L7, CVS Pathology PDF

pathology - CVS RHEUMATIC FEVER LECTURE (7) RHEUMATIC FEVER Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  Acute immunologically mediated , Multi-system inflammatory disease. ①...

pathology - CVS RHEUMATIC FEVER LECTURE (7) RHEUMATIC FEVER Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  Acute immunologically mediated , Multi-system inflammatory disease. ① Heart. ② Joints. ③ Subcutaneous tissue. ④ CNS.  Acute rheumatic fever is autoimmune reactions which is type II hypersensitivity  It affects children between 5-15 years with no gender predilection.  Most common cause of acquired heart disease in children and adolescent.  More prevalent in developing countries.  It remains endemic in parts of Asia, Africa and South America  It occurs (1-4) weeks after an episode of Group A (ß-hemolytic) streptococcal pharyngitis (GAS)  After pharyngeal infection with beta-hemolytic group A streptococcal bacteria, less than 3% of patients develop rheumatic fever.  Antigenic mimicry, genetic predisposition, environmental factors determine susceptibility to RHD Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  Preceding GAS infection is necessary for the development of ARF (Acute rheumatic fever). A) GROUP A  There is 5 strains of GAS from A-E. STREPTOCOCCUS  Pharyngitis-inducing strains of GAS A, B, and C are the more “rheumatogenic” patterns.  Any strain of GAS can cause ARF.  Host susceptibility to ARF is polygenic (influenced by ≥2 genes).  Monozygotic twin demonstrate ≈ 40% concordance risk for ARF.  HLA and tumor necrosis factor polymorphisms and an allele on the B) HOST immunoglobulin heavy chain play a role in genetic susceptibility to ARF. SUSCEPTIBILITY  HLA alleles involve in regulating immune response to infections and autoimmune response by presenting antigens and autoantigens to T-cells receptors.  Cold climate, low socio-economic standards & overcrowding & C) ENVIRONMENTAL malnutrition: PREDISPOSITION ① Repeated exposures to GAS ② Recurrent infections as tonsillitis  Molecular mimicry means that similarities between Streptococcus pyogenes antigens and host peptides may cause an immune response to cross-react with both self and foreign peptides.  The M protein and N-acetyl-β-D-glucosamine (NABG) of GAS species exhibit structural similarity to cardiac myosin.  Besides that, autoantibodies against type I collagen is generated. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  The antibodies produced against streptococcal antigens cross react with antigens in heart tissue or joints which lead to neutrophil and macrophage activation and inflammation.  Antibody-antigen complexes may also deposit in joints leading to the characteristic migratory polyarthritis.  During streptococcal infection:  Antigen presenting cells such as dendritic cells and B cells present the streptococcal antigens to naïve CD4+ T cell and lead to activation to helper T cell.  Activated helper T cells will activate B cells.  Activated B cells in the germinal centers differentiate into plasma cells which then produce antibodies which are part of a normal humoral response against S. pyogenes bacteria.  Type II cytotoxic reaction produces damage of endocardial and myocardial cells with liberation of autoantigens.  The autoantigens stimulate autoantibodies production.  Autoimmune type III and Type IV reactionstarts with formation of allergic granuloma. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER EVIDENCE OF ABNORMAL IMMUNE REACTION. ① Fever occurs 2-4 weeks after infection ② An elevated anti-streptolysin O (ASO) is evidence of recent streptococcal infection (used in diagnosis) ③ The microorganisms are absent. ④ Penicillin prevents the recurrence. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  Characteristic lesion (unit lesion): Aschoff’s body”. DEFINITION  Aschoffbodies are granulomatous formations found on the surface of cardiac valves in patients with RHD. N/E  Small pale foci seen in heart, joints, SC tissue and sometimes CNS  Often perivascular  Central area of fibrinoid necrosis. ME  Collection of chronic inflammatory cells, Anitschkow cells with occasional Aschoff giant cells with a sprinkle of lymphocytes. FATE  Fibrosis. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER A. Cardiac manifestations: Pancarditis ① Pericarditis ② Myocarditis ③ Endocarditis B. Extra-cardiac manifestations  Carditis is the most serious presentation of rheumatic fever (40% of patients with ARF)  RHD accounts for approximately 15 to 20 % of all patients with heart failure in endemic countries. ENDOCARDIUM MYOCARDIUM PERICARDIUM ① Valvular. Ashoff’s nodule Fibrinous ② Mural. Pericarditis 1 RHEUMATIC ENDOCARDITIS VALVULAR ENDOCARDITIS MURAL ENDOCARDITIS  Affects the endocardium lining the valves  Affects the endocardium lining the walls of and cusps cardiac chambers. A VALVULAR ENDOCARDITIS DEFINITION  Inflammation of the cardiac cusps. ① Mitral. ② Mitral and aortic together. SITES ③ Aortic alone. ④ Rarely Tricuspid and pulmonary. ① Acute Valvular Endocarditis. TYPES ② Chronic Valvular Endocarditis. ① Aortic stenosis ② Aortic incompetence ③ Mitral stenosis COMPLICATIONS  The valve has a fish-mouth appearance.  Mitral stenosis → Pulmonary hypertension → Right sided heart failure.  Mitral stenosis results in chronic venous congestion of the lung Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER ACUTE VALVULAR ENDOCARDITIS  Aschoff’s nodules with edema results in swelling of the leaflets of the cusps.  