CRS 202 Lecture 3 - Diseases of the Heart PDF

CRS 202 Lecture 3 by Dr. Kariman Hussein Lecturer of pathology Diseases of heart 1) Endocardial diseases a- acute Rheumatic fever b-valvular diseases c- infective endocarditis 2) Myocardial diseases a- HTN b- Ischemic heart diseases (IHD) c- Myocarditis d- Cardio...

CRS 202 Lecture 3 by Dr. Kariman Hussein Lecturer of pathology Diseases of heart 1) Endocardial diseases a- acute Rheumatic fever b-valvular diseases c- infective endocarditis 2) Myocardial diseases a- HTN b- Ischemic heart diseases (IHD) c- Myocarditis d- Cardiomyopathy 3)Pericardial diseases 4)Heart failure 5) Tumors Theoretical objectives Identify endocardial heart diseases: acute rheumatic fever Valvular disorders types of endocarditis 1-Acute Rheumatic fever  Acute, immunologically mediated, multisystem inflammatory disease that occurs following a few weeks after an episode of group A streptococcal pharyngitis; occasionally, RF can follow streptococcal infections at other sites, such as the skin. Acute rheumatic carditis is a common manifestation of active RF and may progress over time to chronic rheumatic heart disease (RHD), mainly manifesting as valvular abnormalities. RHD →inflammation of all parts of the heart. RHD is the only cause of acquired mitral stenosis. Pathogenesis = cross react  Autoimmune reaction : antibodies against group A streptococcal molecules (M protein) that cross-react with host myocardial antigens and valve components. Characteristic 2- to 3-weeks delay in symptom onset after infection (time needed to generate an immune response) Streptococci are absent from the lesions. Genetic susceptibility: only 3% of infected patients develop rheumatic fever. What are the clinical features of acute RF? RF is diagnosed clinically using Jones criteria, which are divided into two groups: major and minor. The diagnosis is established when two major and one minor or one major and two minor criteria are present. These criteria are listed in the mnemonic C A R D I A C R F: Carditis Arthritis (migratory polyarthritis of the large joints) Random (involuntary) movements (chorea) Dermatologic signs (erythema marginatum= rash and nodosum= nodules) Inflammatory laboratory indices (increased erythrocyte sedimentation rate and C-reactive protein) (minor criterion) Arthralgia (minor criterion) Cardiogram (ECG) (minor criterion) Recurrent attack (previous RF) (minor criterion) Fever (minor criterion)  Clinical Features Most often in children → Acute carditis. 20% occur in adults (predominantly arthritis). < 1% of patients die of acute RF. Acute RF heals without any sequelae in most instances. However, all those who once had RF are at increased risk of recurrence and exacerbation of cardiac lesions following another streptococcal infection. Chronic rheumatic carditis develops in few number of cases. What are the features of acute rheumatic carditis (morphology)? RF involves the entire heart (i.e., it is a pancarditis). It includes: 1)Endocarditis: In the acute stages of the disease, the valves are swollen and focally covered with fibrin-rich exudate that forms nodular excrescences (‘‘vegetations’’). Because these vegetations are anchored to the valve by the underlying granulation tissue in the inflamed valves, they rarely detach to give rise to emboli. Subendocardial lesions, (perhaps exacerbated by regurgitant jets, can induce irregular thickenings) called MacCallum plaques, usually in the left atrium.  2)Myocarditis: Histologically, the myocardium contains Aschoff bodies, which heal over time and transform into fibrotic scars. 3)Pericarditis: Inflammation of the epicardial and pericardial surfaces of the pericardial sac with fibrin-rich exudate (‘‘bread and butter’’ appearance). Fibrinous pericarditis : adhesions develop between the two layers of the pericardial sac. Constrictive pericarditis: This is a rare late.  MORPHOLOGY Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet (arrows). MORPHOLOGY Aschoff body in acute rheumatic myocarditis; there is a circumscribed collection of mononuclear inflammatory cells, including some activated macrophages (Anitschkow cells). Any Question??? 2-Valvular disorders Introduction: Valvular dysfunctions are classified as: Valvular stenosis: The orifice is narrowed because the valves cannot open completely. Valvular insufficiency: The valves do not close completely, thus permitting reflow of blood from one chamber to another (regurgitation). Valvular abnormalities can be congenital or acquired. The most common congenital valvular lesion is a bicuspid aortic valve Valvular diseases (chronic) A) Rheumatic B) Degenerative A) Rheumatic The most important and the most common features of chronic RF are seen on the valves. The valves of the left ventricle (the aortic and mitral valves) are affected more often than those on the right side. Pathologically altered valves show: Deformities of the cusps Shortening and fusion of chordae tendineae Superimposed infection, which may cause ulcerations of the cusps, perforation of valves, and rupture of chordae tendineae Residual fibrinous vegetations, which often become infected with bacteria MORPHOLOGY Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets & commissural fusion “fishmouth” or “buttonhole” stenosis Surgically removed specimen of rheumatic aortic stenosis, demonstrating thickening and distortion of the cusps with commissural fusion.  B) Degenerative A) Calcific Degeneration 1-Calcific Aortic Stenosis (normal(tricuspid) or bicuspid) 2-Annular Mitral Calcification B) Myxomatous Degeneration (Mitral Valve Prolapse MVP) Calcific Aortic Stenosis Most common cause of aortic stenosis. Asymptomatic In sever stenosis → concentric left ventricular hypertrophy→ ischemia, and angina may develop → Systolic & diastolic dysfunction → CHF →50% to 80% of patients die within 2 to 3 years. In anatomically normal valves →manifests at 70s - 80s In bicuspid aortic valves →manifests at 40 - 50 years of age).  