CARDIAC VALVULAR DISEASE AND VASCULITIS
Pathology 655 January 23, 2008
Peter B. Baker, M.D.
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
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
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
1. Clinical manifestations include: fever, heart murmur, fatigue, anemia,
arthralgia, myalgia, and Roth spots (retinal hemorrhages)
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
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.
1. Large vessel
Giant cell (temporal) arteritis
2. Medium vessel
Polyarteritis nodosa (classic)
3. Small vessel
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
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.
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
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
Pathology: Necrotizing granulomas with vasculitis.
D. Buerger’s Disease (Thromboangiitis obliterans)
Etiology: Endothelial injury from a substance in cigarette smoke
Clinical: Usually begins before age 35. Pain and ischemia in extremities.
Pathology: Segmental acute and chronic vasculitis mainly in extremities with
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
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.
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
8. ANCA positive forms of vasculitis: Wegener’s granulomatosis, microscopic
9. Dissecting hematoma: split (hematoma) in the media, complications -
hemorrhage and branch obstruction