儿科七年制 2015,viral myocarditis].ppt

Viral myocarditis(VM)山东大学齐鲁医院儿科山东大学齐鲁医院儿科 赵翠芬赵翠芬齐鲁医院 Viral myocarditis,(VMC)nPrincipal Contents:Etiology of VM;Pathology and pathogenesis of VM;Clinical manifestations and supplementary examinations of VM;Diagnosis and differential diagnosis of VM;Treatment principal of VM.齐鲁医院 Summarizations of VMnDefinition of myocarditis:various infectious,toxic,conjunctive tissue disease factors caused myocardiac inflammation.(是由各种感染性、中毒性、结缔组织性过程侵犯心肌所致的炎症)Viral myocarditis(VMC)is the most common myocarditis.nVMC:virus invades the myocardium directly and causes inflammatory reaction in cardiac.nIt complicated with pericarditis or endocarditis sometimes.齐鲁医院VMC病因病毒种类的演变 Pathogenesis of VMC1.病毒对被感染心肌细胞的直接损害：病毒对被感染心肌细胞的直接损害：在VMC急性期，柯萨奇病毒和腺病毒对细胞的直接损害与心肌细胞的受体有关，病毒通过受体引起病毒复制和细胞变性，导致细胞坏死溶解。Pathogenesis of VMCu心肌细胞膜上的相关受体心肌细胞膜上的相关受体：心肌细胞膜上有柯萨奇病毒-腺病毒共同受体（CAR）及补体促衰变因子（DAF）。CAR：柯萨奇病毒的特异性受体，在感染宿主细胞过程中起着抗原识别和介导作用，其表达水平和分布在VMC易感性上起决定作用。DAF：增强CVB与CAR-DAF受体复合物结合效率的辅助受体，有助于CVB通过CAR介导的内吞作用进入细胞及其在细胞内发生的病毒复制。Pathogenesis of VMC病毒感染心肌细胞的过程病毒感染心肌细胞的过程Pathogenesis of VMC2.病毒触发人体自身的免疫反应病毒触发人体自身的免疫反应：机体的细胞和体液免疫反应使机体产生抗心肌抗体，通过IL-1、TNF-和IFN-诱导，产生细胞黏附因子，促使免疫细胞有选择地向损害心肌组织粘附、浸润。Pathogenesis of VMCu病毒感染第一周病毒感染第一周：主要NK细胞和巨噬细胞浸润心肌。NK细胞释放穿孔素直接杀灭病毒感染的心肌细胞（在 VM早期主要起抗病毒作用）。u 病毒感染第二周病毒感染第二周：T细胞为主要浸润细胞。穿孔素/颗粒酶在靶细胞膜上形成渗透性跨膜通道，使之溶解、坏死或凋亡（适量表达对心肌有保护作用，过量表达则非特异性广泛杀伤心肌细胞，严重损伤心肌）Fas/FasL作用向细胞传递程序性死亡信号心肌细胞凋亡（Fas/FasL存在负反馈机制，不至对心肌产生持续性损害）Pathogenesis of VMCuVMC急性期和恢复期血清中IgA、G、M明显，补体C3，说明体液免疫功能紊乱在VM发病机制中起重要作用。多种细胞因子和炎性因子（IL-I、TNF-和IFN-等）协同网络化参与免疫炎症反应，促成炎症的发生、发展，引起病理性心肌损伤。u VMC患儿血清中可检测出多种抗心肌成分的自身抗体，主要有(myosin)抗体、抗线粒体ADP/ATP载体(ANT)抗体等。病毒感染心肌后大量复制，通过抗原模拟机制诱导产生自身抗体，发生自身免疫反应，损伤自身心肌细胞，演变chronic VM，甚至DCM。Pathologic phases of VMAcute phase:1-3 days;Sub-acute phase:4-14 days;Chronic phase:15-90 days;Transit to myocardiopathy:after 90 days.Pathological slices of VMn（myocardial cell swelling,gross inflammatory cell infiltration.）齐鲁医院Pathological slices of VMLymphocytic myocarditisGiant cell myocarditisClinical classifications Mild VM（轻型VM）;Sub-clinical VM（亚临床型）;Sudden death VM（猝死型）;Hiding onset and progressive VM（隐匿起病进展型）;Acute dilated myocardiopathy VM（急性扩张型心肌病型）;Atrioventricular block VM（房室传导阻滞型）;Like myocardial infarction VM.（酷似心肌梗死型）。Clinical manifestations nSymptoms:Pre-symptoms:AURI or digestive tract infection.Mild cases have no symptoms.Serious cases:Syncope,fatigue palpitation,etc.can be found.齐鲁医院Clinical manifestations nSigns:Cardiac dilation.Congestive heart failure.Cardiac arrhythmia.General no murmur or pericardial friction.Thrombosis.Cardiogenic shock.