Lipids and dyslipoproteinemias

Lipoproteins

Composed of lipids and proteins in varying proportions Lipids in general are insoluble in water and biologic fluids and are dependent on transport proteins The protein fraction of lipopoproteins is composed of polypeptide called APOPROTEINS

Lipoprotein metabolism

Triglyceride (TG) enter the blood stream from exogenous and endogenous(liver) sources. Pancreatic lipase Food----Neutral fat (TG)---------------------- FFA + monoglyceride

Intestine mucosa

Intestinal mucosa----- recombination with TG--------CHYLOMICRONS Chylomicrons are thin outer shell of phospholipid and unesterified cholesterol and proteins Chylomicrons in post prandial smples gives the milky appearance in plasma Chylomicrons enter in the cap of adipose, heart muscle and skeletal muscle where lipoprtein lipase is present

Lipoprotein lipase activated by apo CII splits much TG-------hydrolysis------FFA and glycerol FFA are used for energy in heart and skeletal muscle, some is transported back to the liver or converted back to TG by esterification with glycerol in fat cells and stored for future use The remaining Chylomicron remnants (ApoB. ApoE and cholesterol are taken in the liver and metabolized there

Liver synthesizes TG from FFA and glycerol from Chylomicron Synthesizes also cholesterol, cholesterol esters, apo B 100 and CII and combines this with TG----VLDL In body tissues, lipoprotein lipase hydrolyzes TG to release FFA taken by the liver converted to LDL

LDL

VLDL

Lower TG, higher Cholesterol No C or E apoproteins

Higher TG,lower cholesterol With C or E apoproteins

HDL

Help create LDL from VLDL Transport cholesterol to the peripheral tissue to the liver--- helps protect atheroschlerosis

Laboratory test used to assess risk of CHD

Serum total cholesterol-increases the tendency for atherosclerosis Values

Total cholesterol < 200mg/dl(5.15 mmol/L) Borderline High risk 200-239mg/dl (5.15-6.18 mmol/L) High risk- _>240 mg/dl (6.2mmol/L)

LDL (low density lipoprotein) is Beta electrophoretic Better correlation for risk in CAD Friedwald formula----LDL chole= total chole(HDL chole-TG/5) Values

Desirable LDL _160 mg/dl (4.14 and above)

HDL (High density lipoprotein)-inverse correlation with risk for CAD Some believe that HDL has better correlation to CAD than total cholesterol and LDL Framingham study suggested that every 20 mg/dl (5.2 mmol/L) reduction in HDL cholesterol corresponds to doubling of CHD risks

Serum Cholesterol/HDL cholesterol ratio

Normal risk ratio is 5 Double risk 10 Triple risk 20 Some believe that it is the best single predictor of CHD risk

ApolipoproteinsVLDL B=40% C= 50% E=10% LDL B-98% HDL A1=66% AII= 22% C+D=12%

Apolipoprotein

Apo A is uniquely associated with HDL; it is proposed as a a better risk index of atherogenic risk than HDL chole Apo B comprises the protein component of LDL which is composed of a core of cholesterol esters covered by thin layer of phospholipid and free cholesterol which wrapped by a chainlike molecule of the principal subgroup of ApoB known as ApoB 100

Apolipoprotein

ApoB 48 is produced by the intestines isfound in Chylomicrons ApoA1/ApoB ratio has been suggested as a predictor for CHD Apo E4 gene has been proposed as a risk for Alzheimer`s disease Apolipoprotein assays has noit been widely used because of accuracy problems

Triglyceride/TG

Isfound mainly in chylomicrons and VLDL In fasting plasma, chylomicrons are absent;therefore TG is a good measure of VLDL The correlation of TG to CAD risk is controversial The major use is to calculate the LDL using the friedwald formula to help screen hyperlipidemia and to help establish lipoprotein phenotypes

TG

Nonfasting specimen are frequent source of elevated TG levels Increases 2 hours after meals 12-16 hours is suggested Obesity, stress, pregnancy, estrogen therapy high fat diet, DM, pancreatitis, nephrotic syndrome elevated TG

TGNormal values

30mg/dl------inc CAD risk 2-3folds When inc LDL and Lp (a) coexist---CAD risk inc 5 folds

Diagnosis of CAD

Get Total Cholesterol; then HDL Calculate total chole/HDL ratio LDL can be derived using Friedwald formula Accuracy of the lab test is increased if 2-3 specimen are obtained at least 1 week apart

Lipoprotein phenotyping

1965, Fredrickson, Levy and Lees suggested phenotypes based on electrophoresis Done after 10 hours of overnight fasting

Type I IIa IIb III IV V

Lipoprotein pattern

Extremely elevated TG due to the presence of chylomicrons Elevated LDL Elevated LDL and VLDL Elevated Cholesterol, TG presence of B VLDL; VLDL cholesterol/plasma TG ratio >.03 Elevatated VLDL Elevated VLDL and presence of chylomicrons

Type I I Iia Iib III IV v

Associated conditions Uncontrolled DM, hypothyroidism, dysglobulinemias Porphyria, Hypothyroidism, biliary obstruction, nephrosis, pregnancy, dysglobulinemias Same as Iia Hypothyroidism, ethanol use, dysglobulinemias, Diabetes Diabetes, lipodystrophy, ethanol use, glucocorticoid use, CRF, pregnancy, estrogens, glycogen storage diseases Ethanol use, pancreatitis, dysglobulinemias, diabetes

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