Wk 1 Lipid Disorders Flashcards
What are the 2 major categories of lipid disorder?
- hyperlipidemia - manifests as increased cholesterol, high TGs, or combo of both
- hypolipidemia
Basic physiology of lipid metabolism
- enterocytes endocytose FA and some cholesterol from foods.
- triglycerides are assembled from fatty acids
- chylomicrons are packaged w/ triglycerides, small amount of cholesterol, and lipoproteins
- chylomicrons enter lymphatic vessels
- get dumped into bloodstream in R&L subclavian veins
- lipoprotein lipase in capillaries breaks down chylomicrons, freeing TGs and breaking them down to FAs
Fate of fatty acids after being broken down by LPL
- taken up by tissues for use (muscle)
- storage - adipocytes
What happens to chylomicron remnants?
Made of lipoproteins, TGs, and cholesterol
Go to liver, which synthesizes FA & cholesterol. Liver combines those w/ chylomicron remnants forming VLDLs.
What happens to VLDLs after they are released from liver?
In bloodstream, LPL breaks them down for tissues to use TGs so it becomes an IDL and then LDL
What happens to LDL?
It gets endocytosed by cells with LDLRs, either in the liver or other cells needing cholesterol
What are the 2 classifications of hyperlipidemia?
- Primary - familial, inherited
- Secondary - acquired due to other diseases or meds
What are skin manifestations of hyperlipidemia?
- Xanthomas = deposits of fat under skin and in tendons due to TGs or lipoproteins leak out of blood vessels
- Xanthelasma = deposits around eyes
Xanthelasma
=Xanthomas around eyes
Corneal arcus
= deposits of fat around cornea
Another name for fatty liver disease
= hepatic steatosis
What are manifestations of atherosclerotic cardiovascular disease
- CAD
- stroke
- peripheral vascular disease
- carotid artery stenosis
How are primary hyperlipidemias inherited?
- dominant
- recessive
HIGH YIELD
Most commonly tested types of hyperlipidemias
- Type 1 = recessive, elevated chylomicrons in blood (aka hyperchylomicronemia)
- Type 2 = dominant (aka familial hypercholesterolemia) - most commonly heterozygous FH - high LDL
- Type 3 = autosomal recessive (familial dysbetalipoproteinemia)
- Type 4 = familial hypertriglyceridemia
HIGH YIELD
Type 1 Hyperlipidemia
- econdary to deficiency in LPL or ApoCII (required cofactor for LPL).
- Char by many eruptive (rapid) xanthomas on back, butt - itchy
- Can cause acute pancreatitis - too many FFA can be toxic to pancreatic cells
- Atherosclerotic cardiovascular disease is not a complication b/c not related to hyperchylomicronemia
- can develop hepatosplenomegaly
- If fasting serum chilled, chylomicrons form creamy layer at top of tube
HY
Type 2 Hyperlipidemia
- =familial hypercholesterolemia
- dominant inheritance
- Type A = increased LDL
- Type B = elevated LDL &VLDL
- Due to absent or defective LDLR or ApoB-100 -> increased LDL
- hepatocytes don’t take up LDL, therefore detect low cholesterol and increase VLDL in blood more
- Increased risk of atherosclerosis (early as 20)
- achilles tendon xanthomas
- corneal arcus
- MI at early age in family
Type 3 hyperlipidemia
- rare autosomal recessive disorder
- aka
- familial dysbetalipoproteinemia
- ApoE is defective (normally assists uptake of chylomicron remnants & VLDL by liver)
-> elevated chylo remnants & VLDL -> high cholesterol and TGs - hand xanthomas
- premature atherosclerosis
- tx w/ statins or fibrates
Type 4 hyperlipidemia
- aka familial hypertriglyceridemia
- liver produces lots of VLDL
- LPL activity decreased, so VLDLs & chylomicrons not broken down (both contain triglycerides)
- -> increased triglycerides (over 1k)
- can be due to deficiency of ApoCII (cofactor for LPL)
- premature atherosclerosis
- acute pancreatitis
- liver transplant would NOT be helpful
Causes of acquired hyperlipidemia
- diabetes mellitus (insulin normally increases lipid update in adipose by increasing lipase) -> decreased LPL causing VLDL -> increased LDL in blood
- hypothyroidism - metabolism slows down -> decreased LDLR synthesis (can’t return to liver so sit in blood)
- nephrotic syndrome - albumin lost in urine, liver starts making VLDL to make up for lost plasma protein
- medications - estrogen-containing oral contraceptives, beta-blockers, thiazide diuretics
HY
Most common cause of hypolipidemia
Abetalipoproteinemia - MTP normally packages triglycerides into VLDL, chylomicrons
-recessive
-also caused by ApoB-48 deficiency (made in sm intestine), found in chylomicrons
-or deficiency in ApoB-100, made in liver, found in VLDL and LDL
-both -> low levels VLDL, LDL, & chylomicrons -> low cholesterol and triglyceride levels
presents in infancy. Malabsorption of fat in intestine -> failure to thrive, accumulation of lipids -> steatorrhea (malodorus, floating)
-> fat-soluble vitamin deficiencies
dx by intestinal biopsy
tx - decrease dietary fats, take fat-soluble vitamins
List fat-soluble vitamin deficiencies
- osteomalacia (vit D def)
- retinitis pigmentosa (Vit A def)
- spinocerebellar degeneration & acanthocytosis (Vit E def)
Summary Familial
Summary Acquired
What can increase triglycerides besides genetics?
- low levels of physical activity
- obesity
- diet w/ excess calories/high glycemic load
- Thiazide diuretics
- Beta-blockers
- EtOH use
- Estrogen-containing products
- glucocorticoids
- pregnancy
- diabetes/hyperglycemia
- HIV/HAART use
- hypothyroidism
- SLE
- multiple myeloma
- nephrotic syndrome
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