CVS: Atheroma and Infarction

Question 1

Describe key components of atheromatous plaques

Answer 1

Question 2

Which vessels are most likley sites of atheromas?

Answer 2

• Circle of Willis- circulature of the brain
• Carotid arteries
• Coronary arteries
• Aorta
• Iliac arteries

Question 3

List the major risk factors for atherosclerosis

Answer 3

• Age
• Male sex (premenopausal women protected)
• Genetics
• Hyperlipidaemia
• Smoking
• Hypertension
• Diabetes mellitus
• Obesity
• Metabolic syndrome
• Alcohol
• Drugs
• Systemic inflammation (promotes atheroma- eg rheumatoid arthiritis/ parasite infections)

Question 4

Describe initiation of an atheroma

Answer 4

Circulating inflammatory mediators (LDLs, Ang II) activate endothelial cells. These become dysregulated and express cytokines and adhesion molecules (e.g. VCAM-1)

Circulating monocytes bind to the activated endothelium (rolling hypothesis). They migrate between endothelial cells in the intima.

Monocytes differentiate into tissue macrophages and release inflammatory cytokines into the intima

Question 5

Monocytes differentiate into tissue macrophages and release inflammatory cytokines into the intima. What happens next to cause plaque formation in the atheroma disease process?

Answer 5

Macrophages upregulate ‘scavenging’ receptors which uptake LDLs. Macrophages become lipid-laden foam cells.
Further release of inflammatory mediators, eg citokines stimulates vsmcs to migrate from the media into the intimal space
Vsmcs release growth factors. These stimulate cell division and also makes collagen and elastin.
This= the ‘synthetic phenotype’ as VSMCs loose their contractile properties

Question 6

Describe maturation and calcification of the plaque

Answer 6

Smooth muscle cells start to accumulate LDL to become smooth muscle foam cells.
Both types of foam cell eventually undergo apoptotsis, releasing pools of lipid. These pools form a lipid core within the intima called an atheroma.
A fibrous plaque of extracellular matrix, elastin and collagen form a layer above the atheroma resulting in a fibroatheroma
Calcium is deposited by foam cells that hardens the atheroma. This is a clinical marker of atherosclerosis by imaging

Question 7

Describe what happens in plaque rupture

Answer 7

The lipid core can become necrotic and start to fracture and fragment
This creates fissures within the core.
It can rupture through the endothelial layer, exposing collagen and tissue factor to the blood.
This initiates the clotting cascade, forming a thrombus.

Question 8

Explain the consequences of an atheroma

Answer 8

• Occlusive Thrombosis that can lead to MI
• Thromboembolism: emboli from the carotid artery which travel to cerebral vessels, causing ischaemic stroke
• Peripheral vascular disease e.g. critical limb ischaemia: lack of perfusion means wounds can’t heal
• Atheroma causes aneurysm due to wall weakness e.g. aortic aneurysm

Question 9

Give pharmacological treatments of MI following a plaque rupture

Answer 9

Tissue plasminogen activator, tPA: activates plasminogen into plasmin. Plasmin has a high affinity for fibrin, degrading it. D dimers are generated when cross-linked fibrin is degraded.

FDP (fibrin degradation products) are generated if non-cross linked fibrin or fibrinogen is broken down.

tPA and a bacterial plasminogen activator, streptokinase, cause thrombolysis for MI and stroke (clot busters)

Question 10

Give the long term management after a myocardial infarction

Answer 10

• Smoking cessation
• Physical activity
• Diabetes management
• Diet and weight reduction
• Blood pressure control
• Lipid management
• Management of heart failure or LV dysfunction