Week 2 - Pathophysiology of Atheroma/Atherosclerosis

Question 1

What are the 3 layers of an artery? what are they separated by?

Answer 1

intima, media and adventita/externa. 2 layers of elastic lamina - internal and external

Question 2

What is an atheroma?

Answer 2

elevated focal lesion called plaque in the intima of a large/medium artery.

Question 3

What is arteriosclerosis?

Answer 3

not atheromatous but may coexist. age-related change in muscular arteries causing smooth muscle hypertrophy, intima fibrosis, duplication of elastic lamina, resulting is smaller vessel diameter.

Question 4

What is the early atheorma?

Answer 4

fatty streak in intima, may be see in children. yellow linear elevation in intima

Question 5

What is an early atheromatous plaque?

Answer 5

smooth yellow patches in intima with lipid-laden macrophages (foam cells). progress to plaques

Question 6

What is a fully developed atheromatous plaque?

Answer 6

central lipid core with thick fibrous tissue cap surrounding it. all covered by arterial endothelium. collagen is secreted by smooth muscle cells to provide strength to cap.

Question 7

What occurs in a worsening atheromatous plaque?

Answer 7

foamy macrophages, calcification, atheromas joining together, complicated atheroma (rupture, thrombosis)

Question 8

What is the aetiology of atheroma regarding lipids?

Answer 8

• hyperlipidaemia very big risk factor. causes plaque formation and growth in absence of other risk factors.
• some individuals genetically have lack of LDL receptors, so higher plasma LDL levels.

Question 9

What are signs of atherosclerosis?

Answer 9

signs depend on how you developed it.
- signs of hyperlipidaemia using biochemical evidence,
- corneus arcus (pale ring atound iris), tendon - - xanthoma (lumps in tendons)
- xanthelasma - collections of foamy macrophages in skin and eyes - yellow plaques

Question 10

What are risk factors for atherosclerosis?

Answer 10

smoking, hypertension, obesity, elderly, male. may accelerate plaque formation by lipids

Question 11

What is the order of events leading to formation of an atheromatous plaque?

Answer 11

1) endothelial injury.
2) lipoproteins accumulate in vessel wall, then monocytes are recruited.
3) they migrate into intima and then transform into foamy macrophages.
4) on exposure to platelets, factors are released, recruiting smooth muscle cells and t cells.
5) lipid accumulates in ECM and intima, forming part of foamy macrophage and forming fibrous cap, along with smooth muscle cells

Question 12

Why are injured endothelial cells likely to form a thrombus?

Answer 12

• express more cell adhesion molecules,
• increased permeability to LDL.

more likely to form thrombus and atheromatous plaque

Question 13

How does hypercholesterolaemia lead to foamy macrophage formation?

Answer 13

• increases local production of reactive O2 species, which impairs endothelial cell function.
• lipoproteins which enter intima are modified by free radicals.
• macrophages engulf them but cant degrade them, making macrophages foamy. this is toxic

Question 14

What happens and when do foamy macrophages die?

Answer 14

in advanced plaque formation. they apoptose and release lipid into lipid core, forming chronic inflammatory response. endothelial damage causes growth factor release, tissue repair and fibroblast and smooth muscle proliferation, forming thick fibrous cap to enclose lipid rich core

Question 15

What is progressive lumen narrowing due to high grade plaque stenosis?

Answer 15

50-75% of vessel infiltrated by plaque. reduction in blood flow, but ischaemia is still reversible. may have stable angina, or unstable angina.

Question 16

What is acute atherothrombotic occlusion?

Answer 16

plaque ruptures and exposes highly thrombogenic contents, like collagen, lipid and debris, to the blood stream, causing coagulation. in total occlusion, you have ischaemia and no blood is getting through, so leads to infarction. stroke, MI, limb gangrene in major peripheral arteries (femoral, popliteal).

Question 17

What is embolisation of the distal arterial bed?

Answer 17

thrombus fragments detach and trap in small vessels - cause small infarcts in organs. leads to small foci of necrosis. in heart may cause arrhythmias. In carotid may cause stroke or cerebral infarct, or transient ischaemic attacks.

Question 18

What is a ruptured atheromatous abdominal aortic aneurysm?

Answer 18

plaque in aortic wall weakens gradually, then ruptures. blood escapes into retroperitoneum (area outside peritoneal cavity). abdominal bleeding, high mortality

Question 19

What are the distinct morphological features of a vulnerable plaque?

Answer 19

vulnerable to rupture, haemhorrage.

thin fibrous cap, thick lipid core, high inflammatory activity. this degrades plaque and causes risk of rupture.

Question 20

How would you prevent an atheroma?

Answer 20

• smoking,
• diet,
• weight,
• exercise,
• control BP,

Question 21

How do you treat atheroma aside from lifestyle changes?

Answer 21

cholesterol lowering drugs, aspirin (inhibit platelet aggregation), surgical options

Question 22

What is found in a developed atheromatous plaque?

Answer 22

• Foam cells
• free lipid and cholesterol
• smooth muscle cells
• lymphocytes
• collagen and proteoglycans