Ischemic heart disease I Flashcards
Progression of atherosclerosis
Normal > Fatty streak (endothelial injury, lipid deposition, macrophage and T cell recruitment) > Fibrous plaque (activated macrophages, smooth muscle proliferation forms fibrous cap, progressive lipid accumulation in core of plaque) > Occlusive atherosclerotic plaque (same as processes as in fibrous plaque) <> Plaque rupture/fissure and thrombosis (plaque disruption, thrombus formation, vessel occlusion may occur) > unstable angina, MI, stroke, critical leg ischemia
risk factors for development of coronary atherosclerosis.- treatable with consequent reduced risk
Smoking, Hypertension, Dyslipidemia
risk factors for development of coronary atherosclerosis.- treatable but unclear if risk is reduced by treatment
Diabetes/Insulin Resistance, Obesity, Inflammation, Psychological Stress, Sedentary lifestyle
Diabetes/Insulin Resistance, Obesity, Inflammation, Psychological Stress, Sedentary lifestyle
risk factors for development of coronary atherosclerosis.- Not treatable
Male gender, Age, Most genetic factors
Male gender, Age, Most genetic factors
Describe how smoking affects CAD risk (percentage and mechanism)
~50% increase in CAD risk. Mechanism: Thrombogenic tendency, platelet activation, increased fibrinogen. Aryl hydrocarbon compounds promote atherosclerosis. Endothelial dysfunction, vasospasm. CO decreases myocardial oxygen delivery. Adverse effect on lipoproteins (decreased HDL)
Describe how hypertension affects CAD risk
Risk is graded depending on blood pressure. Mechanisms: 1. increased shear stress on arterial wall causes direct endothelial cell injury. 2. Increased arterial wall stress initiates pathologic cell signaling program causing oxidant stress, cellular proliferation. 3. Circulating hormones increased in HTN (ie. angiotensin, aldosterone, norepinephrine) exert adverse effects on arterial wall. 4. Left ventricular hypertrophy
Describe how diabetes/insulin resistance affects CAD risk
Inflammation, oxidative stress and dyslipidemia predispose to atherosclerosis
What is the dyslipidemic triad
High LDL, low HDL, high triglycerides
Deleterious effects of LDL cholesterol
Oxidized LDL becomes pro-inflammatory and atherogenic: injurs vascular endothelium, impairs endothelial function, deposits in arterial wall and is taken up by macrophages(plaques), activates inflammatory cells (progression of lesions), activates platelets, is pro-thrombotic
Beneficial effects of HDL cholesterol
opposes atherothrombosis: inhibits oxidation of LDL, inibits tissue factor, enhances reverse cholesterol transport, inhibits endothelial adhesion molecules, stimulates endothelial NO
Markers that predict CV events
lipids, CRP (inflammatory markers)
Principle determinants of myocardial oxygen supply and demand.
Supply is determined by coronary blood flow rate (depends on perfusion pressure, perfusion time, vascular resistance) and oxygen content of blood. Demand is determined by heart rate, wall tension and inotropic state
Oxygen delivery equation
Oxygen delivery (mmol/min) = Coronary Blood Flow rate (ml/min) x oxygen content (mmol/ml) Oxygen delivery (mmol/min) = Coronary Blood Flow rate (ml/min) x oxygen content (mmol/ml)
What protects from moderate changes in perfusion pressure? How is this affected in CAD?
Autoregulation occurs at level of small arterioles to protect from changes in perfusion pressure. In CAD, autoregulation may be exhausted when pressure drops across an epicardial coronary stenoses thus a drop in perfusion pressure may occur.
Autoregulation occurs at level of small arterioles to protect from changes in perfusion pressure. In CAD, autoregulation may be exhausted when pressure drops across an epicardial coronary stenoses thus a drop in perfusion pressure may occur.
How does autoregulation occur in CAD
Dilation of resistance vessels may compensate for pressure drop across stenosis. With increasing severity of stenosis, autoregulation measures become exhausted and ischemia can result.
