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What is the function of chylomicrons?
Transport TG from gut to rest of body
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When should chylomicrons be present?
After eating fat contained foods, (absent in fasting state)
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What are chylomicron’s main Apoprotein?
C
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How do VLDL get into blood?
Made by liver from its own fat and c/h
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What do VLDL do? And what is their apoprotein?
Transport TG to peripheral tisseus. ApoC
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Which surgical emergency do high TG lead to?
Acute pancreatitis
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Which lipoproteins are the main contributors to atherosclerosis? And how are they made?
LDL made by VLDL metabolism
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What happens to excess LDL? What is their Apoprotein?
- Taken up by liver via receptors
- ApoB
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How is HDL made?
Liver and intestines
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How are HDL protective?
Reverse transport of cholesterol back to the liver
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What is HDL’s apoprotein?
ApoA-1
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Why are raised TG levels associated with increased coagulability of blood?
Due to increased plasma fibrinogen levels and factor VII activity
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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
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What is the commonest monogenic hyperlipidaemia? And how is it inherited?
- Familial hypercholesterolaemia
- Inheritance: dominant
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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
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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
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When do heterozygous FH get coronary heart disease?
30’s 40s
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What is the age of death in untreated hetero FH?
Before 60
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What are the physical signs in hetero FH?
- Corneal arcus in young
- Xanthelasmata
- Tendon xanthomata
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What are xanthelasmata?
Lipid deposits in eyes
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What are eruptive xanthomata?
Itchy nodules in crops in hypertriglyceridaemia
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What are tuberous xanthomata?
Yellow plaques on elbows and knees
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What are planar/palmar xanthomata?
Orange streaks in palmar creases – virtually diagnostic of remnant hyperlipidaemia
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What is type III disease? And what is it assoc with?
- Combined hyperCHOL and hyperTG
- Assoc with accelerated atherosclerosis
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What are physical signs of type III disease?
- Xanthomata
- Tubero-eruptive xanthomata
- Palmar xanthomata
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What is the defect in type III disease?
ApoE mutation
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What is type III disease associated with?
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Which arteries are more susceptible to athersclerosis in type III disease than other hyperlipidaemias?
leg
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what is the cause of primary hypertriglyceridaemia? (2things)
- Increased hepatic VLDL production in association with decreased TG clearance
- This can be familial or acquired
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What are the acquired causes of primary hypertriglyceridaemia?
Diabetes, alcohol, obesity, BB, oestrogen administration
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What is a rare, familial but serious cause of primary hypertriglyceridaemia?
LPL deficiency (responsible for metab of VLDL and chylomicrons)
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What are 4 features of familial LPL deficiency primary hypertriglyceridaemia?
- Xanthomata
- Hepatosplenomegaly
- Fatty liver
- Recurrent pancreatitis
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Which kidney problems can causes secondary hyperlipidaemia?
- Nephrotic syndrome
- Chronic renal insufficiency
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Which drugs cause secondary hyperlipidaemia?
- Thiazide diuretics
- Protease inhibitors
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What is the effect of oestrogen on lipids?
- Lower LDL and Raise HDL so giving HRT post-menopausal is cardioprotective
- But also raise TG
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Using other values, how do you calculate LDL cholesterol?
Total cholesterol – HDL – TG/2.2
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What type of sample is needed to calculate LDL cholesterol?
Fasting sample
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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
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What are the targets for treatment for chol and LDL-chol
- Total cholesterol < 5
- LDL cholesterol < 3
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Which are the 2 main classes of lipid lowering drugs used?
- Statins: HMG Co-A reductase inhibitors so inhibit cholesterol synthesis
- Fibrates
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What are SE of statins?
- Derangement of LFTs
- Muscle cramps
- Rarely rhabdomyolysis
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What is the action and SE of fibrates?
Action: reduce serum TG, raise cholesterol, may cause myositis
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Which other diseases are associated with high cholesterol?
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How does ezetimibe work?
Block absorption of cholesterol from small intestine, works at brush border
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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
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