Pathology of Cardiovascular System Lecture 1 Rheumatic Fever and Heart Diseases

Dr. Mohamad Nidal Khabaz 19.2.2006

Valvular Heart Diseases

The most common abnormalities of heart valves are: Stenosis of the mitral and aortic valves: valve fails to open completely, so impairing forward blood flow. Regurgitation (Insufficiency): valve fails to close completely, due to cusp abnormality or disease of supporting structures, so allowing reverse flow. Valve abnormalities produce abnormal heart sounds called murmurs

Valvular Heart Diseases

Mechanisms of diseases :
Deformed cardiac valves impose a major hemodynamic load on the cardiac chambers by causing obstruction (stenosis) or (regurgitation). They are more susceptible to infection, thus predispose patients to infective endocarditis.

Acute Rheumatic Fever

Definition
Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease that follows, after (10 days to 6 weeks), an episode of group A beta-hemolytic streptococcal pharyngitis Occurs in only 3% of patients with group A streptococcal pharyngitis.

Peak incidence: ages of 5-15 years. The incidence of rheumatic fever has declined over the past 30 years It affects large joints causing Arthritis. It affects the heart during its acute phase acute rheumatic carditis after many years may cause chronic valvular deformities

Acute Rheumatic Fever

Etiology Rheumatic fever follows usually a group A beta-hemolytic streptococcal pharyngitis. The evidence for this association include: Epidemiological studies and patient history : show that streptococcal pharyngitis are followed by cases of rheumatic fever. Serology: patients have elevated levels of antibodies to streptococcal enzymes such as streptolysin O and DNAse B.
Always remember blood cultures of patients with rheumatic fever are sterile

Acute Rheumatic Fever

Pathogenesis It is strongly suspected that acute rheumatic fever is a hypersensitivity reaction induced by group A streptococci. It is presumed that antibodies directed against the M proteins of group A streptococci cross-react with normal proteins in the tissues, leading to tissue damage. Alternatively it has been proposed that rheumatic fever results from an immune response against the offending bacteria.

Acute Rheumatic Fever

Pathology
Inflammatory infiltrates occur in a wide range of tissues: synovium, joints, skin, and heart. Focal fibrinoid necrosis which provokes inflammatory response Fibrosis is common especially in cardiac tissues.

Acute Rheumatic Carditis (Pancarditis): Pathology

Characterized by inflammatory changes in all three layers of the heart.
Multiple foci of inflammation within the heart connective tissue called: Aschoff Bodies Consisting of central fibrinoid necrosis surrounded by a collection of lymphocytes, and large macrophages (with basophilic cytoplasm and vesicular nuclei) known as Anitschow cells. It may become multinucleated forming Aschoff giant cells (Caterpillar cells or cardiac histiocytes). Acute changes may resolve completely or progress to scarring and chronic valvular deformities.

Acute Rheumatic Carditis (Pancarditis): Pathology

Myocardium
Scattered Aschoff bodies lie in close proximity to a small vessel. Diffuse interstitial inflammatory infiltrates (may lead to generalized dilation of the cardiac chambers).

Endocardium
Common and may affect any valve, mostly mitral and aortic valves. Valves are edematous and thickened with foci of fibrinoid necrosis. (Aschoff nodules uncommon). Formation of small vegetations fibrinous clots along the lines of valve closure (Verrucous Endocarditis).

Pericardial involvement
Fibrinous pericarditis, sometime serosanguinous pericardial effusion. associated with serous or

Acute Rheumatic Carditis (Pancarditis): Clinical Manifestations

Symptoms: Pericardial friction rubs, Weak heart sounds, Tachycardia (rapid beating) and Arrhythmias. In severe cases: myocarditis cardiac dilation functional mitral valve insufficiency or even congestive heart failure.

Acute Rheumatic Heart Disease

Pathogenesis and Key Morphologic Changes

Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet (arrowheads). Previous episodes of rheumatic valvulitis have caused fibrous thickening and fusion of the tendinous cords.

Verrucous Endocarditis in Acute Rheumatic Fever

Aschoff Body in Acute Rheumatic Carditis

Aschoff body in acute rheumatic carditis.

Collection of mononuclear inflammatory cells, including some large histiocytes with prominent nucleoli, a prominent binuclear histiocyte, and central necrosis.

