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CARDIAC VALVULAR DISEASE AND VASCULITIS Pathology 655 January 23, 2008 Peter B. Baker, M.D. Email Peter.Baker@nationwidechildrens.org OBJECTIVES 1. List the pathologic processes that cause valvular stenosis and insufficiency. 2. Know the pathogenesis and complications of infectious endocarditis. 3. Describe the pathology, etiology, and clinical features for each form of vasculitis. 4. Describe the pathology of aortic dissection and know the complications and predisposing factors. REFERENCE: Cotran, Kumar, Robbins, Pathologic Basis of Disease, 8th ed., Chapter 10, pages 359-369 and Chapter 11, pages 401-408. I. VALVULAR DISEASE A. Mitral Stenosis Acquired stenosis is usually due to chronic rheumatic valvular disease. Acute rheumatic fever is a systemic disease which follows a group A beta-hemolytic streptococcal pharyngitis. Acute rheumatic fever (RF) produces myocarditis, pericarditis, arthralgia or arthritis, and other manifestation. The myocarditis is characterized by Aschoff bodies which are collections of mononuclear inflammatory cells and fibroblasts. Recurrent bouts of RF eventually lead to severe fibrosis and calcification of the mitral valve and possibly other heart valves. The disease is thought to be due to the production of antibodies against the streptococcal bacteria which cross react with various antigens in the heart, joints and other sites. B. Mitral Valve Regurgitation This may be caused by a variety of conditions including IHD and endocarditis. Mitral valve prolapse is a condition in which the leaflets balloon into the left atrium during left ventricular contraction (systole). Mild prolapse is very common and occurs in 5-10% of the general population. Severe prolapse may be associated with valvular regurgitation. Some patients also experience chest pain and palpitations. Endocarditis, mitral regurgitation, thromboemboli and sudden death (rare) are potential complications. In severe prolapse (also called floppy mitral valve) the valve cusps are large and microscopically show fragmentation, separation and loss of collagen (myxomatous degeneration). Floppy mitral valve may be an isolated abnormality or part of a systemic connective tissue disorder such as Marfan’s syndrome. C. Aortic Valve Stenosis Fibrosis and calcification reduce the valve cusp mobility. This can be due to chronic rheumatic valvular disease (in these cases the mitral valve is almost always stenotic), or may occur with advanced age (over 65 years). Bicuspid 1 aortic valve is a common congenital malformation and these valves are predisposed to calcification and fibrosis beginning at about 40 years of age. D. Aortic Valve Regurgitation The mechanisms include valve cusp destruction (endocarditis), myxomatous degeneration and dilation of the aortic root. E. Infectious Endocarditis This is usually caused by a bacterial infection in a heart valve, although it may also be caused by fungus or other unusual infections. Predisposing factors include abnormal heart valves, prosthetic valves, intravenous drug use, intracardiac shunts and immunosuppression. The three factors that have been identified as having importance in the pathogenesis include: 1) endocardial damage due to abnormalities in blood flow; 2) fibrin thrombi; and 3) organisms in the blood. 1. Clinical manifestations include: fever, heart murmur, fatigue, anemia, arthralgia, myalgia, and Roth spots (retinal hemorrhages) 2. Complications: a. rupture of chordae tendineae b. spread of infection into myocardium or aorta c. thromboembolism with infarctions d. septic thrombi with metastatic abscesses e. valvular dysfunction and CHF Acute Endocarditis Subacute Endocarditis short duration longer duration virulent organism organism of low virulence (Staphylococcus aureus) (Streptococcus viridans) large friable vegetations small vegetations previously normal valve previously abnormal valve prominent tissue destruction less tissue destruction II. VASCULITIS Vasculitis may be caused by infection (usually due to direct spread of an adjacent infection; some microorganisms infect endothelial cells and cause a vasculitis). Other causes include mechanical trauma, toxins, caustic substances, radiation and immune complexes. A. Classification 1. Large vessel Giant cell (temporal) arteritis