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Lec 1 - Cardiovascular Disease - Atherosclerosis and its Sequelae WITH PICTURES

8 Pages

Course Code
Pathology 3245B
Elena Tugaleva

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Path 3245B - Atherosclerosis and its Sequelae Burden of Cardiovascular disease - leading cause of death, 45%, in developed world - incidence decreasing in developed countries but increasing in developing countries - overall global burden to double in next few decades - more deaths from heart disease in men - although more men have strokes, more women die of them (because men tend to have strokes younger, which allows for more survival) - most cardiovascular disease = atherosclerosis Atherosclerosis - affects large and medium sized arteries, therefore a systemic disease. Note carotid artery, supplying the blood to the brain, is considered a medium to large vessel - Atheromas (fibrofatty plaques that consists of fibrous tissue and fat) forms inside the vessel and causes vessel stenosis (narrowing). Atheromas build in the intima - the (normally) thin endothelial inside lining of the blood vessel. They do NOT extend into the muscle layer of the vessel. - resultant ischemia (blood flow reduction and absense of oxygen) results in end-organ damage (sympotomatic disease) - Early manifestation of atheromas: fatty streaks Pathogenesis of Atherosclerosis Response to Injury Hypothesis: - plaques develop as a result of a chronic inflammatory reaction to various forms of injury/insult to the endothelium - Monocytes grab onto fat in the blood stream and emigrate it into the intima. Inside the intima, fat builds into globules and attracts the migration of smooth muscle to the site (inappropriately). Plaque build-up results in the intima. - Fibrofatty plaque consists of two parts: Fibrous cap (smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, etc) and necrotic center (dead cells) - Atherosclerosis can begin in infancy and increase throughout life - clinical significance begins when artery is narrowed by 70% Risk Factors (many MCQs here) - categorized by major/minor, modifiable/non-modifiable - when multiple risk factors exist, risk is MULTIPLIED, not added Major/non-modifiable Risk Factors - increasing age - male gender (esp after age 45/50. Note Fs suffer most after menopause) - family history Major/modifiable risk factors - hyperlipidemia (obesity) - hypertension (obesity) - cigarette smoking - diabetes Smoking - single most important modifiable risk fator - 400,000 deaths annually in US - 20 cig/day = risk of CV death approximately doubled Hyperlipidemia - cholesterol transported by lipoproteins - LDL (low densitry lipoprotein) = bad cholesterol - HDL = good - LDL/HDL blood levels determined by both genetic influence and diet - pharmacological treatment sometimes necessary Hypertension - genetic and diet - "silent killer" - asymptomatic - underdiagnosed because silent, thus undertreated and undermedicated Diabetes Mellitus - strong risk factor - mechanism of conribution to atherosclerosis is multifactorial Other Risk Factors - obesity - physical inactivity - stress/type A personality (aggressive, high-strung individuals) - high levels of homocysteine - post-menopausal estrogen deficiency Manifestations of Atherosclerosis - Atherosclerosis involves all medium and large sized vessels (systemic). Thus sites of atherosclerotic ischemic injury and clinical disease are widespread. Those that are most clinically important include (although others are involved yet less significant): - heart - brain - extemities - kidneys Brain: Ischemic stroke (infarct) - blockage in artery to brain results in loss of blood supply to a region, which results in ischemic stroke Extremities - loss of blood supply more often occurs to lower extremities (as compared to upper) due to the naturally greater difficulty of circulating blood to here. Ischemia to extremities is first characterized by pain, referred to as claudication. Extended loss of blood supply can result in the death of soft tissue, called gangrene. Coronary Arteries - the main region where atherosclerosis occurs - the heart is a very vascular organ, requiring high supply of blood and oxygen due to high meabolic demands Heart manifestations of atherosclerosis: - Angina Pectoris - exertional ischemic pain behind stermin resolves before necrosis occurs. Patient feels tightness and heaviness behind stermin when engaging in increased activity or stress (anything that causes increased demand on
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