Integrated Microbiology And Pathology 2024 PDF

Welcome To Integrated Microbiology And Pathology YIHS300  Faculty of Health Sciences Medical School 2024 Cardiovascular diseases Systemic pathology Integrated Pathology &Microbiology YIHS300 Topic overview Cardiac pathology is the leading cau...

Welcome To Integrated Microbiology And Pathology YIHS300  Faculty of Health Sciences Medical School 2024 Cardiovascular diseases Systemic pathology Integrated Pathology &Microbiology YIHS300 Topic overview Cardiac pathology is the leading cause of morbidity and mortality. This lecture series is approached from an anatomical perspective ,the diseases reviewed in accordance to the layer of the heart in which the pathology is present namely endocardium , myocardium or pericardium. The endpoint to all pathological processes in this system is cardiac failure. Congenital heart disorders and cardiac neoplasm is reviewed briefly.  Learning outcomes Heart Failure Discuss right heart failure in terms of pathogenesis, clinical features, pathologic features, and the short-term and long-term consequences. Discuss left heart failure. in terms of pathogenesis, clinical features, pathologic features, and the short-term and long-term consequences Compare and contrast left and right heart failure in terms of pathogenesis, clinical features, pathologic features, and the short-term and long-term consequences. Ischemic Heart Disease. Explain how ischemic heart disease can progress while remaining entirely free of symptoms for many years. Angina: Compare and contrast the clinical, physiologic, and morphologic differences between stable angina and unstable angina. Compare and contrast the gross and microscopic features and pathophysiologic changes of acute myocardial infarction Describe the spectrum of changes that occur in myocardial infarction at specific times. Identify short term and long-term complications of myocardial infarction.  Learning outcomes Congenital Heart Disease. Name the most common forms of congenital heart disease and outline their clinical presentation, natural history, and long- and short-term complications. Name several common genetic disorders associated with congenital heart disease, describing the clinical presentations and pathogenesis. Describe a paradoxical embolus and its relationship to congenital heart disease. Define the concepts of left-to-right shunt, right-to-left shunt, and shunt reversal and correlate with clinical presentation. Cardiac Inflammatory Conditions Describe the major cardiac and extracardiac manifestations of rheumatic fever, including its effect on the endocardium, myocardium, and pericardium. Compare and contrast the effects of rheumatic fever and bacterial endocarditis on the heart. Describe the two major patterns of infective endocarditis and the pathologic changes seen in the cardiac valves. Discuss the pathologic features of noninfective endocarditis on the cardiac valves. Describe the clinicopathologic features and common causes of myocarditis and their consequences. Summarize the common causes of pericarditis and the resultant clinicopathologic features.  Learning outcomes Valvular Dysfunction Discuss the underlying causes, clinicopathologic features, and complications associated with cardiac valvular stenosis. Describe the etiologies, clinicopathologic features, and complications of cardiac valvular insufficiency. Compare and contrast valvular stenosis and insufficiency. Outline cardiac disorders that lead to valvular stenosis and insufficiency. Hypertension Describe the pathogenesis and the gross and microscopic adaptive changes in the myocardium that result from pulmonary hypertension. Discuss the pathogenesis and the gross and microscopic adaptive changes in the myocardium that result from systemic hypertension. Describe the mechanisms and epidemiology of primary hypertension and discuss the causes of secondary hypertension. Cardiac Neoplasms Compare and contrast the pathogenesis and clinicopathologic features of primary and secondary cardiac tumors Learning outcomes Pericardial disease Classify Pericarditis: Acute, Chronic , constrictive Compare contrast the clinical features of haemopericardium(acute effusion ) and that of constrictive pericarditis Discuss the pathology of chronic pericarditis associated with infections namely : rheumatic fever and Tb. Discuss the aetiopathogenesis and clinical presentation of haemopericardium(cardiac tamponade) Diseases of the myocardium Myocarditis. Describe the clinicopathologic features and common causes of myocarditis and their consequences. Cardiomyopathy Compare and contrast the clinicopathologic features of dilated, restrictive, and hypertrophic cardiomyopathies Cardiac failure Failure of the heart pump to adequately meet the metabolic demands of peripheral tissues, or only at elevated filling pressures i.e. decreased cardiac output and tissue perfusion Heart failure results when these adaptive mechanisms are overwhelmed: o Systolic