Hyperlipidemia, Metabolic Syndrome, & Obesity Flashcards
What is hyperlipidemia/dyslipidemia?
umbrella term for lipid abnormalities in Total cholesterol, LDL-C, TG, or HDL
What is hypercholesterolemia?
increase in total cholesterol and LDL-C or low HDL
What is triglyceridemia?
increase solely in TG
What is the leading cause of death for men, women, and people of most racial and ethnic groups?
heart disease
What is a major CV risk factor in the development of ASCVD?
hyperlipidemia
Approx ___% of adults have ________ levels.
50, elevated LDL-C
What are the 3 main lipids in the body?
-cholesterol
-triglycerides
-phospholipids
What is cholesterol?
fat-like waxy substance composed of long-chain hydrocarbon fatty acid compounds
insoluble in water
has an essential role in body functions
In excess, cholesterol causes ______ ______ in vessels and ______.
plaque formation, ASCVD
What are the essential roles of good cholesterol?
bile acid synthesis
-digestion of fats
-stored in the gallbladder
-some eliminated in feces
hormone synthesis
-cortisol, aldosterone, testosterone, estradiol, and progesterone
vitamin D3 synthesis
cell membrane structure
Why can excess cholesterol be bad?
excess cholesterol accumulates in arterial walls forming plaques obstructing blood flow
inc risk of MI, stroke, and PVD
Where does cholesterol come from?
hepatocytes- endogenous (primary source)- approx 80% from own body
diet- exogenous (remaining source)
How is cholesterol produced?
-endogenous production
-exogenous production
-reverse cholesterol transport
Where does endogenous cholesterol synthesis occur?
endoplasmic reticulum of hepatocytes
What is the mevalonate pathway for endogenous cholesterol synthesis?
hydrocarbon molecules are broken down through a series of enzymatic reactions
Enzyme HMG-CoA reductase- rate-limiting step
regulated by binding protein SREBPs
low cholesterol levels –> triggers SREBPs to break from its molecule –> binds to HMG-CoA gene –> results in inc HMG-CoA reductase activity –>activates mevalonate –> cholesterol inc
What inhibits HMG- CoA reductase?
statins
What is the exogenous cholesterol pathway?
dietary fat
protein NPC1L1 helps absorb cholesterol from intestinal lumen into cells > bile breaks down fats into triglycerides > chylomicrons transport triglycerides thru circulation > enzyme lipoprotein lipase (LPL) breaks chylomicrons down into fatty acids and glycerol “remnants” > remnants go into muscle and adipose tissue, transported to the liver for storage, or excreted in feces with the help of HDL-C
What protein removes cholesterol from peripheral tissues and arteries?
ABCA1
What enzyme breaks down cholesterol into cholesterol esters?
LCAT
What is on the surface of the HDL lipoprotein that facilitates transportation to the liver for excretion?
Apolipoprotein A1
What is involved in the reverse cholesterol transport pathway for cholesterol excretion?
ABCA1, LCAT, Apolipoprotein A1
How does cholesterol move through the body?
cholesterol and triglycerides require the help of lipoproteins to move through our circulation
What is the structure of the lipoprotein?
lipid core- contains hydrophobic molecules of triglycerides and cholesterol
surface layer- contains phospholipids, free cholesterol, variety of apolipoproteins
What is found on the surface of lipoprotein?
amino acids
What role do amino acids play?
regulate cholesterol excretion by binding to specific chol receptors
metabolism of cholesterol by regulating various enzymes (lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT)
Many types of _____ are found on the surface of a lipoprotein.
apolipoproteins
What are the 4 main types of lipoproteins?
chylomicrons, VLDL, LDL, and HDL
Classes differ by
size
lipid composition/function
types and # of apolipoproteins on their surfaces
What are the largest of the lipoproteins with lowest density?
chylomicrons
Where are chylomicrons synthesized?
in the wall of small intestine
What is the function of chylomicrons?
transports dietary lipids, mainly triglycerides through circulation to the skeletal and adipose tissue and liver
Chylomicrons are dependent on ____ ____ to break down triglycerides down for utilization by the body.
lipoprotein lipase (LPL)
Where are VLDL, HDL, and LDL synthesized?
in the liver
VLDL and LDL are a type of ____ cholesterol.
bad
VLDL carries predominately ____ ___ ____ to peripheral skeletal and adipose tissue and some excess is recycled back to the liver.
triglycerides from liver
____ is the main carrier of cholesterol.
LDL
What cholesterol is most closely associated with cardiovascular disease?
LDL
HDL is mainly composed of _____.
proteins
The good cholesterol removes ____ and _____ for excretion.
cholesterol, adipose cells
Heterozygous familial hypercholesterolemia
2-3x normal
LDL-C
more common
Homozygous familial hypercholesteremia
rare
up to 8x normal and premature ASCVD
markedly high LDL-C
tx may require liver transplant and/or plasmapheresis
Familial chylomicronemia
very high triglycerides (>1000 mg/dL)
inc risk of recurrent pancreatitis and hepatosplenomegaly in childhood
What is an example of a genetic defect?
Marked inc in LDL
-absent/defective LDL receptors m/c
-apolipoprotein B defect (unable to bring LDL-C into lipoprotein
-inc activity of enzyme PCSK9: inc in LDL receptor breakdown
Marked inc in TG
-lipoprotein lipase defect (enzyme unable to breakdown TG)
-additional comp: recurrent pancreatitis and hepatosplenomegaly in childhood
What is an acquired cause of lipid disorders related to lifestyle?
high fat diet, sedentary lifestyle, EtOH
What is an acquired cause of lipid disorders related to meds?
OCP, diuretics, B-blocker, steroids
What is an acquired cause of lipid disorders related to an underlying etiology?
uncontrolled DM, hypothyroidism, nephrotic, CKD, cirrhosis, obstructive liver dz, malignancy, cushing’s syndrome, PCOS
