L15 - Hyperlipidaemias

Question 1

What is the major concern of hyperlipidaemia?

Answer 1

Atherosclerosis - plaque build up in arteries

Question 2

What are the different classes of hyperlipidaemia?

Answer 2

1. Chylomicrons (CM)
2. Very low density lipoproteins (VLDL)
3. Low density lipoproteins (LDL)
4. Intermediate density lipoproteins (IDL)
5. High density lipoproteins (HDL)

Question 3

What are the transport pathways for lipids?

Answer 3

1. Exogenous pathway
2. Endogenous pathway
   (3. Pathway of reverse cholesterol transport)

Question 4

What is hyperlipidaemia?

Answer 4

High level of cholesterol or triglycerides in blood

Question 5

How can atherosclerosis occur and how could it lead to thrombosis?

Answer 5

• Evolves over decades in the walls of arteries
• Endothelial dysfunction due to dec NO (EDRF)
• Injury –> expression of adhesion molecules (monocytes)
• LDLs acc (oxidised by monocytes/ macrophages)
• Oxidised LDL taken up by macrophages (foam cells)
• Foam cells + lymphocytes = fatty streaks
• Macrophages, platelets and endothelial cells release cytokines and growth factors
• Prolif of s. muscle and CT –> fibrous cap overlying lipid core (atheromatous plaque)
• Plaque can rupture –> leading to thrombosis

Question 6

Describe what happens in the exogenous lipid pathway

Answer 6

1. Lipid emulsified by bile acids in GIT
2. Absorbed –> chylomicrons
3. Triglycerides hydrolysed by lipoprotein lipase (muscle/ fat)
4. Chylomicron remnants –> liver

Question 7

Describe what happens in the endogenous lipid pathway

Answer 7

1. [In the liver]
   - Synthesis of chylomicrons and triglycerides (C from exog pathway)
   - VLDL secreted (cholesterol esters and triglycerides)
   - Triglycerides removed –> low density lipoproteins (cholesterol esters)
2. [Extrahepatic] REVERSE CHOLESTEROL TRANSPORT
   - C from cell turnover (And from dev plaques) –> HDL
   - CE transferred to LDL (CETP) –> Liver
   - Increased HDL promotes LDL removal

Question 8

What is the approx percentage of circulating cholesterol?

Answer 8

60-70%

Question 9

What are some of the uses of cholesterol?

Answer 9

• Membranes
• Steroids
• Bile acid production

Question 10

What are the different types of hyperlipidaemias?

Answer 10

1. Primary (genetic)

2. Secondary

Question 11

Describe primary hyperlipidaemia

Answer 11

• Six phenotypes
• Differ in lipoprotein class affected
• e.g. IIa = inc LDL
• IIb = inc LDL and inc VLDL
• Risk of atherosclerosis

Question 12

Describe secondary hyperlipidaemia

Answer 12

• Metabolic disorders
• Diabetes
• Hypothyroidism
• Renal disease
• Alcoholism

Question 13

What are examples of HMG CoA reductase inhibitors?

Answer 13

Statins

• Atorvastatin
• Pravastatin