Endocardial Pathology (PDF)

Cardiovascular system pathology Endocardial diseases  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE What is it? Rheumatic fever (RF) is an immunologically mediated, multisystem inflammatory disease that occurs a few weeks following an episode of group A strepto...

Cardiovascular system pathology Endocardial diseases  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE What is it? Rheumatic fever (RF) is an immunologically mediated, multisystem inflammatory disease that occurs a few weeks following an episode of group A streptococcal pharyngitis. Can be acute or chronic The chronic results from repeated attacks of the disease and affects the heart resulting in permanent damage to the valves. 3 12/11/2013  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE Pathogenesis. Antibodies directed against the M proteins of certain strains of streptococci cross-react with glycoprotein antigens in the heart, joints, and other tissues. Key words are: Cross reacting antibodies 4 12/11/2013  Acute RF Occurs several days following streptococcal pharyngitis Affects the following organs: 1) Brain ➔ chorea 2) Joints ➔ flitting (migrating arthritis) 3) Skin ➔ erythema marginatum 4) Subcutaneous tissue ➔ nodules 5) Heart ➔ carditis N.B. The above 5 clinical features constitute Jones’ Major criteria for clinically diagnosing acute RF. 6 12/11/2013 Acute RF of the heart:- Pathology in the heart:- inflammation of all the layers of the heart i.e. pericarditis, myocarditis, or endocarditis—hence the lesion is called ➔ Pancarditis 7 12/11/2013  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE Pathology:- Acute RF of the heart:- 1- Pericarditis: is a fibrinous or serofibrinous pericardial exudate, described as a "bread-and-butter" or “butter sandwich” pericarditis; resolves without sequelae. 2- Myocarditis: Features of inflammation plus scattered Aschoff bodies within the interstitial connective tissue, often perivascular. 8 12/11/2013  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE Pathology:- Acute RF of the heart:- Myocarditis (continued): Aschoff bodies:- It is pathognomonic for RF. They consist of foci of swollen eosinophilic collagen surrounded by lymphocytes (primarily T cells), occasional plasma cells, and plump macrophages called Anitschkow cells 9 12/11/2013  An Aschoff body within myocardium (myocardium, Anitshkow cell) 10 12/11/2013  Antischkow cells Aschoff bodies Antischkow cells  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE Pathology:- Acute RF of the heart:- 3- Endocarditis (mainly on the left side): a) Inflammatory foci typically results in fibrinoid necrosis within the cusps and/ or along the tendinous cords. b) Vegetations (thrombi of 1- to 2-mm) along the lines of closure of the cusps and on the cords. c) Irregular thickenings called MacCallum patches, usually in the left atrium. 13 12/11/2013  Vegetations on the margin of a cusp (arrows) What are the criteria of RF vegitations? 14 12/11/2013  RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE Chronic RHD: It results from repeated attacks of acute RF Organization of the acute endocardial inflammation and vegetations with subsequent fibrosis. The fibrosis will deform the valves by causing:- 1) Commissural fusion (of the cusps) ➔ stenosis. 2) Leaflet thickening ➔ valve regurgitation 3) Shortening, and thickening and fusion of the tendinous cords ➔ valve regurgitation 15 12/11/2013  Clinicopathological features of RF ❑ Sore throat infection caused by group A ,β- hemolytic streptococci ❑ Clinical diagnosis :According to Jones criteria 2 major criteria OR one major + 2minor. Major criteria:- ❑ PANCARDITIS: 1) Endocarditis, 2) Myocarditis, 3) Pericarditis ❑ Migratory polyarthritis ❑ Subcutaneous nodules ❑ Erythema marginatum ❑ Sydenham chorea Minor criteria: ❑ Fever, arthralgia ,recurrent pharyngeal infection changes, high anti streptolysin( O )titer, anti DNase, high total WBCs ,high ESR, and high CRP.  