Introduction to Cardiovascular Pathology - Fred Clayton

1. Introduction to Cardiovascular Pathology- Fred Clayton • Systemic Pathology of Congestive Heart Failure • Pathology of Myocarditis • Pathology of Cardiomyopathy • Dilated Cardiomyopathy • Hypertrophic Cardiomyopathy • Restrictive Cardiomyopathy

2. Congestive Heart Failure • Cardiac output insufficient for metabolic requirements of the body • Systolic dysfunction – decreased myocardial contractility • Diastolic dysfunction – insufficient expansion for ventricular volume • Problems are accentuated by increased demand – high output heart failure

3. CHF – Body’s Compensation • Tachycardia • Frank-Starling – increased End Diastolic Volume • Myocardial hypertrophy • Renin-angiotensin-aldosterone system • Catecholamines – positive inotropic effect • Adrenergic redistribution of blood flow • Increase oxygen extraction from hemoglobin

4. Left-sided Heart Failure • Ischemic heart disease • Hypertension • Aortic and mitral valve disease • Myocardial disease

6. Lungs – Pulmonary edema • Dyspnea – breathlessness • Orthopnea – dyspnea lying down • Paroxysmal nocturnal dyspnea – extreme dyspnea

7. Lung – Pulmonary Edema – pale pink edema fluid filling alveoli

8. Lung – alveolar hemorrhage, heme-filled macrophages “heart failure cells”, with iron stain to right

9. Kidneys – reduced perfusion • Ischemic tubular necrosis / ATN • Prerenal azotemia

10. Kidney -ATN

11. Brain in CHF – cerebral hypoxia • Irritability • Loss of attention span • Restlessness • Stupor • Coma

12. Right-sided heart failure • Pure cor pulmonale • Consequence of left-sided failure • Myocardial – myocarditis, cardiomyopathy, constrictive pericarditis

14. Right failure - systemic effects • Liver – chronic passive congestion • Spleen – congestive splenomegaly • Kidneys – congestion and hypoxia • Sub-Q – peripheral edema and anasarca • Pleural space – effusions • Brain – venous congestion and hypoxia • Portal - ascites

15. Liver – chronic passive congestion – blood pools near the central veins

16. Liver – chronic passive congestion

17. Liver – chronic passive congestion – blood pools near the central veins

18. Liver – chronic passive congestion – red cell pooling near central veins and pericentral necrosis of the hepatocytes

19. CHF – final pathway to death • Ischemic heart disease • Hypertensive heart disease • Valvular heart disease • Cardiomyopathy • Myocarditis • Specific heart muscle diseases

20. Myocarditis Etiology • Viral – Coxsackie A, ECHO, Influenza • Chlamydia and Rickettsia – psittaci & typhi • Bacteria – diphtheria, TB, Strep • Fungal & Protozoa – Trypanosomes, Toxo • Hypersensitivity – SLE, RHD, drugs • Physical Agents – Radiation • Idiopathic – Giant cell myocarditis

21. Myocarditis Morphology • Gross –dilated, flabby heart, pale patches with hemorrhage • Microscopic – interstitial inflammatory infiltrate with myocyte necrosis, fibrosis • Mononuclear cells – idiopathic or viral • Neutrophils – bacterial • Eosinophils –hypersensitivity or protozoa • Granulomatous – TB or sarcoid

22. Dilated, globoid heart in myocarditis

23. Myocarditis – meets Dallas criteria of a T lymphocyte infiltrate and myocyte necrosis or dropout. This is usually either viral or of unknown cause.

24. Diphtheria myocarditis – due to a toxin rather than bacterial invasion. There is some inflammation, myocyte changes (see the big nucleolus). Myocyte necrosis (not shown) also happens.

25. Bacterial colony in myocarditis

26. Toxoplasmosis

27. Chagas disease

28. Giant Cell Myocarditis • Myocyte necrosis • Multinucleated giant cells • Lymphocytes, plasma cells, macrophages, eosinophils, and neutrophils • Often fulminant, rapid progression to death • Differential diagnosis – cardiac sarcoidosis

29. Giant Cell Myocarditis

30. Giant Cell Myocarditis

31. Cardiomyopathies

32. Dilated Cardiomyopathy • Gross – increased weight, dilatation, endocardial fibrosis, normal valves and coronary arteries • Microscopic – myocyte hypertrophy, myofibrillar loss and interstitial fibrosis • Etiology – viral, genetic, toxins • Clinical significance – heart failure & death

34. Dilated cardiomyopathy

35. Cardiomyopathy – loss of myofibrils

36. Cardiomyopathy – trichrome stain showing extensive fibrosis (blue) between the myocytes. The myocytes also vary in size, and some have partial loss of myofibrils.

37. Normal Heart - EM

38. Loss of fibrils in cardiomyopathy. The myocyte at lower left is about normal; the others have an extensive loss of myofibrils.

39. Cardiomyopathy – loss of fibrils and a small contraction band in the top center.

41. Hypertrophic Cardiomyopathy • Hypertrophy of ventricular septum (95%) • Disarray of myofibers (100%) • Volume reduction of ventricles (90%) • Endocardial thickening of LV (75%) • Mitral valve leaflet thickening (75%) • Dilated atria (100%) • Abnormal intramural coronaries (50%)

43. Hypertrophic cardiomyopathy

44. Hypertrophic cardiomyopathy

45. Hypertrophic cardiomyopathy

46. Hypertrophic cardiomyopathy – myofiber dysarray – not all fibers are pulling the same direction. Thus the contraction is ineffective. However, the cardiac conduction system can have these same problems, which might cause the arrhythmias and sudden death these patients tend to die of.

47. Hypertrophic Cardiomyopathy • Etiology – hereditary, mostly autosomal dominant, can appear sporadically • Clinical significance – syncope, arrhythmias and sudden death with a risk of 2-6% per year • Cannot equate with hypertrophy alone! There is variation in heart size without disease. Large hearts correlate with endurance (Secretariat, Lance Armstrong).

49. Restrictive Cardiomyopathy • Amyloidosis • Endomyocardial fibrosis – subendocardial fibrosis • Loeffler’s endocarditis – eosinophilic infiltrate • Endocardial fibroelastosis

50. Amyloidosis – notice the pink material between the myocytes.