Hyperlipidaemia

Question 0

What amount of total cholesterol gives a mild risk of CHD?

Answer 0

5.2-6.5 mMol/L

Question 1

What is hyperlipidaemia?

Answer 1

Raised plasma cholesterol and raised plasma triacylglycerol

Question 2

What amount of total cholesterol gives a medium risk of CHD?

Answer 2

6.5-7.8mMol/L

Question 3

What amount of total cholesterol gives high risk of CHD?

Answer 3

> 7.8 mMol/L

Question 4

What amount of LDL cholesterol gives a mild risk of CHD?

Answer 4

3.5-4.5 mMol/L

Question 5

What amount of LDL cholesterol gives a medium risk of CHD?

Answer 5

4.5-5.5 mMol/L

Question 6

What amount of LDL cholesterol gives a high risk of CHD?

Answer 6

> 5.5 mMol/L

Question 7

What amount of HDL cholesterol gives a medium/high risk of CHD?

Answer 7

<1.1 women

Question 8

What total TAG amount gives a mild risk of CHD?

Answer 8

<2

Question 9

What total TAG amount gives a medium risk of CHD?

Answer 9

> 2

Question 10

What total TAG gives a high risk of CHD?

Answer 10

> 5

Question 11

What are some secondary causes of hyperlipidaemia?

Answer 11

Diabetes type 2, hypothyroidism, obesity, alcohol abuse, renal failure, pregnancy

Question 12

What are the classifications of hyperlipoproteinaemias?

Answer 12

Phenotype (symptoms), genotype (molecular defects)

Question 13

How to measure traditional classification?

Answer 13

-Serum/plasma cholesterol, lipoprotein electrophoresis, if possible separation of VLDL by ultracentrifugation, HDL by precipitation, total cholesterol - VLDL - HDL = LDL cholesterol, presence of xanthomas

Question 14

In electrophoresis, how is this preformed and what would the plate look like?

Answer 14

Take plasma sample, put on gel and lipid stain it

First is chylomicrons because they are too big to get past into the gel.
Then LDL in the beta position, IDL, then VLDL in the pre-beta position and HDL in the alpha position.

Question 15

What does beta- VLDL contain?

Answer 15

apoB48 and B100

Question 16

What are xanthomas?

Answer 16

• rich in foam cells (resembling those in atherosclerosis)
• yellow or orange plaques or nodules
• occasionally associated with other diseases and must therefore be used together with plasma lipids to diagnose hyperlipidaemia.

Question 17

What happens in disorder of lipoprotein lipase activity (type 1)?

Answer 17

• increase I’m chylomicrons
• lack of lipoprotein lipase activity
• • type 1a: lipase not produced
• • type 2b: ApoCII not produced

Question 18

What does the lipoprotein lipase/ ApoCII interaction look like?

Answer 18

Enzyme is produced in the muscle or adipose tissue and anchors itself to walls. Chylomicrons come floating past and is anchored and starts to break down the chylomicron.

Question 19

What are the similarities between type IV and V?

Answer 19

Both increase production of VLDL by liver.

Don’t understand the difference between IV and V but may be associated with apoE4 phenotype.

Question 20

What does familial hypercholesterolaemia (type IIa) do?

Answer 20

Increased LDL

in most cases LDL receptors either absent of defective

Question 21

What is type IIa heterozygote?

Answer 21

• 1:500 people
• 1 defective gene
• half normal number of receptors
• 2-3 fold increase in LDL
• CHD: if left untreated
• men: can develop in 30s common in 40s, by 60 85% will have had a heart attack, 50%
• women: CHD develops 10 years later despite similar LDL levels

Question 22

What is type IIa homozygote?

Answer 22

• 1:1,000,000
• 2 defective genes
• no functional receptors
• 6 fold increase in LDL
• CHD
• • symptoms seen from 2 years. Heart attack common in teens.
• • death usually before 30 years

Question 23

What are the treatments of type IIa homozygote?

Answer 23

Plasmapheresis, LDL apheresis, liver transplant, gene therapy

Question 24

What are the treatments of type IIa heterozygote?

Answer 24

Statins

Statin and bile acid sequestrants

Question 25

What is gene therapy?

Answer 25

• remove part of liver
• digest and keep hepatocytes in culture
• transfer with retrovirus containing DNA for LDL receptor
• some cells will be re-established themselves in the liver
• modest cholesterol lowering in first attempts (17% down)
• -risk of surgery outweighs the benefits

Question 26

What is familial combines hyperlipidaemia (type IIb)?

Answer 26

Not a single gene defect I.e. Polygenic

Increased VLDL and LDL

Question 27

What causes familial combined hyperlipidaemia (type IIb)?

Answer 27

Possibly a combination of defects in:

• LDL receptors
• structure of apoB
• over - production of VLDL

Question 28

What is remnant hyperlipidaemia (type III)?

Answer 28

Accumulation of remnants particles

– chylomicrons remnants, VLDL, IDL

Question 29

How are chylomicrons, VLDL, IDL usually removed?

Answer 29

From circulation by the liver

• • IDL by the LDL receptors
• • chylomicrons remnants by the LDL receptors related protein

Both recognise apolipoprotein E

Question 30

What is apolipoprotein E?

Answer 30

Glycoprotein found in chylomicrons, VLDL, IDL and HDL

Question 31

What are the three isoforms of apolipoprotein E?

Answer 31

ApoE3 most common
ApoE2 cysteine replaces arginine at position 158
ApoE4 arginine replaces cysteine at position 112

Question 32

What characteristic do people with type III usually have?

Answer 32

90% of people with type III are E2/E2
Appears that the disease only appears in E2/E2 people if the system is ‘stressed’
– e.g, hypothyrodism, diabetes, obesity, genetic environment factors

Question 33

What is tanglers disease characterised by?

Answer 33

• hypertriglyceridaemia
• low LDL
• marked reduction in HDL
• orange tonsils, cloudy corneas
• increased CHD risk

Question 34

What is CETP deficiency characterised by?

Answer 34

• increased HDL cholesterol (particularly HDL2)
• increased apoA1 (but not AII)
• reduced LDL cholesterol
• no other clinical features
• no evidence of increased or reduced risk of CHD

Question 35

What are the two forms of LCAT deficiency?

Answer 35

• very low HDL, cholesterol, apoAI and apoAII

- cloudy cornea, non chromic anaemia, glomerulasclerosis that may progress to kidney failure

Question 36

What is fish eye disease?

Answer 36

Very low HDL cholesterol, apoAI and apoAII

No anaemia or renal disease

Question 37

How is LCAT deficiency not associated with CHD?

Answer 37

• LCAT deficiency not associated with increased risk despite very low HDL levels
• suggested that pre-beta HDL may still be active in removing cholesterol from cells