Lipdaemias And Lipid Lowering Drugs

Question 0

How are lipids transported in the plasma ?

Answer 0

In lipoproteins

Question 1

What is hyperlipidaemia ?

Answer 1

Excess of lipid in plasma - especially CH and TG

Question 2

Explain the structure of the lipoprotein..

Answer 2

Central core containing cholesteryl esters and TG

Hydrophilic mono layer of polar phospholipids, free CH and apoprotein

Question 3

What are the 4 main classes of lipoproteins ?

Answer 3

Chylomicrons
LDLs
VLDLs
HDLs

Question 4

Describe chylomicrons…

Answer 4

High ratio of TG to CH
From GIT taken to tissues where they are hydrolysed by lipoprotein lipase to glycerol and fatty acids
The cholesteryl ester remnants from is is taken up by hepatocytes

Question 5

What happens to cholesterol in hepatocytes ?

Answer 5

Stored
Converted to bile acids
Secreted unaltered in bile acids
Enters endogenous pathway

Question 6

Describe VLDLs …

Answer 6

Lower TG to CH ratio compared to chylomicrons
Transport new synthesised TG and CH to muscle and adipose
TG hydrolysed by tissue and glycerol and fatty acids used by the cells
Left over cholesteryl esters make the VLDLs turn into LDLs

Question 7

Describe LDLs…

Answer 7

Highest density of CH

Some of the CH is taken up by tissues, some by liver

Question 8

What is cholesterol used for in the body ?

Answer 8

Make cell membranes
Synthesis of steroids
It’s a source of bile acids

Question 9

Describe HDLs…

Answer 9

Similar CH levels to VLDLs - have more protein than TG
Absorbe CH produced in tissue breakdown and return it to plasma
cH is ester ivied with long chain fatty acids and then the cholesteryl esters transferred to VLDLs and LDLs in the plasma

Question 10

What protein in the plasma is used to transfer cholesteryl esters to VLDLs and LDLs ?

Answer 10

Cholesteryl ester transfer protein (CETP)

Question 11

Explain the non-specific pathway ..

Answer 11

LDLs taken up by endothelial cells causing monocytes/macrophages to produce free radicals that oxidise the LDLs
Produces modified LDLs that’s taken up by scavenger receptors into macrophages
Activates the macrophage causing the, to release proinflammatory cytokines
Causes a build up of CH

Question 12

What controls the pick up rate of LDLs in the plasma ?

Answer 12

The number of LDL receptors - can be up regulated or down regulated
- up regulation is inhibited by high LDLs levels

Question 13

Why is LDL subtype LPa bad ?

Answer 13

Contains a unique apoprotein with a very similar structure to plasminogen substrate
It competes for the plasminogen receptor in endothelial wall
It prevents secretion of the plasminogen activator which means less plasminogen is produces and therefore fibrinoloysis is inhibited and thrombosis is promoted

Question 14

What does high CH precede ?

Answer 14

Thrombosis
Myocardial infarction
Cerebral vascular blockade
Xanthomas

Question 15

Who is at particular risk of high CH ?

Answer 15

Family history - hypercholesteremia
Smokers
Hypertensives
Diabetics

Question 16

Explain the primary defect that causes high CH..

Answer 16

Genetic defect - dysfunctional LDL receptors or they are not expressed

Question 17

What aRe the secondary aetiology for hyperlipidaemia ?

Answer 17

Diabetes 
Hypothyroidism 
Uraemia
Alcoholism 
Oestrogen contraceptives

Question 18

What does atherogenesis involve ?

Answer 18

1- endothelial dysfunction with altered prostaglandin biosynthesis
2- injury of dysfunctional endothelium causes expression of adhesion molecules - encourages movement of monocytes into the intima
3- LDL particles transported into vessel wall - endothelial cells and monocytes/macrophages produce free radicals which oxidise LDLs
4- oxidised LDLs taken up by macrophages by scavenger receptors which activates macrophages causing release of proinflammatory cytokines
5- sub endothelial accumulation of macrophages and t lymphocytes causes formation of fatty streaks
6-CH can be mobilised for the endothelial cell wall and transported in plasma in form of HDLS
7- more immune response causes proliferation of smooth muscle and deposition of connective tissue
Reducing a dense fibrous cal poberlying the lipid rich core fo ring an atherpmatous plaque