Heart Part 2, UTHSC Fall 2022 D2 Pathology
what is the #1 cause of death in the US?
Myocardial Infarction
Myocardial Infarction epidemiology
~ 10% occur in people < 40 years old, and 45% in those < age 65
Myocardial Infarction has a correlation with what?
genetic and behavioral predispositions to atherosclerosis
Myocardial Infarction (MI) Pathogenesis via Coronary Arterial Occlusion
1. Acute change (hemorrhage, ulceration, rupture) in a coronary artery atheromatous
plaque
2. Platelets adherence and activation following exposed subendothelial collagen,
formation of microthrombi
3. Stimulation of vasospasm by mediators released from platelets
4. Activation of coagulation pathway by tissue factor
5. Expansion of the thrombus within minutes and completely occlusion the vessel lumen
Myocardial Infarction (MI) Pathogenesis via Other Mechanisms
- Vasospasm
- Emboli from the left atrium, vegetations of infective endocarditis, endocardiac
prosthetic material...
- Ischemia without detectable or significant coronary atherosclerosis and thrombosis
(vasculitis, sickel cell disease, amyloid deposition...)
Myocardial Response
Sequence of early biochemical findings and progression of necrosis after onset of
severe myocardial ischemia
what are the early changes of myocardial response?
loss of ATP and accumulation of lactate
how long is the ischemic myocardial injury reversible?
for 30 minutes
when does the progressive loss of viability begin?
by 6 to 12 hours
How are we able to gauge the Myocardial Response to an ischemic attack?
1. Disruption of the integrity of the sarcolemmal membrane, as the earliest detectable
feature of myocyte necrosis
2. Leaking intracellular macromolecules out of necrotic cells into the cardiac interstitium
and ultimately into microvasculature and lymphatics
3. Basis for blood tests sensitively detect irreversible myocyte damage
how does the zone of necrosis spread through the tissue?
from the inside out, endocardium through the myocardium to the epicardium
Progression of Myocardial Ischemic Injury
1. Shift from aerobic to anaerobic metabolism in case of acute and severe ischemia →
intracellular acidosis
2. Lose of the ability of cardiomyocytes for contraction within 2 minutes of onset of
severe ischemia
3. Reversible myocardial injury if ischemia of less than 20 minutes
4. More swelling with precipitates of the mitochondria, and plasma membrane defects
and other changes with increasing duration and severity of ischemia
, 5. Cells death if severe ischemia is prolonged (> 20-40 mins) ATP levels < 10-25% →
cell necrosis
T/F all myocytes are equally ischemic in a myocardial ischemic injury
False
how quick is the onset of ATP depletion in Ischemic Cardiac Myocytes?
Seconds
how quick is the Loss of contractility in Ischemic Cardiac Myocytes?
< 2 min
how quick is the ATP reduced to 50% of normal in Ischemic Cardiac Myocytes?
10 min
how quick is the ATP reduced to 10% of normal in Ischemic Cardiac Myocytes?
40 min
how quick is Irreversible cell injury in Ischemic Cardiac Myocytes?
20-40 min
how quick is Microvascular injury in Ischemic Cardiac Myocytes?
> 1 hr
transmural infarction
myocardial infarction that affects the full thickness of the myocardium and almost
always results in a pathological Q wave in the affected leads.
subendocardial infarction
death of tissue that does not extend through the full thickness of the myocardial wall
How are myocardial infarctions diagnosed?
- Clinical symptoms
- Laboratory tests
- Characteristic electrocardiographic changes
myocardial infarctions and Clinical Symptoms
- Prolonged (more than 30 minutes) chest pain described as crushing, stabbing, or
squeezing, associated with a rapid, weak pulse
- Profuse sweating, nausea and vomiting, and dyspnea
- In 25% of patients, the onset is entirely asymptomatic
Laboratory Evaluation of MI
- Time to evaluation, 3-12 hrs
Onset of myocardial infarction -> Plasma membrane of necrotic myocytes becomes
leaky -> Molecules leak out of cell into circulation
what are the most useful proteins to look for when diagnosing a myocardial
infarction?
Cardiac-specific troponins T and I (cTnT and cTnI) and CK-MB
what are the most sensitive and specific biomarkers for myocardial infarction?
cTnT and cTnI
heart proteins and how long they take to return to normal after a myocardial
infarction
CK-MB returns to normal in 48-72 hrs, cTnI in 5-10 days, and cTnT in 5-14days
how can stem cell therapy help in myocardial infarctions?
stem cells are deposited at the ischemic site, differentiate into cardiac myocytes, and
secrete cytokines that induce angiogenesis
Sudden Cardiac Death
what is the #1 cause of death in the US?
