Atherosclerosis

Question 1

What does sclerosis mean ?

Answer 1

Harderning

Question 2

What causes atherosclerosis ?

Answer 2

Endothelial injury
-Anything that increases endothelial cell injury can initiate the process of atherosclerosis

Question 3

What is haemodynamic injury ?

Answer 3

Sites of turbulent blood flow such as branching sites
-Increased endothelial damage so are more likely to develop atherosclerosis
-Also where there are big turns; e.g. arch of aorta; repeated impacts of pulse

Question 4

What are risk factors for atherosclerosis ?

Answer 4

Haemodynamic Injury
Smoking
Hypertension
Hyperlipidaemia
Diabetes
Age
Being male (esp early in life)
Genetics

Question 5

How does hypertension contribute to atherosclerosis ?

Answer 5

Exaccerbates haemodynamic causes
High blood pressure damages endothelium

Question 6

How does hyperlipidaemia contribute to atherosclerosis ?

Answer 6

Hypercholesterolaemia; causes atherosclerosis in the absence of other risk factors.
Good – High density lipoprotein
Bad – Low density lipoprotein (probably)

TGRL are an independent of LDL/HDL RF – Triglyceride rich lipoproteins.

BIG RISK FACTOR

Question 7

How does diabetes contribute to atherosclerosis ?

Answer 7

Increases cholesterol levels

Creates advanced Glycation End Products (AGE)
-Abnormal cross linking in vessel walls
-Loss of elasticity; more rigid and increased endothelial injury
-Trap cholesterol; LDL

Question 8

How does age affect atherosclerosis ?

Answer 8

40-60 is sus
-Earliest stages of atherosclerosis can be seen at 1 year old; All started to develop by the age of 10
-By 40-60 the abnormality has progressed so as to become clinically relevant

Question 9

How does gender affect atherosclerosis ?

Answer 9

Men more likely to get it; esp when younger
-Ostrogen is protective against, odds balance out post-menopause

Question 10

How do genetics affect atherosclerosis ?

Answer 10

Genetic variation in
1) cholesterol metabolism
2) inflammatory response
3) control of blood pressure

Question 11

Describe stages of development of atherosclerosis ?

Answer 11

1) Primary endothelial injury
-Increases permeability and VCAM-1, more white cell adhesion, monocytes move through and become macrophages
2) Accumulation of lipids and macrophages
-Macrophages eat cholesterol;
-Initial; cholesterol volume is low and remains with the cell
-Fat macrophage gets trapped by deposited LDL, HDL shuttles”back to the liver
3) Migration of smooth muscle cells
-Smooth muscle migrates from media into intima
-Gets stuck and takes on cholesterol
-Produce extracellular matrix – collagen etc,
-Change lesion from fatty streak to fibrofatty plaque
4) Increase in size
-More cholesterol, macrophages, smooth muscle and collagen etc
-Eventually too much cholesterol and a pool of extracellular cholesterol forms the centre of the plaque

VCAM = Vascular cell adhesion molecule

Question 12

What are uncomplicated and complicated plaques ?

Answer 12

Uncomplicated is stable plaque, not yet ruptured or blocking, asymptomatic

Complicated have ruptured causing blockage

Question 13

What is the greater factor affecting flow rate ?

Answer 13

Small changes in the patency of a vessel result in a large reduction in flow
To the power of 4

Patency means being open

Question 14

What is a fatty streak and a fibrofatty plaque

Answer 14

Fatty streak
-Earliest visible sign of atherosclerosis
-Accumulation of fat cholesterolly macrophages in arterial wall

Fibrofatty plaques
-Advanced stage
-Fibrous cap overlaying lipid core; provides stability
-Becomes calcified; risk to break off

Smooth muscle migration causes lesion from change from fatty streak to fibrofatty plaque

Fibrous cap made of collagen extracellular matrix from SMC and the SMCs themselves; walls off lipid core from blood flow

Question 15

What makes atheromatous artery narrowing more likely to produce a critical disease ?

Answer 15

It is the only artery supplying an organ or tissue (i.e. no collateral circulation)

The artery diameter is small (e.g coronary artery versus common iliac artery)

Overall blood flow is reduced (i.e. cardiac failure)

Question 16

What are examples of complications of atherosclerosis ?

Answer 16

ARTERIAL STENOSIS; narrowing
ARTERIAL THROMBOSIS
ANEURYSM
DISSECTION; tear in wall of artery, blood can get in and split layers
EMBOLISM