Atherosclerosis Lecture Notes PDF

36 Atherosclerosis ILOs By the end of this lecture, students will be able to 1. Categorize risk factors to atherosclerosis into major and minor factors. 2. Evaluate progressing morphological changes in relation to blood vessel wall function. 3. Discuss clinicopathological consequences of atheroscler...

36 Atherosclerosis ILOs By the end of this lecture, students will be able to 1. Categorize risk factors to atherosclerosis into major and minor factors. 2. Evaluate progressing morphological changes in relation to blood vessel wall function. 3. Discuss clinicopathological consequences of atherosclerosis. Introduction:   Atherosclerosis = hardening of the arteries; thickening and loss of elasticity. Atherosclerosis underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease and causes more morbidity and mortality (roughly 50% of all deaths) in the Western world than any other disorder. Risk factors for atherosclerosis I. Major Risk Factors A) Modifiable  Dyslipidemia  Hypertension  Diabetes Mellitus  Smoking B) Constitutional  Age  Sex  Genetic Factors  Familial and Racial Factors II. Emerging Risk Factors  Environmental influences  Obesity  Hormones; Oestrogen deficiency, Oral contraceptives  Physical inactivity  Stressful life  Homocystinuria  Alcohol  Prothrombotic factors  Infections (C. Pneumoniae, Herpes virus, CMV)  High CRP Page 1 of 3 Distribution of atherosclerosis  Arteries larger than 2mm in diameter (exposed to high blood pressure)  Veins usually do not develop atherosclerosis except if transplanted into high pressure arterial side of circulation. Pathogenesis The pathogenesis of atherosclerosis is thought to be a response to endothelial injury (response-toinjury hypothesis). This model views atherosclerosis as a chronic inflammatory response of the arterial wall in response to endothelial injury. Lesion progression involves interaction of modified lipoproteins, macrophages, T lymphocytes, and the cellular constituents of the arterial wall. Steps of atherosclerosis: 1. Endothelial injury and resultant endothelial dysfunction leading to increased permeability, leukocyte adhesion, and thrombosis 2. Accumulation of lipoproteins (mainly oxidized LDL and cholesterol crystals) in the vessel wall 3. Platelet adhesion 4. Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and foam cells 5. Lipid accumulation within macrophages, which respond by releasing inflammatory cytokines 6. Smooth muscle cell recruitment due to factors released from activated platelets, macrophages, and vascular wall cells 7. Smooth muscle cell proliferation and extracellular matrix production Page 2 of 3 Morphology  Fatty streaks  develop early in life  begin as minute yellow, flat macules that coalesce into elongated lesions, 1 cm or more in length.  They are composed of lipid-filled foamy macrophages but are only minimally raised and do not cause any significant flow disturbance  Precursor lesion to atheroma  Atherosclerotic Plaque (atheroma):  Occur due to intimal thickening and lipid accumulation  White to yellow raised lesions that range from 0.3 to 1.5 cm in diameter but can coalesce to form larger masses.  Thrombus superimposed on ulcerated plaques imparts a red-brown color  Atherosclerotic plaques have three principal components: (1) cells, including SMCs, macrophages, and T cells; (2) ECM, including collagen, elastic fibers, and proteoglycans; and (3) intracellular and extracellular lipid Types of Atheromatous plaques  A) Stable plaques: thickened, dense collagenous fibrous caps, minimal inflammation and underlying atheromatous core.  B) Vulnerable plaques: thin fibrous caps, large lipid cores with necrosis, and increased inflammatory cells. These plaques are more are likely to complicate or rupture. Complications 1. Plaque rupture or erosion with superadded thrombosis 2. Thromboembolism 3. Hemorrhage into a plaque. The resulting hematoma may cause rapid plaque expansion or plaque rupture 4. Critical stenosis and organ ischemia 5. Aneurysmal dilatation of the arterial wall due to atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue. Page 3 of 3