Lipoprotein Disorders Flashcards
How are diet derived TGs transported in the blood?
Chylomicrons
How are diet derived TGs transported in the blood?
Chylomicrons
What is the least dense lipoprotein?
Chylomicrons
Enterocytes lining villi reabsorb monoglycerides and FAs which are converted into TGs in the cytosol. TGs are then packed into a chylomicron and require an apolipoprotein for asseblym/secretion. What apolipoprotein is required?
apoB48
Where do chylomicrons enter the blood stream?
Thoracic duct
How do nascent chylomicrons become mature chylomicrons?
Obtain apoE/apoC2 from HDL
What enzyme hydrolyzes TGs in chylomicrons?
Lipoprotein lipase
What is the function of apoC2 and apoE with regards to chylomicrons?
apoC2: activates LPL
apoE: removes chylomicrons remnants from the circulation
Where is VLDL synthesized?
Liver
What apolipoprotein is necessary for TG to be packaged into VLDL and secreted into the blood?
apoB100
VLDL is hydrolyzed by LPL. What are the lipoprotein products formed by this reaction?
IDL, and LDL
What is cholesterol ester transport protein (CETP)?
Transfers cholesterol from HDL to VLDL in exchange for TG- leads to removal of HDL from circulation
What is the optimal serum TG level?
Less than 150 mg/dL
What is a high serum TG level?
Greater than 200 mg/dL
TG/5 = ?
VLDL
Enterocytes lining the villi reabsorb monoglycerides and FAs which are then converted into TG in the cytosol. TGs are then packed into a chylomicron and require an apolipoprotein for asseblym/secretion. What apolipoprotein is required?
apoB48
Nascent chylomicrons enter the intestinal lymphatics, where do chylomicrons enter the blood stream?
Thoracic duct
How do nascent chylomicrons become mature chylomicrons?
Obtain apoE/apoC2 from HDL
What enzyme hydrolyzes TGs in chylomicrons?
Lipoprotein lipase
What is the function of apoC2 and apoE with regards to chylomicrons?
apoC2: activates LPL
apoE: removes chylomicrons remnants from the circulation
Where is VLDL synthesized?
Liver
What apolipoprotein is necessary for TG to be packaged into VLDL and secreted into the blood?
apoB100
What effect does VLDL levels have on HDL levels?
Increased VLDL causes decreased HDL
What are the functions of HDL?
Source of apolipoproteins for other lipoproteins (apoE,C2)
Removes CH from fatty streaks and atherosclerotic plaques
What pathology is due to a deficiency of apoE?
Type 3 hyperlipoproteinemia (broad beta disease)- build up of chylomicron remnants
What would a 16 hour standing test show for a patient with familial hyperchylomicronemia?
Turbid supranate
Detail the pathogenesis of genetic type 2a hyperlipoproteinemia (familial hypercholesterolemia).
AD inheritance of deficient LDL receptors
Increased serum TGs is due to an increase in chylomicrons and/or VLDL. How can you differentiate which lipoprotein component is elevated?
Standing chylomicron test- test tube is left in a refrigerator overnight to give TG a change to settle based on density
What physical exam findings are characteristic of familial hypercholesterolemia?
Achilles tendon xanthoma
Xanthelasma
What is LDL derived from?
VLDL
LDL=?
CH-HDL-TG/5
Why is fasting required to accurately calculate LDL?
Increased chylomicrons falsely lower calculated LDL
Small dense LDL particles are associated with increased risk of what disease(s)?
Atherosclerosis, CAD
What is the function of cholesterol?
Synthesis of: vitamin D, adrenal cortex hormones, bile
What is the optimal serum LDL level?
Less than 100
What increases HDL?
Niacin (nicotinic acid), exercise
Detail the pathogenesis of type 1 hyperlipoproteinemia (familial hyperchylomicronemia)
AR inheritance of deficient LPL or apoC2
What are the clinical findings of familial hyperchylomicronemia ?
Pancreatitis
Detail the pathogenesis of genetic type 2a hyperlipoproteinemia (familial hypercholesterolemia).
AD inheritance of deficient LDL receptors.
What does a lipid profile show for a patient with familial hypercholesterolemia?
Elevated CH and LDL, decreased HDL
What physical exam findings are characteristic of familial hypercholesterolemia?
Achilles tendon xanthoma
Xanthelasma
Detail the pathogenesis of type 3 hyperlipoproteinemia (broad beta disease).
AR inheritance of deficient apoE
Patients who are homozygotes for type 2 hyperlipoproteinemia are at an increased risk for having an MI before what age?
20
What physical exam finding is characteristic of broad beta disease?
Palmar xanthomas in flexor creases
Detail the pathogenesis of genetic type 4 hyperlipoproteinemia (familial hypertriglyceridemia).
AD inheritance resulting in overproduction of VLDL
What physical exam finding is characteristic of type 4 hyperlipoproteinemia?
Eruptive xanthomas
What hyperlipoproteinemias can present with acute pancreatitis?
Type 4- familial hypertriglyceridemia
Type 1- familial chylomicronemia
What are acquired causes of type 2 hyperlipoproteinemia?
Hypothyroidism- decreased LDL receptor synthesis
Nephrotic syndrome- increased VLDL synthesis
What are acquired causes of type 4 hyperlipoproteinemia?
Excess EtOH- increased VLDL production
OCPs- increased VLDL production
DM- decreased LPL due to decreased insulin
A standing chylomicron test distinguishes which lipoprotein component is increased. Detail possible outcomes.
Turbid supernate- increased chylomicrons (person did not fast, type 1 hyperlipoproteinemia)
Infranate- increased VLDL (type 4 hyperlipoproteinemia)
Turbid Supranate + infranate- increased chylomicrons and VLDL (type 5 hyperliproteinemia)
