Myocardial Ischemia and infarction Flashcards
What is myocardial ischemia
A condition of reversible inadequate blood supply to the heart due to fixed coronary stenosis, increased myocardial demand, coronary vasospasm, intraplaque hemorrhage, super imposed thrombosis or any combination of these factors
What defines acute ischemia?
Ischemia that has lsted only minutes to hours at the most a few days
What are some of the occurences that happen after only 1 minute of ischemia?
Loss of glycogen, mitochondrial swelling, cellular swelling and loss of contractility occur after only one minute of ischemia, and a fata arrhythmia may preceede irreversible injury to myocytes
Can the manifestation of acute myocardial ischemia be visualized by Light microscopy?
No
How would acutely ischemic myocytes appear under light microscope?
Normal, they are not dead yet but they do not work
What can gradually cause these non-fuctional myocytes of acute ischemia to gradually regain their contractile function?
Restoration of adequate blood supply
What are the features of the “stunned myocytes?”
- Accumulated excess Calcium
- Oxygen derived free radicals
- Damage to its cytoplasmic proteins and organelles which takes time to reverse
What is Chronic Ischemia?
Ischemia last weeks months or years
What are the features of Chronic Ischemia
These myocytes catabiloze their contractile proteins and revert to primitive state limited to survival functions
How would myocytes of the chronic ischemia (hibernating myocytes) appear under light microscopy?
They would show clear vacuolization of their cytoplasm due to the catabolism of contractile proteins
What is Myocytolysis?
The light microscopy appearance of hibernating myocytes
Can function of chronically ischemic myocytes return?
Yes with adequate blood flow restored there will be gradual regeneration of all the normal cytoplasmic proteins
What develops in response to chronic mycardial ischemia?
Collateral coronary arteries
What is ischemic pre-conditioning?
Resistance to mild-moderate ischemia due to induction of protective proteins by brief episodes of ischemia
What is myocardial infarction
The irreversible necrosis of heart muscle due to prolonged ischemia (greater than 20 minutes)
How the the myocardial infarction/necrosis occur?
Thought to occur in a wavefront starting in the subendocardial region and not complete until 6 hours after it is started
What is the time fram where thrombolytic therapy or angioplasty is thought to be beneficial?
20minutes -6hours after the onset of ischemia
What is Chronic ischemia?
Repeated episodes of ischemia too brief to cause infarction or inadequate perfusion that is low injure myocytes but not low enough to kill them
What is the most common cause of Myocardial infarctions?
Coronary atherosclerosis
What are some of the other causes of MI?
- Coronary vascilitis
- Coronary emboli
- Endocarditis
- Vasospasm (Cocaine)
- Antiphospholipid antibody syndrome
What is meant by transmural infaction?
Infaction affecting the full thickening of the heart wall
What is associated with Transmural infarcts 90% of the time?
Occlusive thrombosis superimposed on an Atherosclerotic plaque than undergoes an acute change typically disruption of an unstable vulnerable plaque by ulceration or rupture
What are subendocardial infarctions?
Infarctions involving the inner portion of the heart wall, and are more likely to be patchy and to have episodes of extension with additional infarction at the periphery
What is the gross pathology of an unreperfused myocardial infarction after 01-12 hours?
None
What is the gross pathology of an unreperfused myocardial infarction after 12-24 hours?
Progressive pallor
What is the gross pathology of an unreperfused myocardial infarction after 2-3 days?
Yellow and softened
What is the gross pathology of an unreperfused myocardial infarction after 4-7 days?
Red (granulation tissue) border
What is the gross pathology of an unreperfused myocardial infarction after 1-6 weeks?
Gradual replacement of infarct by red granulation tissue
What is the gross pathology of an unreperfused myocardial infarction after 6-12 weeks?
Gradual white scarring
What is the earliest microscopic finding that is not always present 1-3 hours post infarct?
Thin Wavy myocytes
Thin wavy myocytes are dead and they persist at the periphery of an infarct
What is the characteristic (necrosis) pathology of an unreperfused myocardial infarct?
Coagulation necrosis
What are the three components of coagulation necrosis?
- Hypereosinophilia
- Loss of striations
- Nuclear changes (pyknosis then karyorrhexis, karyolysis and disappearance
When does coagulation necrosis first become visible?
4-12 hours
When is neutrophilic infiltration (acute inflammation) first visible
6-12 hours it follows myocyte necrosis and is usually associated with edema and sometimes hemorrhage as well
When does Neutrophilic infiltration peak?
In the third day
What usually happens during the subacute phase (days4-10)
Characterized by infiltration of lymphocytes, macrophages and fibroblasts
When do the first lymphocytes (small round cells with dense nuclei and scant cytoplasm) sometime arrive?
Day 2
When do the first few Macrophages arrive?
Day 3
When do the fibroblasts first arrive?
day 4
What happens during the Late subacute phase (day 11-week12)
Ingrowth of capillaries (angiogenesis) and proliferation of fibroblasts converts the issue cleared of dead myocytes into granulation tissue
How do fibroblasts replace the granulation tissue
By acellular fibrous collagen scar
What is the form of irreversible myocyte injury associated with reperfusion?
Contraction band necrosis
What are the ways in which one can reperfuse an MI?
- Angioplasty
- Thrombolytic therapy
- Coronary bypass
What is the best way to minimize an MI?
Restoring the blood flow (reperfusion)
What are the benefits of reperfusion?
MI is
- smaller than it would have been
- patchier than it would have been
- with hemorrhage into it
- more contraction band necrosis
- accelerated inflammation and repair
- diffusion of inflammation and repair
- fewer neutrophils
- more macrophages
- more interstitial fibrosis
The gross pathology of an average reperfused myocardial infarction after 1-3 days
Dark mottling and hemorrhage immediately following reperfusion
The gross pathology of an average reperfused myocardial infarction after 4-5 days
Dark mottled red and brown (no change)
The gross pathology of an average reperfused myocardial infarction after 6-10 days
Shrunken red and brown and bits of grey-white
The gross pathology of an average reperfused myocardial infarction after 11-14
Brown and intermingled with grey-white
The gross pathology of an average reperfused myocardial infarction after 2-7 weeks
Progressive white, intermingled normal
What is the microscpic pathology of an average reperfused MI after 1-3 days
- Contraction band necrosis
- Hemorrhage immediately following reperfusion
- Coagulation necrosis occurs too especially in the center of the big infarct
- Followed by neutrophilic infiltration
When is coagulative necrosis first visible following reperfusion?
First visible 2 hours following reperfusion
What is no reflow phenomenon?
Failure of relieving obstruction at the arterial level to restore
What are the causes of no-reflow phenomenon?
- Capillary endothelial swelling
- Capillary plugging by neutrophils
- Microthrombosis
- Microembolism
- The hemorrhage cause by reperfusion also contributes to microvascular injury
How does reperfusion affect macrophage infiltration of an infarct?
Macrophage infiltration is sooner and heavier than in an unreperfused infarct
How does the cell infiltration date change with reperfusion?
- Macrophages arrive in 2 days
2. Fibroblasts arrive in 3 days
What occurs in the early subacute phase (days 4-10) in a repurfused infarct
Infiltration by lymphocytes, eosinophils and sometimes plasma cells followed by formation of granulation tissue, and the collagen
What effect does reperfusion have on infarcts in general?
It accelerates healing from about 12 weeks to about 7 weeks on average an acceleration of 40%
What is reperfusion injury?
Hemorrhage and other injurious phenomena associated with bringing oxygen and calcium to injured tissue, attributed to reactive Oxygen species and metabolic effects of calcium
