4. Dyslipoproteinaemias Flashcards
What are dyslipoproteinaemias and what are the 2 main classes?
Any defect in the metabolism of plasma lipoproteins.
- primary - inherited error in lipoprotein metabolism
- secondary (acquired) - result of diet, drugs or underlying diseases such as diabetes
What are hyperlipoproteinaemias and what are they caused by?
Raised plasma levels of 1 or more lipoprotein classes caused by either:
- over-production
- under-removal
Involve defects in enzymes, receptors or apoproteins.
How many types of hyperlipoproteinaemias are there and how are these classified?
6 classes based on measurement of:
- fasting plasma concentration of glucose
- total cholesterol and TAGs
- examination of results of plasma lipoprotein segragation by electrophoresis
(classification is important because each type has a different risk of CVD, different causes and different treatments)
Describe the cause, signs and CVD risk of 3 classes of hyperlipoproteinaemias.
Type I
- caused by defective lipoprotein lipase
- chylomicrons in fasting plasma
- no link with coronary artery disease
Type IIa
- caused by defective LDL receptor (cells can’t take up LDLs - more risk of oxidation)
- associated with coronary artery disease that may be severe
Type III
- caused by defective apoE (rare, ~1/10,000)
- raised IDL and chylomicron remnants
- associated with coronary artery disease
What are the clinical signs and symptoms of hypercholesterolaemia?
- high cholesterol level in blood
- cholesterol deposits in various body areas
i) xanthelasma: yellow patches on eyelids
ii) tendon xanthoma: nodules on tendon
iii) corneal arcus: obvious white circle around eye. common in older people but can be sign in young
What is the 1st approach to the treatment of hyperlipoproteinaemia?
Diet modifications:
- reduce cholesterol and saturated lipids (but vast maj synthesised by body so not much effect?)
- increase fibre intake
Lifestyle modification:
- increase exercise
- stop smoking to reduce CVD risk
How is hyperlipoproteinaemia treated if diet and lifestyle modifications don’t work?
- statins (e.g. atorvastatin):
- reduce liver cholesterol synthesis by inhibiting HMG-CoA reductase (= 1st enzyme in cholesterol synthesis pathway)
- increased expression of lipoprotein lipase - bile salt sequesterants (e.g. colestipol):
- bind bile salts in GI tract… prevents their reabsorption into heaptic-portal circulation and promotes their loss in faeces… forces liver to produce more bile acids using more cholesterol
How does increased fibre in diet reduce cholesterol levels?
Fibre binds bile salts in GI tract… prevents their reabsorption into heaptic-portal circulation and promotes their loss in faeces… forces liver to produce more bile acids using more cholesterol
What are the recommended concentrations of total cholesterol, non-HDL cholesterol, LDL-C, HDL-C, total cholesterol:HDL-C ratio and triglyceride in the blood?
- total cholesterol: <5mmol/L
- non-HDL cholesterol (total C minus HDL-C): <4mmol/L
- LDL-C: <3mmol/L
- HDL-C: >1mmol/L (men) and >1.2mmol/L (women)
- total cholesterol:HDL-C ratio: above 6 considered high risk (the lower the ratio the better)
- triglyceride: <2mmol/L in fasting sample
What is the consequence of the poor clearance of LDL particles by the liver?
1/2 life of LDL is much longer than VLDL or IDL - more susceptible to oxidative damage which can lead to atherosclerosis and consequent angina, MI or stroke
How does oxidative damage of LDL lead to angina, MI or stroke?
- oxidised LDL recognised and engulfed by macrophages.
- lipid-laden macrophages - foam cells - accumulate in intima of BV walls to form a fatty streak.
- fatty streaks can evolve into atherosclerotic plaque.
- plaque grows and encroaches on lumen of artery…
a) angina if occlusion of coronary artery
b) rupture of plaque triggers acute thrombosis (clot) by activating platelets and clotting cascade… stroke (brain) or MI (coronary artery)
Describe the appearance of a plasma sample of a type I hyperlipidaemia patient.
creamy due to excess chylomicrons
Which 3 types of defect can cause low plasma LPL activity in type I hyperlipidaemia?
Type Ia: mutation in LPL gene
Type Ib: mutation in apoprotein CII (co-factor required for LPL activation)
Tybe Ic: presence of plasma LPL inhibitor
Why is the plasma cholesterol of type I hyperlipidaemia patients also elevated?
chylomicrons contain ~1% cholesterol as well as main TAG content , so increased [chylomicron] would also cause increased [cholesterol]
What are the potential problems of a low-fat diet?
May cause deficiency in essential fatty acids which are required for:
- absorption of fat-soluble vitamins (A, D E and K)
- synthesis of complex fatty acids - omega-3 and -6
