L5 Questions

Question 1

You are tutoring a 2nd year pathology student - how would you explain the difference between reversible and irreversible injury of a cardiac myocyte to your tutee?

Answer 1

Biggest factor is time - timely reperfusion
Location and size
Collateral circulation
Myocardium needs

Question 2

Explain why hypertension is a risk factor for AMI

Answer 2

Hypertension, more constricted vessels —> smaller vessels —> easier to develop blockage

Question 3

Explain why diabetes is a risk factor for AMI

Answer 3

Endothelial injury

Question 4

Explain why smoking is a risk factor for AMI

Answer 4

May impact ability to absorb oxygen well, insufficient oxygenation —> ischaemic injury

Question 5

Explain why hypercholesterolaemia is a risk factor for AMI

Answer 5

LDL build up/ fat build up

Question 6

We know that sudden changes in an atheromatous plaque lead to thrombus formation which can precede an AMI - what are these changes and can you suggest why might they occur?

Answer 6

Rupture, erosion, ulceration, and haemorrhage - due to plaque weakness and inflammation around plaque

Question 7

Explain the relationship between time, myocardial cell necrosis and reperfusion

Answer 7

Cell death by necrosis/apoptosis: occurs rapidly after ischaemic event (apoptosis inhibitors reduce infarct size)
Reperfusion within 20min - myocytes survive
After 20 min: can cause reperfusion injury: post-ischaemic ventricular dysfunction

Question 8

What are the underlying mechanisms which can be targeted by cardioprotective drugs in AMI? How do the drugs work?

Answer 8

▫️inhibitors of xanthine oxidase: reduces ROS/FR when blood is reperfused
▫️downregulation or inhibition of inflammasome components, reduce infarct size
▫️thrombolysis (streptokinase or tissue plasminogen activator): activated fibrinolytic enzyme system - dissolves thrombus

Question 9

How do you tell when a cell is irreversibly injured?

Answer 9

Loss of ATP, increase of ROS, pyknosis, karyorrhexis, karyolysis, loss of nuclei, fragmentation of cells and leakage

Question 10

Define AMI

Answer 10

Macroscopic death of myocardium due to vascular insufficiency

Question 11

Define VI

Answer 11

Myocardial ischaemia, ⬇️oxygen, ⬇️nutrients, ⬇️access to inflammatory cells

Question 12

Risk factors for acute myocardial infarction

Answer 12

Hypertension, diabetes, smoking, hypercholesterolaemia

Question 13

Changes from plaque formation to ischaemia

Answer 13

Atherosclerosis that forms plaque, more injury ➡️ advanced plaque ➡️ aneurysm/rupture, occlusion, crutical stenosis

Question 14

Response of myocardium to ischaemia in: hrs/days and weeks

Answer 14

No reperfusion: necrosis complete in 6-12h
Day 1: infarct
Day 3-4: monocyte infiltration
Day 7-10: phagocytosis of necrotic cells
Day ~21: repair by collagen
After 60 days: scar tissue

Question 15

Reperfusion effects (good)

Answer 15

Within 20 minutes: myocytes survive infarct event

Question 16

Reperfusion problems (w/ ways to overcome this problem)

Answer 16

Reperfusion injury: ROS/FR, increased inflammatory response
Can have xanthine oxidase inhibitors
Blood w/o polymorphs = better outcome