattypeofHFthepatientisaccordingtothefunctionimpaired?4.Pathogenesisofheartfailure(1)Depressedmyocardialcontractility

(systolicphase)(2)Altereddiastolicpropertiesofventricles(diastolicphase)(3)Asymmetryandasynchronisminventricularcontractionandrelaxation(both)Contractionprotein:

thinfilament(actin)myofibril←sarcomerethickfilament(myosin)regulationprotein:TropomyosintroponinThemolecularbasisformyocardialcontraction:Cardiac

MuscleMolecular

Basis

of

Contraction

1)Myocardialcellularinjuries2)Myocardialmetabolicdysfunction3)Dysfunctionofexcitation-contractioncoupling4)Excessivemyocardialhypertrophy(1)Decreasedmyocardialcontractility1)Myocardialcellularinjuries

morphologicchanges:necrosis,apoptosisreasons:

myocardialischemia(myocardialinfarction)myocarditiscardiomyopathyMyocardialInfarctionAtherosclerosisofthelargercoronaryarteriesThequantitativerelationship----------------------------------------------------------sizeofmyocardialcardiacprognosisinfarctionoutput(mortality)-----------------------------------------------------------5~10%normal2%10~20%slightlydecreased10%20~40%decreased22%>40%markedlydecreased60%----------------------------------------------------------2)Myocardialmetabolicdysfunction

(A)DisordersinenergyproductionandliberationDeficiencyofbloodsupplyoroxygensupply(shock,ischemicheartdisease,severeanemia)

→aerobicmetabolismisimpaired→lessproductionofATP.resultsoftheATPdecrease:

TheactivityofmyosinATPasedecreases

Ca2+transportationdisturbance

disfunctionofmitochondriaquantityofthefunctionalproteinsdecrease(B)DisordersinenergyutilizationTherearethreekinds(myosinisozymes)ofATPase:V1(α\αpeptidechain)V2(α\β)V3(β\β)WhiletheV3typeofmyosinATPaseisincreasedinhypertrophicmyocardium.

Excitation-contractioncoupling3)Dysfunctionofexcitation-contractioncoupling(A)Reduceduptake,storingandreleaseofCa2+bysarcoplasmicreticulum(SR)Re-uptake

StoringRelease

MSR

HandlingofcalciumbySRPlaysacriticalroleintheonsetofearlyheartfailure.LevelofSRcalciumbindingproteins(calsequestrinandcalreticulin)hasnotbeenchanged.ATP-dependentpump

Phospholamban(PLB)

Inheartfailure:ExpressionofPLBNE,Beta-adrenoceptoractivationATPsupplyuptake↓storing

↓LevelofSRcalciumbindingproteins(calsequestrinandcalreticulin)hasnotbeenchanged.Ca2+-inducedCa2+

releaseRyanodinereceptor(RyR)

SRCa2+contentdecreaseRyRmRNAandproteinleveldecreaseinacidosis,affinityofcalciumanditsbindingproteinincrease,sothecalciumisdifficulttobereleased.

release

↓How

is

the

process

of

calcium

influx

changed

in

heart

failure?

Twomainpathways

Calciumchannel

Na+-Ca2+exchanger(B)ReducedinfluxofextracellularCa2+

CalciumChannelInfailingmyocardium↓norepinephrine(NE)concentration↓β-receptordensity↓openofCa2+channel↓inwardmovementofCa2+Inaddition,H+maypreventCa2+frommovinginwardbydepressingthesensitivityofbetareceptortonorepinephrine.K+

canalsoimpairinfluxofCa2+bycompetingeffect.

ThequantityofmyoplasmicCa2+isinadequateThecombinativeactivitybetweenCa2+andtroponindecreases

