What are the different sizes of cholesterol esters we carry in our blood?
What apoproteins are found chylomicrons?
ApoB, ApoC and ApoE.
Where is ApoB-100 made. Apo-B48? Where are they found?
ApoB-100 (VLDL, IDL, LDL) = liver. Apo-B48 (chylomicrons) = intestine.
What apoprotein is necessary for triglyceride release from chylomicrons at fat, skeletal muscle and the heart? How do chylomicrons get it?
Apo-CII. It is a necessary cofactor for LPL (lipoprotein lipase) to hydrolyze cholesterol esters. It is given to them by HDL.
Absence of what apoprotein would cause you too see chylomicrons remnants in the blood after a 12 hour fast?
ApoE. It is necessary for binding to liver receptors so the chylomicron remnants can be recycled.
A patient comes in to get their cholesterol levels checked. You notice that his HDL levels are very low. What lipoproteins do you expect to see circulating in high quantities?
VLDL. VLDL not only needs Apo-CII transfer from HDL to be hydrolyzed by LPL, but it also needs ApoE in order to be taken up by the liver. If HDL is low, less ApoE is transferred to VLDL and more will circulate.
Once VLDL is hydrolyzed by LPL, what directions can it go?
It becomes IDL, where it can be taken up by the liver and recycled or transformed into LDL.
What lipoprotein is not LDL, but analogous to LDL?
How does our body take cholesterol out of peripheral tissues and move them to the liver?
HDL is made in the liver and small intestine. It then moves to peripheral tissues where LCAT esterifies cholesterol, pushing it into HDL. HDL can then either go into the liver via scavenger receptors, or transfer the cholesterol via CETP to molecules that can enter the liver through the LDL receptor (VLDLs and chylomicrons).
A patient presents to your clinic with tendon xanthomas and coronary heart disease. How does your treatment of a patient who is homozygous for familial hypercholesterolemia differ from treating someone who is heterozygous?
The homozygous patient will have higher cholesterol levels and accelerated arteriosclerosis due to minimal LDL receptor function. In addition to statins and cholesterol absorption inhibitors, they often need cholesterol apheresis. The heterozygous patients are less severe and can get by with the medications alone.
A patient presents with xanthomas and premature atherosclerosis. What other finding in this patient's history would lead you to suspect sitosterolemia?
Episodes of hemolysis and 40% decrease in plasma cholesterol when put on a low cholesterol diet. This disease is from ABC transporter mutations in the gut and liver so plant sitosterols are not excreted sufficiently. Sitosterols impairs cholesterol trafficking, resulting in increased LDL levels and atherosclerosis and tendon xanthomas.
What is the incidence of sitosterolemia?
1 in a million. It is an autosomal recessive mutation.
What is the incidence of familial hypercholesterolemia?
1 in 500. It is an autosomal dominant mutation.
A 66 year old female comes to see you with early onset coronary heart disease and peripheral vascular disease. Physical exam reveals palmar xanthomas and small papules on her elbows knees and buttocks. What do you expect to be elevated when you analyze her blood plasma?
She has familial dysbetalipoproteinemia. This is a mutation where the ApoE gene is altered and has decreased affinity for the LDL receptor. Consequently, chylomicrons and VLDLs that need ApoE to bind to the LDL receptor will be elevated.
What is the incidence of familial dysbetalipoproteinemia?
1/10,000. It is an autosomal recessive mutation.
What lab results would you expect to see from a patient with familial hypertriglyceridemia?
Elevated plasma triglycerides, decreased plasma HDL, elevated VLDL due to decreased catabolism or increased production, and decreased LDL due to decreased catabolism of VLDL.
What is the incidence of familial hypertriglyceridemia?
1 in 500. It is an autosomal dominant mutation.
How does the Frederickson Levy classification system classify lipoprotein disorders?
By the type of lipoprotein that accumulates. I = chylomicrons. IIa = LDL. IIb = LDL and VLDL. III = Chylomicrons and VLDL remnants. IV = VLDL. V = Chylomicrons and VLDL.
What are the Frederickson Levy classifications of familial hypercholesterolemia, familial dysbetalipoprotenemia, sitosterolemia and familial hypertriglyceridemia?
Familial Hypercholesterolemia = IIa. Familial Dysbetalipoprotenemia = III. Sitosterolemia = IIa. Familial Hypertriglyceridemia = IV and sometimes V.
What are the diagnostic tests for familial hypercholesterolemia, familial dysbetalipoprotenemia, sitosterolemia and familial hypertriglyceridemia?
Familial Hypercholesterolemia = skin biopsy (fibroblasts and leukocytes), blood cholesterol, DNA and family history. Familial Dysbetalipoprotenemia = electrophoresis, centrifugation, protein phenotyping, DNA. Sitosterolemia = gas chromatography. Familial Hypertriglyceridemia = elevated plasma triglycerides, decreased HDL, normal cholesterol levels, decreased LDL.
What are the treatments for familial hypercholesterolemia, familial dysbetalipoprotenemia, sitosterolemia and familial hypertriglyceridemia?
Familial Hypercholesterolemia = HMG-CoA reductase inhibitor, cholesterol absorption inhibitor, LDL apheresis and liver transplant. Familial Dysbetalipoprotenemia = low cholesterol/low fat diet, decrease alcohol intake, HMG-CoA reductase inhibitors, fibrates and niacin. Sitosterolemia = bile acid sequestrants and cholesterol absorption inhibitors. Familial Hypertriglyceridemia = Diet, exercise, fibrates, fish oils and niacin.
How would blood lipid and triglyceride levels differ between a type I diabetic and a type II diabetic?
In type I diabetes, you do not produce insulin, so your body is cranking out fatty acids for energy. You will have elevated blood triglyceride levels. In type II diabetes, you have high levels of insulin which results in elevated triglyceride levels (insulin inhibits LPL, resulting in increased VLDL and chylomicron remnants), elevated dense LDL and decreased HDL.
Why do you usually see a type IV lipoprotein disorder in an alcoholic?
Alcohol stimulates liver VLDL secretion and and increase in plasma triglycerides.