Hyperlipidemia II Flashcards
Outline the process of lipid metabolism (state what happens with VLDLs vs chylomicrons)
Fats digested and converted to lipoproteins in the gut (small intestine) >>
Free cholesterol esterified and packaged into chylomicrons that are released into the lymphatics>>
Chylomicrons/Lipoproteins hydrolyzed by lipoprotein lipase into chylomicron remnants>>
ApoA5 on the chylomicron remnant surface binds to the LDL-receptor in the liver and is taken up by the liver and cleared
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Cholesterol is synthesized in the liver via HMG-CoA-Synthase/HMG-CoA-Reductase pathway as VLDLs>>
VLDLs broken down by hepatic lipase and lipoprotein lipase into cholesterol-enriched remnants, which lose their triglycerides in a series of steps mediated by lipoprotein lipase and hepatic lipase >>
VLDLs become IDLs >> LDLs >> LDLs express ApoB100 which is recognized by cells that express its receptor (so all nucleated cells)>>
LDLs recognized and taken up by LDL receptors in the liver and cleared
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Review triglyceride metabolism
What happens if there is accumulation of remnant particles due to VLDL overproduction or delayed clearance?
There accumulation results in vascular wall macrophages taking up the remnants >> artherosclerosis
In a state of increased triglycerides, ___ (enzyme name) is activated, which mediates transfer of triglyceirdes to LDL and HDL
In a state of increased triglycerides, cholesteryl ester transfer protein (CETP) is activated, which mediates transfer of triglycerides to LDL and HDL
Enrichment of LDL and HDL by CETP results in the formation of ___ HDL and LDL particles. __LDLs have __(increased/reduced) affinity for the LDL receptor >> more time in the blood
Enrichment of LDL and HDL by CETP results in the formation of small, dense HDL and LDL particles. Dense LDLs have reduced affinity for the LDL receptor >> more time in the blood
Because small dense LDLs have less affinity for the LDL receptor in the liver, they spend more time in the blood where they can more easily bind to ___ in the arterial wall and are ___ which promotes endothelial dysfunction + increased uptake by vascular macrophages
Because small dense LDLs have less affinity for the LDL receptor in the liver, they spend more time in the blood where they can more easily bind to glycosaminoglycans in the arterial wall and are oxidized which promotes endothelial dysfunction + increased uptake by vascular macrophages
An ideal triglyceride level is less than ___ mg/dl
An ideal triglyceride level is less than 100 mg/dl
Which apoprotein serves as a cofactor for lipoprotein lipase?
ApoCII
What is/are the pathology(ies) below?
Signs of very high triglycerides
What are some of the signs of high triglycerides?
Milky plasma
Cutaneous xanthoma (A: cutaneous xanthoma filled w/ foam cells appearing as yellow, erythematous, mobiliform eruptions)
Milky retinal vessels and pink retina (lipemia retinalis)
Tuberous xanthomas (D - usually moveable, nontender, foam cells appearing as red-orange shiny nodules)
Palmar crease xanthomas (E: w/ foam cells, appear as yellowish deposits w/in palmar creases) - sign of familial dysbetalipoproteinemia
A defect in ___(Apoprotein) or ___(enzyme) can result in high triglycerides.
___(apoprotein type) inhibits LPL and a defect in this protein helps LPL work more efficiently
A defect in ApoCII or Lipoprotein lipase (LPL) can result in high triglycerides.
ApoCIII inhibits LPL and a defect in this protein helps LPL work more efficiently
____ regulates triglyceride-rich lipoprotein concentrations and can promote inflammation
Apolipoprotein C3 regulates triglyceride-rich lipoprotein concentrations and can promote inflammation
What are 3 categories of secondary causes of hypertriglyceridemia?
Metabolic causes - uncontrolled diabetes, hypothyroidism, nephrotic syndrome
Lifestyle - alcohol cons. w/ fatty liver; diet rich in sat fats
Medications - antiretrovirals, nonselective beta-blockers, oral estrogens, glucocorticosteroids, tamoxifen, isotretinoin
Which group of fatty acids are considered “essential” fatty acids and have a demonstrated effect of lowering triglycerides >> reduces CVD in pts with elevated TGs?
What are 3 types of fatty acids in this group?
Omega 3 fatty acids are considered “essential” fatty acids and have a demonstrated effect of lowering triglycerides >> reduces CVD in pts with elevated TGs
Omega 3 fatty acids include EPA, DHA and ALA**
(note that its EPA and DHA that are found in seafood and can help lower lipids)
Describe how seafood-derived omega 3 fatty acids lower triglyceride levels (and subsequently help prevent CVD)
Omega 3s promote the movement of lipids down the phospholipid synthesis pathway (instead of the triglyceride pathway)
Name 3 other effects of EPA besides lowering triglycerides
Inhibiting oxidative stress (that causes formation of foam cells)
Reduction of inflammation/inflammatory cytokine release
Reduction of platelet aggregation/plaque formation
