Pathophysiology of Rheumatic Heart Disease Precipitating Factors:

Predisposing Factors:

Entry of S. pyogenes via respiratory droplets

M proteins destabilize complement component C3b, thereby interfering with opsonization and lysis

Hyaluronic acid capsule may camouflage the bacterium from phagocytes

Streptokinases are enzymes that break down blood clots

Presumably enable group A streptococci to spread rapidly through damaged tissues

C5a peptidase breaks down complement protein C5a (which is a chemotactic factor)

S. pyogenes decreases movement of leukocytes into the site of infection

M protein, N- acetylglucosamine mimic myocardium and heart valves Beta- hemolytic streptococcus adhere to hearts cell walls Blood vessels are exposed and bacteria gain entry into circulatory system (hematogeneous) Activation of Immune Response Mucoid strains adhere to pharyngeal tissue Streptolysis lyse erythrocytes, leukocytes and platelets Pyrogenic (erythrogenic) toxins stimulate leukocytes to release cytokines

Streptococcal cell wall reacts with cardiac tissue via M protein; the group A M proteins and the heart valve glycoprotein cross react

Tissue damage occurs Macrophage attaches to antibodies and phagocytizes cardiac tissue Antibodies attach to the cardiac tissue with similarstructure to M- protein (antigenantibody complex) Upon arrival at the heart, M protein has already interactwith cardiac tissue and therefore cardiac tissue is also recognized by immune system as a foreign body due to mimicry protein structure to that of M protein B cells release antibodies to counteract antigens found in the body

T cells alerts B cells to the presence of the foreign M protein M proteins attached to myocardium (myosin and tropomyosin) is recognized as an antigen by T cells CD4+ T cells for streptococcal peptides will react with self proteins in the heart
And b -cells who have been activated by the t-cells wil release antibodies which will also attach to the heart tissues which have been distorted by the M-proteins. The antibodies will then serve asa anchor points for complement proteins and macrophages to attach to and easily lyse these tissues. The continous destruction of these tissues thru complementary proteins, macrophages and Killer T-cells activates the inflammatory response. This inflammatory response starts with the release of bradykinins, prostaglandins and other chemical inflammatory mediators. These will activate a cascade of events like

Valves shortening, rigidity, deformity and retraction of mitral cusps Valves Harden

Increase in extracellular matrix by increased collagen and tissue cellularity Scarring Fibrosis Fibroblasts are activated by Arginase, polyaminase, TGF-B Activation of leukocytes and production of cytokines In vascular endothelium: Increase expression of leukocyte adhesion molecules Production of IL-1 and chemokines Increase procoagulant and Decrease anticoagulant activity Inflammatory response in initiated Formation of verrucous vegetations on valve leaflets

Partial opening is created towards the left atrium (Mitral Valve Stenosis)

Blood flow from left atrium to the left ventricle only if propelled by a small though abnormal pressure gradient

Doubling of flow rate quadruples the pressure gradient Transcellular pressure gradient is a function of the square of transvulvular flow rate

Elevated left atrial pressure

Increase rate of blood flow across the mitral orifice Raises pulmonary venous capillary pressure

Reduction in forward cardiac output Decreased diastolic filling time Further elevation of left atrial pressure