Takayasu arteritis 2. Medium vessel 2 Polyarteritis nodosa (classic) Kawasaki syndrome 3. Small vessel Microscopic polyarteritis Wegener’s granulomatosis B. Pathogenesis of immune-mediated vasculitis 1. immune complex formation 2. antineutrophilic cytoplasmic antibodies (ANCA) Perinuclear localization (pANCA) – microscopic polyarteritis Diffuse cytoplasmic (cANCA) – Wegener’s granulomatosis C. Giant Cell (Temporal) Arteritis Etiology: Unknown (?T-cell mediated) Clinical: Fever, weight loss, headache, visual problems, claudication of jaw, pain and tenderness over temporal artery, polymyalgia rheumatica. Rare under the age of 50 years. Pathology: Granulomatous inflammation with giant cells, fibrosis. D. Takayasu’s Arteritis Etiology: Unknown Clinical: Thickening of the wall reduces blood flow in the major branches off the arch (“pulseless disease” due to weak pulses in the arms). Usually affects young women. Pathology: Granulomatous inflammation with fibrosis involving the aortic arch and the arch branches. E. Polyarteritis nodosa Etiology: Unknown in most cases. Thirty percent (30%) have hepatitis B surface antigen in the serum. Clinical: Fever, weight loss, hematuria, renal failure, hypertension, abdominal pain, melena. Clinical presentation may be very confusing due to involvement of multiple organ systems. 3 Pathology: Haphazard and segmental involvement of medium and small muscular arteries. Acute lesions show fibrinoid necrosis, thrombosis, neutrophils, aneurysms. With healing there is predominance of macrophages and plasma cells; progressive fibrous scarring. Usual sites of involvement are: kidneys (85%), heart (75%), liver (65%), and GI tract (50%). F. Kawasaki’s Disease Etiology: It is suspected that a viral infection triggers a hypersensitivity reaction. Clinical: Affects infants and young children. Skin rash, mucous membrane lesions, lymphadenopathy. Usually self-limited but 1-2% die with coronary artery vasculitis. G. Microscopic Polyarteritis Etiology: Often due to antigen-antibody complexes. Clinical: Fever, rash, joint swelling, pleural effusion, pulmonary infiltrates, myocarditis, GI bleeding, renal failure, presence of circulating anti- neutrophilic cytoplasmic antibodies (pANCA). May be manifestation of malignancy, autoimmune disease or other disorder. Pathology: Involves arterioles, capillaries, venules. Fibrinoid necrosis, neutrophils (leukocytoclastic vasculitis). G. Wegener’s granulomatosis Etiology: Probably a form of T-cell mediated hypersensitivity. Clinical: Involves sinuses, lungs and kidneys glomerulonephritis).Associated with the presence of anti-neutrophilic cytoplasmic antibodies (cANCA). Pathology: Necrotizing granulomas with vasculitis. D. Buerger’s Disease (Thromboangiitis obliterans) Etiology: Endothelial injury from a substance in cigarette smoke 4 Clinical: Usually begins before age 35. Pain and ischemia in extremities. Pathology: Segmental acute and chronic vasculitis mainly in extremities with thrombosis. III. DISSECTING AORTIC HEMATOMA (ANEURYSM) A. Longitudinal tear of the aortic media which begins in the ascending aorta and extends variable distance proximal (toward the heart) and distal to the descending aorta. B. Complications: severe hemorrhage from rupture, organ ischemia due to luminal compression by the expanding hematoma. C. Predisposing factors: hypertension, inherited connective tissue disorders (i.e., Marfan’s syndrome) with medial degeneration. Key Points 1. Repeated episodes of acute rheumatic fever; mitral valve fibrosis and calcification; valvular stenosis 2. Histopathologic feature (myxomatous degeneration) and complications of severe mitral valve prolapse 3. Mechanisms of aortic valve stenosis and regurgitation 4. Features (acute and subacute) and complications of endocarditis 5. Giant cell arteritis: large arteries, temporal artery, granulomatous inflammation 6. Polyarteritis nodosa: medium to small arteries, haphazard involvement, fibrinoid necrosis and aneurysm formation 7. Microscopic polyarteritis: microvasculature, fibrinoid necrosis and leukocytoclasis 8. ANCA positive forms of vasculitis: Wegener’s granulomatosis, microscopic polyarteritis 9. Dissecting hematoma: split (hematoma) in the media, complications - hemorrhage and branch obstruction 5
"HYPERTENSION AND VASCULITIS"