Cardiovascular pathology Dr D S O’Briain October 2009
Cardiovascular pathology Systemic pathology Topic: 2-5 min discussion, then summary panel Segments: • Hypertension (12 panels) • Ischaemic heart disease (23 panels) • Valvular heart disease: (14) Rheumatic fever, congenital heart disease • Peripheral vascular disease: atherosclerosis (20), aneurysms (4) vasculitis (7), vessels (3) • Endocarditis, myocarditis, pericarditis: • Pathogenesis of cardiac failure (Dr Crowley) • CPC (Prof O’Leary)
Hypertension • High blood pressure is common and asymptomatic, • 25% of population >140/90 • Incidence increases: age, black, young males, older females • More severe: younger, blacks. • Consequences: Cardiac, cerebral and renal disease
Hypertension • Types: Primary 95% Secondary 5% (renal, vascular, endocrine) • Course: Benign 95% Accelerated (malignant) 5% • Compensated / decompensated. BP = Cardiac output X peripheral vascular (arteriolar) resistance. Factors: Blood volume, ECF volume, total body Na. Regulation: renin-angiotensin-aldosterone system.
Terminology How to say "we have some ideas but we're not sure of the cause" • primary • ideopathic • agnogenic • cryptogenic • essential
Essential Hypertension Pathogenesis: Sodium retention and/or vasoconstriction Upper limit of the continuous variable of blood pressure • Genetic factors (polygenic) : Twin, sibling, familial, racial (blacks), animal (rat strains) Rarely single gene defects for aldosterone metabolism, sodium resorption • Environment: Exiled Chinese incidence increased: behavior, stress, obesity, OCT Dietary sodium: animal study (rats), remote peoples exposed to salt a) defect in Na excretion b) defect in cell membrane Na or Ca transport (Ca - phosphorylation - response to vasoconstrictors) c) sympathetic response (stress, neurogenic factors)
Sodium Homeostasis Total body sodium regulates blood volume and cardiac output • Influenced by: Renin angiotensin system. Blood volume -GFR - proximal tubule Na resorption. Atrial natriuretic factor: inhibits (volume expansion -GFR -distal tubule Na resorption). • Renal vasodepressors: a) prostaglandins, b) kallikrein-kinin system, c) platelet activating factor. Vasoconstrictors: angiotensin II, catechol amines, thromboxane, leukotriene, endothelin
Hypertension - Morphology • Adaptive response to pressure or volume overload: • Myocyte cytoplasm and nucleus enlarged. New myofibrils, filaments, mitochondria, ribosomes (later degeneration, loss of myofibres, cell atrophy, interstitial fibrosis) • Left ventricle: Concentric hypertrophy (normal LV thickness 1.4 cm); dilates with decompensation
Hypertension - Effects • Compensation - none. • Decompensate - CCF • Thick wall: increases 02 requirement and diffusion distance • Dilation - eventually overstretches fibres • Myocyte degeneration and fibrosis - stiffness - impairs diastolic filling (stroke volume) • Atherosclerosis
Benign nephrosclerosis Associations: age, diabetes, hypertension. • a) Arteriole walls thickened, hyaline, and lumen narrowed • Hyaline: plasma protein, lipids, basement membrane, intracellular matrix. • b) Fibroelastic hyperplasia (interlobular & arcuate arteries) - narrowing. Reduplication of elastic lamina, increased fibromuscular tissue in media. • Secondary effects but may sustain & aggravate hypertension. • Effect - loss of tubules, interstitial fibrosis, damaged glomeruli, cortical narrowing, granular kidney surface, mild reduction in size of kidney, mild reduction in function and reserve.