heart failure: decreased ejection fraction (normal = 45-65%) due to progressive deterioration of myocardial contractile function Causes include ischaemia, pressure or volume overload from hypertension or valvular disease, or ventricular dilation o Diastolic heart failure (heart failure with preserved ejection fraction): inability of the heart chamber to relax / expand and fill sufficiently during diastole. Causes include left ventricular hypertrophy e.g. from hypertension, myocardial fibrosis, cardiac amyloidosis, constrictive Pericarditis Cardiac failure Source: Pathology Illustrated Roberts, Fiona, BSc MD FRCPath; 2021  Aetiology 1. Intrinsic pump failure weakening of the ventricular muscle due to disease so that the heart fails to act as an efficient pump. Ischaemic heart disease Myocarditis Cardiomyopathies Metabolic disorders eg beriberi Disorders of the rhythm eg. Atrial fibrillation and flutter. 2. Increased workload on the heart results in increased myocardial demand resulting in myocardial failure. increased pressure load: systemic and pulmonary arterial hypertension. valvular disease eg Mitral stenosis, aortic stenosis, pulmonary stenosis. chronic lung diseases. increased volume load: valvular insufficiency severe anaemia thyrotoxicosis arteriovenous shunts hypoxia due to lung diseases. 3. Impaired filling of cardiac chambers decreased cardiac output and cardiac failure may result from extra-cardiac causes or defect in filling of the heart: Cardiac tamponade e.g. Haemopericardium, hydropericardium Constrictive pericarditis. Cardiac Compensation Compensatory mechanisms: cardiac hypertrophy and dilatation In order to maintain normal cardiac output, several compensatory mechanisms active : Compensatory enlargement in the form of cardiac hypertrophy, cardiac dilatation, or both. Tachycardia (i.e. increased heart rate) due to activation of neurohumoral system e.g. release of norepinephrine and atrial natrouretic peptide, activation of renin-angiotensin-aldosterone mechanism.  if there is just an increased in pressure load then it leads to cardiac Cardiac hypertrophy (Without dilatation ) hypertrophy without dilation but if there is increased pressure load and increase volume load then it leads to both cardiac hypertrophy and dilation Defined as an increase in size and weight of the myocardium. Results from increased pressure load. Increased volume load (e.g. Valvular incompetence) results in hypertrophy with dilatation of the affected chamber Aetiology of Cardiac hypertrophy(Without dilatation ) Right ventricular hypertrophy Left ventricular hypertrophy Pulmonary stenosis and insufficiency Systemic hypertension Tricuspid insufficiency Aortic stenosis and insufficiency Mitral stenosis and/or insufficiency Mitral insufficiency Chronic lung diseases Coarctation of the aorta Left ventricular hypertrophy and failure Occlusive coronary artery disease Congenital anomalies like septal defects and patent ductus arteriosus Conditions with increased cardiac output e.g. thyrotoxicosis, anaemia, arteriovenous fistulae.  Cardiac dilatation Hypertrophy +cardiac dilatation due to Increased volume load (e.g. Valvular incompetence) causes increase in length of myocardial fibres and hence cardiac dilatation as a compensatory mechanism. Causes Valvular incompetence) Left-to-right shunts e.g. in VSD Conditions with high cardiac output e.g. Thyrotoxicosis, Arteriovenous Shunt ,Anaemia, Pagets Disease of the Bone Beri Beri Myocardial diseases e.g. cardiomyopathies, myocarditis Systemic hypertension Morphologic features Hypertrophy of the myocardium without dilatation is referred to as concentric, with dilatation = eccentric. Concentric hypertrophy: the lumen of the chamber is smaller than usual Eccentric hypertrophy the lumen is dilated. Weight of the heart is increased over 500 gm. LV wall : Thickness =/>above 15 mm (excluding trabeculae carneae and papillary muscles) Microscopic features There is increase in size of individual muscle fibres, multiple minute foci of degenerative changes and necrosis in the hypertrophied myocardium. Causes of cardiac failure Pathophysiology Of Symptoms And Signs  Backward and forward heart failure According to this hypothesis Backward heart failure If either of the ventricles fails to eject blood normally, there is a rise of end-diastolic volume in the ventricle and increase in volume and pressure in the atrium which is transmitted backward producing elevated pressure in the veins. Forward heart failure Forward heart failure is the result of impaired myocardial function and results in diminished cardiac output( Decreased systolic function) and cardiogenic shock. Diminished renal perfusion and activation of renin- angiotensin-aldosterone system. Common causes of forward heart failure include Dilated Cardiomyopathy Myocardial failure secondary to end-stage chronic valvular disease, Physical examination :forward heart failure include Decreased myocardial function in combination with hypotension. Heart sounds diminished/heart murmur and/or gallop rhythm Clinical signs of hypoperfusion:hypothermia, pallor, delayed capillary refill time, tachycardia, and poor pulse quality. Pulmonary oedema or pleural effusion will produce characteristic changes on auscultation. Dyspnoea in cardiac failure Acute Pulmonary Oedema In acute left ventricular failure , accumulation of fluid results in dyspnoea and hypoxaemia Chronic Venous Congestion of the Lungs The results of chronic combined (congestive) failure and/or chronic left ventricular failure: The lungs are bulky, congested and brownish in colour..  