What is the function of chylomicrons?
Transport TG from gut to rest of body
When should chylomicrons be present?
After eating fat contained foods, (absent in fasting state)
What are chylomicron’s main Apoprotein?
How do VLDL get into blood?
Made by liver from its own fat and c/h
What do VLDL do? And what is their apoprotein?
Transport TG to peripheral tisseus. ApoC
Which surgical emergency do high TG lead to?
Which lipoproteins are the main contributors to atherosclerosis? And how are they made?
LDL made by VLDL metabolism
What happens to excess LDL? What is their Apoprotein?
- Taken up by liver via receptors
How is HDL made?
Liver and intestines
How are HDL protective?
Reverse transport of cholesterol back to the liver
What is HDL’s apoprotein?
Why are raised TG levels associated with increased coagulability of blood?
Due to increased plasma fibrinogen levels and factor VII activity
What are most cases of primary hypercholesterolaemia due to?
- Polygenic disorders which make increased susceptibility: ie overproduction of VLDL by liver which is converted to LDL leading to overloading of LDL receptor and decreased clearance from body
- And increased dietary fat and obesity
What is the commonest monogenic hyperlipidaemia? And how is it inherited?
- Familial hypercholesterolaemia
- Inheritance: dominant
What is the problem in FH?
- Absent or defective cell surface receptors which mediate uptake of LDL
- Or problem with ApoB so less uptake of LDL more in circulation and so more atherosclerosis
What are the features of homozygous FH? Age of athero, physical signs, chol level, age of death
- Age of athero: childhood
- Cutaneous xanthomata in childhood
- Cholesterol > 15mmol/l
- Untreated: die < 30
When do heterozygous FH get coronary heart disease?
What is the age of death in untreated hetero FH?
What are the physical signs in hetero FH?
- Corneal arcus in young
- Tendon xanthomata
What are xanthelasmata?
Lipid deposits in eyes
What are eruptive xanthomata?
Itchy nodules in crops in hypertriglyceridaemia
What are tuberous xanthomata?
Yellow plaques on elbows and knees
What are planar/palmar xanthomata?
Orange streaks in palmar creases – virtually diagnostic of remnant hyperlipidaemia
What is type III disease? And what is it assoc with?
- Combined hyperCHOL and hyperTG
- Assoc with accelerated atherosclerosis
What are physical signs of type III disease?
- Tubero-eruptive xanthomata
- Palmar xanthomata
What is the defect in type III disease?
What is type III disease associated with?
Which arteries are more susceptible to athersclerosis in type III disease than other hyperlipidaemias?
what is the cause of primary hypertriglyceridaemia? (2things)
- Increased hepatic VLDL production in association with decreased TG clearance
- This can be familial or acquired
What are the acquired causes of primary hypertriglyceridaemia?
Diabetes, alcohol, obesity, BB, oestrogen administration
What is a rare, familial but serious cause of primary hypertriglyceridaemia?
LPL deficiency (responsible for metab of VLDL and chylomicrons)
What are 4 features of familial LPL deficiency primary hypertriglyceridaemia?
- Fatty liver
- Recurrent pancreatitis
Which kidney problems can causes secondary hyperlipidaemia?
- Nephrotic syndrome
- Chronic renal insufficiency
Which drugs cause secondary hyperlipidaemia?
- Thiazide diuretics
- Protease inhibitors
What is the effect of oestrogen on lipids?
- Lower LDL and Raise HDL so giving HRT post-menopausal is cardioprotective
- But also raise TG
Using other values, how do you calculate LDL cholesterol?
Total cholesterol – HDL – TG/2.2
What type of sample is needed to calculate LDL cholesterol?
In patients who have had a cardiovascular event, when do they need to be treated?
- If their total cholesterol > 5; or LDL-cholesterol > 3
- Ie secondary prevention
What are the targets for treatment for chol and LDL-chol
- Total cholesterol < 5
- LDL cholesterol < 3
Which are the 2 main classes of lipid lowering drugs used?
- Statins: HMG Co-A reductase inhibitors so inhibit cholesterol synthesis
What are SE of statins?
- Derangement of LFTs
- Muscle cramps
- Rarely rhabdomyolysis
What is the action and SE of fibrates?
Action: reduce serum TG, raise cholesterol, may cause myositis
Which other diseases are associated with high cholesterol?
How does ezetimibe work?
Block absorption of cholesterol from small intestine, works at brush border
How does cholestyramine work?
- Bile acid sequestrant, formed into complexes, excreted
- So more plasma cholesterol is used to make bile acids, thereby reduced plasma cholesterol levels