Accelerated (malignant) hypertension - Clinical • Medical emergency; effects young, male, blacks • CNS: papilloedema, visual effects, encephalopathy headaches, nausea, vomiting, coma, fits • CVS: failure • Renal: proteinuria, haematuria (microscopic or gross), altered renal function, later failure 50% mortality in 3 months untreated - 50% mortality in 5 years treated. Death - uremia (CNS or CVS disease)
Hyperplastic arteriosclerosis - Pathology • De novo. • On benign hypertension. • On renal disease (GN, reflux, scleroderma ) a) fibrinoid necrosis of arterioles (fibrin ± necrotising inflammation) b) hyperplastic arteriolitis (arterioles and interlobular arteries) onion-skinning with smooth muscle and collagen. • Effect: narrowed arterioles, necrotic glomeruli, thrombosed capillaries, ischaemic atrophy, infarction, high renin, endothelial injury (activated platelets, coagulation system - thrombus).
Secondary Hypertension (Mechanisms) • Renal • a) Renin increase : renovascular • b) Volume excess: acute GN • c) Mixed. • Other (examples) • Primary hyperaldosteronism ( blood volume) • Phaeochromocytoma (vasoconstriction - (nor)adrenaline • Oral contraceptives (renin angiotensin) • Periarteritis nodosa (renin angiotensin)
Renal Artery Stenosis Goldblatt. Hypertension proportional to constriction in one renal artery (Dog). Increased renin from JGA; reverse with surgery or angiotension II antagonists. But secondary renal changes may lead to persisting hypertension • 70% have atheromatous plaque at origin of artery (males, diabetes, age) 2/3 curable • 30% fibromuscular dysplasia (females,young) 90% curable Fibromuscular thickening of intima, media or adventitia; multiple (or single) artery (or branches) unilateral (or bilateral) Morphology- In ischaemic kidney: ischaemic changes, JGA hyperplastic, arterioles normal. In other kidney: hypertensive changes. Clinical: (Bruit) IVP: small kidney, delayed function. Arteriogramvisualise stenosis, segmental beaded effect. Measure renal vein renin.
Ischaemic Heart Disease Imbalance in the supply and demand for oxygen (also for nutrients and for removal of metabolites) in cardiac muscle. • Increased demand: Exercise, emotion • Decreased supply: Reduced oxygen (anaemia, cyanosis, carbon monoxide, cigarettes). Reduced coronary flow (atheroma, thrombus, spasm, shock).
Ischaemic Heart Disease Epidemic • Causes 80% of cardiac mortality • Peaked in US in 1960s, 40% decline since • Different patterns in some Western countries • Cause of decline: • Changing lifestyle (diet, smoking, exercise) • Better therapy (CCU, thrombolysis, arrhythmia therapy, CABG, angioplasty)
Atherosclerotic Coronary Artery Disease: Distribution • Narrowing of greater than 75% is clinically significant • In 1/3 of patients one vessel is involved, in 1/3, two vessels and in 1/3, three vessels. • Sites: Proximal 2 cm of LAD and circumflex, proximal 1/3 of right coronary artery. • Less frequent: Secondary diagonal, obtuse, marginal branches and posterior descending artery. • Rare: Intramyocardial branches
Atherosclerotic Coronary Artery Disease: Clinical Syndromes • Silent Infarct • Angina Pectoris • Myocardial Infarct • Chronic Ischaemic Heart Disease • Sudden Death
Angina Pectoris • Stable: Pain with exercise, emotion or other increases in demand. • ST segment depressed—subendocardial ischaemia • Prinzmetal: Rest pain • ST segment raised —transmural ischaemia. • Due to spasm, (? cause: vasoconstrictive humoral factors, mast cells, nerves • atherosclerosis usually present. • Unstable: Pain, increasing in duration and severity with less effort or at rest, • (also called preinfarction angina or acute coronary insufficiency). • Caused by: plaque enlarging, fissured, ulcerated, ruptured, vasospasm, platelet aggregation and activation
Atherosclerotic Coronary Artery DiseaseVascular obstruction • Plaque ulceration, fissure or rupture • platelets to adhere and become activated • thrombus forms (activated thrombin transforms fibrinogen to fibrin) • release of histamine, other vasoactive factors • microemboli may occur • Vasospasm: Demonstrated angiographically • rarely causes infarct in absence of atheroma • may rupture plaque, role of nerve supply and vasoactive factors • Other: Emboli, trauma, arteritis (SLE, PAN, etc), cocaine (arrhythmia, spasm)
Myocardial Infarct - Coronary Artery Lesions • 90% of infarcts are supplied by an artery which has a thrombus over an ulcerated or fissured plaque • Platelets activated — aggregate to form thrombus (embolus) — vasospasm, occlude. • Deaths under 4 hours — 90% have thrombus; over 12 hours — 60% have thrombus (thrombolysis) • 10% without thrombus: (usually have severe atherosclerosis) Spasm, platelet aggregates, emboli (mural thrombus, endocarditis, paradoxical), arteritis, cocaine, tachycardia or arrhythmia
Evolution of infarct • 4 hours: No morphological changes (subtle ultrastructural changes). • 8 hours: Oedema, myocytolysis, contraction band necrosis, wavy fibres. • 24 hours: Grossly pale, acute inflammatory infiltrate. • Days: Infarct becomes clearly defined grossly, centre softens, a hyperaemic rim appears, granulation tissue appears. • Weeks: Organisation proceeds leaving an organised scar by about six weeks.
