Pathology of ischemia and infarction

Question 1

What can cause ischemia?

Answer 1

Reduced blood flow

• CA obstruction
• Tachycardia (dec diastole)
• Dec CO

Increase in myocardial demand

• Inc workload
• Hypertrophy

Question 2

In what direction does coronary blood flow and when?

Answer 2

Epicardium to endo and during diastole

Question 3

What kind of necrosis occurs with severe/irrev ischemia?

Answer 3

Coagulative or contraction band necrosis (if reperfused)

Question 4

What happens in the first 20-40 minutes of ischemia?

Answer 4

Predominantly functional changes

• Anaerobic glycolysis begins
• Cessation of contraction
• Altered electrical activity
• Relaxation of myofibrils–>stretch (contraction of adj cells)

–>myocytes begin to die 20 min after loss of perfusion

Question 5

Are early changes of ischemia reversible?

Answer 5

Reversible by reperfusion for up to 20-40 min

Question 6

What happens after 20-40 min of ischemia

Answer 6

Becomes severe/irrev ischemia leading to necrosis

Question 7

What happens 1-3 days after severe ischemia?

Answer 7

Necrosis followed by phagocytosis

-polys then macrophages

Question 8

What happens weeks to months after severe ischemia?

Answer 8

healing by replacement with granulation tissue progress to scar

Question 9

What is prinzmetal’s/variant angina?

Answer 9

Cardiac pain occurring at rest/during sleep. Due to vasospasm,

Question 10

What are acute coronary syndromes?

Answer 10

unstable angina, acute MI, sudden death

Question 11

What causes acute coronary syndromes?

Answer 11

Acute plaque changes like a rupture wiht superimposed thrombus

Question 12

What are the properties of a plaque susceptible to rupture?

Answer 12

Thin fibrous cap, lots of lipid, less muscle and/or more inflammation. Disruption of the plaque leads to a superimposed thrombus that can be occlusive or non occlusive

Question 13

Consequences of incomplete obstruction by a thrombus

Answer 13

Unstable Angina

Subendo MI

Sudden Death

Question 14

Consequences of complete obstruction by a thrombus

Answer 14

Lethal injury in 15-30 minutes in subendocardium, then injury progresses through endocardium in waves that may take 4-6 hours

Transmural MI

Sudden Death

Question 15

Consequences of vasospasm

Answer 15

Can contribute to narrowing

Question 16

What are the 2 possible fates of non-lethal thrombi?

Answer 16

• Can become organized and incorporated into the plaque, contributing to narrowing
• Can be lysed spontaneously or medically

Question 17

What happens microscopically in acute MI in minutes?

Answer 17

Thin, wavy/stretched myocytes

• still have nuclei and cross striations
• lack of contractile fxn

Question 18

What happens microscopically in acute MI in 6-24 hours?

Answer 18

Coagulative necrosis:

• loss of nuclei
• cross striations
• hypereosinophelia

Question 19

What happens microscopically in acute MI in 6hr-3 days?

Answer 19

Infiltration by polys

Question 20

What happens microscopically in acute MI in 7-10 days?

Answer 20

Infiltration by macrophages for clearance

Question 21

What happens microscopically in acute MI in max 2-4wks?

Answer 21

Ingrowth of granulation tissue

Question 22

What happens microscopically in acute MI in 8-10 wks

Answer 22

Development of collagenized scar (advanced scar in months to years)

Question 23

In which direction does ultimate scar formation occur?

Answer 23

From the periphery of the affected area towards the center. It is dependent on the migration of inflammatory cells and neovascularization of neighboring collateral vessels

(ie can have a scar on the outside and necrosis in the center because the outer layer has progressed faster than the inner)

Question 24

After how long can gross changes be identified in an acute MI?

Answer 24

No gross changes in the first 12 hours

Question 25

How do we determine where the infarct is within the hours of no gross changes?

Answer 25

Stain for LDH which is present in alive tissue only

Question 26

Gross image at 12-24 hours

Answer 26

Dark mottling (trapped deoxy blood)

Question 27

Gross image at 1-3 days

Answer 27

Progressive tan-yellow pallor (necrosis)

Question 28

Gross image at 3-10 days

Answer 28

Hyperemic border (reactive hyperemia-->brings all of the inflamm agents, polys) with softened yellow, progressively depressed, pale necrotic center

Question 29

Gross image at 10-14 days

Answer 29

Grey-red depressed periphery (Advancing granulation tissue)

Question 30

Gross image at 2-8 wks

Answer 30

Grey-white scar progressing from periphery to center

Question 31

Consequences of reperfusion after ischemic injury

Answer 31

1. rescue of nonlethally injured myocytes 2. alter pattern of necrosis via contraction band necrosis 3. cause additional reperfusion injury

Question 32

What is contraction band necrosis?

Answer 32

Cells have already undergone ischemia but are reperfused before coagulative necrosis. When myocardium is reperfused, it is overly leaky. It gets flooded with Ca leading to hypercontraction of myofibrils -this is a marker for reperfusion

Question 33

What is reperfusion injury?

Answer 33

Myocardium that was not lethally injured gets reperfused and dies because of ROS leading to permeability changes in the mitochondria. Messes with the microvessels and can be associated with myocardial interstitial hemorrhage (white to red infarct)

Question 34

Danger in evaluating impaired contractility

Answer 34

Amt of irrev injured myocardium may be overestimated due to stunning and hibernation

Question 35

Complications of MI

Answer 35

- Dysrhythmias - Contractile dysfunction leading to pul edema or cardiogenic shock - Mural thrombus with or w/o embolization - Mitral valve regurge - Pericarditis (autoimmune, usually transmural, associated with inflammation-->friction rub due to fibrinous exudate on epicardial surface) - Ventricular rupture of free wall, IV septum, pap m-->tamponade - Aneurysm - Remodeling (infarct expansion, distortion by scar, hypertroph of remaining myoc, chamber dilation, interference w mitral valve) - TGF beta and ACEi and ARBs have a possible role

Question 36

Why do aneurysms form with MI?

Answer 36

Late complication of transmural MI due to progressive outward bulging and thinning of the area of forming a non contractile scar