Valve cusps are swollen, red, and lost their transparency.  Friction of their free borders leads to injury of the endothelium and thrombosis (vegetations). N/E  Rheumatic vegetations:  Small (1-2 mm) adherent valvular thrombi (no emboli).  Found on the atrial surface, appear small, beaded and pale.  Found on the free border of the valve mainly mitral and aortic.  Fate: heal by fibrous tissue.  Valve cusps are edematous and vascular.  Infiltrated diffusely by inflammatory cells. M/E  Occasional Aschoff's bodies.  Vegetations are formed of platelets and fibrin. PIC Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER CHRONIC VALVULAR ENDOCARDITIS  Most important consequence of rheumatic fever  After multiple episodes of RF, progressive fibrosis of heart valves can occur, which can lead to rheumatic valvular heart disease. INTRODUCTION  If valvular heart disease remains untreated, then heart failure or death.  Inflammatory deformity of valves  Almost always involve mitral valve  Involvement of aortic or other valves ① Fibrosed, thickened cusps. ② Deformities: healing of acute lesion by fibrosis leads to: a) Stenosis: fusion of cusps result in inability of valve to open properly b) Incompetence: contraction of the cusps result in inability of the valve to close properly c) Combined d) Shortening, thickening and fusion of chordae tendinae ③ Calcification can occur in any form. N/E  Valve cusps are fibrosed.  Contain thick walled vessels and some lymphocytes. M/E  Patches of calcification may be seen.  Vegetations are fibrosed. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER B MURAL ENDOCARDITIS  It affects mainly the Mac-callum’s area in posterior wall of left atrium above the mitral valve. CHARACTERS  The characteristic rheumatic reaction is seen with Aschoff's bodies.  Heals by fibrosis.  Resultant rough surface commonly complicated by thrombosis. 2 RHEUMATIC MYOCARDITIS SITE  Myocardium of left side is affected especially the left atrium.  The muscle is swollen, flabby and the chambers are dilated. N/E  Aschoff's bodies may be seen as scattered pale foci.  Aschoff's bodies seen in interstitial tissue commonly on endocardial side.  Interstitial oedema and inflammation. M/E  Cloudy swelling or necrosis of myocardium.  The lesions heal by fibrosis. FATE  The condition is usually mild, but may rarely produce left ventricular failure Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER 3 RHEUMATIC PERICARDITIS  Rheumatic fever is the commonest cause of sero-fibrinous pericarditis mainly at the heart base. DEFINITION  The pericardial sac is filled with serous fluid and fibrin is deposited on both visceral and parietal pericardium. ① White patches of fibrosis at the surface of the heart (milk patches). ② Adhesions between visceral and parietal pericardium (bread and butter N/E appearance) ③ Adhesions between parietal pericardium & adjacent mediastinal structures (adherent mediastino-pericarditis) → interferes with cardiac contractions  As any sero-fibrinous inflammation M/E  + Aschoffs' bodies may be seen. SEROFIBRINOUS PRICARDITIS, ROUGH SURFACE SEROFIBRINOUS PRICARDITIS, FIBRIN THREADS Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER COMPLICATIONS OF RHEUMATIC CARDITIS ① Cardiac arrhythmias especially atrial fibrillation. ② Valvular lesions. ③ Sub-acute bacterial endocarditis  Fleeting polyarthritis occurs more in adults  Affects large joints e.g. knee, ankle and wrist one after the other.  M/E: ① MIGRATORY  The synovial membrane and periarticular tissue show POLYARTHRITIS characteristic Rheumatic reaction.  The joint cavity contain sero-sanguinous fluid.  Complete resolution with no after effects.  Oval or spherical nodules, may be attached to deeper structures.  Formed of central fibrinoid necrosis surrounded by chronic inflammatory cells and fibrous tissue.  It is more in children. ② SUBCUTANEOUS NODULES  Def: Annular erythema that occurs more in children.  Site:  Trunk and upper arms and legs.  Never on face, palms or soles.  GAS share epitopes with keratin, and cross-reactivity may lead to erythema marginatum ③ ERYTHEMA  It may persist intermittently for weeks to months, even after MARGINATUM successful treatment of ARF. Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER  Chorea minor  It is a mild meningoencephalitis of basal ganglia  Late neurological manifestation;3 months after the episode of ARF  Is more common in females  Emotional changes may be the first feature.  Followed by purposeless involuntary movements of the hands, feet or face. ④ SYDENHAM CHOREA MAJOR CRITERIA MINOR CRITERIA ① Carditis. ① Fever ② Polyarthritis. ② Arthralgia ③ Chorea. ③ Increased ESR or CRP ④ Dermatologic affection. ④ Raised ASO titre. ⑤ Subcutaneous nodules ⑤ ECG changes ⑥ Leucocytosis Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER NORMAL VALVE SLE RHEUMATIC SUBACUTE ENDOCARDITIS ACUTE ENDOCARDITIS VEGETATIONS Dr. M. Shalaby pathology - CVS RHEUMATIC FEVER COMPARISON OF THE FOUR MAJOR FORMS OF VEGETATIVE ENDOCARDITIS. ① Rheumatic fever phase of rheumatic heart disease (RHD):  Marked by small, warty vegetations along the lines of closure of the valve leaflets. ② Infective endocarditis (IE):  Large, irregular masses on valve cusps that can extend onto chordae ③ Nonbacterial thrombotic endocarditis (NBTE):  Typically exhibits small, bland vegetations  Usually attached at the line of closure.  One or many may be present. ④ Libman-Sacks endocarditis (LSE):  Has small or medium-sized vegetations on either or both sides of the valve leaflets. Dr. M. Shalaby