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1、 Viral myocarditis(VM)山東大學齊魯醫(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胞的直接損害:在VMC急性期,柯薩奇病毒和腺病毒對細胞的直接損害與心肌細胞的受體有關,病毒通過受體引起病毒復制和細胞變性,導致細胞壞死溶解。Pathogenesis of VMC心肌細胞膜上的相關受體:心肌細胞膜上有柯薩奇病毒-腺病毒共同受體( CAR)及補體促衰變因子(DAF)。 CAR:柯薩奇病毒的特異性受體,在感染宿主細胞過程中起著抗原識別和介導作用,其表達水平和分布在VMC易感性上起決定作用。 DAF:增強CVB與CA
4、R-DAF受體復合物結合效率的輔助受體,有助于CVB通過CAR介導的內吞作用進入細胞及其在細胞內發(fā)生的病毒復制。Pathogenesis of VMC病毒感染心肌細胞的過程Pathogenesis of VMC2.病毒觸發(fā)人體自身的免疫反應: 機體的細胞和體液免疫反應使機體產生抗心肌抗體,通過IL-1、TNF-和IFN-誘導,產生細胞黏附因子,促使免疫細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細胞和巨噬細胞浸潤心肌。 NK細胞釋放穿孔素直接殺滅病毒感染的心肌細胞(在 VM早期主要起抗病毒作用)。 病毒感染第二周:T細胞為主要浸潤細胞。穿
5、孔素/顆粒酶在靶細胞膜上形成滲透性跨膜通道,使之溶解、壞死或凋亡(適量表達對心肌有保護作用,過量表達則非特異性廣泛殺傷心肌細胞,嚴重損傷心?。?Fas/FasL作用向細胞傳遞程序性死亡信號心肌細胞凋亡(Fas/FasL存在負反饋機制,不至對心肌產生持續(xù)性損害)Pathogenesis of VMCVMC急性期和恢復期血清中IgA、G、M明顯,補體C3,說明體液免疫功能紊亂在VM發(fā)病機制中起重要作用。多種細胞因子和炎性因子(IL-I、TNF-和IFN-等)協同網絡化參與免疫炎癥反應,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制,通過抗原模擬機制誘導產生自身抗體,發(fā)生自身免疫反應,損傷自身心肌細胞,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(隱匿起病進展型);Acute dilated myocardiopathy VM(急性擴張型心肌病型);Atrioventricular block VM(房室傳導阻滯型);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,導致心排血量絕對或相對不足而不能滿足機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)現明顯且多變,一般病程在半年內。Protraction stage: 臨床癥狀反復出現,客觀檢查指標遷延不愈,病程多在半年以上。Chronic stage: 進行性心臟增大,反復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加權像, 顯示局部水腫。C: 長軸;D:短軸; T1加權像 顯示典型延遲強化MRI of viral myocarditis炎癥部位對PDG吸收增強PET/CT局部炎癥部位代謝活性增強,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,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):心肌有炎性細胞浸潤和附近心肌細胞的壞死和/或退行性變,但非缺血性損害。心肌細胞壞死或退行性變?yōu)樾募⊙椎闹匾C據。缺點:取樣太少,不能代表心肌全貌;僅取材右心室;病情的進展各例病人不同,各期表現有異;心臟病理專家主觀標準不一。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):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(心臟擴大).EKG findings:CK-MB or cTnI or cTnT elevated.齊魯醫(yī)院 Pathogenetic diagnosis basis Definite criteria(確診指標): 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):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,確診VM;具備病原參考依據之一,臨床診斷VM;不具備確診依據,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(風濕熱): Congenital heart disease;Endocardial fibroelastosis(心內彈):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):310ug/kg/minMilrinone(密力農): 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
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