心肌梗死病理、病理生理和临床表现ppt课件

急性心肌梗死病理、病理生理及临床,.,【急性心肌梗塞(AMI)】定义,梗死：血管闭塞引起的组织坏死。AMI是急性心肌缺血性坏死，大多是在冠状动脉病变的基础上发生冠状动脉血供急剧减少或中断，使相应的心肌严重而持久地急性缺血所致,.,CoronaryArtery,BloodClot(Thrombus),UnstablePlaqueRupture,CoronaryArtery,Infarcted(dead)orinjured(dying)tissue,HealthyHeartMuscle(Myocardium),MyocardialInfarction,原因通常是在冠状动脉粥样硬化不稳定斑块病变的基础上继发血栓形成导致冠脉持续、完全阻塞,.,【急性心肌梗塞(AMI)】定义,临床诊断要求有病史和应用生化方法、心电图和显像方法的得到心肌坏死间接证据综合评定病理诊断要求有心肌细胞坏死的证据，坏死是缺血时间过长导致的。细胞坏死的特征性表现包括细胞凝固性坏死和（或）收缩带的坏死，常伴有梗死灶周围的斑片状心肌细胞溶解区。,.,急性心肌梗死的新定义,（1）典型的心肌坏死生物标志物浓度升高（肌钙蛋白）超过参考值上限（URL）99百分位值并有动态变化，同时伴有以下一项心肌缺血的证据：缺血性症状ECG提示新发的缺血性改变（新发的ST段变化或左束支传导阻滞LBBB）心电图提示病理性Q波形成影像学证据提示新发的节段性室壁运动异常或存活心肌丢失,.,新定义,；（2）突发的心源性死亡（包括心脏停搏），通常伴有心肌缺血的症状新发ECG缺血性改变或LBBB和（或）经冠状动脉（冠脉）造影（或尸检）证实的新发血栓证据，但死亡常常发生在获取血标本或发现心肌酶学标志物升高之前；,.,新定义,（3）基线cTn水平正常者接受经皮冠状动脉介入治疗（PCI）后，如果心脏标志物水平升高超过URL99百分位值，则提示围手术期心肌坏死；如果心脏标志物水平超过URL99百分位值的3倍，则定义为与PCI相关的心肌梗死；,.,新定义,（4）基线cTn水平正常者接受冠状动脉旁路移植术（CABG）后，如果心脏标志物水平升高超过URL99百分位值，则提示围手术期心肌坏死；如果心脏标志物水平超过URL99百分位值的5倍，同时伴有以下任何一项：新发的病理性Q波、新发的LBBB、冠脉造影证实新发桥血管或自身冠脉闭塞、新出现的存活心肌丢失的影像学证据，则定义为与CABG相关的心肌梗死；（5）病理检查时发现急性心肌梗死。,.,心肌坏死生化标志物,新定义建议采用cTn，即在症状发生后24小时内，cTn的峰值超过正常对照值的99百分位。因为cTnI或cTnT具有高度的心肌组织特异性和敏感性，即使心肌组织发生微小区域的坏死也能检查到cTn的升高，因此是评价心肌坏死的首选标志物。如果没有条件检测cTn，也可以采用CK-MBmass作为最佳替换指标，诊断标准与cTn相同。由于CK广泛分布于骨骼肌，缺乏特异性，因此不再推荐用于诊断心肌梗死。,.,在cTn升高但缺少心肌缺血临床证据时，应寻找其他可能导致心肌坏死的病因，包括急性和慢性充血性心力衰竭、肾功能衰竭、快速性或缓慢性心律失常、急性神经系统疾病、肺栓塞和肺动脉高压、心脏挫伤/消融/起搏/复律、浸润性心脏疾病（如淀粉样变性和硬皮病）、炎性疾病（如心肌炎）、药物毒性、主动脉夹层、肥厚型心肌病、甲状腺功能减退、心尖球型综合征、横纹肌溶解伴心肌损伤、败血症等严重全身性疾病等。,.,按病因将心肌梗死分为5型,1型：自发性心肌梗死，由于原发的冠状动脉事件如斑块破裂等引起的心肌缺血；2型：心肌梗死继发于心肌的供氧和耗氧不平衡所导致的心肌缺血，如冠状动脉痉挛、贫血、冠状动脉栓塞、心律失常或低血压等；3型：心源性猝死，有心肌缺血的症状和新出现的ST段抬高或新的LBBB，但未及采集血样之前就死亡；4型：与因缺血性冠脉事件而进行的PCI相关的心肌梗死；4a4b5型：与因缺血性冠脉事件而进行的CABG相关的心肌梗死。,.,60%NarrowingofCoronaryArtery,.,痉挛NormalCoronaryArteryCrossSection,.,CoronaryArteryThrombus,Source:UniversityofUtahWebPath,Theexternalanteriorviewoftheheartshowsadarkclotformationinthisartery,.,.,陈旧性心肌梗死的定义标准为：（1）新出现的病理性Q波，伴或不伴症状；（2）影像学证据提示心肌变薄或瘢痕化，失去收缩力或无存活性；（3）病理检查时发现已经或正在愈合的心肌梗死。,.,.,【发病机理】,.,冠状动脉粥样硬化造成管腔狭窄和心肌供血不足，而侧支循环尚未建立时，下列原因加重心肌缺血即可发生心肌梗塞。一、冠状动脉完全闭塞二、心排血量骤降三、心肌需氧需血量猛增,.,一、冠状动脉完全闭塞,1、病变血管粥样斑块内或内膜下出血，2、血小板聚集管腔内血栓形成，3、动脉持久性痉挛。,.,二、心排血量骤降,休克、脱水、出血、严重的心律失常或外科手术等引起心排出量骤降,.,三、心肌需氧需血量猛增,重度体力劳动、情绪激动或血压剧升时，左心室负荷剧增，儿茶酚胺分泌增多，心肌需氧需血量增加。,.,诱因：,1、饱餐（尤其是进食大量脂肪）因餐后血脂增高，血液粘稠度也高，血小板粘附性增强，局部血流缓慢，血小板易于聚集以致血栓形成；2、睡眠迷走神经张力增高，易引起冠状动脉痉挛；3、用力大便增加心脏负荷。心肌梗塞后发生的严重心律失常，休克或心力衰竭，均可使冠状动脉灌流量进一步降低，心肌坏死范围扩大。