心衰.ppt

HeartFailureandAdvance,ZhouXiaoyanPh.D.Dept.Pathophysiology,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscusstheresponseofbodytoheartfailureDiscussmainmechanismsDiscusstheclinicalmanifestationsDiscussthetreatprinciples,Introduction,Cardiacoutput,Determinantsofcardiacfunction,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscussmainmechanismsDiscusstheresponseofbodytoheartfailureDiscusstheclinicalmanifestationsDiscussthetreatprinciples,Heartfailureistheinabilityofthehearttosupplyadequatebloodflowandgenerateacardiacoutputsufficienttomeetthemetabolicdemandsofthebody.,Definition,机体需要不能满足,心输出量降低,心脏收缩舒张功能障碍,各种致病因素,各种致病因素,心脏收缩舒张功能障碍,各种致病因素,心脏收缩舒张功能障碍,各种致病因素,心输出量降低,心脏收缩舒张功能障碍,各种致病因素,心输出量降低,心脏收缩舒张功能障碍,各种致病因素,心功能不全:各种原因导致心脏泵血功能降低包括心脏泵血功能下降但处于完全代偿直至失代偿的整个过程。,心力衰竭患者出现明显的症状和体征，属于心功能不全的失代偿阶段。,Prevalence,5million,500,000newcases/year,Incidencerate1.9%;65y6-10%;menwomen,American(China):,24million,2millionnewcases/year,Aroundtheworld:,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscussmainmechanismsDiscusstheresponseofbodytoheartfailureDiscusstheclinicalmanifestationsDiscussthetreatprinciples,Etiology,Predisposingcause(90%),SystemicInfectionElectrolyte&Acid-baseDisturbanceArrhythmiaPregnancyLabour&Others,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscussmainmechanismsDiscusstheresponseofbodytoheartfailureDiscusstheclinicalmanifestationsDiscussthetreatprinciples,Classification,NYHAClassification,CO4L/min,cardiacindex2.5L/min/m2COmaybenormalatrestbutmaysimplyfailtorisesufficientlyonexertion,cardiacoutputmaybewithinnormalrangeorevenelevated,suchashyperthyroidism,anemia,AVfistulaorberiberi.,低输出量型心衰,高输出量型心衰前,高输出量型心衰,正常心输出量,正常人,Leftventricular,rightventricular,pulmonarycongestionshortnessofbreathfatigueandcoughing,Partinitiallyinvolvedinthepathologicalchanges,Intheearlystages,fluidbuild-upintheveinsandswellinginthelegsandankles,wholeheartfailure,Rheumaticmyocarditis,Veryseriousanemia,Inabilityofthehearttorelaxproperlyandfillwithbloodasaresultofstiffeningoftheheartmuscle.,Diastolicheartfailure,Systolicheartfailure,Inabilityofthehearttocontractwithenoughforcetopumpadequateamountsofbloodthroughthebody.,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscusstheresponseofbodytoheartfailureDiscussmainmechanismsDiscusstheclinicalmanifestationsDiscussthetreatprinciples,slightsevereCompensationdecompensationThereactionstotheinitiatingevent,suchasincreasedpreloadandafterloadetc,donotchangethroughthewholeperiod.,Responseofthebody,Cardiaccompensation,Systemiccompensation,Neurohormonalcompensation,Cardiaccompensation,Hypertrophy,Increaseofheartrate,Expansionoftheheart（紧张源性与肌源性扩张）,Myocardialcontractilityincrease,压力感受器效应：COBP颈动脉窦和主动脉弓压力感受器心迷走N，交感N心率容量感受器效应：心力衰竭心房淤血容量感受器交感N心率化学感受器效应：缺氧主动脉体和颈动脉体化学感受器心率,Increaseofheartrate,心率加快的意义,动员迅速，见效快，贯穿始终一定程度的心率加快可以增加心输出量,心率过快时（180次/分）增加心肌耗氧缩短心脏舒张期，心脏充盈不足、冠脉供血减少,Frank-Starling定律,1.72.12.22.7m,收缩力,肌节初长,Expansionoftheheart,CardiacMuscle,Itmeanstheenlargementorovergrowthofheartduetoanincreaseinsizeofitsconstituentcells.,Hypertrophy,Dependingonthetypeofhemodynamicloadproducingthefailure,sarcomeresdevelopeitherinparallelorinseries.,-Increasethecontractileforceofheart-Reduceventricularwalltensiontowardsnormalandthenreduceoxygenconsumingofheart,Whatistheeffectofhypertrophy?,Physiological,Pathological,Associatedwithahighriskofcardiacmortality,Howhypertrophyturnsintodecompensation?,Lopsidedgrowth,Remodelingofextracellularmatrix,Intrinsicdefect,Changeofphenotype,心肌生长速度与交感神经肥大心肌细胞与线粒体肥大心肌与毛细血管肥大心肌肌球蛋白ATP酶活性低肥大心肌肌浆网Ca2+处理障碍,Myocardialcontractilityincrease,心肌功能受损,交感-肾上腺髓质系统兴奋,胞浆cAMP浓度增高,激活蛋白激酶A,心肌膜钙通道蛋白磷酸化,CAs增多激活受体,胞浆钙浓度升高,正性肌力作用,Systemiccompensation,Increaseinbloodvolume(SNSRAASADHANP)（GFR、重吸收）Redistributionofbloodflow(SNS)Increaseoferythrocyte(EPO)Increasedabilityoftissuestoutilizeoxygen（酶、线粒体）,Neurohormonalcompensation,OverloadofheartIncreaseoxygenconsumingArrhythmiaInjurybycytokinesMyocardialremodelingRetentionofwaterandsodium,Adverseeffects,Myocardialremodeling,Changesinshapeandsizeofthechamberinvolveschangesinthestructure,function,andgeneexpressionofthemyocardialcell.,TheheartiscomposedofCardiacmyocytesNonmyocytecellsExtracellularmatrix(ECM),心肌细胞的凋亡、坏死、肥大、延长、心肌肥厚心肌间质纤维胶原合成和降解动态平衡破坏Fibrosis,心室重塑,SympatheticnervoussystemHormonalalterationsHemodynamicalterations,Whyventricularremodelingoccurs?,ACEI(angiotensinconvertingenzymeinhibitors)andBetablockershaveadirectantagonisticeffectontheremodelingprocess,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscusstheresponseofbodytoheartfailureDiscussmainmechanismsDiscusstheclinicalmanifestationsDiscussthetreatprinciples,CardiacMuscle,MolecularBasisofContraction,Weakenofcontractility,Abnormityofdiastolicpropertiesofventricle,Asynergiaofventricularcontractionandrelaxation,Mechanismsforheartfailure,(1)Damageofmyocardialcells(2)Myocardialmetabolicdysfunction(3)DysfunctionofECcoupling(4)Hypertrophy,Weakenofcontractility,收缩力下降,Cellswellsandruptures.Cellcontentsspillout.,Necrosis,MyocardialInfarction心肌梗死,MyocardialischemiaHypoxiaVirusorbacterialinfection,Atherosclerosisofthelargercoronaryarteries,ActiveEnergy-requiringGene-directedSignal-dependent,Apoptosis,DNAladder,DetectionofDNAfragmentation,Apoptosisindex35.5%,(1)Damageofmyocardialcells(2)Myocardialmetabolicdysfunction(3)DysfunctionofECcoupling(4)Hypertrophy,Weakenofcardiaccontractility,Energymetabolismofcardiacmyocyte,acetyl,Disordersinliberationofenergy,Occursinischemicheartdisease,shock,severeanemiaandhypoxia.ThereducedcontractilityismainlybecauseofthedecreasedlevelofATP.,Disordersinstoringofenergy,creatinephosphatekinase磷酸肌酸激酶,Disordersinutilizationofenergy,Keyproblemishowmuchtheefficiencyofactomyosin-ATPaseis.Thisenzymereducesitsactivityinheartfailure.MyosinisozymeV3isincreasedespeciallyduringhypertrophy.,(1)Damageofmyocardialcells(2)Myocardialmetabolicdysfunction(3)DysfunctionofECcoupling(4)Hypertrophy,Weakenofcardiaccontractility,正常心肌兴奋-收缩偶联,Dysfunctionofexcitation-contractioncoupling,Howistheprocessofcalciuminfluxchangedinheartfailure?,Dysfunctionofcalciuminflux,Calciumchannel,Thedensityof-adrenoceptorandgenerationofnorepinephrine(NE)decreased.AcidosisbluntedsensitivityofNEto-adrenoceptor.Hyperkalemiainhibitedthecalciuminflux.,Whathappenedtothechannelinheartfailure?,肥大心肌-R密度相对NE酸中毒时，H+降低-R对NE的敏感高钾血症,Re-uptake,Storing,Release,M,SR,HandlingofcalciumbySR,DysfunctionofcalciumhandlingbySR,Re-uptakecalciumofSR,Ca2+-inducedCa2+release(CICR),Ryanodinereceptor(RyR),ReleasecalciumfromSR,Concentrationofcytosoliccalcium,Normalaffinityoftroponintocalcium,(1)Damageofmyocardialcells(2)Myocardialmetabolicdysfunction(3)DysfunctionofECcoupling(4)Hypertrophy,Weakenofcardiaccontractility,Weakenofcontractility,Abnormityofdiastolicpropertiesofventricle,Asynergiaofventricularcontractionandrelaxation,Mechanismsforheartfailure,Myocardialrelaxationisanactiveprocess,notmerelyanintermittentrestperiodbetweensystolicperiods.Upto15%ofmyocardialenergymaybeexpendedforthatrelaxation.Diastolicstageisimportanttobloodsupplyforheartitselfanditisalsonecessaryforthevenousreturn.,Diastolicpropertiesofventricle,(1)Delayedcalciumdecrease(2)Impaireddissociationoftheactin-myosincomplex(3)Decreaseddiastolicpotentialenergyofventricles(4)Reducedcomplianceofmyocardium,Abnormityofdiastolicpropertiesofventricle,Aftereachsystole,theconcentrationofmyoplasmicCa2+needtodecreasefrom10-5mol/Lto10-7mol/L,allowingseparatingoftheactin-myosincross-bridges.WithoutadequateATP,Ca2+isdelayeduptakedbySRanddelayedeffluxfromthemyocyte.Thus,Ca2+stillcombineswithtroponinandmyocardiumcannotrelaxfully.,Delayedcalciumdecrease,Myocardialrelaxationisnotapassive,butratherisanenergy-requiringactivity.ATPisneededforactin-myosincomplextodissociate,SoinadequateATPsupplymayleadtoimpairmentofactin-myosindecoupling.Obviously,anypathologicfactorwithdisordersinenergymetabolismmayresultinheartfailureviadiastolicdysfunction.,Impaireddissociationoftheactin-myosin,Earlydiastolicrecoiloftheventricularwallsinconjunctionwithreleaseofelasticpotentialenergystoredduringsystoledeformation,generatingsuctionandthuscontributingtodiastolicfilling.,Decreaseddiastolicpotentialenergyofventricles,Manypathologicfactorsaccountedfordepressedmyocardialcontractilitymayleadalimitedloadingofventricleaswellasdiastolicpotentialenergy.,Reducedcomplianceofmyocardium,Theabilityofabloodvesseloracardiacchambertochangeitsvolumeinresponsetochangesinpressurehasimportantphysiologicalimplications.,Weakenofcontractility,Abnormityofdiastolicpropertiesofventricle,Asynergiaofventricularcontractionandrelaxation,Mechanismsforheartfailure,部分心肌收缩性减弱部分心肌没有收缩性部分心肌收缩性膨出心脏各部收缩不协调,LearningObjectives,DiscussthedefinitionDiscusstheetiologyDiscusstheclassificationDiscussmainmechanismsDiscusstheresponseofbodytoheartfail