Aschoff Body with Caterpillar Nuclei

Fibrinous Pericarditis in Acute Rheumatic Fever

Chronic Rheumatic Heart Disease

Characterized by irreversible deformity of one or more cardiac valves. Mitral valve is abnormal in 95% of cases. Combined oartic and mitral valve disease is present in 25% of cases. Aortic valve alone is rarely affected. Pulmonary and Tricuspid valves are extremely rare to be affected.

Clinical manifestations: depend on which valve is involved

Cardiac murmurs, Arrhythmia, Hypertrophy, Dilation, Congestive heart failure, Thromboembolic complications and infective endocarditis

Pathological changes:
Chronic scarring and calcification of the valve leaflets, which invert the valve into stiff and thickened structure which may lead to: Valve orifice becomes stenotic Improper closure (regurgitation). Shortening and fusion of the chordae tendineae.

Chronic Rheumatic mitral valvulitis

It is the most common cause of mitral stenosis It causes stenosis > regurgitation, and occurs in females > males. In Mitral Stenosis: Leaflets are thick, rigid, and inter-adherent. Mitral orifice is narrowed fish mouth deformity. Dilatation and hypertrophy of left atrium. Endocardium is thickened particularly above posterior mitral leaflet . Mural thrombi may be present Lungs: firm and heavy (result of chronic passive congestion). In Mitral Regurgitation: Valve leaflets are retracted Left ventricular dilatation and hypertrophy.

Mitral valve, rheumatic mitral stenosis

The mitral valve demonstrates the typical "fish mouth" shape with chronic rheumatic scarring.

Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrow)

Chronic Aortic Valvulitis

Males > females and usually associated with mitral valvulitis. May occur in congenital bicuspid aortic valve (2%) Aortic stenosis: Valve cusps are thickened, firm and adherent to each other the aortic valve orifice is reduced to a rigid triangular channel. Aortic stenosis increases the pressure load on left ventricle causing hypertrophy. Subsequent left ventricular failure is associated with dilation of the chamber.

Surgically removed specimen of rheumatic aortic stenosis demonstrating thickening and distortion of the cusps with commissural fusion (rigid triangular channel)

Calcific Aortic Stenosis DCAS (degenerative calcific aortic stenosis)

Part of normal aging process is degenerative changes in the cardiac valves but it can develop to cause pathologic stenosis.

The aortic valve leaflets are rigid and deformed by calcified masses, so fibrosis and calcification of the valve cusps lead to valve sclerosis.
The calcium deposits lie behind the valve cusps (at the bases of the cusps). The free edges of the cusps are usually not affected. Calcific stenosis does not fuse the cusps.

Symptom: severe cases may cause angina, syncope (fainting), congestive heart failure, L.V. hypertrophy, sudden death due to arrhythmia.

Degenerative calcific aortic stenosis of a normal valve having three cusps. Nodular masses of calcium are heaped up within the sinuses of Valsalva (arrow). Note that the commissures are not fused, as in post-rheumatic aortic valve stenosis

Mitral Valve Prolapse

It is a common cardiac disorder (3-5% of adult population, mainly females, ages 20-40 years).
It is usually an isolated problem but it may arise as a complication of certain connective tissue disorders (e.g. Marfan syndrome). It has been reported as an isolated autosomal dominant condition that maps to chromosome 16p. Less commonly, as an x-linked recessive disorders. Most patients are asymptomatic, some have palpitations and fatigue, or atypical chest pain, and mid-systolic click with a late systolic murmur.

Mitral Valve Prolapse

Pathology The valve leaflets (posterior cusp) are soft and enlarged causing a characteristic ballooning of the valve leaflets into the left atrium during systole. The chordae tendineae, which are often elongated and fragile, may rupture in severe cases. The valve annulus may be dilated. Microscopic examination Reveals excessive amounts of loose, edematous, faintly basophilic tissue within the middle layer (spongiosa) of the valve leaflets and chordae. Complications Mitral regurgitation and congestive heart failure. Sudden death caused by ventricular arrhythmias. Infective endocarditis.

Long axis view of the left ventricle demonstrating ballooning with prolapse of the posterior mitral leaflet into the left atrium (arrow). The left ventricle is on the right.

Opened valve showing pronounced hooding of the posterior mitral leaflet with thrombotic plaques at sites of leafletleft atrium contact (arrows).