Left sided cardiac failure Causes Clinical features and morphologic effects Ischaemic heart disease clinical manifestations of left-sided heart failure result from decreased left ventricular output and hence Systemic Hypertension there is accumulation of fluid upstream in the lungs. Aortic and mitral valvular 1. Passive congestion in pulmonary circulation(earliest) diseases-(stenosis) Primary myocardial diseases Cough and dyspnoea initially only with exertion but later also when lying flat (orthopnoea), at night :cardiomyopathy (paroxysmal nocturnal dyspnoea) Myocarditis Pulmonary congestion and oedema with haemosiderin-laden macrophages (‘heart failure cells’) Restrictive pericarditis Pleural effusion results from transudation of fluid due to elevated pleural capillary and lymphatic pressure 2. Blood stasis in left heart chambers - Usually left ventricular hypertrophy and dilation (except for heart failure due to mitral stenosis and restrictive cardiomyopathies) - Secondary left atrial dilation usually follows with mitral regurgitation, blood stasis especially in the atrial appendage and risk of thrombus formation, atrial fibrillation that further reduces ventricular filling and ventricular stroke volume 3. Organ dysfunction from inadequate peripheral perfusion - Kidneys: Decreased renal perfusion activates the RAAS as a compensatory mechanism, leading to salt and water retention and expansion of interstitial and intravascular fluid volumes (which further worsen pulmonary oedema). Severe renal hypoperfusion results in pre-renal azotaemia - Brain: Hypoxic encephalopathy with altered mental status Congested cardiac failure Hepatomegaly due to CPVC+ fatty change. Congestion of the systemic venous circulation is a result Distension of of the veins causes enlargement of the liver. The of right heart failure. The basic mechanism is: parenchymal cells furthest from the arterial blood supply, i.e. around the hepatic venules, undergo degeneration with atrophy and ultimately disappear. Cells nearer the arteries show an accumulation of fat. Fluid Retention----leads to Pleural effusion and ascites due reduced output from the LV: the mechanism involves retention of sodium and water. Low Output Failure In cardiac failure output is low with respect to body requirements, and is lower than the normal output. High cardiac output failure The cardiac failure complicates a pre-existing state in which the output before failure was greater than normal. Although cardiac output is higher than the normal , it is still insufficient to meet the body requirements In both types of failure, venous overfilling IS PRESENT , but in high output failure venous overfilling is usually present before failure ensues, reflecting the increased blood volume. Right sided cardiac failure Aetiology Clinical features and morphologic effects Consequence of LVF Irrespective of the underlying cause, the clinical manifestations of right-sided heart failure are Cor pulmonale upstream of the right heart such as systemic (due to caval blood) and portal venous congestion, and Pulmonary or tricuspid reduced cardiac output. valvular disease. Pulmonary hypertension 1 Blood stasis in right heart chambers secondary to pulmonary :Hypertrophy and dilation of right atrium and ventricle thromboembolism. Reduced cardiac output resulting in circulatory stagnation causing anoxia, cyanosis and coldness of Myocardial disease extremities. affecting right heart. 2. Engorgement of portal venous system Congenital heart disease Liver: Congestive hepatomegaly due to passive congestion around the central veins +/- centrilobular with left-to-right shunt necrosis and fibrosis (‘cardiac cirrhosis’) Spleen: Congestive splenomegaly due to portal venous hypertension, resulting in platelet sequestration Bowel: Chronic congestion and oedema of the bowel wall can interfere with nutrient and/or drug absorption 3. Engorgement of systemic venous system - Pleural, pericardial and peritoneal effusions (ascites) - Peripheral oedema (especially in dependent areas) If severe, generalised (anasarca) - Kidneys: Renal congestion leads to renal ischaemia and its consequences, worsening fluid retention - Brain: Venous congestion and hypoxia can manifest as altered mental status Systemic (left-sided) hypertensive heart disease Defined as: 1. Left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular pathology; 