Ischemic heart disease I Flashcards
what can cause ischemia of the heart?
- decreased perfusion due to coronary artery disease
- increased demand due to left ventricular hypertrophy
what does intermittent ischemia cause?
angina
what does chronic ischemia cause?
heart failure
what does acute ischemia cause?
myocardial infarction
unstable angina
happens at rest and is unresponsive to nitro
ECG: ST elevation or new LBBB or true positive MI
means STEMI
ECG: shows ST depression or T inversion and raised troponin
NSTEMI
ECG: shows ST depression or T inversion and NO raised troponin
unstable angina
most common cause of death with acute MI
ventricular arrhythmias
before you get to necrosis, what must you have?
ischemia
-dysfunction and arrhythmias
epidemiology of ischemia heart disease
-leading cause of death in industrialized nations
(500,000 die per year in US)
- >11 million in US have coronary artery disease
- responsible for 80% of cardiac-related deaths
- >45 y.o.; blacks=whites; 10% <40; nearly half occur
before age 65
-women protected during reproductive years; increases
dramatically after menopause
-physical activity, moderate EtOH also protective
what is the most important clinical correlation for ischemia heart disease
atherosclerosis
risk factors for ischemia heart disease?
- Smoking
- Hypertension
- Obesity
- Diabetes
- Hypercholesterolemia
what are some other associated problems with ischemic heart disease?
-thromboemboli, particularly from valvular
vegetations
-coronary artery spasm (cocaine)
-coronary arteritis (Kawasaki disease)
-increased work load or decreased oxygen
delivery of any cause
-anomalous origin of the left coronary artery
-chest trauma
pathogenesis of ischemia heart disease
-Ischemia results from oxygen supply/oxygen
demand mis-match
-Ischemia precedes infarction, but the two are not
equivalent
-Infarction can be due to chronic insufficiency (chronic
congestive heart failure) or acute obstruction (thrombosis
or vasospasm) leading to myocardial infarction
MOA for inadequate O2 delivery
- Decreased perfusion
-most common cause: progressive stenosis with or
without associated formation of thrombus
-thromboembolus
-vasospasm
-vasculitis
-hypoperfusion secondary to hypovolemia
MOA for inadequate O2 delivery
Decreased oxygen perfusion -other causes of decreased oxygenation -anemia -carbon monoxide -congenital heart disease -asphyxia -lung disease -inadequate O2 secondary to increased demand (work)
Major association: occlusive disease
- Atherosclerosis (stenosis)
-present as main etiologic factor in 90% of heart
disease
-important underlying principles for chronic progressive
stenosis vs. acute occlusion:
-no specific correlation between the extent of
stenosis and type or severity of IHD (up to a point)
-more important: rapidity of decreased perfusion,
tendency of thrombus formation
-CRITICAL EVENT: ABRUPT MISMATCH OF
PERFUSION TO DEMAND
when does occlusive disease get bad?
-once stenosis reaches 75%, decreases ability to
meet an increase in demand
-severe or fatal disease often involves a >70%
reduction in diameter which occludes flow >90%
-majority have multiple vessel disease: 1/3 1-
vessel; 1/3 2-vessel; 1/3 3-vessel
Major association: thrombus formation in occlusive disease
-only 50% of patients who die of MI’s show occlusion of
a coronary artery at autopsy; with angiography,
almost invariably found
-thrombus occurs usually in the first 2 cm. of the coronary
vessel of LAD or left circumflex; occurs in proximal and
distal 1/3 of right coronary
-LAD (40-50%) > RC (30-40%) > LC (15-20%)
-usually results from rupture of fissure of plaque with
platelet aggregation, release of TXA2
vasospams
-associated with adrenergic stimulation, local
factors (decreased nitric oxide, endothelin,
platelets factors including thromboxane)
-clear association with stress, excitement; more
MI’s occur between 6 AM and noon
-may be mediated by hypertension, increased
platelet activity
MI injury: oxygenation of myocardial tissue
-epicardial coronary vessels: conductance
vessels – major site of atherosclerosis
-intramyocardial coronary vessels: resistance
vessels (major determinant of autoregulation
and flow)
-blood flow is greatest during diastole
myocardial injury
hypoxia
ischemia
infarction
cellular breakdown of myocardial injury
-with decrease in O2, cells switch to anaerobic
glycolysis within minutes
-glucose is broken down into lactate; pH is
reduced; impaired cell membrane function results
in leakage of potassium and uptake of sodium
-cardiac dysfunction with decreased contractility,
change in depolarization, impulse conduction
within minutes
timeline for myocardial injury
-injury reversible if perfusion re-established within
20-40 minutes
-after 40 min., reversible injury becomes
irreversible injury
-irreversible injury results in necrosis and
permanent loss of functional myocardium
acute myocardial injury
-involves coronary vessel, an entire region
of myocardium may become necrotic = myocardial
infarction
chronic myocardial injury
-involve loss of individual myocytes and
diffuse fibrosis, resulting in myocardial dysfunction
and cardiac failure over a long period of time
chronic ischemic heart disease
- Occlusion >90% (atherosclerotic heart disease)
- Chronic supply/demand mismatch
- Periodic exacerbations (angina)
- Ischemia on stress test
- Subendocardial ischemia
- Loss of individual cells
- Chronic congestive heart failure
acute ischemia- MI
- sudden occlusion in previously compromised vessels (atherosclerotic heart disease)
- thrombosis of vessel: acute coronary syndrome
- acute ischemic without re-perfusion infarction in 40 minutes
- transmural infarction
- loss large areas of myocardium
- acute congestive heart failure of acute worsening of heart failure
morphological correlations
- ntermittant, but reversible ischemia: Reversible
injury - “stunned myocytes“
-mitochondrial swelling
-relaxation of myofibrils
-distortion of cristae - Also seen in first few minutes of myocardial
infarction (before cells die)
-involvement of septum – arrhythmias
-involvement of ventricular wall – acute CHF/pulmonary
edema
morphological correlations for chronic ischemia
*progresses to irreversible injury
-chronic loss of individual myocytes, particularly
in the subendocardial region
-ischemia results in coagulative necrosis and
apoptosis
-difficult to see loss of individual or groups of
cells, but with time, area eventually becomes
fibrotic
morphological correlations: irreversible injury
-chronic ischemia can result in subendocardial
band of infarcted myocardium
-caused by chronic intermittent ischemia, or reversible
ischemia from hypotension, coronary spasm
-“subendocardial” infarct
-see band of fibrosis adjacent to endocardium along
watershed
-gradual increase in myocardial dysfunction
summary of ischemic changes: intermittent ischemia
-loss of individual cells in subendocardial region (both coagulative necrosis and apoptosis
summary of ischemic changes: chronic ischemia
increasing loss of subendocardial myocytes with fibrosis
summary of ischemic changes: acute occlusive ischeima
rapid development of transmural infarction with coagulative necrosis
clinical presentation of ischemic heart disease
- angina pectoris
1. anginal variants - stable
- unstable
- prinzmetals
- (cocaine)
ECG: ischemia
-t wave inversion
ECG: injury
ST segment elevation
-also can mean acuteness of MI
ECG: infarction
pathological Q wave
-indicates tissue death
chronic ischemic heart disease: presentation
-most common form of IHD
-history of angina or MI in previous 5-10 years
-cardiac decompensation due to slow myocardial
atrophy
chronic ischemic heart disease: pathophysiology/pathology
-progressive ischemic myocardial injury resulting in
eventual congestive heart failure
-diffuse coronary artery atherosclerosis in association
with myocardial fibrosis, patchy myocardial scars