INFECTIVE ENDOCARDITIS (IE) 17 12/11/2013 Infectious endocarditis & definition &epidemiology Definition: Infection on endothelial surfaces of heart which includes: Mural endocardium, Valves and their apparatuses, Prosthetic or implanted components, like: (valves, homograft, pacemakers, intracardiac defibrillators(ICD) ,surgical shunts and septal defect occluders, endovascular devices or clips) Epidemiology : High morbidity and mortality, despite advances in diagnosis and treatment. The mean age of patients :between 28 and 32 years in studies from Saudi Arabia  Subclasses of IE 1) Acute IE days to 6 wks. 2) Subacute IE weeks to few months, Caused by low virulence organisms. Affects an abnormal heart (with a pathology), 3) Chronic for one year Other classification : according to the causative agents(New) Or the type of involved valves: native valves or prosthetic valves  Infective Endocarditis (IE) Risk Factors to the SIE :- 1) Heart abnormalities: RHD valve pathology, myxomatous mitral valve, degenerative calcific valve stenosis, bicuspid aortic valve (whether calcified or not), and artificial (prosthetic) valves, …etc. 2) Host factors: Immunodeficiency, malignancy, therapeutic immunosuppression, diabetes mellitus, and alcohol or intravenous drug abuse. 3) Bacteraemia : The portal of entry of the organisms into the bloodstream may be:- an obvious infection elsewhere, a dental or surgical procedure, delivery (childbirth) injection of contaminated material directly into the bloodstream by intravenous drug users, or an occult source from the gut, oral cavity, or trivial injuries 20 12/11/2013  Infective Endocarditis (IE) Low virulence organisms of SIE:- 1. Streptococcus viridans mouth commensal (50% to 60% of cases) 2. HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella), commensals in the oral cavity 3. Staph. epidermidis which is a skin commensal (prosthetic valves). 4. Stretococcus feacalis from the intestine 5. Other agents causing endocarditis include gram-negative bacilli, fungi, rickettsiae (Q fever), and chlamydiae. 6. In about 10% of cases of endocarditis, no organism can be isolated from the blood ("culture-negative" endocarditis). 21 12/11/2013  Pathogenesis 2 factors are needed to establish endocardial infection: Endothelial denudation over valve cusp with platelet deposition (thrombus) Episode of bacteremia Endothelial damage can be due to turbulent flow in the setting of diseased cardiac valves , septal defects or direct trauma from intravascular devices platelet / fibrin clot is formed over the exposed underlying extracellular matrix as the reparative process ensues Organism proliferates within the thrombus, forming infective vegetations, which elicits inflammatory response and damage  Pathogenesis (in brief): So, clinico-pathological effects result from the 3 mechanisms:- (1) embolism (septic) (2) immune complex vasculitis and (3) Direct infection (e.g. of the heart) & the presence of the bacteria in blood (antigenemia/bacteremia) ➔ fever, splenomegaly N.B. these explains most of the features in the coming 3 slide. 23 12/11/2013  Infective Endocarditis (IE) Pathology (in the heart and other organs): a) Endocarditis complicated by the presence of :- 1- Vegitations on the heart valves, features are: - Friable, bulky, and destructive. Contain: fibrin, inflammatory cells, and bacteria or other organisms. May be single or multiple May involve more than one valve. Detachable ➔embolism ➔infected infarcts and in the brain vessels cause mycotic aneurysms. 2- Erotion into the underlying myocardium by the vegetations producing an abscess cavity (ring abscess). 24 12/11/2013  Infective Endocarditis (IE) b) Systemic emboli may occur ➔infracts abscesses often develop at the sites of such infarcts (septic infarcts). Or aneurysms (mycotic aneurysms) c) Immune complex deposition➔ glomerulonephritis, cutaneous and subungal bleedings, …… d) Splenomegaly 25 12/11/2013  Clinicopathological features Vague constitutional symptoms such as fever, rigors, night sweats, anorexia, weight loss, arthralgia, (bacteremia and antigenemia) Development of new murmur or change in nature of an existing murmur (valvular damage) Skin lesions (immune complex): Osler nodes: tender lesions found on finger pulps and thenar / hypothenar eminences Janeway lesions: transient, nontender macular