齐鲁医院 Clinical manifestationsnCardiac enlargement:X-ray of thorax:Percussion:Ehcocardiogarphy:齐鲁医院 X-ray of thorax齐鲁医院心尖四腔心切面示心尖四腔心切面示:心脏被大量心包腔内液心脏被大量心包腔内液性暗区所包绕性暗区所包绕 ECHO of pericardial effusion Congestive heart failure,CHFnDefinition of CHF:CHF is the clinical condition in which the cardiac output fails to meet the circulatory and metabolic needs of the body.n是因心肌收缩或舒张功能下降，导致心排血量绝对或相对不足而不能满足机体组织代谢需要的病理状态。齐鲁医院 Clinical manifestationsnThe diagnostic criteria of CHF:HR160 or 180beats/min in quiet;it can not be explained by fever and hypoxia;R60/min,dyspnea,cyanosis;Heptomegaly,3cm below the rib;The heart sound dullness significantly or gallop rhythm;Sudden dysphoria,pale or gray face,no other cause can explain;Oliguria,both lower extremities edema,excluding malnutrition,nephritis,vitamin B1 deficient.齐鲁医院 Clinical StagesAcute stage:新发病，症状及体格检查阳性发现明显且多变，一般病程在半年内。Protraction stage:临床症状反复出现，客观检查指标迁延不愈，病程多在半年以上。Chronic stage:进行性心脏增大，反复心力衰竭或心律失常，病情时轻时重，病程1年以上。Supplementary examinationsnElectrocardiography:ST-T segment move down;T wave low.Conduction block:Ectopic rhythm:pre-systole:Tachycardia:Flutter or fibrillation齐鲁医院 ECG findingElectrocardiograpy:Abnormalities of the ST segment and T wave 齐鲁医院and degree type-AV block齐鲁医院Two degree AV-block：齐鲁医院Superventricular proiosystole齐鲁医院Ventricular proiosystole齐鲁医院Superventricular tachycardia齐鲁医院Ventricular tachycardia齐鲁医院尖端扭转型室速尖端扭转型室速Torsade de pointes,TDP齐鲁医院Atrial flutter and fibrillation 齐鲁医院 Supplementary examinationsnThoracic X-ray:Pulmonary blood is normal in most patients.Cardiac contour is normal.Pericardial and pleural effusion can be found.齐鲁医院 Thoracic X-rayFibrinous pericarditis：Normal cardiac contour Excudative pericarditis enlarged cardiac contour,like flask Echocardiography of VMA:长轴；B：短轴：T2加权像，显示局部水肿。C:长轴；D：短轴；T1加权像 显示典型延迟强化MRI of viral myocarditis炎症部位对PDG吸收增强PET/CT局部炎症部位代谢活性增强，能显示炎症部位以及炎症演变过程。局部炎症部位代谢活性增强，能显示炎症部位以及炎症演变过程。价格昂贵、禁饮食等价格昂贵、禁饮食等PET/CT局部炎症部位代谢活性增强，能显示炎症部位以及炎局部炎症部位代谢活性增强，能显示炎症部位以及炎症演变过程。症演变过程。左房、右房炎症 6月后炎症消退 Laboratory examinations nSerum enzyme:AST increased;CPK(creatine phosphokinase)increased;CK-MB elevated;LDH,LDH1 elevated;nCardiac troponin I(cTnI)elevated;or cardiac troponin T(cTnT)elevated.齐鲁医院Endomyocardial biopsy(EMB)Dallsa criteria(1984):心肌有炎性细胞浸润和附近心肌细胞的坏死和/或退行性变，但非缺血性损害。心肌细胞坏死或退行性变为心肌炎的重要证据。缺点：取样太少，不能代表心肌全貌；仅取材右心室；病情的进展各例病人不同，各期表现有异；n心脏病理专家主观标准不一。Endomyocardial biopsy Laboratory examinationsnPathogenic examinations:Viral separation from secretion;Specific IgM 1:128(+);Finding viral nucleic acid（病毒核酸）齐鲁医院 Diagnosis of VMnClinical diagnosis basis(临床依据临床依据):Cardiac dysfunction（心功能不全）or Cardiogenic shock（心源性休克）or Cardio-encephala syndrome（心脑综合症）.Cardiac enlargement（心脏扩大）.EKG findings:CK-MB or cTnI or cTnT elevated.