pathophysiology of atheroma

Question 1

what is atheroma/ATHEROSCLEROSIS

Answer 1

Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries

Question 2

what causes ischaemia?

Answer 2

atheromatous plaques narrow lumen

Question 3

what are the serious consequences of atheroma?

Answer 3

angina due to myocardial ischaemia

Question 4

what are characteristics of early atheromatous plaque?

Answer 4

Young adults onwards
Smooth yellow patches in intima
Lipid-laden macrophages
Progress to established plaques

Question 5

what are characteristics of fully developed arethromatous plaque?

Answer 5

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)

Soft, highly thrombogenic, often rim of “foamy” macrophages (“foamy” due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor)

Question 6

what complicated atheroma?

Answer 6

Features of established atheromatous plaque (lipid-rich core, fibrous cap) plus
Haemorrhage into plaque (calcification)
Plaque rupture/fissuring
Thrombosis

Question 7

whats the aetiology of arethroma?

Answer 7

Hypercholesterolaemia most important risk factor

Importance of LDL cholesterol

1/500 Caucasians heterozygous for this type mutation: ↓ functional receptors on cell surfaces, elevated plasma LDL cholesterol levels

Rare patients homozygous (1/million): much higher cholesterol levels, usually die from coronary artery atheroma in infancy/teens

Question 8

what are signs of major hyperlipidaemia?

Answer 8

Biochemical evidence: LDL, HDL, total cholesterol, triglycerides

Corneal arcus (premature)
Tendon xanthomata (knuckles, Achilles)
Xanthelasmata

Question 9

what are risk factors for atheroma?

Answer 9

Smoking
Hypertension
Diabetes mellitus
Male
Elderly
Accelerate process of plaque formation driven by lipids

Question 10

what are less strong risk factors of atheroma?

Answer 10

Obesity
Sedentary lifestyle
Low socio-economic status
Low birthweight
?role of micro-organisms

Question 11

what is the 2 step process of atheromatous plaques

Answer 11

Injury to endothelial lining of artery

Chronic inflammatory and healing response of vascular wall to agent causing injury

Question 12

what is 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

what are consequences of atheroma?

Answer 13

Progressive lumen narrowing due to high grade plaque stenosis

acute atherothrombotic occlusion

Embolisation of the distal arterial bed

Ruptured atheromatous abdominal aortic aneurysm

Question 14

what is Progressive lumen narrowing due to high grade plaque stenosis

Answer 14

Stenosis of > 50-75% of vessel lumen → critical reduction of blood flow in distal arterial bed → reversible tissue ischaemia

Question 15

what is acute atherothrombotic occlusion

Answer 15

Major complications: rupture of plaque → acute event
Rupture exposes highly thrombogenic plaque contents (collagen, lipid, debris) to blood stream → activation of coagulation cascade and thrombotic occlusion in very short time
Total occlusion → irreversible ischaemia → necrosis (infarction) of tissues

Question 16

what is Embolisation of the distal arterial bed

Answer 16

Detachment of small thrombus fragments from thrombosed atheromatous arteries → embolise distal to ruptured plaque
Embolic occlusion of small vessels → small infarcts in organs

Question 17

what is Ruptured atheromatous abdominal aortic aneurysm

Answer 17

Media beneath atheromatous plaques gradually weakened (lipid-related inflammatory activity in plaque)
→ Gradual dilatation of vessel
Slow but progressive, seen in elderly, often asymptomatic
Sudden rupture → massive retroperitoneal haemorrhage (high mortality)
Aneurysms > 5cm diameter at high risk of rupture
Mural thrombus → emboli to legs

Question 18

what are characteristics of vulnerable plaques?

Answer 18

Typically thin fibrous cap, large lipid core, prominent inflammation

Question 19

what is the therapy of atheroma?

Answer 19

Stop smoking
Control blood pressure
Weight loss
Regular exercise
Dietary modifications

Secondary prevention:
Cholesterol lowering drugs, aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)

Surgical options