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Cardiovascular Pathology (modification of Dr. Veinots presentation) Michel Dionne MD FRCPC for John P. Veinot MD FRCPC Professor of Pathology University of Ottawa Pathology and Laboratory Medicine Ottawa Hospital You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation online or distribute it without the permission of the author. Overview uAtherosclerosis uAneurysms uIschemic heart disease uCardiomyopathies uValvular heart disease uHypertension CVS Anatomy 101 Endothelium adventitia intima media muscular artery Aorta Media of aorta an elastic artery Atherosclerosis u Disease of large and medium sized arteries (elastic and muscular), particularly: aorta, iliac, coronary, popliteal, carotid, circle of Willis u Develop intimal lesions called atheromas or atheromatous plaques which: protrude into the lumen resulting in stenosis (narrowing of lumen) and possibly occlusion (lumen blocked) can weaken the underlying media, possibly leading to aneurysm formation Atherosclerosis - risk factors uHyperlipidemia high LDL low HDL uHypertension uSmoking uDiabetes uAge uMale gender uFamily history/ genetics Other: physical inactivity, diet, obesity etc. Atherosclerosis - pathogenesis uChronic endothelial injury* resulting in endothelial dysfunction increased permeability increased adhesion of leukocytes (monocytes and lymphocytes) and platelets accumulation of lipids in intima uMigration of monocytes into intima leading to formation of foam cells (lipid-laden macrophages) uRelease of cytokines and growth factors result in smooth muscle cell migration into intima, proliferation of smooth muscle cells, deposition of extracellular matrix (e.g. collagen) * From hemodynamic forces, hyperlipidemia, HTN, smoking etc. From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition Aorta fatty streaks Aorta fibrofatty/atheromatous plaques Aorta complicated plaques Aortic arch vessels advanced plaques causing severe stenosis Coronary artery Atheromatous material foam cells (lipid laden macrophages) and cholesterol clefts From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition Atherosclerosis - complications u Calcification u Plaque hemorrhage and rupture u Plaque erosion/ulceration u Thrombosis u Embolization of atheromatous material (atheroemboli) u Aneurysm formation and rupture Renal infarct from embolization Atherosclerosis - major consequences u Symptomatic disease most often affects the heart, brain, kidneys and lower extremities Heart: angina and myocardial infarction Brain: cerebral infarction (stroke) Aorta (particularly abdominal): Aneurysms Stenosis of ostia of major branches leading to visceral ischemia Lower extremities: peripheral vascular (arterial) disease claudication, gangrene Aneurysm - definition a localized abnormal dilatation of a vessel Aneurysm types Atherosclerotic aneurysms are the most common, but there are other types! Aneurysms - complications uStasis of blood uThrombosis u obstruction u embolism uMass effect uRupture Abdominal Aortic Aneurysm (AAA) thrombus Aneurysm rupture thrombus tear vessel wall blood lumen AAA rupture Hemorrhage into surrounding tissue Dissecting “aneurysm” Coronary artery aneurysms secondary to vasculitis (inflammation of blood vessels) Left atrium Right ventricle Left ventricle Right atrium Pericardium Right lung Left lung Aorta SVC Right atrium Left atrium Right ventricle Left ventricle Interventricular septum Coronary artery anatomy /diagnoseCAD.html Coronary artery atherosclerosis uaffects the epicardial arteries; tends to be more pronounced in the proximal portion of these vessels ucan involve 1, 2 or all 3 of the main vessels +/- their large branches uif degree of obstruction is significant, can result in angina (pain from myocardial ischemia) uan atherosclerotic plaque can become unstable (acute plaque lesion): intraplaque hemorrhage plaque rupture or erosion resulting in thrombosis uacute plaque lesions can result in an “acute coronary syndrome” (unstable angina, myocardial infarct) Myocardial infarct terminology Recent MI - about 24 hours old Contraction band necrosis Recent MI - about 3 days old Recent MI - interstitial infiltrate of neutrophils Recent MI - 5-7 days old Recent MI - 7-10 days old Residual necrotic myocytes Phagocytosis of dead cells at margin of infarct “Sick” myocytes bordering the infarct Remote myocardial infarcts Transmural rupture Infarct rupture and tamponade Papillary muscle rupture Left ventricle aneurysm Ischemic heart disease - interventions Non-surgical uthrombolysis uPTCA / stenting uatherectomy urotablation Surgical uCoronary Artery Bypass Grafting (CABG) typically using saphenous vein grafts and/or internal thoracic arteries uendarterectomy Atherectomy device PTCA balloon Angiogram pre/post PTCA Aortic valve - normal Mitral valve - normal Aortic stenosis - causes Aortic stenosis causing LVH Mitral stenosis - rheumatic Floppy mitral valve - mitral valve prolapse (MVP) Hypertension uPRIMARY (ESSENTIAL) Genetic and environmental factors Defects in sodium homeostasis, vascular smooth muscle structure, regulation of vascular tone uSECONDARY renal disease vascular disease endocrinopathies drugs neurogenic etc Reno-vascular hypertension Hypertension - complications uenhance other diseases (risk factor) usmall vessel changes scarring/sclerosis microaneurysms ularge vessel changes ectasia / aneurysms / aortic regurgitation dissection uvessel rupture ucardiac hypertrophy uetc Arteriolo-nephrosclerosis Brain hypertensive bleed Hypertensive brain stem bleed LVH (look familiar?) Cardiomyopathy - definition uHeterogenous group of diseases of the myocardium associated with mechanical or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. uCardiomyopathies are either confined to the heart or are part of generalized systemic disorders often leading to cardiovascular death or progressive heart failure related disability. Circulation 2006 113:1807-1816 Cardiomyopathy types (clinical/functional/morphologic patterns) u Dilated (DCM) 90% u Hypertrophic (HCM) u Restrictive Primary cardiomyopathy (confined to the heart) - etiology uGenetic e.g. HCM, ARVC, mitochondrial defects, channelopathies (e.g. LQTS) uAcquired e.g. due to myocarditis (inflammation of the myocardium) uMixed uIdiopathic Secondary cardiomyopathy (part of generalized systemic disorder) examples of etiologies uAmyloidosis uHemochromatosis uSarcoidosis uMedication/Toxin induced - e.g. cancer chemotherapy, alcoholism uAutoimmune diseases - e.g. SLE, rheumatoid arthritis uInfections uEndocrine disorders - e.g. hypothyroidism uNeuromuscular diseases - e.g. muscular dystrophies uStorage diseases - e.g. glycogen storage disease uNutritional deficiencies - e.g. thiamine Primary dilated cardiomyopathy uPrimary myocardial abnormality uNO SIGNIFICANT: coronary artery disease valve disease systemic arterial hypertension systemic disorder, history of toxin exposure etc. Non-specific myocardial degenerative changes DCM - clinical presentation uProgressive heart failure systolic dysfunction 4 chamber dilatation hypokinesis uArrhythmias uThromboembolism uSudden death Familial (genetic) DCM uAbout 30 % of DCM uOften asymptomatic LV dilatation at detection - minority progress uExamples: muscular dystrophy mitochondrial defects - maternal inheritance inherited metabolic disorders Cardiomyopathy genetic abnormalities Dilated - cytoskeletal elements largely affected udystrophin - X-linked, some muscular dystrophies ulamin udesmin uactin uetc umitochondrial genes Hypertrophic - contractile elements affected (sarcomeric genes) umyosin utroponin utropomyosin umyosin binding protein C uetc Viral myocarditis and DCM uEnteroviral protease cleaves dystrophin uDi