齐鲁医院 Pathogenetic diagnosis basis nDefinite criteria(确诊指标确诊指标)：From myocardium,endocardium,pericardium or pericardium fluid:Virus being separated(分离到病毒);Vpecific virus antibody positive(特异抗体);Virus nucleic acid has been detected(病毒核酸).齐鲁医院 Pathogenetic diagnosis basis:nReference basis（参考指标）（参考指标）:nForm blood,feces,throat swab:Virus being separated.Vpecific antibody positive(IgM).Virus nucleic acid has been found.齐鲁医院 Diagnosis criterian两项临床诊断依据可临床诊断；发病同时有病毒感染史支持诊断：同时具备1项病原确诊依据，确诊VM;具备病原参考依据之一，临床诊断VM；不具备确诊依据，随诊；除外其它疾病所致心肌损害或心律失常。Differential diagnosis nRheumatic myocarditis（风湿热）:nCongenital heart disease;nEndocardial fibroelastosis（心内弹）:齐鲁医院 Treatment of VMnResting:1m general.3m with cardiac failure or enlargement.6m with cardiac failure and enlargement.nDrug therapy:Viremia phase:genciclovir;ribavirin齐鲁医院 Treatment of VMDrug therapy:Aimed at myocardium therapy:High dosage vitamin C:100-200mg/kg.d;FDP:150-250mg/kg.d;Creatine Phosphate Sodium:0.51g/d,qd or bid;Vitamin:CoQ10,vitaminE,vitaminBco.Traditional medical herbs:黄芪，生脉.齐鲁医院 Treatment of VMnCorticoid hormone:Indications:Complicated with cardiogenic shock;Fatal arrhythmia(AVB,ventricular tachycardia);齐鲁医院 Treatment of VMnCorticoid hormone:uUsage:Adequate dosage;Applying early;Hydrocorticoid（氢考）:10mg/kg.d.Methylprednisolone:12mg/kg.d or shock therapy.齐鲁医院 Treatment of VMnAnticardiac failure therapy:Sedation:phenobarbial,morphine;Oxygen inhalation;Cardiac tonic:digitalis;Diuresis;Dilating blood vessel.齐鲁医院 Treatment of VMnHow to use cardiac tonic agents:Preparations:digoxin.Usage:digitalization dosage and persistent dosage（洋地黄化和维持治疗）.齐鲁医院How to use cardiac tonic agentspreparation digoxin cedilanidage 2year2yearusageParenteral or oralparenteralDigitalization dosageIv 0.05-0.06mg/kg 0.03-0.05mg/kgIv 0.03-0.04mg/kg 0.02-0.03mg/kgPersistent dosagePo 0.01mg/kg.d1/41/5 digitalization dosageHow to use cardiac tonic agentsnCautions:2-3w recent digitalis use condition;Various myocarditis dosage minus 1/3;Premature baby dosage minus 1/2-1/3;Avoiding digitalis companied with calcium preparation;Prevention and correction hypokalemia齐鲁医院How to use cardiac tonic agentsnDigitalis poisoning:Cardiac arrhythmia:atrioventricular conduction block,ventricular pre-systole;Gastrointestinal system signs:nausea,vomiting;Neurologic system signs:somnolence(嗜睡),syncope.齐鲁医院How to use cardiac tonic agentsnTreatment of digitalis poisoning:Stopping digitalis quickly;Giving potassium chloride（氯化钾）;Antiarrhythmia agents（抗心律失常）.