Cardiovascular Nutrition and Hyperlipidemia Flashcards Preview

PNS/Cardiology > Cardiovascular Nutrition and Hyperlipidemia > Flashcards

Flashcards in Cardiovascular Nutrition and Hyperlipidemia Deck (24):

What molecules are on the outer surface of lipoprotein particles?

Apolipoproteins, phospholipids


What molecules are in the inner core of lipoprotein particles?

Triglycerides and cholesteryl esters


What apoprotein is on LDL and other atherogenic lipoproteins?



What apoprotein is on HDL and other antiatherogenic lipoproteins?



Describe the endogenous pathway of VLDL and LDL cholesterol transport

Liver secretes VLDL (composed of cholesterol, triglycerides)
VLDL gets hydrolyzes to IDL and triglycerides
IDL can be taken up via LDL-receptor into liver or hydrolyzed to form LDL particles
LDL particles (primarily cholesterol) are normally taken up by liver, but can also get modified (glycosylated), allowing them to be taken up by macrophages (foam cells) and be atherogenic


How is LDL metabolized in hepatocytes?

Apo B on LDL binds LDL receptors and LDL/LDL-R complex is internalized in clathrin-coated vesicles
Vesicles fuse with endosome, complex dissociates
Free LDL-Rs recycle back to surface
Free LDL particles are transported to lysosomes and degraded


What protein targets LDL receptor and traps it with the LDL particle, inducing lysosomal degradation?



What occurs if there is a gain of function mutation in PCSK9?

Lack of LDL-Rs will result in build up of LDL in blood stream where it will get taken up by macrophages and promote atherogenesis


What is the defining characteristic of familial hypercholesterolemia (FH)?

High LDL cholesterol levels, causing premature CAD


What is the most common genetic defect causing FH?



What are physical findings of FH?

Thickened Achilles tendon
Xanthelasmas - nonspecific cholesterol deposits that encircle eye
Arcus - grayish blue ring along surface of cornea, diagnostic of FH!


What usually causes familial combined hyperlipidemia (FCH)?

Overproduction of ApoB-100


What is deficient when someone has Apo-E2 homozygosity?

IDL particles cannot be cleared efficiently by the liver from the circulation
Remnant particles can build up and be pro-atherogenic


In addition to Apo-E2 homozygosity, what is needed to develop full clinical presentation of Type III hyperlipidemia?

Metabolic abnormality like T2DM


What are physical findings of Type III hyperlipidemia?

Yellow streaks in palmar creases
Tuberous xanthomas


How are dietary triglycerides metabolized? (step by step)

Triglycerides catabolized to free fatty acids by lipases
FFAs are re-esterified and packaged as chylomicrons
Chylomicrons are hydrolyzed by lipoprotein lipase (LPL) to FFAs and chylomicron remnants (CMR)
CMR can be directly removed by hepatocytes or, when in excess, be taken up by macrophages in vascular wall --> foam cell --> atherosclerosis


What metabolic consequences occur when you have hypertriglyceridemia? (step by step)

Hypertriglyceridemia causes excess VLDL secretion
Higher VLDL-TG output activates cholesteryl ester transfer protein (CETP) that exchanges TG from VLDL for CE from HDL or LDL
This results in TG-enrichment of LDL and HDL
TG content within these particles is hydrolyzed by HTGL resulting in small, dense cholesterol rich LDL and HDL particles


Why are small, dense HDL and LDL bad?

Small HDL: particles more rapidly cleared by kidneys, cannot exert anti-atherosclerotic effect

Small LDL: decreased affinity for LDL-R, will remain in circulation longer --> increased atherogenicity


What is a normal triglyceride level?



What are physical signs of high triglycerides?

Creamy layer in refrigerated plasma
Cutaneous xanthomas
Creamy retinal layer
Tuberous xanthomas and yellow streaking on palm


What is the process of reverse cholesterol transport?

HDL takes lipids (free cholesterol) from vascular macrophages, mediated by ABCA1 protein
Free cholesterol on HDL gets esterified into cholesteryl ester (CE) by LCAT
HDL can do 3 things with CE:
- Deliver CE to hepatocytes via LDL-R
- Donate CE to LDL, VLDL in exchange for TG by CETP
- Donate CE to steroidogenic tissues (ovaries, testes)


What occurs if you have defect in ABCA1?

Lipid accumulation in macrophages
Causes yellow-orange tonsils seen in Tnagier Disease


What occurs if you have defect in LCAT?

Lipids accumulate in eye and kidney, causing corneal opacification and/or renal failure


Why are saturated fats particularly bad for cholesterol?

Inhibits LDL receptor activity
Prothrombotic and proinflammatory