L32. Myocarditis - Pericarditis PDF

Pathology of Cardiovascular System Cardiomyopathies, pericarditis and myocarditis 2 9 Q Dr Motaz Fadul MBBS, MSc, PhD Department of Pathology Faculty of Medicine - Rabigh – KAU...

Pathology of Cardiovascular System Cardiomyopathies, pericarditis and myocarditis 2 9 Q Dr Motaz Fadul MBBS, MSc, PhD Department of Pathology Faculty of Medicine - Rabigh – KAU 2022 – 2023 [email protected] https://www.askdrray.com/wp-content/uploads/2015/05/bigstock-Blood-Heart-Circul ation-66364177.jpg Lecture Outlines Cardiomyopathy Myocardial disease Pericarditis Cardiomyopathies Cardiomyopathies Cardiomyopathies are cardiac diseases due to intrinsic myocardial dysfunction. Dilated Most Common Primary: Cardiomyopathy (DCM) 90% of cases Principally confined to the myocardium Hypertrophic Classification cardiomyopathy (HCM) Secondary: Presenting as the cardiac manifestation of a systemic Restrictive Least Common disorder cardiomyopathy  α Dilated Cardiomyopathies (DCM) Diastolic DCM is characterised by progressive cardiac dilation and contractile (systolic) dysfunction. It is characterized by the dilation of all heart chambers, with thinner walls and weak contraction Sarcomere are added in SERIES to the existing ones Dilated Cardiomyopathies (DCM) Familial (genetic) Pregnancy (Peripartum cardiomyopathy) DCM have a familial (genetic) form and result Infection Iron overload from various acquired myocardial insults. Alcohol or other Stress-provoked toxic exposure Tachycardia-induced  Familial (genetic) DCM has a hereditary basis in 20% to 50% of cases. - Most of the genes are mutated with autosomal dominant inheritance - Mutations affecting cytoskeletal proteins or proteins that link the sarcomere to the cytoskeleton (e.g., α-cardiac actin) are most commonly involved. - X-linked DCM – Dystrophin mutation Duchin -(for other mutations see Robbin's page 430)  The exact mechanism is unknown. Infection The likely mechanism: immune mediated and direct viral Coxsackievirus B and other enteroviruses cytotoxicity. Can be detected in the myocardium from late-stage DCM patients. stage Kearney MT, Cotton JM, DCM Richardson PJ et al. Postgrad Med J. 2001; 77:4-10. Alcohol or other toxic exposure - Alcohol abuse is strongly associated with the development of DCM. - Alcohol and its metabolites have a direct toxic effect on the myocardium. Vit BI deficiency, introducing an - Chronic alcoholism can be associated with thiamine element of Beriberi heart disease. Alcohol affects thiamine absorption and storage - Chronic cocaine use may cause the development of dilated cardiomyopathy - Other toxic exposure like chemotherapeutic drug.  Pregnancy (peripartum cardiomyopathy) - Late in gestation or several weeks to months postpartum. - The etiology is multifactorial, including: - pregnancy-associated hypertension - volume overload - nutritional deficiency - gestational diabetes and immunologic response. - One half of these patients spontaneously recover normal function. Iron overload Either from hereditary hemochromatosis or from multiple transfusions. Hemochromatosis: Stress-provoked - HFE gene mutation - Iron build up in skin, liver, heart, pancreas … Tachycardia-induced DCM - Morphology GROSS: The heart is characteristically enlarged (up to 2 to 3 times the normal weight). flabby, with dilation of all chambers. Valvular and vascular lesions (e.g., atherosclerotic coronary artery disease) that can cause cardiac dilation secondarily are absent. What does the white arrow show? muralthrombus DCM - Morphology Microscopic: Most myocytes exhibit hypertrophy with enlarged nuclei, but many are attenuated, stretched, and irregular. Variable interstitial and endocardial fibrosis (blue). DCM secondary to iron overload, there is a marked accumulation of intramyocardial hemosiderin. Dilated Cardiomyopathies (DCM) – Clinical features DCM most commonly is diagnosed between 20 and 50 years of age. The fundamental defect in DCM is ineffective contraction, this will result in: Ejection fraction typically is less than 25% (normal is 50% to 65%). Secondary mitral regurgitation and abnormal cardiac rhythms. Embolism from intracardiac (mural) thrombi. Mitral Valve regurgitation? Cardiac transplantation is the only definitive treatment. Because there is valve stretching, which cannot close very well You can read more about DCM https://emedicine.medscape.com/article/2017823-overview  diastolic Hypertrophic Cardiomyopathy (HCM) It is characterised by myocardial hypertrophy, defective diastolic filling, and— in one third of cases—ventricular outflow obstruction. Sarcomere are added in parallel to Pathogenesis: the existing ones - Most cases of HCM are caused by missense mutations in genes encoding proteins that form the contractile apparatus. (sarcomeric proteins and increase myofilament function). - β-myosin heavy chain is most frequently involved. - It is usually autosomal dominant. HCM- Morphology GROSS: massive myocardial hypertrophy without ventricular dilation Classically, there is disproportionate thickening of the ventricular septum relative to the left ventricle free wall (so-called asymmetric septal hypertrophy). On longitudinal sectioning, the