Hyperlipidaemia Flashcards
What amount of total cholesterol gives a mild risk of CHD?
5.2-6.5 mMol/L
What is hyperlipidaemia?
Raised plasma cholesterol and raised plasma triacylglycerol
What amount of total cholesterol gives a medium risk of CHD?
6.5-7.8mMol/L
What amount of total cholesterol gives high risk of CHD?
> 7.8 mMol/L
What amount of LDL cholesterol gives a mild risk of CHD?
3.5-4.5 mMol/L
What amount of LDL cholesterol gives a medium risk of CHD?
4.5-5.5 mMol/L
What amount of LDL cholesterol gives a high risk of CHD?
> 5.5 mMol/L
What amount of HDL cholesterol gives a medium/high risk of CHD?
<1.1 women
What total TAG amount gives a mild risk of CHD?
<2
What total TAG amount gives a medium risk of CHD?
> 2
What total TAG gives a high risk of CHD?
> 5
What are some secondary causes of hyperlipidaemia?
Diabetes type 2, hypothyroidism, obesity, alcohol abuse, renal failure, pregnancy
What are the classifications of hyperlipoproteinaemias?
Phenotype (symptoms), genotype (molecular defects)
How to measure traditional classification?
-Serum/plasma cholesterol, lipoprotein electrophoresis, if possible separation of VLDL by ultracentrifugation, HDL by precipitation, total cholesterol - VLDL - HDL = LDL cholesterol, presence of xanthomas
In electrophoresis, how is this preformed and what would the plate look like?
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.
What does beta- VLDL contain?
apoB48 and B100
What are xanthomas?
- 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.
What happens in disorder of lipoprotein lipase activity (type 1)?
- increase I’m chylomicrons
- lack of lipoprotein lipase activity
- type 1a: lipase not produced
- type 2b: ApoCII not produced
What does the lipoprotein lipase/ ApoCII interaction look like?
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.
What are the similarities between type IV and V?
Both increase production of VLDL by liver.
Don’t understand the difference between IV and V but may be associated with apoE4 phenotype.
What does familial hypercholesterolaemia (type IIa) do?
Increased LDL
in most cases LDL receptors either absent of defective
What is type IIa heterozygote?
- 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
What is type IIa homozygote?
- 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
What are the treatments of type IIa homozygote?
Plasmapheresis, LDL apheresis, liver transplant, gene therapy
What are the treatments of type IIa heterozygote?
Statins
Statin and bile acid sequestrants
What is gene therapy?
- 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
What is familial combines hyperlipidaemia (type IIb)?
Not a single gene defect I.e. Polygenic
Increased VLDL and LDL
What causes familial combined hyperlipidaemia (type IIb)?
Possibly a combination of defects in:
- LDL receptors
- structure of apoB
- over - production of VLDL
What is remnant hyperlipidaemia (type III)?
Accumulation of remnants particles
– chylomicrons remnants, VLDL, IDL
How are chylomicrons, VLDL, IDL usually removed?
From circulation by the liver
- IDL by the LDL receptors
- chylomicrons remnants by the LDL receptors related protein
Both recognise apolipoprotein E
What is apolipoprotein E?
Glycoprotein found in chylomicrons, VLDL, IDL and HDL
What are the three isoforms of apolipoprotein E?
ApoE3 most common
ApoE2 cysteine replaces arginine at position 158
ApoE4 arginine replaces cysteine at position 112
What characteristic do people with type III usually have?
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
What is tanglers disease characterised by?
- hypertriglyceridaemia
- low LDL
- marked reduction in HDL
- orange tonsils, cloudy corneas
- increased CHD risk
What is CETP deficiency characterised by?
- 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
What are the two forms of LCAT deficiency?
- very low HDL, cholesterol, apoAI and apoAII
- cloudy cornea, non chromic anaemia, glomerulasclerosis that may progress to kidney failure
What is fish eye disease?
Very low HDL cholesterol, apoAI and apoAII
No anaemia or renal disease
How is LCAT deficiency not associated with CHD?
- 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
