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What are components of lipid transport?
Cholesterol (C), Triglycerides (TGs), Lipoproteins (LPs), and apolipoproteins (ALPs)
What are the sizes of LPs?
chylomicrons > chylomicron remnants > VLDL > IDL > LDL > HDL
VLDL is made by liver.
IDL is metabolized to LDL metab to HDL
What are apolipoproteins?
"biochemical keys" - allow LP access to specific sites for delivery, modification
What is exogenous lipid metabolism?
Dietary fats acquire APLs (from HDL) to form chylomicrons.
TGs hydrolyzed by lipoprotein lipase (LPL) to free fatty acids to go to adipose/storage or muscle/energy.
The do not contribute to AS, but remnants removed by liver can be taken up by macrophages and contribute to AS.
What is endogenous lipid metabolism?
Fats into liver are either stored or exported as VLDL (not atherogenic).
LPL act on VLDL>>>fatty acids released into tissues & VLDL metab to IDL (not atherogenic).
IDL metab to LDL in liver which has C & LPs, but no TGs.
Most LDL is taken up by liver, but some to tissues>>>taken up by macrophages, oxidized and contribute to AS. (LDL is seen more in pts w/high TGs)
What is a rare genetic defect in RCT (reverse cholesterol transport)?
CETP(C ester transfer protein) defect which is high HDL but high CV events
What are lipid-activated nuclear receptors?
Fibrates activate PPARs (peroxisome proliferator-activated receptors) which accelerate fatty oxidation in liver & elevate HDL.
Glitazones active PPARs in muscle/adipose.
PPAR agonists & CETP inhibitors have no benefit.
What does resins do?
Decrease bile acids from being absorbed>>> dec C in liver>>>in LDL receptors in liver>>> dec LDL (but inc TGs)
What are disorders of lipid metabolism?
FH (familial hypercholesterolemia)
FCH (familial combined hyperlipidemia)
FHT (familial hypertriglyceridemia)
What is FH?
Autosomal Dom; 1/500
High C, LDL & NL TGs
w/xanthomas (knees & hands), xanthelasma, & arthralgias
What is FCH?
Autosomal Dom; 1/50
High TG; High LDL; High TG & LDL; or High TG & low HDL (FH w/premature CAD)
What is chylomicronemia syndrome?
xanthomas on back, butt, knees, elbows
pancreatitis, hepatosplenomegaly, SOB, lymphadenopathy, memory loss, peripheral neuropathy
How is chylomicronemia syn caused?
LPL gene defect; TGs>2000
Occurs w/FCH or FHT + DM, obese, or steroid/estrogen tx.
What are secondary causes of hyperlipidemia?
DM, ETOH, hypothyroidism, diuretics (BBs), diuretics, estrogens, & antipsychotics
What labs are for hyperlipidemia?
12h fast (q 5yrs if NL)
Calculated LDL = C - HDL - (TG/5)
TG - normal = <150 (500 is very high)
What is high risk of hyperlipidemia?
10yr risk >20% (CAD, DM, AAA, carotid dz, peripheral vascular dz)
What do statins (HMG CoA reductase inhibitors) do?
lower LDL by 40%
Stop if liver enzymes 3 x NL or inflammed
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