兒科七年制 Viral myocarditis(VM) 課件

1、 Viral myocarditis(VM)山東大學(xué)齊魯醫(yī)院兒科 趙翠芬齊魯醫(yī)院 Viral myocarditis,(VMC)Principal 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.齊魯醫(yī)院 Summarizations of VMDefinition of

2、myocarditis: various infectious, toxic, conjunctive tissue disease factors caused myocardiac inflammation.(是由各種感染性、中毒性、結(jié)締組織性過程侵犯心肌所致的炎癥)Viral myocarditis(VMC) is the most common myocarditis .VMC: virus invades the myocardium directly and causes inflammatory reaction in cardiac.It complicated with pe

3、ricarditis or endocarditis sometimes.齊魯醫(yī)院VMC病因病毒種類的演變 Pathogenesis of VMC1. 病毒對被感染心肌細(xì)胞的直接損害：在VMC急性期，柯薩奇病毒和腺病毒對細(xì)胞的直接損害與心肌細(xì)胞的受體有關(guān)，病毒通過受體引起病毒復(fù)制和細(xì)胞變性，導(dǎo)致細(xì)胞壞死溶解。Pathogenesis of VMC心肌細(xì)胞膜上的相關(guān)受體：心肌細(xì)胞膜上有柯薩奇病毒-腺病毒共同受體（ CAR）及補(bǔ)體促衰變因子（DAF）。 CAR：柯薩奇病毒的特異性受體，在感染宿主細(xì)胞過程中起著抗原識別和介導(dǎo)作用，其表達(dá)水平和分布在VMC易感性上起決定作用。 DAF：增強(qiáng)CVB與CA

4、R-DAF受體復(fù)合物結(jié)合效率的輔助受體，有助于CVB通過CAR介導(dǎo)的內(nèi)吞作用進(jìn)入細(xì)胞及其在細(xì)胞內(nèi)發(fā)生的病毒復(fù)制。Pathogenesis of VMC病毒感染心肌細(xì)胞的過程Pathogenesis of VMC2.病毒觸發(fā)人體自身的免疫反應(yīng)： 機(jī)體的細(xì)胞和體液免疫反應(yīng)使機(jī)體產(chǎn)生抗心肌抗體，通過IL-1、TNF-和IFN-誘導(dǎo)，產(chǎn)生細(xì)胞黏附因子，促使免疫細(xì)胞有選擇地向損害心肌組織粘附、浸潤。Pathogenesis of VMC病毒感染第一周：主要NK細(xì)胞和巨噬細(xì)胞浸潤心肌。 NK細(xì)胞釋放穿孔素直接殺滅病毒感染的心肌細(xì)胞（在 VM早期主要起抗病毒作用）。 病毒感染第二周：T細(xì)胞為主要浸潤細(xì)胞。穿

5、孔素/顆粒酶在靶細(xì)胞膜上形成滲透性跨膜通道，使之溶解、壞死或凋亡（適量表達(dá)對心肌有保護(hù)作用，過量表達(dá)則非特異性廣泛殺傷心肌細(xì)胞，嚴(yán)重?fù)p傷心?。?Fas/FasL作用向細(xì)胞傳遞程序性死亡信號心肌細(xì)胞凋亡（Fas/FasL存在負(fù)反饋機(jī)制，不至對心肌產(chǎn)生持續(xù)性損害）Pathogenesis of VMCVMC急性期和恢復(fù)期血清中IgA、G、M明顯，補(bǔ)體C3，說明體液免疫功能紊亂在VM發(fā)病機(jī)制中起重要作用。多種細(xì)胞因子和炎性因子（IL-I、TNF-和IFN-等）協(xié)同網(wǎng)絡(luò)化參與免疫炎癥反應(yīng)，促成炎癥的發(fā)生、發(fā)展，引起病理性心肌損傷。 VMC患兒血清中可檢測出多種抗心肌成分的自身抗體，主要有 (myosi

6、n )抗體、抗線粒體ADP/ATP載體(ANT)抗體等。病毒感染心肌后大量復(fù)制，通過抗原模擬機(jī)制誘導(dǎo)產(chǎn)生自身抗體，發(fā)生自身免疫反應(yīng)，損傷自身心肌細(xì)胞，演變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 VM（myocardial cell swelling, gross inflamma

7、tory cell infiltration.）齊魯醫(yī)院Pathological slices of VMLymphocytic myocarditisGiant cell myocarditisClinical classifications Mild VM（輕型VM）;Sub-clinical VM（亞臨床型）;Sudden death VM（猝死型）;Hiding onset and progressive VM（隱匿起病進(jìn)展型）;Acute dilated myocardiopathy VM（急性擴(kuò)張型心肌病型）;Atrioventricular block VM（房室傳導(dǎo)阻滯型）;L

