Atherosclerosis

Question 1

3 Stages of Arteriosclerosis

Answer 1

Endothelial Damage
Uptake of modified LDL particles
Adhesion + infiltration of macrophages
Smooth muscle proliferation + formation of fibrous cap

Question 2

Vasodilators

Answer 2

NO

PGI2

Question 3

Vasoconstrictors

Answer 3

Angiotensin II

Endothelin

Question 4

Fibrinolysis

Answer 4

Process that prevents blood clots

Question 5

Endothelium dysfunction

Answer 5

Imbalance between vasodilating + vasoconstricting substances

Question 6

Endothelium Damage causes

Answer 6

Shear stress
Toxic damage
High lipid levels
Viral/bacterial infection
Dysfunctional damaged endothelium

Question 7

Lipoproteins

Answer 7

Lower the density of a lipoprotein, the more lipid it contains relative to protein

Question 8

Lowest to highest density lipoprotein

Answer 8

Chylomicron –> VLDL –> IDL –> LDL –> HDL

Question 9

Chylomicron Main component + Apoprotein

Answer 9

TG

B48 (A,C,E)

Question 10

VLDL Main component + Apoprotein

Answer 10

TG

B100 (A,C,E)

Question 11

IDL Main component + Apoprotein

Answer 11

TG + cholesterol

B100, E

Question 12

LDL Main component + Apoprotein

Answer 12

Cholesterol

B100

Question 13

HDL Main component + Apoprotein

Answer 13

Protein

AI, AII (C,E)

Question 14

Biggest Lipoprotein –> smallest

Answer 14

Chylomicron –> VLDL –> IDL –> LDL –>HDL

Question 15

Oxidation of LDLs

Answer 15

Facilitated by reactive O2 species (free radicals)
Decreased by antioxidants in fruit + veg
Stimulates expression of inflammatory mediators including adhesion molecules

Question 16

Glycation of LDLs

Answer 16

High glucose levels
Higher glycated LDLs in diabetes
Glycated LDL more likely to get oxidised

Question 17

Infiltration of macrophages

Answer 17

Endothelial Damage/oxidised LDLs –> attract monocytes
Monocytes bound to/cross endothelium
Transformed into macrophages –> accumulate oxidised LDLs
Fat-laden foam cells appear as fatty streaks

Question 18

Normal LDL uptake

Answer 18

LDL receptor recognises B100
Internal accumulation of LDL by macrophages
Lower LDL surface receptors –> lower uptake

Question 19

Modified LDL uptake

Answer 19

Modified LDL not recognised by LDL receptor
Instead taken up via scavenger receptor
NO negative feedback
LDL accumulates in large droplets- FOAM CELLS

Question 20

Fibrous cap formation

Answer 20

Damage to Endothelium
LDL oxidation + entry
Taken up by macrophages
Lipid filled foam cells
Create subendothelial pool
Cytokines secreted by endothelium + macrophages stimulates migration of SMC
Secrete collagen forming a fibrous cap
Rupture can lead to thrombus formation

Question 21

Stable Plaque

Answer 21

Slow growing
Fibrin cap matures (not prone to rupture)
Reduced blood flow
Stable angina (exertional)

Question 22

Unstable Plaque

Answer 22

Grow quickly - rapid lipid deposition
Thin fibrin cap
Fragile cap ruptures 
Thrombus formation
Reduced lumen diameter
May occlude lumen completely (MI)

Question 23

Fragile cap rupture

Answer 23

Haemorrhage from plaque
Release of platelet tissue factor (clotting cascade)
Collagen exposed causing platelet aggregation

Question 24

Total cholesterol adult

Answer 24

under 200mg/dl

Question 25

LDL adult

Answer 25

Under 130 mg/dl

Question 26

HDL adult

Answer 26

over 40mg/dl

Question 27

triglyceride range

Answer 27

10-190 mg/dl

Question 28

Homocystinaemia

Answer 28

RF for unstable plaque Increased homocysteine (B6, B12 + folic acid deficiencies) Increase oxidant stress Need to up B vitamin intake to combat

Question 29

B vitamin uptake pathway

Answer 29

Methionine --> homocysteine in bloodstream Homocysteine --> cysteine (B6) (cell folding/antioxidant) Homocysteine --> back to methionine (B12)

Question 30

Lipoprotein (a)- LDL + extra apolipoprotein

Answer 30

RF for unstable plaque | More firmly retained in arterial wall

Question 31

Infection

Answer 31

Unstable plaque RF Chlamydia pneumoniae inflammation of endothelium

Question 32

Treatment Unstable Plaques

Answer 32

Modifiable risk factors Statins Polypill

Question 33

Statins MOA

Answer 33

``` Inhibit HMG CoA Decrease cholesterol in liver cells increase uptake from circulating blood plasma increase LDL receptors decrease plasma cholesterol ```

Question 34

Polypill

Answer 34

``` More than 80% CV disease reduction Statin x 3 BP lowering drugs (thiazide, B blocker, ACE inhibitor) B vitamins Aspirin ```

Question 35

Atherosclerosis Complications

Answer 35

``` Coronary Artery disease (Angina, MI) Peripheral vascular disease (ulcers) Stroke aneurysm renal artery stenosis ```

Question 36

Stent

Answer 36

Maintains patency of blood vessel