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Lipids and Lipoproteins
Lipids• A group of water-insoluble substances that
are extractable by nonpolar (fat) solvents, such as alcohol and ether.
• Include: fatty acids, neutral fats, waxes andsteroids.
• Compound lipids: glycolipids, lipoproteins, and phospholipids.
• Main groups: cholesterol and esters, glycerolesters (TG), fatty acids, phospholipids.
Cholesterol
• A sterol that is turned into bile acids and steroid hormones and is a key constituent of cell membranes.
• Largely endogenous and synthesized in liver.• Diet influences blood levels by 10 to 20%. • 30 to 60% of cholesterol in diet is absorbed
mixed with conjugated bile acids, phospho-lipids, fatty acids, and monoacylglycerides.
Triglycerides
• Most abundant dietary fat and compose 95% of all fat stored in adipose tissue.
• Prime function: furnish energy for the cell.• In the intestines, in the presence of lipases and
bile acids are hydrolyzed into fatty acids, glycerol and monoglycerides.
• After absorption, are reconstituted into chylo-microns.
• Unlike cholesterol, diet greatly affects levels.
Lipoproteins• Lipid-protein complexes in which lipids (which
are hydrophobic) are transported in the blood.
• Lipoprotein particles consist of a spherical hydrophobic core of TG or cholesterol esters surrounded by an amphophilic mono- layer of phospholipids, cholesterol, and apolipoproteins.
Lipoprotein Metabolism• Exogenous metabolism: from dietary fat to
chylomicrons to glycerol, free fatty acids, and monoglycerides.
• Endogenous metabolism: from chylomicron remnant to the liver to synthesis of VLDL, IDL, LDL, HDL.
Liver
IDL
Glycerol,free fatty acids,monoglycerides
Glycerol,free fatty acids,monoglycerides
Chylo-micron
RemnantRemnant
Lpl
Glycerol,free fatty acids,monoglycerides
Glycerol,free fatty acids,monoglycerides
Triglycerides (stored)Triglycerides (stored)
Energy (cells)Energy (cells)
VLDL
Lpl
Nascent HDL
HDL
Stored CholesterolStored CholesterolIntestinesIntestines
LCAT
Lpl
Lpl
LDLPeripheral
Tissues and Liver
Peripheral Tissues
and Liver
Lpl=lipoprotein lipase
EXOGENOUS LIPOPROTEIN METABOLISM
ENDOGENOUS LIPOPROTEIN METABOLISM
Chylomicrons
• Large particles produced by the intestines that are very rich in triglycerides (90%) of dietary origin, poor in cholesterol and phospholipids, and low in protein (1%).
• Less dense than water due to high lipid to protein ratio and floats.
• Cause of “milky” plasma.• Due to action of lipoprotein lipase, becomes
triglyceride-poor: REMNANT.
VLDL• Very-low-density lipoproteins.• Like chylomicrons, are triglyceride-rich (50%),
can float and make plasma turbid.• Unlike chylomicrons, are endogenous (liver).• Contains cholesterol and phospholipids (40%),
and protein (10%).• Action of Lpl gives rise to IDL.
LDL• Low-density lipoproteins• Make up 50% of total lipoproteins.• Even when in high concentration, does not
cause turbidity of plasma.• Esterified cholesterol makes up 50% of mass.• Subfraction: small particles with lower
cholesterol/apoB ratio that are seen in dyslipoproteinemia
associated with CAD.
HDL
• High-density lipoproteins• Contain 50% protein, mostly apoA-I and II.• Subclasses: HDL2 and HDL3.
• Low levels of apoA-I related to Coronary Artery Disease.
Apolipoproteins The hydrophilic components of lipoproteins (Lipids must
be in water soluble micellar structures for transport in plasma.)
Grouped by function: * ApoA: major protein of HDL; ApoA-I
activates LCAT, which esterifies cholesterol in plasma. * ApoB: major protein (95%) of LDL.