Myocardial Infarct, Morphology • Experimentally after 20 minutes of occlusion • ischaemic necrosis begins in the subendocardium (least collaterals and vessels most compressible) • Infarct size: • Proportional to extent and duration of ischaemia, collateral supply, metabolic demands; may be transmural or subendocardial. • Infarct site: • Left ventricle (If adjacent, right ventricle is involved in 25%, adjacent atrium in 5%) • Isolated right ventricle in 1% (usually following marked right ventricle hypertrophy and strain). • Distribution: • LAD (50%) Anterior 2/3 septum, anterior wall, apex. • RCA (35%) Posterior wall and septum. • LCA (15%) Lateral left ventricular wall • Infarcts are usually single • may extend (retrograde thrombus, vasospasm, arrhythmia), reperfusion injury.
Cardiac Enzymes • Creatine Kinase • MB isoenzyme specific for heart • Rises 4-8h, peaks 18h, falls 2-3d • Troponin T or I • Similar start, remain for 7-14d
Myocardial Infarct, Clinical • Asymptomatic (15%). • Symptomatic (60%). • Sudden pain, crushing character, retrosternal, radiation (left shoulder, arm, jaw), associated sweating, nausea, vomiting, dyspnoea, indigestion. • Sudden death (25%). • ECG: • new Q waves, ST and T wave abnormalities, arrhythmias • evolving pattern, 20% are non-specific or silent. • Enzymes: • Soluble cytoplasmic enzymes (CK 4h-4d, Troponin I and T 4h-14d • Image: Echo (mural dyskinesia), Angiography, perfusion scintography, MRI.
Effects of Myocardial Infarction • Decompensation: • Muscle is dead, injured, stunned, disorganised, • Infarct dyskinesia: • May cause aneurysm, mural thrombus, embolism. • Infarct rupture: • tamponade, septal shunt. • Papillary muscle infarct or rupture • mitral valve dysfunction • Arrhythmias provoked in injured tissue • Haemorrhagic pericarditis.
Myocardial infarct — complications • Uncomplicated (15%) • Sudden death (25%) • Arrhythmia • (sinus brady-, tachy-cardia, ventricular tachycardia, PVC, V fibrillation, asystole, block) • Left ventricular failure (60%) • Pump failure (40% of myocardium damaged) • Shock (10%) • Rupture (free wall, septum, papillary muscle) • Thromboembolism • Mortality 35% in one year (50% sudden, 25% in hospital. 10% die each subsequent year.