,【病理】,.,CoronaryArteryWithPlaqueandThrombusFormation,A-CoronaryArterycross-sectionB-LumenC-FissuredPlaquew/oCapD-Acutethrombus,Source:EmergencyCardiovascularCareLibrary(CD-ROM),AmericanHeartAssociation,Dallas1997,.,.,ThrombusCausingMI,“Needle-Like”whitespotsarecholesterolcrystals,Thrombusocludingartery,Likelysiteofplaquerupture,.,高倍镜下可见粥样斑块中有许多泡沫细胞（即吞噬大量脂质的巨噬细胞）和胆固醇结晶。,.,动脉粥样斑块比右边残存的动脉中膜要厚。可见大量针状的胆固醇结晶（针状空隙），左边有新鲜出血，血栓可在这样的斑块顶部形成。,.,31,MyocardialIschemia,MyocardialcellmetabolicdemandsnotmetTimeframeofcoronaryblockage:10secondsfollowingcoronaryblockDecreasedstrengthofcontractionsAbnormalhemodynamicsSeeashiftinmetabolism,sowithinminutes:AnaerobicmetabolismtakesoverGetbuild-upoflacticacid,whichistoxicwithinthecellElectrolyteimbalancesLossofcontractibility,.,32,20minutesafterblockageMyocytesarestillviable,soIfbloodflowisrestored,andincreasedaerobicmetabolism,andcellrepair,IncreasedcontractilityAbout30-45minutesafterblockage,ifnoreliefCardiacinfarct328:981-8.,.,AcuteRightVentricularWallMIRightSidedLeads,.,七、生物标志物浓度的改变：,ShapiroBP,JaffeAS.Cardiacbiomarkers.In:MurphyJG,LloydMA,editors.MayoClinicCardiology:ConciseTextbook.3rded.Rochester,MN:MayoClinicScientificPressandNewYork:InformaHealthcareUSA,2007:77380.AndersonJL,etal.JAmCollCardiol2007;50:e1e157,Figure5.,.,NonACScausesofTroponinElevation,Trauma(includingcontusion;ablation;pacing;ICDfirings,endomyocardialbiopsy,cardiacsurgery,after-interventionalclosureofASDs)Congestiveheartfailure(acuteandchronic)AorticvalvediseaseandHOCMwithsignificantLVHHypertensionHypotension,oftenwitharrhythmiasNoncardiacsurgeryRenalfailureCriticallyillpatients,especiallywithdiabetes,respiratoryfailureDrugtoxicity(eg,adriamycin,5FU,herceptin,snakevenoms)HypothyroidismCoronaryvasospasm,includingapicalballooningsyndromeInflammatorydiseases(eg,myocarditis,Kawasakidisease,smallpoxvaccination,Post-PCIPulmonaryembolism,severepulmonaryhypertensionSepsisBurns,especiallyifTBSAgreaterthan30%Infiltrativediseases:amyloidosis,hemachromatosis,sarcoidosis,andsclerodermaAcuteneurologicdisease,includingCVA,subarchnoidbleedsRhabdomyolysiswithcardiacinjuryTransplantvasculopathyVitalexhaustion,ModifiedfromAppleFS,etalHeartJ.2002;144:981-986.,并发症,.,AcuteMyocardialInfarctionComplications,Death(18%within1hour,36%within24hours)Non-fatalarrhythmiaAcuteleftventricularfailureCardiogenicshockPapillarymuscleruptureandmitralregurgitationMyocardialruptureandtamponadeVentricularaneurysmandthrombus,.,AcuteMI:AcuteComplications,PostinfarctionVSDFreewallrupturePostinfarctionventricularaneurysmassociatedwithventriculartachyarrhythmias/CHF,.,ComplicationsofMI,CardiacTamponade:Fluidbetweenpericardium/myocardiumPericarditis:InflammationofthepericardiumEmboli:FromeitherMIthrombusoratrialclotsformedwithatrialpooling,.,.,.,.,MostCommonComplications:,CongestiveHeartFailure:75%ofMIsexperienceovertCHFFluidbacksup25%ofMIsexperience“compensated”CHFreducedperfusionto“vitalorgans”?Dysrhythmias:TheimportanceofECGmonitoringpost-MI,.,Cyanosis(bluefingernails24:2866.,.,目的,.,原则,如果开始PCI治疗的时间要比开始药物纤溶的时间延迟60分钟以上，那么PCI治疗可能并不能降低死亡率及时采用合适的再灌注治疗比选择治疗方式更重要,.,IschemicCoronarySyndromes,“Ischemicandinjuredtissuehavereducedbloodflowbutmaybesalvaged.TheareaofthePenumbramaybeviableforseveralhoursafteronsetofocclusion.”Source:EmergencyCardiovascularCareLibrary(CD-ROM),AmericanHeartAssociation,Dallas,1997,.,TreatmentofAcuteMISummary,.,INFLUENCEOFTIME-TO-TREATMENTONTHEODDSRATIO(OR)OFMORTALITY,Boersmaetal.Lancet1996;348:771775.,ABSOLUTEBENEFITPER1,000TREATEDPATIENTS,TREATMENTDELAYINHOURS,0,3,6,9,12,15,18,21,24,0,20,40,60,80,The“goldenhour”:65livesaresavedforevery1,000patientstreatedwhenthetreatmentisinitiatedwithinthefirsthourofsymptomonset!,.,IMPACTOFTIME-TO-TREATMENTAND30-DAYMORTALITYPCIVS.THROMBOLYSIS,30-35-DAYMORTALITY(%),Thrombolysis,PCI,Cannonetal.JThrombThrombol1994;1:2734.Cannonetal.JAMA2000;283:29412947.Huberetal.EurHeartJ2005;26:10631074.,TIMEFROMONSETOFPAINTOTHERAPYINHOURS,0,6,12,2,4,2,4,6,8,10,8,0,1,3,5,7,.,102,ESCSTEMIGUIDELINES2008:REPERFUSIONSTRATEGIES,VandeWerfetal.EurHeartJ2008;29:2909-2945.,Ambulance,FirstMedicalContact(FMC),PCI-capablehospital,Non-PCI-capablehospital,primaryPCI,rescuePCI,angiography,Pre-,in-hospitalfibrinolysis,2h,12h,24h,TimeLimits,*TimeFMCtofirstballooninflationmustbeshorterthan90mininpatientspresentingearly(2haftersymptomonset),withlargeamountofviablemyocardiumandlowriskofbleeding.,#IfPCIisnotpossible2hofFMC,startfibrinolytictherapyassoonaspossible.,Notearlierthan3hafterstartfibrinolysis.,24/7service,successful,failed,PCI2hpossible*PCI90%)Nitrates(SLx3Oral/topical.IVforongoingiscemia,heartfailure,hypertension)OralB-blockersinFirst24-hoursifnocontraindications.(IVB-blockersclassIIaindication)Non-dihydropyridineCa-channelblockersforthosewithcontraindicationfoB-blockersACEinhibitorsinfirst24-hoursforheartfailureorEF40%(ClassIIaforallotherpts)(ARBsforthoseintolerant)Statins,.,EarlyHospitalCareAnti-IschemicTherapy,ClassIIINitratesifBP0.24sec,2ndor3rddegreeheartblock,activeasthma,orreactiveairwaydiseaseNSAIDSandCox-2inhibitors,.,EarlyHospitalCareAnti-PlateletTherapy,ClassIAspirin(162-325mg),nonentericcoatedClopidogrelforthosewith