2. Clinical history or pathologic evidence of hypertension in other organs (e.g. kidney) Pathogenesis Stimulus to LVH is pressure overload on the ventricular wall. myocardial fibres hypertrophied. Genetic and haemodynamic factors contribute to LVH. Macroscopic changes: Marked hypertrophy of the heart, >left ventricle, Weight increases to 500 gm or more (normal weight about 300 gm). LV Thickness wall increases from its normal 13 to 15 mm up to 20 mm or more. The increased thickness IN LV wall causes stiffness that impairs diastolic filling , leading to left atrial enlargement Initially, there is concentric hypertrophy of the left ventricle (without dilatation) With cecompensation and cardiac failure supervene, there is eccentric hypertrophy (with dilatation) with thinning of the ventricular wall and there may be dilatation and hypertrophy of right heart as well. Clinical presentation: Atrial fibrillation due to left atrial enlargement, Development of ischaemic heart disease (due to hypertension potentiating coronary artery disease and increased risk of ischaemia due to hypertrophic muscle) Progressive congestive heart failure or sudden cardiac death, or Direct effects of hypertension on other organs (renal damage, stroke) Hypertensive heart disease  Pulmonary (right-sided) hypertensive heart disease (COR Pulmonale) Right side heart disease resulting from disorders of the lungs. Characterised by rv dilatation or hypertrophy, or both. Depending upon the rapidity of development, cor pulmonale may be acute or chronic: Acute occurs following massive pulmonary embolism resulting in sudden dilatation of the pulmonary trunk+ rv Chronic preceded by chronic pulmonary hypertension PATHOGENESIS chronic lung diseases + diseases of the pulmonary vessels cause increased pulmonary vascular resistance. Pulmonary hypertension causes pressure overload on the right ventricle and hence right ventricular enlargement. Gross: In Acute Cor Pulmonale, there is characteristic ovoid dilatation of the right ventricle without hypertrophy , +/- right atrium. In there is increase in thickness of the right ventricular wall from its normal 3 to 5 mm up to 10 mm or more. Chronic COR PULMONALE can lead to compression of the left ventricle or tricuspid valve thickening and regurgitation Myocardial ischaemia Myocardial ischaemia imbalance between myocardial supply (perfusion) and cardiac metabolic demands. LV more prone due to greater bulk, work requirement and its higher oxygen demand. Aetiology Reduced blood flow from atherosclerosis in the coronary arteries (coronary artery disease); coronary emboli, myocardial vasculitis, vascular spasm; Conditions that reduce oxygen availability in blood e.g. anaemia Pathogenesis: IHD is usually due to either chronic progressive atherosclerosis and or superimposed acute plaque change, thrombosis and vasospasm o Chronic vascular occlusion: >90% of patients with IHD have atherosclerosis in one or more of coronary arteries and/or its branches. >70% occlusion (critical stenosis) results in exertional angina; >90% occlusion causes inadequate perfusion even at rest. However, slowly developing obstruction can induce formation of collateral vessels to perfuse at-risk myocardium o Acute plaque change sudden conversion of a stable atherosclerotic plaque to an unstable life-threatening atherothrombotic lesion through rupture, erosion, ulceration or deep haemorrhage, which occludes the artery Manifests as acute coronary syndromes (unstable angina, acute myocardial infarction, sudden death) Four common clinical presentations of myocardial ischaemia Angina pectoris, acute myocardial infarction, chronic ischaemic heart disease with heart failure, sudden death: 1.Angina pectoris: episodes of chest discomfort caused by transient myocardial ischaemia insufficient to cause infarction 2.Acute myocardial infarction (AMI) (‘heart attack’): Myocardial necrosis from prolonged ischaemia Usually due to atherosclerosis Frequency also increases with age; for middle age, m>f but for postmenopausal women Pathogenesis: Coronary arterial occlusion: 90% from acute plaque change with superimposed Thrombus formation) Area at risk = anatomic region supplied by that artery eg. Left anterior descending branch (LAD)CA Extent necrosis depends On location Rate of development and duration of blood flow deprivation; Size and metabolic/oxygen needs of the area at risk Extent of vascular collaterals; Presence of coronary artery spasm and other factors E.G. Blood oxygenation, cardiac rhythm, HR Evolution of Acute myocardial infarction Non-transmural (subendocardial) infarcts can Under what conditions does (subendocardial) infarcts occur ? 1. When the coronary thrombus from acute plaque change lyses before transmural necrosis occurs. 2. Prolonged severe reduction in systemic hypotension e.g. shock on top of chronic otherwise non-critical coronary stenoses; tend to be circumferential in distribution Clinical features: Crushing prolonged chest pain (>30 mins) with breathlessness, diaphoresis, nausea ,vomiting ECG: ST elevation in transmural infarcts; non-ST elevation infarcts in subendocardial infarcts. Consequences and complications: Mortality for out-of-hospital AMI much worse than in-hospital death rates. ~75% of patients experience complications after AMI, depending on the infarct size, location, transmural vs subendocardial infarct: Contractile dysfunction(cardiogenic shock if severe) Complications Papillary muscle dysfunction(causing postinfarct mitral regurgitation) Myocardial rupture (~1-5%, fatal) - occurs 3-7 days after infarction, when lysis of necrotic myocardium is greatest Left ventricular free wall rupture:resulting in haemopericardium and cardiac tamponade; Ventricular septum rupture creating a VSD with left-to-right shunting; Papillary muscle rupture with mitral regurgitation. Arrhythmias: the infarct causes myocardial irritability and conduction disturbances that can cause sudden death (greatest risk in 1st hr post-MI) Pericarditis: fibrino haemorrhagic, in transmural Acute MI (usually 2-3 days after Acute MI. Dressler syndrome = intense pericarditis weeks after MI due to formation of antibodies against damaged myocardium Mural thrombus: due to combination of stasis (decreased contractility), chamber dilation and endocardial damage (forming a thrombogenic surface); risk of thromboembolism Ventricular aneurysm: late complication, due to a large transmural anteroseptal infarct that heals with formation of thin scar tissue (risk of mural thrombi, arrhythmias and heart failure but does not rupture because it is fibrous) Ventricular remodelling: compensatory hypertrophy and dilation of the non-infarcted segments of the ventricle; initially adaptive but can be maladaptive due to increased oxygen demand exacerbating ischemia and decrease cardiac output Morphological changes occurring following myocardial infarction. Restoration of tissue perfusion: Reperfusion injury can occur and modify overall infarct size and the return of function of salvaged myocardium may thus be delayed for hours or days (post-ischaemic ventricular dysfunction ) 3.Chronic IHD with heart failure: ischaemic cardiomyopathy Progressive congestive heart failure due to ischaemic myocardial damage and/ inadequate compensatory responses. Usually post-infarction or in severe CADX Morphology: Cardiomegaly with LVH and dilation, usually accompanied with coronary artery atherosclerosis. May have scars (healed infarcts) and mural thrombi. 4.Sudden cardiac death (SCD) Unexpected death from cardiac causes, either without symptoms or within 1-24h of symptom onset Pathogenesis: Fatal ventricular arrhythmia (e.g. asystole, ventricular fibrillation) initiated anywhere in the conduction system Aetiopathogenesis Alteration in conduction system firing due to Ischaemic injury or via heart chamber dilation that alters conduction system firing Clinical presentation: Asymptomatic, palpitations, syncope (due to decreased CO from sustained arrhythmia) or sudden cardiac death Endocardial disorders  Valvular diseases Valves of the left side of the heart are involved much more frequently than those of the right side of the heart The mitral valve is affected most often, followed in descending frequency, by the aortic valve, and combined mitral and aortic valves. Valvular deformities may be of 2 types: stenosis and insufficiency: Stenosis :failure of a valve to open completely during diastole resulting in obstruction to the forward flow of the blood. Insufficiency or incompetence or regurgitation is the failure of a valve to close completely during systole resulting in back flow or regurgitation of the blood. Diseases that may deform the heart valves : RHD, Endocarditis and its complications Myxomatous degeneration (floppy valve syndrome) Carcinoid heart disease. Acute Rheumatic Fever Inflammation and Aschoff bodies – composed of T cells, occasional plasma cells, plump macrophages called Anitschkow cells – in all 3 layers of the heart (pancarditis). Valvular vegetations (verrucae) may be present Source : Kumar et al , 2020 A-Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet (arrows). Previous episodes of rheumatic valvulitis have caused fibrous thickening and fusion of the chordae tendineae. B: Microscopic appearance of an Aschoff body The myocardium has a circumscribed nodule of mixed mononuclear inflammatory cells with associated necrosis; within the inflammation, large activated macrophages show prominent nucleoli, as well as chromatin condensed into long, wavy ribbons (= Anitschkow myocytes /caterpillar cells; arrows ) Rheumatic heart disease Rheumatic fever is an autoimmune disorder that can occur 2–3 weeks after a group A β-Hemolytic streptococcal infection. , usually tonsillitis or pharyngitis, Can result in development of rheumatic heart disease. > Children aged 5–15 years :most frequently seen in parts of central Africa, the Middle East and India. Pathogenesis Susceptible individuals develop antibodies to antigens produced by specific strains of group A beta haemolytic streptococci.These antibodies then cross-react with host antigens, causing inflammation and fibrosis. The disease is a systemic disorder affecting the heart, joints, skin and arteries. The most important target organ is the heart. Repeated attacks of rheumatic fever lead to progressive fibrosis of the endocardium and valves, which is the main cause of chronic scarring of the valves.  