Ischemia pathophysiology Flashcards
(41 cards)
Ischemia represents an imbalance between oxygen supply and demand due to impaired or inadequate perfusion. It includes effects of both ______ and _______.
-hypoxia and accumulation of waste products -differs from anoxia which is oxugen deprivation with nl perfusion to remove waste
Oxygen demands of the myocardium are dynamic and increase several fold during ______ and may decrease with ______.
-exertion -cooling
Determinants of myocardial demand and supply of oxygen
-demand: wall tension (laplace), heart rate, contractility -supply: coronary blood flow as determined by diastolic perfusion pressure and coronary vascular resistance and also the oxygen carrying capacity of blood (O2 sat, Hb concentration)
myocardial ischemia occurs due to imbalance between supply and demand due to :
-increased demand: exercise, aortic stenosis, febrile illness, positive ionotropic drugs -decrease supply: anemia, hypoxia, atherosclerosis, spasm, thrombosis -both
Coronary resistance is dynamic and is affected by _______ and ________.
-neural and vasoactive stimuli -reactive hyperemia (augment CBF under conditions of higher O2 demand) and autoregulation (goal to maintain nl CBF)
Ratio of maximal to resting CBF is called
-coronary flow reserve (CFR)
CBF should increase in proportion to _____.
-myocardial oxygen consumption At light to moderate work rates coronary blood flow increases linearly in proportion to myocardial oxygen consumption At high work rates the increase in flow lags a little and oxygen extraction rises (as high as 90%) Regulation occurs on a second to second basis
Impaired CFR and stenosis
-requires a pretty significant lesion diameter of about ~60-70% before see a decrease in CFR
Effects of ischemia on glycolysis
-with ischemia, lactic acid builds up inhibiting glycolysis, more FFA are then utilized -FFAs are inefficient source of energy and toxic TG build up during anaerobic metabolism -if ATP levels drop, sarcolemma integrity can be lost and result in cell death, Na accumulation, and Ca depletion
Which part of the myocardium is most vulnerable to effects of ischemia?
-subendocardium: overall flow to subendo at rest is no different due to greater vasculature, however, it is more susceptible to ischemia when coronary perfusion is impaired. -intramural compressive forces increase resistance in the subendocardium -autoregulation is more effective in epicardium
Electrophysiologic effects of ischemia
-disruption of sarcolemma integrity, failure of Na/K pump, rise in extracellular K+, rise in intracellular Na+, acidosis -lead to reductions in RMP, phase 4 upstroke, AP amplitude and duration, conduction velocity
The voltage gradient between normal and ischemic zones of cardiac muscle lead to current flow between these regions (toward the inner or subendo region) causing _________.
-ST depressions in ECG leads opposite the areas of ischemia
In ischemia, the combo of acidosis, hypoxia, and Ca2+ accumulation leads to conduction delay and heterogenous refractory periods, predisposing to _____ and ______.
-automaticity and re-entry arrhythmias
Effects of ischemia on diastole
-impaired active relaxation in early diastole (isoV relaxation is active) -causes regional stiffness (decreased compliance) shifting PV relation up and left: high EDP, impairs ventricular filling -very sensitive, early measure of ischemia
Effects of ischemia on systolic function
- contraction decreases proportionally to decrease in flow
- involves interference with Ca2+ release or binding to troponin, impairing a-m interaction
- decreased SV
Ischemic impairment is _______.
- local
- dyskinesis in central zone due to hyperkinesis
- hypokinesis/akinesis in adjacent areas
- compensatory hyperkinesis due to adrenergic stim and starling
Infarction vs stunning vs hibernation
- prolonged ischemia leads to irreversible contractile dysfunction (infarction)
- acute ischemia (with reperfusion) can cause prolonged contractile dysfunction (stunning); ex of this is from cardiopulmonary bypass
- hibernation: chronic hypoperfusion causing contractile dysfunction (but still reversible with reperfusion)
Mechanism of stunning
- acute ischemia with reperfusion can cause prolonged contractile dysfunction
- due to accumulation of toxins (acidosis, inorganic P, alter Ca2+ uptake)
- recovery may take days to weeks
When does hibernation occurs?
- occurs with severe CAD impairing resting coronary blood flow
- chronic process
Angina
- chest discomfort produced by ischemia
- due to anerobic byproducts (lactate, bradykinin) effect on cervicothoracic receptors)
- chest tightness radiating to left arm, neck, jaw
Where does angina pain possibly radiate to?
-left arm, neck, jaw
Clinical patterns of angina
- stable: chronic, transient, demand-related
- unstable: increased frequency, reduced precipitants, supply related; an acute change due to active progression
- variant: Printzmetal’s: vasospasm and nonatherosclerotic
- silent ischemia: increased in DMs, transplant
In what settings does silent ischemia occur:
DM, transplants
Symptoms, signs, lab tests of ischemia
- angina or dyspnea
- signs: diaphoresis, CHF
- Lab tests: ECG showing ST depression, T wave inversion, transient ST elevation
- echo: regional wall motion abnormalities
- cath: coronary artery occlusion
- stress test: accenuate supply/demand imbalance; stressor (exercise, dobutamine), imager
