Cardiovascular system and diseases II 2024.PDF

Cardiovascular system and diseases-II Atherosclerosis ◼ Ischemic heart disease ◼ Heart failure ◼ Learning outcomes To understand pathological features atherosclerosis and its complications ◼ To describe major forms of ischemic heart disease ◼ To understand causes and consequences of heart failure ◼...

Cardiovascular system and diseases-II Atherosclerosis ◼ Ischemic heart disease ◼ Heart failure ◼ Learning outcomes To understand pathological features atherosclerosis and its complications ◼ To describe major forms of ischemic heart disease ◼ To understand causes and consequences of heart failure ◼ Cardiovascular system and diseases-II Atherosclerosis ◼ Ischemic heart disease ◼ Heart failure ◼ Atherosclerosis ◼ Atherosclerosis ("hardening of the arteries") is a generic term for thickening and loss of elasticity of arterial walls ◼ Characterized by intimal lesions (atheromatous or fibrofatty plaques) which protrude into and obstruct vascular lumens ◼ Atherosclerotic plaques develop primarily in elastic arteries (e.g., aorta, carotid) and large and medium sized muscular arteries (e.g., coronary arteries) ◼ Associated with increased LDL-cholesterol and reduced HDL-cholesterol ◼ Causes of atherosclerosis are still unclear Risk Factors – non-modifiable Age ◼ Gender M>F ◼ Positive family history ◼ Genetic abnormality (eg, ACE gene) ◼ Risk Factors – modifiable Hyperlipidemia ◼ Hypertension ◼ Smoking ◼ Diabetes ◼ Obesity ◼ Physical inactivity ◼ Pathological feature - Atherosclerotic plaques ◼ Characterized by intimal lesions - atheromas (atheromatous or atherosclerotic plaques) ◼ The plaques protrude into vessel lumens ◼ The plaque consists of a raised lesion with a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters) covered by a white fibrous cap Structure of atherosclerotic plaques ◼ A superficial fibrous cap – SM cells, relatively dense collagen ◼ Beneath and to the side of the cap ("shoulder") - a more cellular area containing macrophages, T cells, SM cells ◼ Necrotic core (deep to the fibrous cap, containing lipid, debris from dead cells, foam cells, fibrin, variably organized thrombus, and other plasma proteins) ◼ The cholesterol, frequently present as crystalline aggregates or "clefts” ◼ Neovascularization at the periphery of the lesions Nature Reviews Cardiology 2015 3 principal components: 1. Cells: SMCs, macrophages, and other leukocytes 2. Extracellular matrices: collagen, elastin, proteoglycans 3. Intracellular and extracellular lipid Morphology of the Lesions ◼ Earliest aortic atherosclerosis ◼ fatty streaks lipid-filled foamy macrophages  begin as multiple minute flat yellow spots  ◼ Advanced complicated atherosclerosis in abdominal aorta many of the lesions have ruptured ◼ become thrombosed ◼ Pathogenesis Key pathogenic events ◼ Endothelial injury: increases vascular permeability, leukocyte adhesion, and thrombosis ◼ Accumulation of lipoproteins: (mainly LDL) in the vessel wall ◼ Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells ◼ Platelet adhesion ◼ Factor release from activated platelets, macrophages, and vascular wall cells → SMC recruitment and further accumulation of macrophages ◼ SMC proliferation and ECM production ◼ Lipid accumulation: both extracellularly and within cells (macrophages and SMCs) Consequences of atherosclerotic plaques ◼ Rupture, ulceration, or erosion of the intimal surface → highly thrombogenic substances → thrombosis ◼ Haemorrhage into a plaque. Rupture of the fibrous cap → intra-plaque haemorrhage → plaque rupture ◼ Atheroembolism. Plaque rupture → atherosclerotic debris into bloodstream → microemboli ◼ Aneurysm formation. Atherosclerosis-induced pressure, ischemic atrophy, loss of elastic tissue → weakness → aneurysmal dilation and potential rupture Stages of atherosclerotic pathogenesis and complications Clinical outcomes of atherosclerotic diseases The principal outcomes depend on  Size of the involved vessels  Relative stability of the plaque itself  Degree of degeneration ( underlying arterial wall) Major consequences: ◼ Myocardial infarction (heart attack) ◼ Cerebral infarction (stroke) ◼ Aortic aneurysms ◼ Peripheral