Cardiac manifestations of RH Disease Pancarditis : All the layers of the heart namely pericardium, myocardium and endocardium are involved. Characteristic aschoff bodies may be seen which later undergo organisation and fibrosis. 1.Rheumatic endocarditis Endocardial lesions -valvular and mural endocardium, causing rheumatic valvulitis and mural endocarditis, respectively. Rheumatic valvulitis acute RF :valve thickening and loss of translucency of the valve leaflets or cusps. multiple, small (1 to 3 mm in diameter), warty vegetations or verrucae located on the free margin of the leaflets and cusps. >vegetations on left side valves.Mitral valve Most frequently affected Gross ‘fish mouth’ or ‘button hole’ stenosis. 2. Rheumatic myocarditis tiny pale foci of the aschoff bodies may be visible throughout the myocardium. Frequent in the interventricular septum, left ventricle and left atrium. 3. Rheumatic pericarditis Gross:‘fibrinous/serofibrinous exudate = as ‘bread and butter’ pericarditis The pericardium, which is regularly smooth and bright, becomes opaque and granular,  Extracardiac lesions ‘Migratory polyarthritis :Acute and painful inflammation of the synovial membranes of some of the joints, especially the larger joints of the limbs. As pain and swelling subside in one joint, others tend to get involved, producing the characteristic ‘migratory polyarthritis’ involving two or more joints at a time. Subcutaneous nodules. painless nodules over joints (such as the elbows, knees, ankles, and knuckles), the back of the scalp, and the vertebrae (backbone) Small (0.5 to 2 cm in diameter), spherical or ovoid and painless. They are attached to deeper structures like tendons, ligaments, fascia or periosteum Erythema marginatum blanchable, nonpruritic macular rash seen on the trunk and proximal parts of the extremities. Rheumatic arteritis involves coronary arteries ,the aorta ,renal, mesenteric and cerebral arteries. Sydenham’s chorea or saint vitus’ dance a movement disorder characterized by involuntary, purposeless, widespread, fidgety or dancing movements.Delayed manifestation of RF Anti-basal ganglia antibodies attack the cells of the basal ganglia. Pleuritis is often accompanied with serofibrinous pleural effusion. Diagnostic criteria for rheumatic fever Rheumatic heart disease Chronic RHD: Leaflet thickening, commissural fusion and shortening, thickening and fusion of the tendinous cords Source :Cross et al,(2019) Mitral stenosis 40% of all patients with RHD. About 70% of the patients are women. Latent period between the rheumatic carditis and development of symptomatic mitral stenosis is 20 YRS Macroscopically valve leaflets are diffusely thickened by fibrous tissue, calcific deposits, especially towards the closing margin. In less extensive involvement, the bases of the leaflets of mitral valve are mobile while the free margins have puckered and thickened tissue with narrowed orifice; this is called as ‘purse-string puckering’. Advanced :have rigid, fixed and immobile diaphragm-like valve leaflets with narrow, slitlike or oval mitral opening, commonly referred to as ‘button-hole’ or ‘fishmouth’ mitral orifice. Effects : 1. Dilatation and hypertrophy of the left atrium. 2. Normal-sized or atrophic left ventricle due to reduced inflow of blood. 3. Pulmonary hypertension resulting from passive backward transmission of elevated left atrial pressure which causes: i) chronic passive congestion of the lungs; ii) hypertrophy and dilatation of the right ventricle; and iii) dilatation of the right atrium when right heart failure supervenes. Mitral valve disease In rheumatic heart disease, combined stenosis and incompetence are often seen. In mitral disease, the back pressure in the left atrium is transmitted to the pulmonary veins, and by raising pulmonary arterial pressure it causes effects on the right side of the heart.In the acute types of mitral incompetence, the sudden change in the intracardiac haemodynamics very seriously aggravates the heart failure already present due to the primary disease.  