ventricular cavity loses its usual round-to-ovoid shape and is compressed into a “banana-like” configuration. HCM - Morphology Microscopic: The characteristic histologic features in HCM are marked myocyte hypertrophy, haphazard organization of myocyte (and myofiber) disarray, and interstitial fibrosis. HCM – Clinical features Typically manifests during the post-pubertal growth spurt. Reduced cardiac output and a secondary increase in pulmonary venous pressure cause exertional dyspnea, with a harsh systolic ejection murmur. A combination of massive hypertrophy, high left ventricular pressure, and compromised intramural arteries frequently leads to myocardial ischemia, even in the absence of concomitant coronary artery disease. E Roughly 25% of patients have dynamic obstruction to the left ventricular outflow by the anterior leaflet of the mitral valve. HCM is an important cause of sudden cardiac death. One third of cases of sudden cardiac death in athletes younger than 35 years of age. Restrictive Cardiomyopathy Systolic Characterised by a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole (the wall is stiffer). May be: Idiopathic Or associated with systemic diseases that affect the myocardium, such as: radiation fibrosis, amyloidosis, sarcoidosis, or products of inborn errors of metabolism.  Three forms of restrictive cardiomyopathy: Amyloidosis Endomyocardial Loeffler fibrosis endomyocarditis  Deposition of extracellular proteins with a tendency for forming insoluble β-pleated sheets. Amyloidosis Can occur in the setting of systemic amyloidosis (Amyloid light chain - AL-type) or can be predominantly restricted to the heart (transthyretin). Disease of children and young adults in Africa and other tropical areas. Endomyocardial Characterised by dense diffuse fibrosis of the ventricular endocardium and subendocardium, fibrosis often involving the tricuspid and mitral valves. The fibrous tissue markedly diminishes the volume and compliance of affected chambers, resulting in a restrictive physiology. Endocardial fibrosis, typically associated with formation of large mural thrombi. Loeffler endomyocarditis Characterized by peripheral hypereosinophilia and eosinophilic tissue infiltrates; release of eosinophil granule contents Restrictive Cardiomyopathy - Morphology Gross: the ventricles are of approximately normal size or only slightly enlarged, the cavities are not dilated, and the myocardium is firm. - both atria are typically dilated because of restricted ventricular filling and pressure overloads. Microscopic: variable degrees of interstitial fibrosis. - Although gross morphologic findings are similar for restrictive cardiomyopathy of disparate causes, endo-myocardial biopsy often can reveal a specific etiology. Robbins Basic Pathology: Page.430 Myocardial Disease Myocarditis It encompasses a diverse group of clinical entities in which infectious agents and/or inflammatory processes target the myocardium. Viral Infectious Myocarditis Non-viral Pathogenesis Non-infectious Myocarditis – Infectious causes - Offending agents can be identified by serologic Viral: Non-viral: studies that show rising antibody titers or through Coxackieviruses A and B viruses molecular diagnostic Cruzi Trypanosoma techniques – Chagasusing diseaseinfected and other enteroviruses are the tissues. Toxoplasma Gondii- most common causes of Immunocompromised individuals myocarditis. - In most cases the and Trichinosis injury results Lyme from an immune Disease response directed against virally infected cells, Bacteria: however in some cases the virus directly damage Neutrophilic infiltrate CMV, HIV, and influenza virus are the myocyte or may trigger a reaction against Abscess (sometimes) less common. cross-reacting proteins such as myosin heavy chain. Myocarditis – Non-Infectious causes Systemic diseases of immune origin: Systemic Lupus Erythematous (SLE) Polymyositis – generalized inflammation of the muscles Drug Hypersensitivity Reactions penicillin  Myocarditis - Morphology GROSS: In acute myocarditis the heart may appear normal or dilated -In advanced stages the myocardium typically is flabby and often mottled with pale and hemorrhagic areas. -Mural thrombi may be present. Epicardial surface of the heart is smooth and glistening, with small scattered pinpoint yellowish microabscesses.  Myocarditis - Morphology Microscopic: It is characterized by edema, interstitial inflammatory infiltrates, and myocyte injury. A diffuse lymphocytic infiltrate is most common. The inflammatory involvement is often patchy and can be “missed” on endomyocardial biopsy. It may resolve without significant sequelae or heal by progressive fibrosis Microscopic appearance of a microabscess, center consists of blue bacterial colonies surrounded by acute inflammatory cells. Lymphocytic myocarditis  penicillin Lymphocytic myocarditis Hypersensitivity myocarditis: interstitial and perivascular infiltrates are composed of lymphocytes, 0 macrophages, and a high proportion of eosinophils.  Giant cell myocarditis: Characterized by widespread inflammatory cell infiltrates containing multinucleate giant cells This variant carries a poor prognosis.  