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.
How does tachycardia affect coronary flow?
LV perfusion occurs during diastole because coronary vessels are compressed during systole. When HR increases, diastole is shortened and LV perfusion can be compromised
How does vasomotor tone affect coronary stenosis
Frank spasm can cause angina at rest. Increased vascular tone can cause exercise induced angina. Decreases vascular tone can reduce obstruction so there is no angina
Determinants of wall tension
Systolic blood pressure and cardiac chamber dimension
pathophysiology and signs of stable coronary heart disease.
Obstructive coronary lesion limits coronary flow and causes myocardial ischemia (tissue blood flow insufficient to meet oxygen requirements), particularly when cardiac work and oxygen demand increase. Results in angina pectoris (chest pain)
Treatement of stable coronary heart disease.- related to oxygen supply
Increase oxygen supply: Prevent hypotension (increase perfusion pressure), rate-slowing drugs such as beta blockers (increase diastolic time), vasodilators, coronary angioplasty or bypass surgery (decrease coronary resistance), treat anemia and hypoxemia (increase oxygen sypply).
Treatement of stable coronary heart disease.- related to oxygen demand
Reduce oxygen demand: Antihypertensive drugs (decrease systolic pressure), rate slowing drugs (decrease HR), Limit LV size by limiting preload using diuretics, nitrates (decrease wall tension), negative inotrophes (decrease inotropic state)
pathophysiology of unstable coronary heart disease
Inflammation in arterial wall, Weakening of fibromuscular cap, Abrupt plaque fissure or rupture, Thrombogenic components (lipids, tissue factor) exposed to blood, Thrombosis with partial or complete vessel occlusion,
Myocardial injury and/or necrosis (serum markers)
Cardiac dysfunction, risk of arrhythmias, death
Describe unstable angina
Near-complete occlusion of vessel with thrombus causes a threatened heart attack. Troponin and other biomarkers usually negative. May not result in permanent myocardial damage if treated successfully but High risk of recurrent events in first year
Describe acute MI
•Persistent and severe coronary flow reduction, Thrombus usually with complete vessel occlusion, Wavefront of myocardial necrosis; leads to cardiac dysfunction and failure; biomarkers (troponin) elevated, Cardinal symptom: severe and unremitting chest discomfort at rest. High early mortality. late mortality related to extent of LV dysfunction
What happens within the first hour of an acute coronary occlusion
w/in minutes: 1. Impaired calcium re-uptake into SR during diastole > diastolic dysfunction (filling impairment) > increased LV filling pressure > pulmonary congestion and edema. 2. Depletion of high energy phosphates, intracellular acidosis > systolic dysfunction (contractile failure). 3. ECG signs of myocardial injury. 4. Symptoms (chest pain, dyspnea, arrhythmias). Within 1 hour: Myocardial necrosis and infarction
Markers of unstable CAD
Inflammatory markers (CRP) due to inflammed aterial atheroma upstream of blocked area, cardiac markers ( troponin, CK) downstream of injury