Mitral valve disease Acute Mitral Incompetence, sudden change in the intracardiac haemodynamics very seriously aggravates the heart failure already present due to the primary disease. Complications of chronic mitral disease 1. Atrial fibrillation is common. Fibrillation → thrombosis in atrial appendage → systemic embolism 2. Infective endocarditis. Mitral insufficiency caused by RHD in about 50% of patients but in contrast to mitral stenosis, pure mitral insufficiency occurs more often in men (75%). Associated with some degree of mitral stenosis. Morphologic features varies according to the underlying cause. In myxomatous degeneration of the mitral valve leaflets (floppy valve syndrome), there is prolapse of one or both leaflets into the left atrium during systole. In non-inflammatory calcification of mitral annulus seen in the aged, there is irregular, stony-hard, bead-like thickening. Effects : 1. Dilatation and hypertrophy of the left ventricle. 2. Marked dilatation of the left atrium. 3. Features of pulmonary hypertension such as: i) chronic passive congestion of the lungs; ii) hypertrophy and dilatation of the right ventricle; and iii) dilatation of the right atrium when right heart failure supervenes. Aortic Valve Stenosis Aetiology Scarring and calcification occurring in a congenitally abnormal valve (usually bicuspid) Anatomically normal valve previously damaged by rheumatic fever or endocarditis (bacterial). In adults, severe aortic stenosis usually requires valve replacement. Source: Pathology Illustrated Roberts, Fiona, BSc MD FRCPath; 2021  Aortic stenosis Aortic stenosis comprises about one-fourth of all patients with chronic valvular heart disease. 1. Non-calcific aortic stenosis The most common cause of non-calcific aortic stenosis is chronic RHD. 2. Calcific aortic stenosis Various causes include healing by scarring followed by calcification of aortic valve such as in RHD, bacterial endocarditis, Brucella endocarditis, Mönckeberg’s calcific aortic stenosis. EFFECTS Three cardinal symptoms Exertional dyspnoea results from elevation of pulmonary capillary pressure. Angina pectoris usually results from elevation of pulmonary capillary pressure and usually develops due to increased demand of hypertrophied myocardial mass Syncope results from accompanying coronary insufficiency. Sudden death may also occur in an occasional case of aortic stenosis Aortic Insufficiency 75% males with some having family history of Marfan’s syndrome. Macroscopic features aortic valve cusps :thickened, deformed and shortened and fail to close. distension and distortion of the ring. Effects As a result of regurgitant aortic orifice, there is increase of the LV end-diastolic volume. Leads to hypertrophy and dilatation of the left ventricle producing massive cardiac enlargement so that the heart may weigh as much as 1000 gm. Failure of the LV increases the pressure in the left atrium and eventually pulmonary hypertension and right heart failure occurs Aortic incompetence Main causes 1.Scarring of the cusps due to rheumatic fever or infective endocarditis, 2.Dilatation of the valve ring due to disease (e.G. In ankylosing spondylitis: marfan syndrome) or degeneration in old age. Source: Pathology Illustrated Roberts, Fiona, BSc MD FRCPath; 2021 Tricuspid valve incompetence Carcinoid Heart Disease Aetiology Uncertain pathogenesis Occurs in carcinoid syndrome developing in patients with extensive hepatic metastases from a carcinoid tumour: increased blood level of serotonin secreted by the tumour Effects Valves and endocardium right side of the heart. Both pulmonary and tricuspid valves +endocardium of the right chambers show cartilage-like fibrous plaques. Results in thickening and contraction of the cusps and leaflets of the valves of the outflow tracts of the right heart result mainly in pulmonary stenosis and tricuspid regurgitation  Myxomatous degeneration of mitral valve= mitral valve prolapse =‘floppy valve syndrome’ Occurs in patients between the age of 20 and 40 years More common in women. Common: Seen in 5% of general adult population. ETIOLOGY Cause not known Some cases genetically determined collagen disorder: Association with Marfan’s syndrome,Ehlers-Danlos syndrome and in myotonic dystrophy. Macroscopic features Mitral valve is affected most frequently. Ballooning or aneurysmal protrusion of the affected leaflet Microscopic features :Enlarged cusp shows loose connective tissue with abundant mucoid or myxoid material due to abundance of mucopolysaccharide  Infective (bacterial) endocarditis infection of the valvular and mural endocardium by of microorganisms Depending upon the severity of infection, BE is subdivided into 2 clinical forms: Acute bacterial endocarditis (ABE) is fulminant and destructive acute infection of the endocardium by highly virulent bacteria in a previously normal heart and almost invariably runs a rapidly fatal course in a period of 2-6 weeks. Subacute bacterial endocarditis (SABE) caused by less virulent bacteria in a previously diseased heart and progressive cardiac failure in a period of 6 weeks to a few months. Aetiology: 90% cases of BE are caused by streptococci and staphylococci Predisposing factors Bacteraemia, septicaemia and pyaemia: Bacteria gain entry to the blood stream causing transient and clinically silent bacteraemia in a variety of day-to-day procedures eg dental extractions Previously diseased heart valves, whereas the ABE is common in previously normal heart. Impaired host defences Infective endocarditis Source: Pathology Illustrated Roberts, Fiona, BSc MD FRCPath; 2021  Specific Types Of Infective Endocarditis Based on etiologic agent, following specific types of IE are described: 1. Tuberculous endocarditis: characterised by presence of typical tubercles on the valvular as well as mural endocardium and may form tuberculous thromboemboli. 