Percutaneous Transluminal Coronary Angioplasty • Mechanisms • Plaque compression—redistribute soft contents (most human plaques are hard) • Plaque fracture—breaking, cracking, splitting; • Stretching of plaque-free wall (70% of all, 24% severe plaques, are eccentric) • Early closure • Spasm • Thrombus • Dissection with large intimal flap • Relaxation of overstretched wall of eccentric plaque • Subintimal bleed (concurrent thrombolysis) • Late chronic stenosis (20-50%) • Fibrocellular intimal proliferation • Progression of plaque
Myocardial Infarct, Demography • Age (only 5% under 40) • Male (risk x 6 under 45, less when older) • Smoker (risk x 5, proportional to number smoked) • Other: personality (type A: increased risk), exercise and moderate alcohol protect • Western countries: risk was high, now falling
Chronic Ischaemic Heart Disease Insidious congestive cardiac failure (possibly remote myocardial infarct or angina) • Findings: possibly: left ventricular dilation, murmur, calcification • Morphology: patchy fibrosis, old infarcts • ECG: Normal, bundle branch block or non -specific changes
Sudden Cardiac Death • Ischaemic heart disease (at least 75% stenosis) • occluding thrombus in 1/2, new infarct in 1/4, old infarct in 1/3 • Other coronary artery disease: anatomic anomalies, embolism, arteritis, dissection • Myocardial disease: hypertrophic obstructive cardiomyopathy, right ventricular dysplasia, myocarditis, amyloid, sarcoid • Valve disease: aortic valve stenosis, floppy mitral valve infective endocarditis. • Conduction defects • Electrolyte abnormalities
Congestive Cardiac Failure State resulting from impaired cardiac function and resulting in insufficient output for the metabolic requirements of tissues and organs • Excess Load. • Decreased pumping ability. • Muscle fibre • a) death • b) dysfunction . • Decreased output - Forward failure. • Damming back - Backward failure.
Cardiac Failure - Compensation • Dilation: produces increased force of contraction and stroke volume (Starling) • Hypertrophy • Increased blood volume • But increased muscle mass and blood volume require more work — excess dilation — reduced efficiency No morphological difference between compensated and non-compensated heart — look for hypoxic and congestive effects remote from the heart
Left Ventricular Failure • Heart: • Hypertrophy and dilation of left ventricle (except mitral stenosis) • Lungs: • Congestion, oedema of lung and pleural space • Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, cough with frothy blood-tinged sputum • Kidney: • Decreased perfusion (ischaemic tubular changes) • renin angiotensin aldosterone system (increased NaCl, H20, ECF and blood volume) • Brain: • Hypoxia — irritable, decreased concentration and attention span, stupor, coma
Right Ventricular Failure Secondary to A) Left ventricular failure B) Other causes: cor pulmonale, cardiomyopathy, constrictive pericarditis, tricuspid and pulmonary valve disease • Liver: • Enlarged, chronic passive congestion (nutmeg) • if severe: central necrosis with fibrosis result in cardiac sclerosis (cardiac cirrhosis) • Spleen: • Enlarged, congested, dilated sinusoids and fibrotic walls • Kidney: • Congested • Subcutis: • Oedema, anasarca • Pleura: • Effusion (especially on right) • Portal System: • Congestion of GIT, spleen; ascites
Cor Pulmonale Right ventricular enlargement secondary to disordered structure or function of lungs Causes: • Lung parenchymal disease: COAD, pulmonary fibrosis, cystic fibrosis • Vascular disease: pulmonary embolism, vasculitis • Chest disorders: Kyphoscoliosis, obesity, neuromuscular disorders Effect: Narrowing of pulmonary vascular bed (hyperviscosity-polycythemia) • Pulmonary hypertension -> cor pulmonale: acute (due to eg pulmonary embolism) -or chronic). Right ventricular wall hypertrophies then dilates and fails
Rheumatic fever Acute recurrent inflammation associated with reaction to streptococcal infection. Occurs 1-5 weeks after Group A, ß haemolytic streptococcal infection, mainly children (5-15 years)
Rheumatic Fever, Jones Criteria Major criteria of Jones • Polyarthritis — sequential involvement of large joints • Erythema marginatum • Subcutaneous nodules • Sydenham's chorea — rapid purposeless movements. • Carditis Also (minor criteria): fever, arthralgia, previous rheumatic fever, prolonged PR interval, acute phase reactants (ESR, CRP or WCC increased) Jones (AHA): 2 major or 1 major and 2 minor criteria: high probability of rheumatic fever. Recent streptococcal infection increases probability
Rheumatic Fever, Pathogenesis • 1. Follows streptococcal infection but lesions sterile • 2. Streptococcal antibodies — anti streptolysin 0 (AS0) & hyaluronidase • 3. Most frequent after severe streptococcal infections • 4. Recur with repeated streptococcal infection • 5. 99.9% decline in incidence—better living conditions, antibiotics, organism has changed. • 6. Individual susceptibility — genetic.