齐鲁医院How to use cardiac tonic agentsnNon digitalis agents:-adrenergic agonists(激动剂)IV:Dopamine(多巴胺):210ug/kg/min;Dobutamine(多巴酚丁胺):210ug/kg/min;Phosphodiesterase inhibitors(磷酸二脂酶)IV:Amrinone（氨力农）:310ug/kg/minMilrinone（密力农）:0.250.75ug/kg/min.齐鲁医院 How to use diureticspreparationdosageoralFurosemide(速尿)Loop diruetic 20mg/amper 1mg/kg,intravenously2-3mg/kg.d,tidHydrochlorothiazide(双克),distal tubular diuretics25mg/tablet1-5mg/kg.d,bidSpironolactone(螺内酯),Aldosterone inhibitor diuretic20mg/tablet1-2mg/kg.d,bid Afterload-reducing agentsnACEI:Captopril(capoten)PO:0.10.5mg/kg/dose,q8q12h，maximum:4mg/kg/day;Enalapril PO:0.080.5mg/kg/dose,q1224h;nACEI-receptor inhibitor:Losantan(罗沙坦):Irbesantan(缬沙坦)：齐鲁医院 Anti-arrhythmia agentsn:Na+fast channel inhibitora:prolong repolarization:quinidine sulfate;b:shorten repolarization:lidocaine;c:broad spectrum antiarrhythmia:propafenone;n:-receptor blockers:propranolol;n:prolong repolarization:amiodarone;n:calcium channel blocker:verapamil;nOthers:adenosine,digoxin.齐鲁医院 Immunotherapy of VM:nImmune inhibitor:Corticoids hormone:prednisone Cyclosporin ACTXnImmune regulator:Gammaglobulin;Thymosin.Antiviral drug:interferin virazole齐鲁医院免疫吸附治疗免疫吸附治疗血滤器能吸附血液中的炎症因子与自身抗体，改善心脏功能。血滤器能吸附血液中的炎症因子与自身抗体，改善心脏功能。经皮临时性起搏器经皮临时性起搏器主动脉内气囊反搏(IABP)体外循环膜氧合器（ECMO）泵泵氧合器氧合器气流计气流计变温器变温器监视器监视器环路和插管环路和插管Echocardiography 大而薄大而薄 室壁运动减弱室壁运动减弱 二尖瓣口呈钻石样改变二尖瓣口呈钻石样改变 Prognosis of VM DCM病例讨论u病史病史：患儿女性，患儿女性，4 4岁岁1 1月，因月，因“恶心、呕吐恶心、呕吐3 3天，加重伴精神不好天，加重伴精神不好1 1天天”入入院。入院查体：神志清，精神差，呼吸促，口周发绀，咽充血，扁桃体院。入院查体：神志清，精神差，呼吸促，口周发绀，咽充血，扁桃体度肿大，双肺呼吸音粗，度肿大，双肺呼吸音粗，HR135HR135次次/分，心音低钝，各瓣膜区未及病理性杂分，心音低钝，各瓣膜区未及病理性杂音；腹略胀，肝肋下音；腹略胀，肝肋下5cm5cm，质地韧，双下肢凹陷性水肿（，质地韧，双下肢凹陷性水肿（）。）。u辅助检查辅助检查：WBC:11.6WBC:11.610109 9/L/L，L 0.6L 0.6；心肌酶谱：心肌酶谱：CK:2208U/L,CK-MB:20.2ng/ml;LDH:471U/L,LDH1:136U/LCK:2208U/L,CK-MB:20.2ng/ml;LDH:471U/L,LDH1:136U/L；CTnICTnI:3.29ng/ml(0-0.06ng/ml):3.29ng/ml(0-0.06ng/ml)；肝功能：肝功能：ASTAST升高；升高；EKG:EKG:高侧壁、前壁心肌损害图形，高侧壁、前壁心肌损害图形，ST-TST-T改变；改变；超声心动图：超声心动图：LVEF:0.40LVEF:0.40，心肌病变，左心扩大，左室收缩功能减低。，心肌病变，左心扩大，左室收缩功能减低。病例讨论u诊疗经过：诊疗经过：l诊断：急性病毒性心肌炎（重症）诊断：急性病毒性心肌炎（重症）l治疗：氧气吸入；治疗：氧气吸入；营养心肌；营养心肌；抗病毒；抗病毒；大剂量激素和免疫球蛋白；大剂量激素和免疫球蛋白；大剂量维生素大剂量维生素C，强心、利尿、扩血管；，强心、利尿、扩血管；血管活性药物应用。血管活性药物应用。2周后，心肌酶谱及肌钙蛋白均恢复正常。周后，心肌酶谱及肌钙蛋白均恢复正常。EKG及超声心动图及超声心动图明显改善。明显改善。病例分析nEKG（入院时,2013.9.16）病例分析nEKG（出院时，2013.10.15）病例分析n超声心动图（入院时，2013.9.16）病例分析n超声心动图（出院时，2013.10.17）问题？问题？u该患儿诊断及诊断依据？u可能的病因及发病机理？u临床表现及辅助检查？u处理流程如何？Questions and referencesn何谓病毒性心肌炎？n病毒性心肌炎诊断标准。v薛新东主编，儿科学，第二版，人民卫生出版社，2010.v杨思源主编，小儿心脏病学，第三版，人民卫生出版社，2005.v胡亚美，江载芳主编，诸福棠实用儿科学，第八版，人民卫生出版社，2013.vBehrman RE主编，Nelson Textbook of Pediatrics,第19版，科学出版社，2013.v汪曾伟，刘维永，张宝仁主编，心脏外科学，人民军医出版社，第一版，2003.齐鲁医院