Pathology of the failing heart

Question 1

ATHERLOSCLEROSIS PROGRESSION

i) in what layer of the vessel does the first process occur? what happens in the first step?
ii) what are the three possible situations as the plaque progresses? which one has the highest risk of rupture?
iii) what is the clinical horizon?
iv) what are the three sudden events and two outcomes that can occur?

Answer 1

i) starts as an intimal process - go from normal lumen to fatty streak

ii) plaque progresses to either thin cap, thick cap or a fibrotic plaque
- thin cap has highest risk of rupture as there is only thin tissue covering it > risk of rupture and thrombosis

iii) clinical horizon = time which process goes from asymptomatic > sudden event
- patient may be asymp but there is a high risk of an event

iv) sudden events > plaque rupture, erosion and thombosis, fibrocalcific plaque
- can either cause sudden cardiac death or critical stenosis (narrowing)

Question 2

ATHEROSCLEROSIS SEQUENCE

i) what does it always start with? name three things that can cause this?
ii) name three cells that are recruited to the site
iii) what accumulates in the inflammatory environment? (3)
iv) what is synthesised?
v) what may reverse coronary artery disease?

Answer 2

i) always starts with endothelial injury/dysfunction > inflam cascade
- caused by smoking, hyperlipidaemia, ageing

ii) recruitment of monocytes, macrophages, histiocytes

iii) accum of oxidised lipids (LDL and cholesterol), growth factors and pro inflam cytokines
- also recruit smooth muscle cells and fibroblasts

iv) synth of ECM
v) plant based diet

Question 3

THE CLINICAL HORIZON

i) name four characteristics of a stable plaque?
ii) name three events that precipitate the clinical horizon? what does each lead to?
iii) what may be seen in relation to cholesterol on staining?

Answer 3

i) stable plaque = thick fibrous cap, lots of collagen, lots of smooth muscle cells, small lipid pools and few inflamatory cells

ii) ppt by plaque rupture/mural thrombosis > sudden occlusion/vessel rupture
- plaque haemmorhage > sudden occlusion, dissection, vessel rupture
- progressive increase in plaque size > critical stenosis (<1mm diam lumen) = increased risk of sudden cardiac death

iii) cholesterol staining

Question 4

CONSEQUENCES OF PLAQUE RUPTURE

i) name five consequences?
ii) is ischaemia or hypoxia more damaging?
iii) name two things that may be seen macroscopically in myocardial necrosis?

Answer 4

i) occulsion of vessel > reduced/stops blood flow
ischaemia (lack of blood flow) in ds areas supplied
hypoxia (lac of oxygen)
accum of harmful metabolites
reversible/irreversible cell injury
cell death (myocardial necrosis)

ii) ischaemia is more damaging than hypoxia (heart can still work in hypox)
iii) myocardial necrosis > haemmorhagic rim and sandy coloured tissue

Question 5

SEQUENCE OF NECROSIS

i) what happens first? what is then damaged?
ii) which ion rushes in? what accumulates?
iii) name three consequences of this? what test does this aid?
iv) is there always an acute inflammatory response?

Answer 5

i) ATP depletion > mitochondrial damage
ii) influx of calcium and accum of free oxygen derived radicals

iii) inc in membrane perm, DNA/protein damage, disintegration of cells
- leakage of troponin, dissapearing nuclei (trop can be detected)

iv) always an acute inflam response

Question 6

TIMINGS IN MI

i) what two things are seen at 24hrs?
ii) which cells are also seen at 48hrs?
iii) what is seen at day 3-5? (3)
iv) which two things happen at day 5?
v) how many days does it take for granulation tissue to form and early scarring? what two things are depos to allow early scar?
vi) what is the heart vulnerable to when there is lots of granulation tissue?

Answer 6

i) coagulative necrosis and haemorrhage
ii) also see neutrophils
iii) day 3-5 > coag necrosis, haem and many neutrophils
iv) day 5 = macrophages and neovaascularisation

v) day 7-14 = granulation tissue and early scarrring
- depos of fibosis and ECM

vi) granulation tissue is very weak so risk of myocardial rupture

Question 7

REPAIR BY SCARRING

i) what is the problem of heart tissue repairing with a scar?
ii) which cells produce ECM proteins (collagen)

Answer 7

i) scar tissue is electrically inactive
ii) fibroblasts > ECM > remod and contraction of the area