vascular disease (gangrene of the legs) Cardiovascular system and diseases-II Atherosclerosis ◼ Ischemic heart disease ◼ Heart failure ◼ Ischemic heart disease Ischemic heart disease (IHD) is the leading cause of death worldwide for both men and women In more than 90% of cases, the cause of myocardial ischemia is reduced blood flow due to obstructive atherosclerotic lesions in the coronary arteries Clinical manifestations: ◼ Angina pectoris ◼ Myocardial infarction, the most important form of IHD ◼ Heart failure ◼ Sudden cardiac death Angina pectoris (chest pain) ◼ ◼ ◼ ◼ Characterized by paroxysmal and usually recurrent attacks substernal or precordial chest discomfort variously described as constricting, squeezing, choking, or knifelike caused by transient (15 seconds to 15 minutes) myocardial ischemia Patterns of angina pectoris Three overlapping patterns: 1) Stable or typical angina 2) Variant (Prinzmetal, vasospastic) angina 3) Unstable (crescendo) angina ST depression Not all ischemic events are perceived by patients (silent ischemia) Myocardial Infarction (MI) Known as "heart attack," is the death of cardiac muscle due to prolonged severe ischemia Pathogenesis: Coronary arterial occlusion Causes of coronary arterial occlusion ◼ Coronary atherosclerosis (90%) ◼ Vasospasm with or without coronary atherosclerosis ◼ Emboli from the left atrium in association with atrial fibrillation ◼ Others Clinical Features ◼ The most frequent symptom of acute myocardial infarction is severe chest pain ◼ This often develops suddenly but may build up gradually, and generally lasts for several hours ◼ Pain is usually accompanied by profuse sweating, nausea and vomiting ◼ Many patients give a previous history of angina or non-specific chest pain in the weeks before the acute event ◼ In at least 10% of patients, myocardial infarction is painless or 'silent'; this is particularly true in the elderly ECG changes of MI Before Minutes afterwards Hours afterwards Days afterwards Weeks afterwards Progression of IHD Cardiovascular system and diseases-II Atherosclerosis ◼ Ischemic heart disease ◼ Heart failure ◼ Heart failure Heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation. It is often called congestive heart failure (CHF), is a common, usually progressive condition with a poor prognosis. CHF occurs when the heart 1. Is unable to pump blood at a rate sufficient to meet the metabolic demands of the tissues or 2. Can do so only at an elevated filling pressure Different forms of heart failure ▪ Acute heart failure ▪ Myocardial infarction ▪ Chronic heart failure ▪ Valvular defects ▪ Left heart failure ▪ Hypertension, ischemic heart disease ▪ Right heart failure ▪ Severe pulmonary hypertension; secondary to left hear failure Left-sided heart failure Most common causes: ▪ Ischemic heart disease ▪ Hypertension ▪ Aortic and mitral valvular diseases ▪ Myocardial disease The morphological and clinical effects of left-sided CHF primarily result from 1) congestion of the pulmonary circulation 2) stasis of blood in the left-sided chambers 3) hypoperfusion of tissues leading to organ dysfunction Morphology of left heart failure Heart: Left ventricle hypertrophy and dilation Left atrium dilation Lungs: Pulmonary congestion and oedema Perivascular and interstitial oedema Interlobular septa Alveolar septa Alveolar oedema Right-sided heart failure Most commonly a secondary consequence of left-sided heart failure due to increase in pressure in the pulmonary circulation Morphology: ◼ Heart: Hypertrophy and dilation of the right atrium and ventricle ◼ Liver: Congestive hepatomegaly ◼ Spleen: Congestive splenomegaly ◼ Lung: Pulmonary oedema ◼ Accumulation of fluid in pleural, pericardial, or peritoneal spaces (effusions) ◼ Oedema of the peripheral: Ankle (pedal) and pretibial oedema is a hallmark of right-sided heart failure. In lecture question and discussion When the coronary arteries become clogged and blood flow to the heart is reduced, a person may experience cramping chest pain upon exertion, prior to a full-blown heart attack. This condition is called ________. a) stroke b) myocardial infarction c) cardiac arrest d) angina pectoris e) stress