| What are normal values of lipid profile? | Cholesterol <200 (total)
TG<150
HDL >40 (men) and >50 (women)
LDL (Diabetic <70, Prediabetic <100, Normal <130) |
| What is corneal arcus? | Sign of hypercholesterolemia, seen in young pt, loses specificity for older/ black pt. |
| When do we find multiple tendon xanthomas? | More common for primary hypercholesterolism, uncommon in secondary hyperCT. |
| What are first two steps in familial hypercholesterolemia dx? | First give lovastatin (statin - inhibit HMG-CoA reduces cholesterol synthesis), then exclude 2ary causes that lead to increase in LDL (hypothyroid, steroids, Cushing's, Accutone, Nephrotic syndrome) |
| What is the difference between hetero familial hypercholesterolemia and homo? | LDL (Hetero [200-500], Homo >500)
Total cholesterol (Hetero [300-500], Homo [500-1000])
LDL receptors (hetero half are still normal, homo no receptors)
CHD (hetero btw 30-50 years, homo at age 10 and rare survival to age 20)
Response To Therapy (hetero respond to activators of LDL Recpetors, Homo no response) |
| What are findings in non-familial hypercholesterolemia? | LDL not above 200 (<190 if due to lifestyle and >190 if due to medication) |
| What is the tx of familial homo hypercholesterolemia? | Refreezing to decrease LDL |
| What are the pathophysio of familial hypercholesterolemia? | LDL increase due to inherited mutation of LDL receptors (that remove LDL from circulation), ApoB, PCSk9GOF (bind and destroy LDL receptors) |
| What are findings of Williams disease? | CT>310 FH |
| Describe Chylomicron formation and metabolism cycle? | Intestinal mucosal cells secrete nascent TG rich chylomicrons produced from dietary lipids, then ApoCII and ApoE are transferred from HDL to chylomicron, then LPL which is activated by ApoCII degrades TGs of chylomicrons, to release fatty acids to adipose and glycerol to liver.
ApoCII goes back to HDL, and we get remnant chylomicron again with ApoE and B48 only, then it binds to liver by ApoE and lose it to become chylomicron remnant again. |
| What do we get due to LPL deficiency? | LPL deficiency or ApoCII deficiency will lead to accumulation of chylomicrons in plasma due to stopped metabolism of chylomicrons in capillaries by LPL. |
| Describe VLDL formation? | Nascent VLDL w/high TG and ApoB100 are produced by liver, which receive ApoCII and ApoE from HDL to become VLDL, in capillaries bind LPL removes TGs, fatty acids to adipose and glycerol to liver, producing IDL, which lose ApoCII and ApoE to HDL and become LDL, bind to extrahepatic tissues and are endocytosed, go to liver and become nascent VLDL again. |
| What are functions of HDL? | Circulating reserve of ApoE and ApoCII for chylomicrons and VLDL
Remove unesterified cholesterol and esterify them by enzymes activated by ApoA1
Deliver cholesterol external to liver and reverse cholesterol transport |
| How is formation of HDL? | Nascent pre-beta-HDL w/ApoAI are modified by LCAT to become a-HDL, which is preserved and increased by CETP enzyme |
| How is LDL pathophysiology intracellular? | LDL containing cholesterol esters and ApoB100 are endocytosed to peripheral tissues and liver, get into lysosome, and give cholesterol to cell, which have many pathways, ACAT lead to cholesterol storage, HMG-CoA reductase induces synthesis of cholesterol is inhibited by increased cholesterol stored, and same mechanism for LDL receptors (decrease w/increase in cholesterol intracellular |
| What is type I hypercholesterolemia? | Familial LPL deficiency (familial hypercholesterolemia)
Causes decrease LPL, abnormal LPL, decrease ApoCII lead to slow chylomicron clearance |
| What is type II hypercholesterolemia? | Familial Hypercholesterolemia, LDL receptor defect. |
| What is type III hypercholesterolemia? | Familial dysbetalipoproteinemia, remnant removal disease, broad beta disease, ApoE deficiency, causes elevated Chylomicrons and VLDL |
| What is familial hyperalphaproteinemia? | increase HDL, rare beneficial condition good for longevity |
| What is familial alpha lipoprotein deficiency? | Tangier's disease, yellow tonsils due to cholesterol deficiency, fish eye disease, ApoAI and CIII deficiency, reduced levels of HDL get tendency to hyperTGs, elevated VLDL, several corneal opacities fish eye disease. |
| What is tx of FH (LDL increase)? | Statins (stop synthesis of endogenous cholesterol, may be combined w/cholesterolamine, increase risk for diabetes, decrease HbA1C, and risk of CAD)
Ezetemibe (inhibit absorption of cholesterol given if LDL above target or statin contraindicated (2nd line) |
| What is tx of TGs? | Fibrotes (first line), Omega-3 (2nd line) |