MORPHOLOGY Calcific aortic stenosis of a previously Calcific aortic stenosis of a congenitally normal valve bicuspid valve MORPHOLOGY Mitral calcification, with calcific nodules within the annulus (arrow). Left atrial view. Arrhythmias and occasionally sudden death by penetration of calcium deposits to a depth sufficient to impinge on the atrio-ventricular conduction system B)Myxomatous degeneration Primary or secondary. Primary : One of the most common forms of valvular heart disease. Females affected almost 7-fold more often than males. Secondary: male = female. Associated with mitral regurgitation caused by some other underlying cause (e.g., IHD). Pathogenesis: -Unknown. -Possible intrinsic defect of connective tissue -Common feature of Marfan syndrome (due to fibrillin-1 mutations). -In primary mitral disease, concomitant tricuspid valve involvement (20% to 40% of cases); less commonly, aortic and pulmonic valves  Clinical Features Most are asymptomatic. Minority of cases: palpitations, dyspnea, or atypical chest pain. Mid-systolic click / ECHO 3% develop complications such as mitral regurgitation and CHF, particularly if the chordae or valve leaflets rupture. Risk for infective endocarditis ventricular arrhythmias, sudden death. Stroke (thrombo-embolism). MORPHOLOGY Mitral leaflets are “floppy” and prolapse—they balloon back into the left atrium during systole (arrow) 3-Infective endocarditis (vegetations) 1- Acute endocarditis refers to destructive infections, frequently involving a highly virulent organism attacking a previously normal valve/heart. High morbidity and mortality, even with appropriate antibiotic therapy and/or surgery. 2- Sub acute endocarditis refers to infections by organisms of low virulence affecting a previously abnormal valve/heart. Insidious (even if untreated), follows a protracted course of weeks to months; most patients recover after appropriate antibiotic therapy. Both form vegetations. Neutropenia, immunodeficiency, malignancy, diabetes mellitus, and alcohol or intravenous drug abuse also increase the risk for IE and adversely affect outcomes What is the difference between acute and subacute infective endocarditis? Bacteriology: SIE is most often caused by bacteria of low virulence, such as streptococcus viridans, or commensals in the oral cavity. AIE is most often caused by highly virulent S. aureus. Infections with aerobic gram-negative bacilli or fungi are associated with fatality rate of approximately 50%. Pathology: The vegetations found in SBE are smaller, less friable, and associated with fewer destructive lesions. ABE is characterized by large fragile vegetations associated with ulceration of the valves, perforation of valves, and rupture of chordae tendineae. Clinical features??: SIE is a slowly evolving disease that usually presents with nonspecific symptoms, such as fever. Cardiac symptoms such as tachycardia, murmurs, and systemic emboli may or may not be present. In AIE, the symptoms are more pronounced and develop much faster. What is the pathogenesis of complications of infective endocarditis (Acute) ? Destruction of valves: perforation, rupture of c. tendineae, or abscesses. Stenosis may also develop in the healing stages of the disease, characterized by fibrosis and calcification of cusps. Dissemination of bacteria: The patient typically has symptoms of sepsis. Blood culture will reveal the causing bacteria. Embolization: Fragments of infected endocardial vegetations causing infarcts. Bacteria residing in the emboli and transform infarct into abscesses. Immune complexes: Antibodies form against antigens constantly released from bacteria in the infected endocardial vegetations. It circulate and deposited in glomeruli and small blood vessels. Non infective vegetations 1) Nonbacterial Thrombotic Endocarditis Deposition of small sterile thrombi. Histologically, bland thrombi that are loosely attached to the underlying valve they can be the source of systemic (sterile) emboli that produce significant infarcts in the brain or elsewhere. An underlying systemic hypercoagulable state: In debilitated patients, cancer, deep venous thromboses, or other. 2)Systemic Lupus Erythematosus Libman-Sacks endocarditis sterile vegetations. Immune complex deposition → inflammation+ fibrinoid necrosis of valve → fibrosis. Anywhere on the valve surface, on the cords, or even on the atrial or ventricular endocardium.  Major forms of vegetative endocarditis a. Acute rheumatic heart disease (RHD): small, warty, inflammatory vegetations along the lines of valve closure; as the inflammation resolves, substantial scarring can result.??? b. IE: large, irregular, often destructive masses that can extend from valve leaflets onto adjacent structures (e.g., chordae or myocardium) c. Nonbacterial thrombotic endocarditis (NBTE): small- to medium-sized, bland, nondestructive vegetations at the line of valve closure. d. Libman-Sacks endocarditis (SLE) is characterized by small- to medium-sized inflammatory vegetations that can be attached on either side of the valve leaflets; these heal with scarring. a b c d References -Pocket companion to Robbins & Cotran Pathologic Basis of Disease, 9th edition. Richard N. Mitchell, Vinay Kumar, Abul K. Abbas & Jon C. Aster. Elsevier, 2017. -Robbins & Cotran Pathologic Basis of Disease, 10th edition. Vinay Kumar, Abul K. Abbas & Jon C. Aster. Elsevier, 2018. -Pathology secrets, Ivan Damjanov. MOBSY Elsevier, 3rd edition. Thank you