8、ike myocardial infarction VM.（酷似心肌梗死型）。 Clinical manifestations Symptoms:Pre-symptoms: AURI or digestive tract infection.Mild cases have no symptoms.Serious cases: Syncope , fatigue palpitation, etc. can be found.齊魯醫(yī)院Clinical manifestations Signs: Cardiac dilation.Congestive heart failure.Cardiac ar

9、rhythmia.General no murmur or pericardial friction.Thrombosis .Cardiogenic shock.齊魯醫(yī)院 Clinical manifestationsCardiac enlargement:X-ray of thorax:Percussion:Ehcocardiogarphy:齊魯醫(yī)院 X-ray of thorax齊魯醫(yī)院心尖四腔心切面示: 心臟被大量心包腔內(nèi)液性暗區(qū)所包繞 ECHO of pericardial effusion Congestive heart failure, CHFDefinition of CHF:

10、 CHF is the clinical condition in which the cardiac output fails to meet the circulatory and metabolic needs of the body.是因心肌收縮或舒張功能下降，導(dǎo)致心排血量絕對或相對不足而不能滿足機(jī)體組織代謝需要的病理狀態(tài)。齊魯醫(yī)院 Clinical manifestationsThe diagnostic criteria of CHF:HR160 or 180beats/min in quiet; it can not be explained by fever and hypox

11、ia; 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.齊魯醫(yī)院 Clinical StagesA

12、cute stage: 新發(fā)病，癥狀及體格檢查陽性發(fā)現(xiàn)明顯且多變，一般病程在半年內(nèi)。Protraction stage: 臨床癥狀反復(fù)出現(xiàn)，客觀檢查指標(biāo)遷延不愈，病程多在半年以上。Chronic stage: 進(jìn)行性心臟增大，反復(fù)心力衰竭或心律失常，病情時輕時重，病程1年以上。 Supplementary examinationsElectrocardiography: ST-T segment move down; T wave low .Conduction block:Ectopic rhythm: pre-systole: Tachycardia:Flutter or fibrilla

13、tion齊魯醫(yī)院 ECG findingElectrocardiograpy: Abnormalities of the ST segment and T wave 齊魯醫(yī)院and degree type-AV block齊魯醫(yī)院Two degree AV-block：齊魯醫(yī)院Superventricular proiosystole齊魯醫(yī)院 Ventricular proiosystole齊魯醫(yī)院Superventricular tachycardia齊魯醫(yī)院Ventricular tachycardia齊魯醫(yī)院尖端扭轉(zhuǎn)型室速Torsade de pointes, TDP齊魯醫(yī)院Atrial

14、 flutter and fibrillation 齊魯醫(yī)院 Supplementary examinationsThoracic X-ray:Pulmonary blood is normal in most patients.Cardiac contour is normal.Pericardial and pleural effusion can be found.齊魯醫(yī)院 Thoracic X-rayFibrinous pericarditis： Normal cardiac contour Excudative pericarditis enlarged cardiac contou

15、r, like flask Echocardiography of VMA: 長軸；B：短軸： T2加權(quán)像， 顯示局部水腫。C: 長軸；D：短軸； T1加權(quán)像 顯示典型延遲強(qiáng)化MRI of viral myocarditis炎癥部位對PDG吸收增強(qiáng)PET/CT局部炎癥部位代謝活性增強(qiáng)，能顯示炎癥部位以及炎癥演變過程。價格昂貴、禁飲食等PET/CT局部炎癥部位代謝活性增強(qiáng)，能顯示炎癥部位以及炎癥演變過程。左房、右房炎癥 6月后炎癥消退 Laboratory examinations Serum enzyme: AST increased; CPK (creatine phosphokinase)

16、 increased;CK-MB elevated;LDH , LDH1 elevated;Cardiac troponin I (cTnI) elevated; or cardiac troponin T (cTnT) elevated.齊魯醫(yī)院Endomyocardial biopsy (EMB)Dallsa criteria (1984):心肌有炎性細(xì)胞浸潤和附近心肌細(xì)胞的壞死和/或退行性變，但非缺血性損害。心肌細(xì)胞壞死或退行性變?yōu)樾募⊙椎闹匾C據(jù)。缺點：取樣太少，不能代表心肌全貌；僅取材右心室；病情的進(jìn)展各例病人不同，各期表現(xiàn)有異；心臟病理專家主觀標(biāo)準(zhǔn)不一。Endomyocardial

17、 biopsy Laboratory examinationsPathogenic examinations:Viral separation from secretion;Specific IgM 1:128(+);Finding viral nucleic acid（病毒核酸） 齊魯醫(yī)院 Diagnosis of VMClinical diagnosis basis (臨床依據(jù)):Cardiac dysfunction（心功能不全） or Cardiogenic shock（心源性休克） or Cardio-encephala syndrome（心腦綜合癥）.Cardiac enlarge