papules on palms or soles. dermal. micro abscess Splinter hemorrhages Petechiae (embolic or vasculitis) Clubbing: in long standing disease Eyes: Roth spots (boat shaped hemorrhages with pale centers, in retina) and conjunctival splinter hemorrhages immune complexes and vasculitis Neurological (embolic) and renal manifestations both (embolic and immune complex) Splenomegaly (bacteremia and antigenemia) & splenic infarction due to emboli  Investigations Diagnostic Tests: 1) Blood Culture: the main diagnostic lab test. & 2) Echocardiography: to See vegetations. Blood count: normochromic normocytic anemia, neutrophilia. High ESR Renal and liver function test: raised levels of creatinine, & of liver enzymes. High CRP Urine microscopy: microscopic hematuria is common in early disease Electrocardiography (ECG): ECG regularly (daily if aortic or septal root abscess is suspected) Culture negative endocarditis: Serology or PCR  Complications of IE 1- Cardiac : Valvular stenosis or insufficiency Perforation, rupture and aneurysm of valve leaflets Abscess in the valve( ring abscess) Myocardial abscesses Suppurative pericarditis Cardiac failure from one or more of the foregoing complications Peri annular abscess(Aortic root abscess) 2- Extracardiac: Emboli to the kidney ,spleen ,brain, lung  Non bacterial thrombotic endocarditis NBTE also known as Marantic endocarditis ▪Defininition: Vegetations on the valve surface, rich in fibrin and platelet aggregates but devoid of inflammation or infective organisms. ▪Causes: – Malignancies: e.g ca pancreas, ca lung, ca breast, – Autoimmune diseases: (Liebmann sack endocarditis) (Verrucous ) associated with SLE, Antiphospholipid syndrome, vasculitis, Bechet's disease – Hypercoagulability states: DIC, protein C&S deficiency, microangiopathy – Chronic inflammatory diseases: Tuberculosis, Uncontrolled HIV, Chronic pyelonephritis and chronic osteomyelitis  NBTE Pathogenesis & Pathology Thrombotic endocarditis develops due to endothelial damage and subsequent exposure of the subendothelial connective tissue to circulating platelets The factors involved in pathogenesis can be divided into initiating NBTE and subsequent development of vegetation. Initiation Factors: (a) immune complexes: Liebman-Sacks endocarditis is the prototype associated with SLE (b) hypoxia (c)hypercoagulability: DIC & (d) carcinomatosis: Mucin producing adenocarcinoma from the gut, lung and ovary and acute promyelocytic leukemia are common. Pathology : Deposition of vegetation on the leaflets of the valves, which are: small masses of fibrin, platelets, and other blood components. Can cause: Cardiac failure Secondary to valvular dysfunction (most commonly mitral regurgitation), Systemic thromboembolism, e.g. Cerebrovascular thromboembolism Secondary infective endocarditis  VALVULAR DEGENERATION CAUSED BY CALCIFICATION Calcific deposits (composed of calcium phosphate mineral) can occur on valves. Conditions :- -calcific aortic stenosis -calcification of a congenitally bicuspid aortic valve, and -mitral annular calcification 31 12/11/2013  MITRAL VALVE PROLAPSE MYXOMATOUS DEGENERATION OF THE MITRAL VALVE In this valvular abnormality, one or both mitral leaflets are "floppy" and prolapse, or balloon back into the left atrium during systole most often in young women Histologically: 1) The essential change is attenuation of the fibrosa layer (f) Accompanied by 2) Focal thickening of the spongiosa layer (s). 3) Deposition of mucoid (myxomatous) material N.B. in histopathology mucous (mucoid) = Myxoma) 32 12/11/2013  Carcinoid heart disease Occurs as a sequalae of a rare neuroendocrine malignancy in which vasoactive substance serotonin( 5 Hdroxy tryptamine) leads to deposition of carcinoid plaque on the right-sided heart chamber and tricuspid valve 33 12/11/2013  References ❑ Robbin basic pathology ❑ https://www.pathologyoutlines.com/topic/heartnontumornoninfecendo.html ❑ Amita R. Infective endocarditis. PathologyOutlines.com website. ▪ Pedro Apolinário, Isabel Campos, Cátia Oliveira, Carina Infective endocarditis: Epidemiology &prognosis,Revista Portuguesa de Cardiologia,Volume 41, Issue 4,2022, pages 283-294