302 Pathophysiology of ischaemic heart disease and MI

Question 1

Describe the development of athersclerosis

Answer 1

-Endothelial injury/dysfunction
-Recruitment of monocytes/macrophages/histiocytes
-Accumulation of oxidized lipids (mainly LDL+cholesterol)
-Accumulation of growth factors and pro-inflammatory cytokines
-Recruitment of smooth muscle cells, fibroblasts
-Synthesis of ECM
-Intimal plaque (stable/unstable)

Question 2

Is atherosclerosis reversible?

Answer 2

There is evidence of effectiveness of whole food plant based diet (WFPBD) to stabilize plaques and/or reverse atheroma size

Question 3

Describe the structure of a stable atherosclerotic plaque

Answer 3

Thick fibrous cap, lots of collagen, lots of smooth muscle cells

Small lipid pools, few inflammatory cells

Question 4

Describe the structure of a vulnerable atherosclerotic plaque

Answer 4

The opposite of a stable plaque

Plaque rupture and mural thrombosis (possibly with embolization) leading to sudden occlusion or vessel rupture

Plaque haemorrhage leading to sudden occlusion, dissection or vessel rupture
Progressive increase in size leading to critical stenosis (<1mm diameter lumen)

Question 5

What are the consequences of coronary vessel occlusion?

Answer 5

-Hypoxia (lack of oxygen)
-Accumulation of harmful metabolites
-Reversible cell injury
-Irreversible cell injury
-Cell death (myocardial necrosis)

Ischaemia is much more damaging than hypoxia

Question 6

What are the consequences of cell necrosis?

Answer 6

-ATP depletion
-Mitochondrial damage
-Influx of calcium
-Accumulation of free oxygen derived radicals
-Increase in membrane permeability
-DNA and protein damage
-Disappearing nuclei
-Disintegration of the cells
-Leakage of troponin

Acute inflammatory response

Question 7

Describe the histology of the heart tissue following an MI

Answer 7

24 hours
-Coagulative necrosis and haemorrhage

48 hours
-Coagulative necrosis, haemorrhage, and neutrophils

day 3-5
-Coagulative necrosis, haemorrhage, and many neutrophils

from day 5
-Macrophages, neovascularisation

day 7 to 14
-Granulation tissue and early scarring

Question 8

Do myocardial scars conduct?

Answer 8

No, they are electrically inactive (isolators)