Pathophysiology of Atheroma

Question 1

arteriosclerosis vs atheroma/athersclerosis vs aneurysms

Answer 1

arteriosclerosis: chronic and abnormal thickening of the arterial walls with resulting loss in elasticity
atheroma: plaque formation at the intima layer of blood vessel walls
aneurysm: dilation of the vessels (not thickening of the walls) due to weakened T media muscle layer due to the inflammatory actions of the plaque

Question 2

presentation of arteriosclerosis

Answer 2

• MI
• stable angina if plaque is small and unstable angina if plaque is bigger
• infarction, stroke
• decreased lumen area and smooth muscular hypertrophy

Question 3

things present in the plaque

Answer 3

• LDL, cholesterol
• foamy macrophages
• T cells, mast cell, and other lymphocytes (reside in the fibrous cap, are recruited there by the endothelium)
• fibrous cap (made of collagen)
• epithelial cover

Question 4

3 complications of plaque rupture

Answer 4

1. damage to epithelium –> plaque contents spilling into the lumen –> thrombus formation
2. damage to the epithelium –> plasma contents spilling into the plaque –> inflammatory response –> scar formation and calcification
3. haemorrhage of the arteries

Question 5

most important risk factor for atheroma

Answer 5

hypercholesterolaemia: decrease in functional receptors on ell surfaces resulting in elevated LDL and cholesterol levels
- common in Caucasians, is genetic
- also results in production of free radicals (O2 species) that modifies the LDL in the intima and lead to the formation of foamy macrophages

(also haemodynamic balances, or turbulent blood flow is another common cause for endothelium injury which leads to atheroma)

Question 6

presentation of atheroma

Answer 6

• corneal arcus: lipid inflitration into the ring of the cornea
• tendon xansthomata: nodules found in the tendons of the hands and feet due to hypercholesterolaemia
• xanthelasmata (iris): bumps on the skin from accumulated subcutaneous fat

Question 7

development of atheromatous plaque

Answer 7

• injury to endothelium. Damaged epithelium will have increased permeability to LDL and will express more adhesion molecules, increased chances of thrombosis
• LDL and cholesterol accumulation in T intima
• inflammatory response starts: platelet aggregation occurs, free radicals convert lipids into foamy macrophages
• factors released from platelets and macrophages (cytokines) leads to smooth muscle cells recruitment and they will produce extracellular matrix and recruit more T cells. This will lead to even more lipid accumulation
• in advanced plaque formation, the smooth muscle cells will respond to the PDGF growth factors secreted by macrophages, platelets, and injure endothelium by producing collagen, elastin, mucopolysaccharide, which will lead to the formation of the fibrous cap

Question 8

4 clinical manifestations of atheroma

Answer 8

1. progressive lumen narrowing: angina or tissue ischaemia, severity varies (stenosis from 50-75%)
2. acute atherothrombotic occlusion: from plaque rupture, results in MI, stroke, ischaemia
3. embolism of distal arterial bed: caused by small embolic occlusion in distal small vessels, affecting multiple organs like the heart (fatal), kidneys, brain (stroke), and ischaemia
4. ruptured atheromatous abdominal aortic aneurysm: aneurysm resulting from weakening of T media muscle layer due to inflammatory activity of the plaque –> dilating of the abdominal aorta of more than >5cm

Question 9

characteristics of vulnerable atheromatous plaque (ones that will likely lead to thrombosis)

Answer 9

• thin fibrous cap
• large fatty core
• intense inflammation –> more weakening of structures –> easier to rupture
• inflammatory cell secretion of proteolytic enzymes, cytokines, reactive O2 species

Question 10

treatment of atheromas

Answer 10

• weight loss
• bp control
• aspirin (inhibits platelet aggregations)
• cholesterol lowering drugs
• surgery in severe cases