Atherosclerosis

Question 1

what makes atheromas more likely to form?

Answer 1

• cigarette smoking
• hypertension
• hyperlipidemia
• diabetes
• age (older)
• sex (male)
• genetics

Question 2

what is haemodynamic injury?

Answer 2

haemodynamic injury = damage to tissues by abnormal flow or pressure (hypertension is a cause)

• they are sites of turbulent blood flow (most branching sites)
• this is how you can predict where atherosclerosis might affect

Question 3

how does smoking cause atheromas?

Answer 3

unknown mechanism of endothelial injury
- we just know that cessation (stopping) greatly reduces risk therefore modifiable risk factor

Question 4

what is hyperlipidemia?

Answer 4

lots of lipids in blood

hypercholesterolaemia = causes atherosclerosis in absence of other risk factors

Question 5

how does diabetes cause atherosclerosis?

Answer 5

• increase cholesterol levels
• advanced glycation end products (AGE) - complex mechanism for causing atherosclerosis, endothelial dysfunction, triggered immune response, stress etc
• abnormal cross linking in vessel walls (more gaps more getting stuck)
• loss of elasticity - more rigid and increased endothelial injury
• trap cholesterol - LDL (accumulation and less to cells)

Question 6

what are 2 independent risk factors for atherosclerosis?

Answer 6

1. age = 40-60’s = although early stage occurs young by old age abnormality progressed to become clinically relevent
2. gender (males) = not really sure why

Question 7

how is genetics involved in causing atherosclerosis?

Answer 7

complicated:

1. cholesterol metabolism
2. inflammatory metabolism
3. control of blood pressure (see CVS lecture)

Question 8

how is flow rate affected by atherosclerosis?

Answer 8

small changes in diameter of vessel make massive changes in rate of flow - to the power of 4

Question 9

what are the 4 stages of atheroma formation?

Answer 9

1. primary endothelial injury
2. lipids accumulation
3. smooth muscle migration
4. progression

Question 10

what is first phase of atheroma formation - primary endothelial injury?

Answer 10

• endothelial dysfunction - increased permeability and increased white cell adhesion (they don’t have anywhere to go - no chemotaxis to take them somewhere)
• increased VCAM 1 etc (adhesion molecules)

(monocytes attach & migrate through wall and become macrophages)

Question 11

what is second phase of atheroma formation -lipid accumulation?

Answer 11

• macrophages gobble up cholesterol (engulf LDL cholesterol →making foam cells which are cells laden with cholesterol)
• initially the volume of cholesterol within foam cells is low but as more LDL is taken up and turned to foam cells = large amounts of cholesterol accumulate →contributes to formation of fatty streak
• as foam cells accumulate and fatty streak progress - plaque is formed and can trap foam cells
• LDL cholesterol that has penetrated arterial wall contributes to lipid-rich core of plaque (hallmark of advanced lesion)
• HDL shuttles back to the liver - HDL is good cholesterol and can help remove cholesterol from arterial wall and transport it back to liver

Question 12

what is fatty streak?

Answer 12

early stage of atherosclerotic lesions, they consist of accumulated foam cells, lipids, immune cells and cellular debris

= as more LDL is taken up and turned to foam cells = large amounts of cholesterol accumulate →contributes to formation of fatty streak

Question 13

what is third phase of atheroma formation - smooth muscle migration?

Answer 13

• smooth muscle migrates from media into the intima (response to signals & changes in microenvironment within wall)
• once in intima, smooth muscle cells can adhere to developing atheroma - they get stuck and take up cholesterol adding to lipid content of lesion
• smooth muscle cells produce extracellular matrix components – collagen, elastin etc = contributes to structural integrity of plaque
• accumulation of smooth muscle cells + extracellular matrix components = change lesion from fatty streak to fibrofatty plaque

Question 14

what is 4th phase of atheroma formation - progression?

Answer 14

• more cholesterol
• more macrophages
• more smooth muscle and collagen etc
• eventually too much cholesterol and a pool of extracellular cholesterol forms the centre of the plaque

= associated with further loss of luminal patency and arterial wall weakness

Question 15

when does atheroma become big issue?

Answer 15

• it is big issue if only artery supplying an organ or tissue (no collateral circulation)
• big issue if arterial diameter already small
• big issue if overall blood flow is reduced (i.e. cardiac failure)