L5 13 Mar 2019

Question 1

acute myocardial infarction

Answer 1

AMI: macroscopic death of myocardium due to vascular insufficiency

Question 2

vascular insufficiency

Answer 2

VI: myocardial ischaemia, balance between perfusion and demand for oxygenated blood

Question 3

ischaemic heart disease

Answer 3

IHD: imbalance between cardiac blood supply and myocardial oxygen demand; caused by: increased demand, lower oxygen carrying capacity and reduced coronary flow –> OBSTRUCTIVE ATHEROSCLEROSIS

Question 4

outcomes of ischaemic heart disease

Answer 4

stable angina, unstable angina and myocardial infarction

Question 5

factors affecting ischaemia outcome

Answer 5

• locations, severity and rate of occlusion, size of vascular bed perfused by obstructed vessel, duration of occlusion, metabolic demand, extent of collateral supply
• other: heart rate, cardiac rhythm and blood oxygenation

Question 6

atherosclerosis

Answer 6

chronic inflammatory and healing response of arterial wall to endothelial injury

Question 7

steps in vascular injury

Answer 7

1. recruitment of SMCs or SMC progenitors to intima
2. SMC mitosis
3. ECM elaboration leads to intimal thickening, calcification and fragility: impeded vascular flow and rupture of vessel wall

Question 8

pathogenic events of atherosclerosis

Answer 8

1. Endothelial injury
2. Increased vascular permeability, leukocyte adhesion, thrombosis
3. Accumulation/oxidation of LDL in intima
4. Platelet adhesion
5. Release of factors
6. SMC recruitment, and proliferation and synthesis of ECM
7. T-cell recruitment
8. Lipid accumulation within foam cells (macrophages) and SMC

Question 9

Structures of an atherosclerotic plaque

Answer 9

Necrotic center in the intima covered by a fibrotic cap

Question 10

What is in the fibrotic cap?

Answer 10

SMC, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation

Question 11

What is in a necrotic center?

Answer 11

Cell debris, cholesterol crystals, foam cells and calcium

Question 12

Pathogenesis of AMI

Answer 12

1. Atheromatous plaque developed
2. Irreversible damage - occurs first in sub-endocardial zone and then progresses across the whole cardiac wall ▶️location + size depends on location/severity of plaque, duration, collateral circulation, needs of myocardium
3. Cell death then reperfusion/no reperfusion

Question 13

pathogenesis of AMI a t cellular level

Answer 13

1. Cell necrosis and apoptosis, occur rapidly post ischaemia —> apoptosis inhibitors reduce infarct size
2. Reperfusion: within 20 min OR
3. No reperfusion: necrosis complete in 6-12h

Question 14

Evolution of AMI infarct size in surviving patient

Answer 14

• Day 1: infarct begins
• Day 3-4: monocyte infiltration
• Day 7-10: phagocytosis of necrotic cells
• ~Day 21: repair with collagen
• > Day 60: scar tissue

Question 15

Troponin in arterial occlusion

Answer 15

1. AMI occurs
2. Plasma membrane of necrotic myocytes becomes leaky
3. Molecules (e.g. troponin) leak out of cell into circulation —> can check troponin levels to see duration of AMI ***can be used as diagnostic biomarkers

Question 16

What can be done to treat AMI?

Answer 16

🔘restoration of coronary blood flow

🔘thrombolysis

🔘balloon angioplasty

🔘coronal arterial bypass graft (CABG)

Question 17

Reperfusion injury

Answer 17

⚫️ROS/FR in ischaemic myocardium - overexuberance of ROS

⚫️increased ROS/FR: produced by reperfusing polymorphs (neutrophils) - super sensitive to injury

Question 18

Complications of AMI

Answer 18

Contractile dysfunction, arrhythmia, rupture - w/ severe effect, pericarditis, infarct expansion