Pathophysiology of Atheroma

Question 1

What is the role of lipids in the aetiology of atheroma

Answer 1

Hypercholesterolaemia most important risk factor

Causes plaque formation and growth in absence of other known risk factors

Question 2

What are the signs of major hyperlipidaemia?

Answer 2

• Familial/primary vs acquired/secondary (?idiopathic)
• Biochemical evidence: LDL, HDL, total cholesterol, triglycerides
• Corneal arcus (premature)
• Tendon xanthomata (knuckles, Achilles)
• Xanthelasmata
• Risk/premature/family history MI/atheroma

Question 3

What is atheroma/atherosclerosis?

Answer 3

Formation of focal plaques in intima of large and medium-sized arteries

Question 4

How is ISCHAEMIA causes?

Answer 4

By narrowing of lumen due to atheromatous plaques in coronary arteries

Question 5

What is ARTERIOsclerosis?

Answer 5

Not atheromatous
Age-related change in muscular arteries
Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae, intimal fibrosis → ↓ vessel diameter

Question 6

What are the 3 types of atheroma?

Answer 6

FATTY STREAK

EARLY ATHEROMMATOUS PLAQUE

FULLY DEVELOPED ATHEROMATOUS PLAQUE

Question 7

What are the components of atheromatous plaques? FATTY STREAK

Answer 7

• young children
• May disappear
• No clinical significance
• Yellow linear elevation of intimal lining
• Comprises masses of lipid-laden macrophages

Question 8

What are the components of atheromatous plaques? EARLY ATHEROMATOUS PLAQUE

Answer 8

• young adults onwards
• smooth yellow patches in intima
• lipid-laden macrophages
• progresses to establish plaques

Question 9

What are the components of atheromatous plaques? FULLY DEVELOPED ATHEROMATOUS PLAQUE

Answer 9

• Central lipid core with fibrous tissue cap, covered by arterial endothelium
• Collagens (produced by smooth muscle cells) in cap provide structural strength
• Inflammatory cells (macrophages, T-lymphocytes, mast cells) reside in fibrous cap: recruited from arterial endothelium
• Central lipid core rich in cellular lipids/debris derived from macrophages (died in plaque)
• Form at arterial branching points/bifurcations (turbulent flow)

Question 10

Risk factors for atheroma

Answer 10

• Huge variation in disease severity among patients with same cholesterol levels
• Smoking
• Hypertension
• Diabetes mellitus
• Male
• Elderly
• Accelerate process of plaque formation driven by lipids

LOWER RISK FACTORS
- Obesity
- Sedentary lifestyle
- Low socio-economic status
- Low birthweight

Question 11

What’s the 2 step process to development of atheromatous plaques

Answer 11

Two-step process:
1. injury to endothelial lining of artery
2. chronic inflammatory and healing response of vascular wall to agent causing injury

Chronic/episodic exposure of arterial wall to these processes → formation of atheromatous plaques

Question 12

What are the order of events for the pathogenesis of atherosclerosis?

Answer 12

• Endothelial injury and dysfunction
• Accumulation of lipoproteins (LDL) in vessel wall
• Monocyte adhesion to endothelium → migration into intima and transformation to foamy macrophages
• Platelet adhesion
• Factor release from activated platelets, macrophages → smooth muscle cell recruitment
• Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment
• Lipid accumulation (extracellular and in foamy macrophages)

Question 13

Describe the development of advanced plaque formation

Answer 13

• Large numbers macrophages, T-lymphocytes
• Lipid-laden macrophages die through apoptosis → lipid into lipid core
• Response to injury = chronic inflammatory process: 1. inflammatory reaction 2. process of tissue repair
• Growth factors (PDGF) → proliferation intimal smooth muscle cells, subsequent synthesis collagen, elastin, mucopolysaccharide
• Fibrous cap encloses lipid rich core
• Growth factors secreted by platelets, injured endothelium, macrophages and smooth muscle cells