18、ment（心臟擴(kuò)大）.EKG findings:CK-MB or cTnI or cTnT elevated.齊魯醫(yī)院 Pathogenetic diagnosis basis Definite criteria(確診指標(biāo))： From myocardium, endocardium, pericardium or pericardium fluid :Virus being separated(分離到病毒);Vpecific virus antibody positive(特異抗體);Virus nucleic acid has been detected(病毒核酸).齊魯醫(yī)院 Pathog

19、enetic diagnosis basis:Reference basis （參考指標(biāo)）:Form blood, feces, throat swab :Virus being separated.Vpecific antibody positive (IgM).Virus nucleic acid has been found.齊魯醫(yī)院 Diagnosis criteria兩項臨床診斷依據(jù)可臨床診斷；發(fā)病同時有病毒感染史支持診斷：同時具備1項病原確診依據(jù)，確診VM;具備病原參考依據(jù)之一，臨床診斷VM；不具備確診依據(jù)，隨診；除外其它疾病所致心肌損害或心律失常。 Differential di

20、agnosis Rheumatic myocarditis（風(fēng)濕熱）: Congenital heart disease;Endocardial fibroelastosis（心內(nèi)彈）:齊魯醫(yī)院 Treatment of VMResting: 1m general.3m with cardiac failure or enlargement.6m with cardiac failure and enlargement.Drug therapy:Viremia phase: genciclovir; ribavirin齊魯醫(yī)院 Treatment of VMDrug therapy:Aimed

21、 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: 黃芪，生脈. 齊魯醫(yī)院 Treatment of VMCorticoid hormone:Indications:Complicated with cardiogenic shock;Fatal arrhythmia (

22、AVB, ventricular tachycardia); 齊魯醫(yī)院 Treatment of VMCorticoid hormone:Usage:Adequate dosage;Applying early;Hydrocorticoid（氫考）:10mg/kg.d.Methylprednisolone : 12mg/kg.d or shock therapy.齊魯醫(yī)院 Treatment of VMAnticardiac failure therapy:Sedation: phenobarbial, morphine;Oxygen inhalation;Cardiac tonic: dig

23、italis;Diuresis;Dilating blood vessel.齊魯醫(yī)院 Treatment of VMHow to use cardiac tonic agents:Preparations: digoxin.Usage: digitalization dosage and persistent dosage（洋地黃化和維持治療）.齊魯醫(yī)院How to use cardiac tonic agentspreparation digoxin cedilanidage 2year2yearusageParenteral or oralparenteralDigitalization

24、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 agentsCautions:2-3w recent digitalis use condition;Various myocarditis dosage minus 1/3;Premature baby dosage minus 1/2-1/3;Avoiding digitalis com

25、panied with calcium preparation;Prevention and correction hypokalemia齊魯醫(yī)院How to use cardiac tonic agentsDigitalis poisoning:Cardiac arrhythmia: atrioventricular conduction block, ventricular pre-systole;Gastrointestinal system signs: nausea, vomiting;Neurologic system signs: somnolence(嗜睡), syncope.

26、 齊魯醫(yī)院How to use cardiac tonic agentsTreatment of digitalis poisoning:Stopping digitalis quickly;Giving potassium chloride（氯化鉀）;Antiarrhythmia agents（抗心律失常）.齊魯醫(yī)院How to use cardiac tonic agentsNon digitalis agents:-adrenergic agonists (激動劑) IV:Dopamine(多巴胺): 210ug/kg/min;Dobutamine(多巴酚丁胺): 210ug/kg/mi

27、n;Phosphodiesterase inhibitors(磷酸二脂酶) IV:Amrinone（氨力農(nóng)）:310ug/kg/minMilrinone（密力農(nóng)）: 0.250.75ug/kg/min.齊魯醫(yī)院 How to use diureticspreparationdosageoralFurosemide(速尿)Loop diruetic 20mg/amper 1mg/kg, intravenously2-3mg/kg.d ,tidHydrochlorothiazide(雙克), distal tubular diuretics25mg/tablet1-5mg/kg.d,bidSpir

28、onolactone(螺內(nèi)酯),Aldosterone inhibitor diuretic20mg/tablet1-2mg/kg.d, bid Afterload-reducing agentsACEI:Captopril(capoten) PO:0.10.5mg/kg/dose, q8q12h，maximum: 4mg/kg/day;Enalapril PO: 0.080.5mg/kg/dose, q1224h;ACEI-receptor inhibitor:Losantan(羅沙坦):Irbesantan(纈沙坦)：齊魯醫(yī)院 Anti-arrhythmia agents: Na + fa

29、st channel inhibitora: prolong repolarization: quinidine sulfate;b: shorten repolarization: lidocaine;c:broad spectrum antiarrhythmia: propafenone;:-receptor blockers: propranolol;:prolong repolarization: amiodarone;:calcium channel blocker: verapamil;Others: adenosine, digoxin.齊魯醫(yī)院 Immunotherapy of VM:Immune inhibitor:Corticoids hormone: prednisone Cyclosporin ACTXImmune regulator:Gammaglobulin;Thymosin.Antiviral drug: i