Myocardial Infarction
Myocardial Infarction epidemiology
~ 10% occur in people < 40 years old, and 45% in those < age 65
Myocardial Infarction has a correlation with what?
genetic and behavioral predispositions to atherosclerosis
Myocardial Infarction (MI) Pathogenesis via Coronary Arterial Occlusion
1. Acute change (hemorrhage, ulceration, rupture) in a coronary artery atheromatous
plaque
2. Platelets adherence and activation following exposed subendothelial collagen,
formation of microthrombi
3. Stimulation of vasospasm by mediators released from platelets
4. Activation of coagulation pathway by tissue factor
5. Expansion of the thrombus within minutes and completely occlusion the vessel lumen
Myocardial Infarction (MI) Pathogenesis via Other Mechanisms
- Vasospasm
- Emboli from the left atrium, vegetations of infective endocarditis, endocardiac
prosthetic material...
- Ischemia without detectable or significant coronary atherosclerosis and thrombosis
(vasculitis, sickel cell disease, amyloid deposition...)
Myocardial Response
Sequence of early biochemical findings and progression of necrosis after onset of
severe myocardial ischemia
what are the early changes of myocardial response?
loss of ATP and accumulation of lactate
how long is the ischemic myocardial injury reversible?
for 30 minutes
when does the progressive loss of viability begin?
by 6 to 12 hours
How are we able to gauge the Myocardial Response to an ischemic attack?
1. Disruption of the integrity of the sarcolemmal membrane, as the earliest detectable
feature of myocyte necrosis
2. Leaking intracellular macromolecules out of necrotic cells into the cardiac interstitium
and ultimately into microvasculature and lymphatics
3. Basis for blood tests sensitively detect irreversible myocyte damage
how does the zone of necrosis spread through the tissue?
from the inside out, endocardium through the myocardium to the epicardium
Progression of Myocardial Ischemic Injury
1. Shift from aerobic to anaerobic metabolism in case of acute and severe ischemia →
intracellular acidosis
2. Lose of the ability of cardiomyocytes for contraction within 2 minutes of onset of
severe ischemia
3. Reversible myocardial injury if ischemia of less than 20 minutes
4. More swelling with precipitates of the mitochondria, and plasma membrane defects
and other changes with increasing duration and severity of ischemia
, 5. Cells death if severe ischemia is prolonged (> 20-40 mins) ATP levels < 10-25% →
cell necrosis
T/F all myocytes are equally ischemic in a myocardial ischemic injury
False
how quick is the onset of ATP depletion in Ischemic Cardiac Myocytes?
Seconds
how quick is the Loss of contractility in Ischemic Cardiac Myocytes?
< 2 min
how quick is the ATP reduced to 50% of normal in Ischemic Cardiac Myocytes?
10 min
how quick is the ATP reduced to 10% of normal in Ischemic Cardiac Myocytes?
40 min
how quick is Irreversible cell injury in Ischemic Cardiac Myocytes?
20-40 min
how quick is Microvascular injury in Ischemic Cardiac Myocytes?
> 1 hr
transmural infarction
myocardial infarction that affects the full thickness of the myocardium and almost
always results in a pathological Q wave in the affected leads.
subendocardial infarction
death of tissue that does not extend through the full thickness of the myocardial wall
How are myocardial infarctions diagnosed?
- Clinical symptoms
- Laboratory tests
- Characteristic electrocardiographic changes
myocardial infarctions and Clinical Symptoms
- Prolonged (more than 30 minutes) chest pain described as crushing, stabbing, or
squeezing, associated with a rapid, weak pulse
- Profuse sweating, nausea and vomiting, and dyspnea
- In 25% of patients, the onset is entirely asymptomatic
Laboratory Evaluation of MI
- Time to evaluation, 3-12 hrs
Onset of myocardial infarction -> Plasma membrane of necrotic myocytes becomes
leaky -> Molecules leak out of cell into circulation
what are the most useful proteins to look for when diagnosing a myocardial
infarction?
Cardiac-specific troponins T and I (cTnT and cTnI) and CK-MB
what are the most sensitive and specific biomarkers for myocardial infarction?
cTnT and cTnI
heart proteins and how long they take to return to normal after a myocardial
infarction
CK-MB returns to normal in 48-72 hrs, cTnI in 5-10 days, and cTnT in 5-14days
how can stem cell therapy help in myocardial infarctions?
stem cells are deposited at the ischemic site, differentiate into cardiac myocytes, and
secrete cytokines that induce angiogenesis
Sudden Cardiac Death