* ApoC: major protein of VLDL. ApoC-IIactivates lipoprotein lipase.
* ApoD and ApoE
Patient Preparation• Cholesterol:
* Nonfasting acceptable for screening* 12-14 hr fast for diagnosis
• HDL / LDL Cholesterol: 12 hr or more fasting• Triglycerides: 12 hr or more fasting• Apolipoproteins: 12 hr or more fasting
General Lab Precautions
Interference in laboratory testing will occur in specimens that are:* lipemic* turbid* hemolyzed* icteric
Do not use lubricated test tube stoppers for Triglyceride test as free glycerol can increase value (correct with sample blank).
Physiologic Variation*
Component Coefficient of Variation
• Total Cholesterol 5.0%• Triglycerides 17.8%• LDL-cholesterol 7.8%• HDL-cholesterol 7.1%• ApoA-1 7.1%• ApoB 6.4%
* Kafonek, 1992CV= SD/mean x 100
LIPID PROFILETotal Cholesterol, triglyceride, VLDL, HDL,
total cholesterol:HDL ratio,coronary heart disease risk
LIPID PROFILETotal Cholesterol, triglyceride, VLDL, HDL,
total cholesterol:HDL ratio,coronary heart disease risk
CholesterolCholesterol
>200 mg/dl
2 fastingsamples
TriglycerideTriglycerideNonfasting or fasting
< 200 mg/dl
Males > 160 mg/dlFemales > 135
Assessment of Lipids
2 fastingsamplesNormal
STOP
No 2o disorder 2o disorder presentPrimaryhyper-
lipidemia
Monitor lipid
profile
Screen for 2o disorders
HyperlipoproteinemiaTYPE LIPOPROTEIN PATTERN
I Extremely elevated TG due to chylomicrons
IIa Elevated LDLIIb Elevated LDL and VLDLIII Elevated cholesterol; presence of
-VLDL; VLDL-C/plasma TG ratio >0.3
IV Elevated VLDLV Elevated VLDL with chylomicrons
Fredrickson Classification*
Type Refrigerator Test Electrophoresis• I +, clear plasma Normal• IIa -, clear plasma High band• IIb -, cloudy plasma High & pre-• III +, cloudy plasma Broad band• IV -, cloudy plasma High -2band• V +, cloudy plasma High -2 band
*original method of classifying lipid-related diseases that enabled correlation of clinical disease syndromes to laboratory assessment.
PLA
SM
A A
T 4
o C
ClearFaintlyTurbid
1to2+Turbid
1to2+Turbid
Creamylayer
1to2+TurbidClear
Creamylayer
I II-A II-B III IV V
Standing Plasma Test
1. 2 ml of plasma in a test tube is allowed to stand inside a refrigerator
at 4o C undisturbed overnight.2. Chylomicrons accumulate as a floating “cream” layer.3. A turbid plasma contains excessive VLDL.
Lipid Disease Patterns• High cholesterol with High LDL-C• High Triglycerides with Normal Cholesterol• High Cholesterol and High Triglycerides with or
without Low HDL-C• Low Total Cholesterol with Low or Normal HDL• Isolated Low HDL• Isolated High HDL• Lp (a) Lipoprotein Excess
Diagnosing Hypertriglyceridemia
200-500 mg/dl >500 mg/dl< 200 mg/dl
Diet andretest inone year
Evaluate for risk factors:
AlcoholismDiabetes MellitusGlycogen Storage
DiseaseHypertensionHyperuricemiaHypothyroidism
MedicationsOral contraceptives
PancreatitisPregnancy
Renal disorder
No riskfactors+ Risk factor or+ Family history
Diet anddrugsDiet
Male > 160 mg/dl Female > 135 mg/dl
Lipid Interpretation for Coronary Heart Disease
Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl
Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl
Repeat after 5 yrsRepeat after 5 yrs
Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl
Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl
Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl
