chempath tutorial 2 - lipids & lipoproteins Flashcards
What are the most abundant lipids in the plasma?
Triglycerides
Where are triglycerides synthesised?
The liver
How are endogenous triglycerides primarily transported in the plasma?
Via VLDL
What is the metabolic fate of triglycerides?
They will circulate in the plasma until energy is required, then they will be broken down into fatty acids and glycerol for energy via the process of lipolysis
How are exogenous triglycerides primarily transported in the plasma?
Via chylomicrons
What are endogenous lipoproteins?
Lipoproteins created from dietary lipids
What are exogenous lipoproteins?
Lipoproteins synthesised by the liver
Which lipoprotein is the precursor to LDL?
IDL
What are the components of a typical lipoprotein?
Lipids (apolar), lipid surface phospholipids (polar), apoproteins
How are fatty acids transported in the plasma?
Bound to plasma proteins such as albumin
Which lipoprotein has the highest proportion of proteins?
HDL
Which lipoprotein has the highest proportion of cholesterol?
LDL
What appearance would you expect of a plasma sample refrigerated overnight of a patient with raised chylomicrons?
Thick cream layer on the top of the sample
What appearance would you expect of a plasma sample refrigerated overnight of a patient with elevated VLDL?
Cloudiness (turbidity) due to elevated TAGs
What appearance would you expect of a plasma sample refrigerated overnight of a patient with raised LDL?
Sample will appear normal, but may have an orange tint
What appearance would you expect of a plasma sample refrigerated overnight of a patient with elevated IDL?
Usually a thin cream layer on top of sample due to presence of chylomicron remnants, and usually a degree of cloudiness/turbidity
What appearance would you expect of a plasma sample refrigerated overnight of a patient with elevated HDL?
There are no changes to the serum if HDL is raised, because it contains mostly proteins so will not rise to the top, and it does not generate turbidity
Which lipoprotein levels are likely to raised in plasma sample with elevated total cholesterol but no elevation in TAG?
LDL
Which lipoprotein levels are likely to raised in plasma sample with elevated total cholesterol and elevated TAG?
IDL, VLDL
Which lipoprotein levels are likely to raised in plasma sample with elevated TAG but normal cholesterol?
Chylomicrons
What is the abnormality in lipoprotein metabolism in diabetes mellitus?
Insulin resistance results in increased TAG synthesis in the liver, resulting in elevated VLDL circulation. Also will see decreased HDL.
What is the abnormality in lipoprotein metabolism in hypothyroidism?
Increases LDL levels by increasing cholesterol, and can also down-regulate LDL receptors, further increasing LDL concentration in the plasma.
What is the abnormality in lipoprotein metabolism in nephrotic syndrome?
Nephrotic syndrome involves the loss of proteins, including apoprotein B, through the kidneys, which causes elevated LDL and VLDL (which have little protein content), and the loss of HDL (high protein)
What is the abnormality in lipoprotein metabolism in cholestasis?
Decreased excretion of bile salts into the intestine impairs the absorption of dietary fats, but aggregations of cholesterol form LDL-like aggregations
What is the abnormality in lipoprotein metabolism in liver cirrhosis?
Liver damage alters the synthesis and/or secretion of lipoproteins, including HDL and VLDL, reducing their levels. Thus, can be issues with TAG clearance if unable to transported via VLDL
What lipoproteins are most important in determining a person’s risk of atherosclerosis?
HDL cholesterol, LDL cholesterol
What does total plasma cholesterol concentration infer about a patient’s risk of developing atherosclerosis?
Implies an elevated LDL, which increases risk of atherosclerosis
What cholesterol levels decrease the risk of developing atherosclerosis?
Low total cholesterol, low LDL cholesterol, high HDL cholesterol
What are the 2 key classifications of hyperlipidaemias?
Primary (inherited/genetic), Secondary (acquired)
What are the clinical characteristics of Familial hypercholesterolaemia?
Elevated cholesterol from childhood, early onset of coronary heart disease, early mortality, strong family history
What is the most common type of genetic mutation that causes familial hypercholesterolaemia?
Mutations causing dysfunction/lack of production of LDL receptors
What are the clinical characteristics of Remnant Hyperlipoproteinaemia?
- Presence of excess IDL and chylomicron remnants in the plasma
- fat deposits in palmar creases, etc.
- increased risk of CHD/PVD
What gene is affected in remnant hyperlipoproteinaemia?
apo E gene, with dysfunction causing impaired uptake of IDL by the liver
What are the clinical characteristics of familial chylomicronaemia?
- elevated chylomicrons in the blood due to poor clearance
- xanthomata (fatty depositions)
- recurrent pancreatitis
What genetic abnormality commonly causes familial chylomicronaemia?
Lipoprotein Lipase gene leading to enzyme deficiency and insufficient breakdown of cholesterol
What are the clinical characteristics of familial hypertriglyceridaemia?
- elevated chylomicrons leading to fatty deposits, i.e. eruptive xanthomata
What are the clinical characteristics of familial combined hyperlipidaemia?
- Elevated VLDL and LDL levels
- Elevated cholesterol and/or TAG levels
- increased risk of IHD
What is the function of Apolipoprotein A?
Structural component of HDL
What is the function of Apolipoprotein B?
Protein found in lipoproteins: chylomicrons, VLDL, IDL and LDL
What is the function of Apolipoprotein C?
Lipoprotein metabolism, by activating metabolic enzymes, e.g. lipoprotein lipase
What is the function of Apolipoprotein E?
Metabolism of TAG lipoproteins - chylomicrons and VLDL