Chagas myocarditis: Characterised by the parasitization of scattered myofibers by trypanosomes (arrow). Accompanied by an inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and occasional eosinophil.  Myocarditis – Clinical Features Clinical spectrum of myocarditis is broad Myocarditis Asymptomatic Fatigue Pain Symptomatic Dyspnea Fever patients recover without sequelae Palpitations Heart Sudden Arrhythmias Failure Death Occasionally myocarditis progress to DCM. Other Causes of Myocardial Disease Cardiotoxic Drugs: - chemotherapeutic agents (anthracyclines doxorubicin and daunorubicin) are associated with toxic myocardial injury, which often takes the form of a dilated cardiomyopathy and heart failure. - Microscopic examination reveal myofiber swelling, cytoplasmic vacuolization, and fatty change. - Discontinuing such agents can lead to complete resolution, with no apparent sequelae. - Sometimes, however, more extensive damage produces myocyte necrosis and leads to a dilated cardiomyopathy. Other Causes of Myocardial Disease Catecholamines: - Foci of myocardial necrosis with contraction bands, often associated with a sparse mononuclear inflammatory infiltrate (mostly macrophages), - Can occur in individuals with pheochromocytoma (a tumor that elaborates catecholamines). - Similar changes can occur with a variety of agents like cocaine, high doses of ephedrine or vasopressor. Pericarditis Pericarditis Is an inflammation of the pericardium my In most cases, pericarditis is secondary to acute MI or cardiac surgery (so- called “Dressler’s syndrome”), radiation to the mediastinum, or processes involving other thoracic structures (e.g., pneumonia or pleuritis). Primary pericarditis is uncommon. It is typically due to viral infection (often with concurrent myocarditis) Bacteria, fungi, or parasites may also be involved. Pericarditis renalfailure Uremia is the most common systemic disorder associated with pericarditis. Less common secondary causes include rheumatic fever, systemic lupus erythematosus, and metastatic malignancies. Pericarditis can: (1) Cause immediate hemodynamic complications if it elicits a large effusion (resulting in cardiac tamponade) abnormalfluid in pericardium (2) Resolve without significant sequelae or (3) progress to a chronic fibrosing process. Pericarditis - Morphology In acute bacterial pericarditis, the exudate is fibrinopurulent (suppurative), often with areas of frank pus Acute suppurative (purulent, exudative) pericarditis, caused by extension from a pneumonia. Pericarditis - Morphology In acute viral pericarditis or uremia, the exudate typically is fibrinous, imparting an irregular, shaggy appearance to the pericardial surface (so- called “bread and butter” pericarditis). Tuberculous pericarditis can exhibit areas of caseation. Acute fibrinous or fibrinopurulent pericarditis resolves without any sequelae. With extensive suppuration or caseation, however, healing can result in fibrosis (chronic pericarditis). Pericarditis - Morphology Malignancy is often associated with an exuberant shaggy fibrinous exudate and a bloody effusion, also metastases can be grossly evident. Chronic pericarditis may be associated with delicate adhesions or dense, fibrotic scars that obliterate the pericardial space In extreme cases, the heart cannot expand normally during diastole resulting in the condition known as constrictive pericarditis. Fibrinous Pericarditis Deposits of fibrin on the pericardium Strands of fibrinous material “bread and butter”  appeared gaggy Fibrinous Pericarditis P F Pericardial surface shows strands of pink Pink meshwork of fibrin exudate (F) overlies the fibrinous material with underlying inflammation pericardial surface (P) Extra resources – Fibrinous Pericarditis https://medicine.nus.edu.sg/pathweb/virtual-pathology- museum/01699-2/ Hemorrhagic Pericarditis Hemorrhagic pericarditis mostly caused by: - Tuberculosis - Direct malignant neoplastic involvement - Cardiac surgery Fibrinous pericarditis with hemorrhage Purulent Pericarditis Note the yellowish exudate (pus) in the lower pericardial sac Pericarditis – Clinical features Atypical chest pain (not related to exertion and worse in recumbency/rest) Prominent friction rub – on auscultation Cardiac tamponade – when associated with significant fluid accumulation. Chronic restrictive pericarditis produces a combination of Right-sided venous distention Low cardiac output, like the clinical picture in restrictive cardiomyopathy.  Pericardial Effusion Accumulation of fluid in the pericardium. Fluid nature varies with the cause. Major type and causes are: Pericardial effusion white gray serouswithblood fat white Fibrinous Blood Serous Serosanguineous Chylous Serofibrinous (Hemopericardium) CHF Blunt chest trauma Mediastinal lymphatic CT disease Ruptured aortic aneurysm Hypoalbuminemia Malignancy obstruction MI Ruptured MI Trauma Penetrating traumatic Uremia injury to the heart References https://emedicine.medscape.com/article/2017823-overview https://www.bostonscientific.com/content/gwc/en- US/patients/health-conditions/cardiomyopathy/dilated-- cardiomyopathy.html Robbins Basic Pathology 10th edition https://webpath.med.utah.edu/ Thank you [email protected]