2. Syphilitic endocarditis: aortic valvular incompetence. 3. Fungal endocarditis Opportunistic fungal infections like candidiasis and aspergillosis are een more commonly in patients receiving long-term antibiotic therapy, intravenous drug abusers and after prosthetic valve replacement Infective endocarditis (IE) continued Source :Cross et al,(2019)  Non-rheumatic endocarditis… …Non-bacterial thrombotic (cachectic, marantic) endocarditis Involvement of the heart valves by sterile thrombotic vegetations. Etiopathogenesis Exact pathogenesis:not clear. The following diseases and conditions are frequently associated with their presence: 1. In patients having hypercoagulable state from various etiologies. 2. Occurrence of these lesions in young and well-nourished patients is Explained on the basis of alternative hypothesis such as allergy, vitamin C Deficiency, deep vein thrombosis, and endocardial trauma. GROSS Verrucae located on mitral cardiac valves(most often). Less often aortic and tricuspid valve. Non-rheumatic endocarditis……. Atypical Verrucous (Libman-sacks) Endocarditis Aetiopathogenesis Manifestation of ‘collagen diseases’. Seen in 50% cases of acute systemic lupus erythematosus (SLE); other diseases associated with this form of endocarditis are systemic sclerosis, thrombotic thrombocytopenic purpura (TTP). Gross Most frequently involves mitral and tricuspid valves. Vegetations :small (1 to 4 mm in diameter), granular, multiple and tend to occur on both surfaces of affected valves. The vegetations are sterile unless superimposed by bacterial endocarditis. Microscopy Verrucae of libman-sacks endocarditis are composed of fibrinoid material with superimposed fibrin and platelet thrombi. Endocardium underlying the verrucae shows fibrinoid necrosis, proliferation of capillaries and infiltration by histiocytes, plasma cells, lymphocytes, neutrophils and the pathognomonic haematoxylin bodies of Gross Complications of endocarditis Prosthetic valves Prosthetic valves Endocarditis comparative summary Myocardium Myocarditis Myocarditis Cardiomyopathy Primary Cardiomyopathy ………Idiopathic dilated (congestive) cardiomyopathy This is a group of myocardial diseases of unknown cause. It is subdivided into the following 3 pathophysiologic categories: Idiopathic dilated (congestive) cardiomyopathy This type of cardiomyopathy is characterised by gradually progressive cardiac failure along with dilatation of all the four chambers of the heart. The condition occurs more often in adults and the average survival from onset to death is less than 5 years. AETIOLOGY A few hypothesis have been proposed: i) Possible association of viral myocarditis. ii) Association with toxic damage from cobalt and chemotherapy. iii) Inherited mutations. iv) Chronic alcoholism. v) Peripartum association. Macro :The heart is enlarged and increased in weight (up to 1000 gm). The most characteristic feature is prominent dilatation of all the four chambers giving the heart typical globular appearance. Primary Cardiomyopathy ………Idiopathic restrictive (obliterative or infiltrative) cardiomyopathy This form of cardiomyopathy is characterised by restriction in ventricular filling (diastolic)due to reduction in the volume of the ventricles. Restrictive cardiomyopathy includes the following entities: Cardiac amyloidosis may occur in any form of systemic amyloidosis or may occur as isolated organ amyloidosis in amyloid of ageing and result in subendocardial deposits Endomyocardial fibrosis: The endocardium and parts of inner third of the myocardium show destruction of normal tissue and replacement by fibrous tissue Löeffler’s endocarditis :a variant of endomyocardial fibrosis. However, it differs in the following respects There is a peripheral blood eosinophilic leucocytosis. The inflammatory infiltrate in the endocardium and affected myocardium consists of eosinophils Primary Cardiomyopathy ………Idiopathic hypertrophic cardiomyopathy Occurs more frequently between the age of 25 and 50 years. AETIOLOGY: i) Autosomal dominant inheritance ii) Inherited mutations Macro: cardiac enlargement, increase in weight, normal or small ventricular cavities and asymmetrical myocardial hypertrophy. The hypertrophy of the myocardium :asymmetrical and affects the interventricular septum more than the free walls of the ventricles. Micro :The classical feature is the myocardial cell disorganisation in the ventricular septum Pericardial disorders Pleural effusion and haemopericardium Pleural effusion and haemopericardium Normally, pericardial sac contains