Crash dieter - Lipid disorders

Question 1

APOLIPOPROTEINS

i) Which type of lipoprotein are AI and AII a major component of?
ii) which lipoprot is the ligand for LDLR?
iii) what is the principal apoprot in chylomicron?
iv) which enzyme do CII and CIII control?

Answer 1

i) HDL
ii) B100
iii) B-48
iv) lipoprotein lipase

Question 2

ENDOGENOUS LIPID CYCLE

i) when is this active?
ii) what type of lipoprotein does the liver produce and which type does it remove?
iii) in what form of lipoprotein are lipids exported from the liver to the peripheries? which enzyme acts on it to break down to FFA and glycerol?
iv) which lipoprotein delivers cholesterol to peripheral cells?
v) which lipoporein absorbs cholesterol from cells in the vasc endothelium and recycles it back to the liver?
vi) which organ produces HDL?

Answer 2

i) during fasting
ii) liver produces VLDL and removes LDL

iii) Liver > peripheries as VLDL
- lipoprotein lipase breaks down to FFA and glycerol

iv) LDL delivers cholesterol to peripheral cells
v) HDL - causes cholesterol to be recycled back to the liver as HDL
vi) liver

Question 3

EXOGENOUS LIPID CYCLE

i) when is this activated?
ii) which cells absorb cholesterol and fatty acids from digestion?
iii) what system do cholesterol esters/triglyceride enter the systemic circulation via? what are they secreted as?
iv) what is leftover when fatty acids and glycerol have been used up? what happens to this molecule?
v) what two things does the liver produce that allow creation of micelles and therefore lipid abs from the gut?

Answer 3

i) during feeding
ii) intestinal mucosa cells
iii) enter systemic circ via the lymphatic system (thoracic duct) > secreted as chylomicrons
iv) use up FA & glycerol > chylomicron remnant
v) liver produces bile acids and choleserol that create micelles for lipid absorption from the gut

Question 4

LIPASES

i) what is the co factor for lipoprotein lipase? does hepatic lipase have a co factor?
ii) which two tissues are lipoprot and hepatic lipases found in?
iii) what regulates LPL activity? (3)
iv) which lipase uses chylomicrons and VLDL as a substrate?

Answer 4

i) LPL = apo-CII
- hepatic doesnt have a substrate

ii) LPL = adipose and skel muscle
hepatic = liver and adrenals

iii) LPL reg by fasting, feeding and exercise
iv) LPL

Question 5

HEALTHY CHOLESTEROL LIMITS

i) what is the optimum serum cholesterol in individuals without CVD?
ii) between which serum cholesterol levels does CHD quadruple?
iii) what is the upper limit of normal for fasting serum triglyceride?
iv) how are HDL-C correlated to CAD risk? is risk correlated to LDL-C?

Answer 5

i) <5
ii) between 5 and 7.8
iii) 1.7mmol/L

iv) HDL-C is inv prop witth CAD risk
- correlation is indep of LDL-C

Question 6

PRIMARY DYSLIPIDAEMIAS

i) what must be excluded first?
ii) may these patiens respond to lifestyle modification?
iii) which type of proteins may there be mutations in?
iv) what may be seen on extensor tendons of the hands?

Answer 6

i) exclude secondary causes of dyslipidaemia
ii) yes
iii) muts in proteins associated with lipid metabolism
iv) see tendon xanthomas on ext tendons of hands

Question 7

FAMILIAL HYPERCHOLESTEROLAEMIA

i) is it auto dom or recessive? what % chance do 1st degree relatives have of inheriting the affected gene?
ii) which lipoprotein is raised in the blood?
iii) what is seen in the skin/tendons?
iv) how may the achilles appear?
v) why is it difficult to diagnose?
vi) name the three main genes mutations are found in

Answer 7

i) autosomal dominant
- 50% chance in first degree relatives

ii) raised LDL
iii) tendon and skin xanthomata
iv) enlarged achilles
v) may be hard to diagnose as there are overlapping cholesterol levels with non FH people - especially if LDL is not measured
vi) APOB (ligand for LDL R), PCSK9 and LDLR

Question 8

SECONDARY DYSLIPIDAEMIAS

i) name four causes if hypertryglyceride
ii) name two drugs that cause hypertrigly
iii) name four causes of hypercholesterol

Answer 8

i) hypertrigly - obesity, diabetes, excess ETOH, renal fail
ii) thiazides, beta blockers
iii) hypothyroid, nephrotic syndrome, high sat fat diet, anorexia

Question 9

METABOLIC SYNDROME

i) how is glucose tolerance affected?
ii) is there high or low insulin in the blood?
iii) how is BP affected?
iv) where is most fat found?
v) what happens to clotting?
vi) what happens to LDL and HDL-C levels?

Answer 9

i) reduced gluc tol
ii) high insulin in blood
iii) high BP
iv) visceral fat
v) clotting disorders

vi) normal or mod raised LDL
low HDL

Question 10

CONCLUSIONS

i) what are the two main pathways for lipid metabolism
ii) what are lipoproteins complexes of that allow transport?
iii) what is familial hypercholesterol assoc with?
iv) what are the four characs of metabolic syndrome?
v) which drugs are effective at reducing LDL choles and CVD risk?

Answer 10

i) endogenous (fasting) and exog (fed)
ii) lipoprots complexed to apoprots to allow transport
iii) familail hyperchol assoc with early CVD if left untreated
iv) metbolic syndrome - insulin resis, hypertension, central obesity and dyslipiaemia
v) statins