Atherosclerosis Disorders of Cardiovascular System PDF

Disorders of arterial circulation Atherosclerosis OBJECTIVE: ▪ 8.1.2. Describe the etiology and pathogenesis of atherosclerosis.  ATHEROSCLEROSIS Atherosclerosis is a type of arteriosclerosis or hardening of the arteries. The term atherosclerosis, which comes from...

Disorders of arterial circulation Atherosclerosis OBJECTIVE: ▪ 8.1.2. Describe the etiology and pathogenesis of atherosclerosis.  ATHEROSCLEROSIS Atherosclerosis is a type of arteriosclerosis or hardening of the arteries. The term atherosclerosis, which comes from the Greek words atheros (“gruel” or “paste”) and sclerosis (“hardness”), denotes the formation of fibro fatty lesions in the intimal lining of the large- and medium-sized arteries such as: ✔The aorta and its branches ✔The coronary arteries and ✔The large vessels that supply the brain.  ATHEROSCLEROSIS Atherosclerosis begins as an insidious process, and clinical manifestations of the disease typically do not become evident for 20 to 40 years or longer.  ATHEROSCLEROSIS ETIOLOGY AND RISK FACTORS Modifiable: Hypercholesterolemia (major) Non-modifiable: Increasing age (men ≥ 45 years; women ≥ 55 years) History of premature CHD Male sex  ATHEROSCLEROSIS ETIOLOGY AND RISK FACTORS ❖ Traditional Cardiovascular Risk Factors: Cigarette smoking High LDL levels Obesity & visceral fat Hypertension (increases incidence by two fold) DM (type 2 DM - increases incidence by two fold).  ATHEROSCLEROSIS ETIOLOGY AND RISK FACTORS ❖ Non-traditional Cardiovascular Risk Factors: C – reactive protein levels (increased in vascular disease) Serum homocysteine levels Serum lipoprotein levels Infectious agents: ✔ Chlamydia pneumoniae ✔ Herpes virus ✔ Cytomegalo virus (increases risk of vascular disease)  ATHEROSCLEROSIS PATHOGENESIS ▪ The lesions associated with atherosclerosis are of three types: The fatty streak The fibrous atheromatous plaque and The complicated lesion. The latter two are responsible for the clinically significant manifestations of the disease.  ATHEROSCLEROSIS PATHOGENESIS The fatty streaks: Thin, flat, yellow intimal discolorations that progressively enlarge by becoming thicker and slightly elevated as they grow in length. The fibrous atheromatous plaque: (a) The accumulation of intracellular and extracellular lipids, (b) proliferation of vascular smooth muscle cells and (c) formation of scar tissue. The complicated lesion: Contains haemorrhage, ulceration, and scar tissue deposits.  ATHEROSCLEROSIS PATHOGENESIS The development of atherosclerotic lesions is a progressive process involving: (1) Endothelial cell injury (2) Migration of inflammatory cells (3) SMC proliferation and lipid deposition (4) Gradual development of the atheromatous plaque with a lipid core.  ATHEROSCLEROSIS PATHOGENESIS: 1.ENDOTHELIAL CELL INJURY ▪ The vascular endothelium consists of a single layer of cells with cell-to-cell attachments, which normally protects the sub-endothelial layers from interacting with blood cells and other blood components. Agents such as smoking, elevated LDL levels, immune mechanisms, and mechanical stress associated with hypertension share the potential for causing endothelial injury with adhesion of monocytes and platelets.  ATHEROSCLEROSIS PATHOGENESIS: 1.ENDOTHELIAL CELL INJURY  ATHEROSCLEROSIS PATHOGENESIS: 2. MIGRATION OF INFLAMMATORY CELLS Early in the development of atherosclerotic lesions, endothelial cells begin to express selective adhesion molecules that bind monocytes and other inflammatory cells that initiate the atherosclerotic lesions. After monocytes adhere to the endothelium, they migrate between the endothelial cells to localize in the intima, transform into macrophages, and engulf lipoproteins, largely LDL.  ATHEROSCLEROSIS PATHOGENESIS: 2. MIGRATION OF INFLAMMATORY CELLS  ATHEROSCLEROSIS PATHOGENESIS: 3. SMC PROLIFERATION AND LIPID DEPOSITION ▪ Although the recruitment of monocytes, their differentiation into macrophages and subsequent ingestion of lipids, and their ultimate transformation into foam cells is protective in that it removes excess lipids from the circulation, progressive accumulation eventually leads to lesion progression. Activated macrophages release toxic oxygen species that oxidize LDL; they then ingest the oxidized LDL to become foam cells. They also produce growth factors that contribute to the migration and proliferation of SMCs and the elaboration of ECM.  ATHEROSCLEROSIS PATHOGENESIS: 3. SMC PROLIFERATION AND LIPID DEPOSITION  ATHEROSCLEROSIS PATHOGENESIS: 4. DEVELOPMENT OF THE ATHEROMATOUS PLAQUE WITH A LIPID CORE. ▪ Atherosclerotic plaques consist of an aggregation of SMCs, macrophages, and other leukocytes; ECM, including collagen and elastic fibers; and intracellular and extracellular lipids. ▪ Typically, the superficial fibrous cap is composed of SMCs and dense ECM. ▪ Immediately beneath and to the side of the fibrous cap is a cellular area (the shoulder) consisting of macrophages, SMCs, and lymphocytes. ▪ Below the fibrous cap is a central core of lipid-laden foam cells and fatty debris. ▪ Rupture, ulceration, or erosion of an unstable or vulnerable fibrous cap may lead to hemorrhage into the plaque or thrombotic occlusion of the vessel lumen.  ATHEROSCLEROSIS PATHOGENESIS: 4. DEVELOPMENT OF THE ATHEROMATOUS PLAQUE WITH A LIPID CORE.