e.g.ischemia,hypoxia,acidosis(C)dysfunctionofCa2+bindingtotroponin4)ExcessivemyocardialhypertrophyMechanism:Theconcentrationofnorepinephrineinhypertrophicmyocardiumisreduced→myocardialcontractilitydecreasedTheproliferationofmitochondrianumbercannotkeeppacewiththeproliferationofmyocardialfilaments.Inaddition,oxidative-phosphorylationinmitochondriaisalsoimpaired.→EnergygenerationdecreasedTheproliferationofthecapillariesnumbercannotmatchwiththeproliferationofthemyocardialfilament.Inaddition,oxygenconsumptionofhypertrophicmyocardiumincreases.→oxygenandbloodsupplytohypertrophicmyocardiumisinadequate.TheactivityofmyosinATPasedecreases→defectinutilizationofenergyThefunctionofcalciumpumpinSRisdecreased→calciumionreleasereduced→excitation-contractioncouplingimpairedDecreasedmyocardialcontractility1)Myocardialcellularinjuries2)Myocardialmetabolicdysfunction3)Dysfunctionofexcitation-contractioncoupling4)ExcessivemyocardialhypertrophySummary(2)Altereddiastolicpropertiesofventricles1)Inadequatereductionofmyoplasmic[Ca2+]2)Impaireddissociationoftheactin-myosincomplex3)Decreasedventriculardiastolicpotential4)Reducedventricularcompliance1)Inadequatereductionofmyoplasmic[Ca2+]WhentheATPisdecreased:(a)theuptakeofCa2+bysarcoplasmicreticulumisreduced(b)theoutwardflowofCa2+isreduced2)Impaireddissociationoftheactin-myosincomplexinadequateATPsupply3)Decreasedventriculardiastolicpotential4)ReducedventricularcomplianceConcept:Ventricularcomplianceindicatestheratioofthechangeinvolumetothechangeinpressure

“dV/dP”.

Reasons:myocardialhypertrophy;inflammation;edema;fibrosis.

Effects:ventricularfillingisreduced,theCO/strokeisreduced.themyocardialtensionisincreased.Itwillelevatesthemyocardialoxygenrequirement;compressesthecoronaryarteriolesandreducethebloodsupplytothemyocardium.diminishedcontractionnormalabsentcontractionAsymmetrymeans:regionalabnormalcontraction;diminishedcontraction;absentcontraction.(3)Asymmetryandasynchronisminventricularcontractionandrelaxation

Asynchronismmeansthecontractionofventricleisnotatthesametime.Pathogenesisofheartfailure(1)Depressedmyocardialcontractility

(systolicphase)(2)Altereddiastolicpropertiesofventricles(diastolicphase)(3)Asymmetryandasynchronisminventricularcontractionandrelaxation(both)CaseofHFA60-year-oldmansustainedanextensiveacutemyocardialinfarction4yearsbeforehisrecentadmission.Sincethattime,hehasbecomeprogressivelymorebreathlessonexertion.

Thequestionis:

whatarethepathogenesisofHFinthispatient?

5.CompensatorymechanismsinheartfailureTheProgressiveDevelopmentofCardiovascularDisease(1)CardiaccompensationincreasedHRandcardiaccontractilityCardiacdilatation(TheFrank-Starlingmechanism)Myocardialhypertrophy(2)SystemiccompensationIncreasethebloodvolumeRedistributionofbloodflowIncreaseoferythrocytesIncreasedabilityoftissuestoutilizeoxygen(3)neurohormonalcompensationSympatheticnervoussystemRenin-angiotensinsystemAtrialnatriureticpeptide;endothelin(1)Cardiaccompensation1)IncreasedHRandcardiaccontractilitymechanism:circulatingcatecholaminesandsympathetictone↑CO/min=CO/stroke×HR(strokes/min)WhenHRhigherthan180/min→decompensationNormallythelengthofsarcomereis1.65~2.25μm.

Whencardiacoutputisreduced↓theend-diastolicpressureisincreased↓theforce-generatingcrossbridgesareincreased↓thecontractilitywillincrease↓thecardiacoutputwillincreasing.2)Cardiacdilatation(TheFrank-Starlingmechanism)

Ifthelengthofsarcomereisover2.25μm,

↓thenumberofforce-generatingcrossbridgeswilldecrease,

↓thecontractionforcewillreduce,↓decompensation.Typesofmyocardialhypertrophy------------------------------------------------------------------typeconcentrichypertrophyeccentrichypertrophy-------------------------------------------------------------------causepressureoverloadvolumeoverload-------------------------------------------------------------------cardiacchambernoyesdilation--------------------------------------------------------------------patternofincreasedinparallel.inseriessarcomeres(standsidebyside)--------------------------------------------------------------------3)Myocardialhypertrophy正常壓力負(fù)荷過重容量負(fù)荷過重向心性肥大離心性肥大ConcentrichypertrophyEccentrichypertrophyCompensatorymechanism:overallmyocardialcontractility