Rheumatic Fever, Pathogenesis Aetiology : • Cross reaction • Hyaluronate of humans—streptococcal capsule. • Streptococcal membrane—muscle sarcolemma • Streptococcal M protein—cardiac myosin • Autoimmune - antiheart antibody (but ? cross reaction) Pathology: • Aschoff Body: Fibrinoid necrosis surrounded by mononuclear cells with Anitschkew cells (with caterpillar nucleus) • Pericarditis (bread &butter) • Myocarditis • endocarditis (verrucae on lines of closure) & McCallum's patches. • Heal by scarring - distort valve
Rheumatic Fever: Cardiac involvement Acute - in 2/3 of children, 1/3 of adults. Pericarditis, arrhythmias (atrial fibrillation), prolonged PR interval, auricular thrombus, cardiac dilation (MI murmur). Valve involvement (MI, AI), (death 1%)) Chronic - if first attack severe or when very young. • MV in 2/3, MV & AV 1/4, TV (Few), PV rare • Valve fibrosis, calcification, fused commissures (fish mouth) & chordae. • Mitral stenosis: LA dilation, auricular thrombus, pulmonary congestion, RVH
Congenital Heart Disease - Varieties a) Shunts: Chamber (or vessel) to chamber (or vessel). • Right to left - Early cyanosis, clubbing, hypertrophic osteoarthropathy, polycythemia (cerebral thrombosis). • Left to right - cyanose tardive. Increased pulmonary flow with vascular sclerosis, pulmonary hypertension, reversed flow (right to left). • Shunt complication. paradoxical embolism, infected embolism, infective endocarditis. b) Obstruction: Non-cyanotic. Failure to thrive, retarded development, intercurrent diseases of childhood. c) Malposition: Ectopia, dextrocardia (isolated or other anomalies) situs inversus totalis (Kartagener; sinusitis, bronchiectasis, immotile cilia).
Congenital Heart Disease - Early Cyanosis 1. Tetralogy of Fallot • VSD, overriding aorta, right ventricular outflow obstruction, RVH. • Outflow obstruction (infundibular, valve, supravalve) dictates severity. 2. Transposition (multiple combinations with atria, ventricles, vessels) • Mixing essential: ASD in all, most also have PDA, or VSD. 3. Truncus arteriosus • Common aorta & PA • Usually other cardiac defects 4. Tricuspid Atresia
Congenital Heart Disease Late Cyanosis—septal development 1. Ventricular septal defect • Development of septum (week 5-6): common ventricle divided by muscular & membranous septum 2. Atrial septal defect • Development of septum (week 4): atrial canal closed by septum primum, (ostium primum). Valve effect allows RA-LA flow, closes at birth 3. Patent ductus arteriosus • Ductus closes day 1-2 (High 02, low PGE)
Congenital Heart Disease - Late Cyanosis Ventricular septal defect Size dictates effect: • Small — 5mm: (Roger), well tolerated, 50% close spontaneously, loud murmurs & thrill, endocarditis • Large: pulmonary hypertension, shunt reverses Atrial septal defect Ostium primum defect (5%). Often Down's syndrome Ostium secundum (90%). Often other defects Patent ductus arteriosus • 90% PDA isolated (important for survival in other forms of CHD). • Machinery murmur, systolic thrill. LVH, dilated PA
Congenital Heart Disease - Obstructive 1. Coarctation of Aorta - systolic murmur & thrill • Preductal: infants, (PDA) RVH with cyanosis of lower body • Postductal: adults (PDA in 50%) • hypertension in upper body insufficiency (claudication, cold) in lower body. • Large collateral vessels: intercostal, axillary, mammary with rib notching 2. Pulmonary stenosis 3. Aortic stenosis