Ischemia pathophysiology Flashcards

1
Q

Ischemia represents an imbalance between oxygen supply and demand due to impaired or inadequate perfusion. It includes effects of both ______ and _______.

A

-hypoxia and accumulation of waste products -differs from anoxia which is oxugen deprivation with nl perfusion to remove waste

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2
Q

Oxygen demands of the myocardium are dynamic and increase several fold during ______ and may decrease with ______.

A

-exertion -cooling

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3
Q

Determinants of myocardial demand and supply of oxygen

A

-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)

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4
Q

myocardial ischemia occurs due to imbalance between supply and demand due to :

A

-increased demand: exercise, aortic stenosis, febrile illness, positive ionotropic drugs -decrease supply: anemia, hypoxia, atherosclerosis, spasm, thrombosis -both

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5
Q

Coronary resistance is dynamic and is affected by _______ and ________.

A

-neural and vasoactive stimuli -reactive hyperemia (augment CBF under conditions of higher O2 demand) and autoregulation (goal to maintain nl CBF)

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6
Q

Ratio of maximal to resting CBF is called

A

-coronary flow reserve (CFR)

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7
Q

CBF should increase in proportion to _____.

A

-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

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8
Q

Impaired CFR and stenosis

A

-requires a pretty significant lesion diameter of about ~60-70% before see a decrease in CFR

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9
Q

Effects of ischemia on glycolysis

A

-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

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10
Q

Which part of the myocardium is most vulnerable to effects of ischemia?

A

-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

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11
Q

Electrophysiologic effects of ischemia

A

-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

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12
Q

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 _________.

A

-ST depressions in ECG leads opposite the areas of ischemia

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13
Q

In ischemia, the combo of acidosis, hypoxia, and Ca2+ accumulation leads to conduction delay and heterogenous refractory periods, predisposing to _____ and ______.

A

-automaticity and re-entry arrhythmias

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14
Q

Effects of ischemia on diastole

A

-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

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15
Q

Effects of ischemia on systolic function

A
  • contraction decreases proportionally to decrease in flow
  • involves interference with Ca2+ release or binding to troponin, impairing a-m interaction
  • decreased SV
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16
Q

Ischemic impairment is _______.

A
  • local
  • dyskinesis in central zone due to hyperkinesis
  • hypokinesis/akinesis in adjacent areas
  • compensatory hyperkinesis due to adrenergic stim and starling
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17
Q

Infarction vs stunning vs hibernation

A
  • 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)
18
Q

Mechanism of stunning

A
  • 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
19
Q

When does hibernation occurs?

A
  • occurs with severe CAD impairing resting coronary blood flow
  • chronic process
20
Q

Angina

A
  • chest discomfort produced by ischemia
  • due to anerobic byproducts (lactate, bradykinin) effect on cervicothoracic receptors)
  • chest tightness radiating to left arm, neck, jaw
21
Q

Where does angina pain possibly radiate to?

A

-left arm, neck, jaw

22
Q

Clinical patterns of angina

A
  • 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
23
Q

In what settings does silent ischemia occur:

A

DM, transplants

24
Q

Symptoms, signs, lab tests of ischemia

A
  • 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
25
Q

ECG of ischemia

A
  • ischemic cells have decreased RMP with current flowing from normal myocardium into ischemic zone
  • this results in ST depression in leads opposite the area of ischemia
26
Q

treament goal and modalities of ischemia

A
  • goal: restore supply demand balance by improving flow or reducing demand
  • reduce demand: nitrates (reduce LVEDP and vasodilate coronaries), B blockers, Ca2+ channel blockers
  • pharm agents to improve supply: antiplatelet agents (aspirin, clopidogrel), anticoagulants (hepatin, LMWH, DTI)
  • mechanical: PCI, stent implantation, CABG
27
Q

3 things a rupture atherosclerotic plaque can cause

A
  • unstable angina :acute coronary syndrome
  • acute MI
  • ischemic stroke
28
Q

MI is often preceded by ______.

A

-unstable angina (USA): about 10% of pts with USA progress to MI

29
Q

3 causes of acute MI

A

-1. plaque rupture due to macrophage derived MMPs degrading fibrous cap=THROMBUS

2-3. rare non thrombotic causes include: embolism and vasospasm

30
Q

MI: definition, incidence, mortality, factors affecting extent

A
  • def: irreversible heart muscle necrosis resulting from prolonged ischemia
  • incidence: 1.5 milion/year
  • mortality: 25% of overall mortality, 50% occur before hospitalization, after hospitalization, 1 year mort. 5-10%
  • factors: location of plaque, size of vasc bed, collaterals, local tissue factors, time of occlusion/reperfusion
31
Q

Symptoms, signs, lab tests of MI

A
  • chest pain that is chronic!!! USA that doesn’t stop!
  • signs: diaphoresis, tachycardia, dyspnea
  • ECG ST ELEVATION, later Q waves, serum enzyme elevation, imaging showing akinesis on echo, cath
32
Q

ECG in ischemia vs infarction

A

Cariac enzymes that may be elevated in infarction

33
Q

Cariac enzymes that may be elevated in infarction

A

myoglobin, MB isoforms, CK-MB, troponin T, tropon I

34
Q

Arrhythmias and MI

A
  • sinus tachy is most common (pain, anxiety, or shock)
  • sinus brady with inferio MI (vagal efferents in inferior wall)
  • conduction blow
  • ventricular arrhythmias due t acidosis, reentry, autonomic tone
  • treated if they increase oxygen demand or cause hemodynamic instability
35
Q

LV dysfunction and MI

A
  • acute diastolic dysfunction: pulm edema
  • systolic dysfunction: systemic hypoperfusion; extensive myonecrosis (>40%) causes shock
  • pericarditis:
  • ventricular free wall rupture, ventricular septal rupture, rupture of pap muscle
36
Q

Pericarditis

A

-inflammation with or without effusion (15%) up to 10 wks post MI due to transmural infarct or immunologic response (Dresslers syndrome)

37
Q

Specific mechanical complications of MI

A
  • usually occur 3-6 days after MI
  • ventricular free wall rupture
  • ventricular septum rupture
  • rupture of pap muscle

aneurysm formation/remodeling?

38
Q

LV remodeling

A
  • structural alterations during healing: consists of expansion in infarcted region due to loss of myocytes, thinning (aneurysm); compensatory dilation/hypertrophy elsewhere
  • in some pts, LVH is inadequate leading to progressive dilation, further wall stress elevation, CHF, sudden death (adverse remodeling)
  • ACEIs favorably alter the remodeling process
39
Q

2 historical options to treat MI and restore reperfusion

A
  • thrombolysis
  • primary PTCA: lower mortality, favored, avoids hemorrhage
  • best if
40
Q

Pharmacologic adjuncts to reperfusion (PCI/stent vs fibrinolysis)

A
  • aspirinL improves lytics and PTCA results
  • clopidogrel
  • heparin or LMWH
  • role for GP 11b3b esp with PTCA
  • B blockers to reduce infarct size
  • o2 and morphine to result pain, demand
41
Q

Is aspirin or streptokinase better for acute MI rx?

A

-aspirin is slightly better, but best if used together