↑

tension↓;Oxygenconsumption↓

(2)SystemiccompensationIncreaseofthebloodvolumeA.GFR

↓decreasedcardiacoutput↓reducedrenalbloodflow↓↓stimulatetheR-A-Asystem←stimulatesympatheticsystem↓↓GFR↓

B.Reabsorptionofwaterandsodium↑

RedistributionofbloodflowinkidneyEF↑R-A-A-S↑,ADH↑PGE2↓,ANP↓2)Redistributionofbloodflowreducedcardiacoutput↓increasedactivityofsympatheticnervoussystem↓

increasedsecretionofcatecholamine↓contractionoftherenal,muscular,skinarteries(moreα-receptor)↓morebloodsupplytoheart↓

increasethecontractilityofmyocardium3)Increaseoferythrocytes(EPO)decreasedcardiacoutput↓reducedrenalbloodflow↓StimulatethesynthesisandreleaseofEPO↓StimulatethebonemarrowandregulatetheproductionofEPO↓Increasesoxygensupplytothetissues4)IncreasedabilityoftissuestoutilizeoxygenHF→chronichypoxia→Thequantityofmitochondriaandtheirsurfacearea↑

Theamountandtheactivitiesofmanyenzymesintherespiratorychain↑phosphofructokinaseisactivated→anaerobicglycolysis↑→ATP↑myoglobin↑→acompensatorymechanismofoxygenstorage(3)Neurohormonalcompensation

1)sympatheticnervoussystem(A)Cause:reducedcardiacoutput

↓reducedbaroreceptoractivity.(incarotidsinusandaorticarch)

↓increasedsympatheticexcitability

↓increasedreleaseofcatecholamine(adrenaline+noradrenalin)fromadrenalmedullary(B)Effectofincreasedcatecholamine(a)openthechannelofCa2+

↓increase[Ca2+]inmyoplasm

↓increasedmyocardialcontractility(thepositiveinotropiceffect)

↓increasedCO/stroke.

(b)Increasetheheartrate(thepositivechronotropiceffect)toincreaseCO/min.(c)Constrictthecapacityofveinstoincreasethevenousreturn.ThecontractilitywillincreasebytheFrank-Starlingmechanism.(C)Injuryeffectofexcessivesympatheticnervousactivity

↙↓↘

↓

.

tachycardia↑demandofO2ofheartmuscle↑peripheralresistance↓fillingtimeforventricles

↑afterloadofventricles↓fillingtimeforcoronaryartery↓CO/strokecontractionofbloodvessel2)Renin-angiotensinsystemdecreasedcardiacoutput↓reducedrenalbloodflowandGFR↓

stimulatetheR-A-Asystem↓renin↑,AngⅡ↑,aldosterone↑↓↓

GFR↓increasedreabsorptionofsodiumincreasedADHrelease

↓↓

increasedwaterretention6.FunctionalandmetabolicalterationsinHFlowCO→poorperfusionoforgans(forwardfailure)blooddamminginthevein→pulmonaryorsystemicedema(backwardfailure)(1)CongestionofpulmonarycirculationInLHF,theleftventricularpressure↑→leftatriumpressure↑→pulmonaryveins,capillaries→pulmonarycongestionandpulmonaryedemaleftheartfailure(increasedLVEDP)increasedpulmonaryvenouspressure↓pulmonarycongestionandpulmonaryedema↓↓increasedairwayresistancereducedcomplianceoflung↓↓decreasedO2inhalation

moreworkofbreathingtodistendthestifflungs↓increasedO2consumptionhypoxemia+metabolicacidosisdyspnea↓↓1)dyspneaA.ExertionaldyspneaConcept:

Thepatientwithexertionaldyspneahasnodyspneaatrest,butwillfeelbreathlessifhehadaexercise.Mechanism:

theneedforoxygeninexercise↑

HR↑，diastolicphase↓bloodbacktoheart↑,pulmonarycongestion↑,Pulmonarycompliance↓B.OrthopneaOrthopneaindicatesthesituationthatthedyspneawillberelievedbysittingorstanding,andwillaggravateintherecumbent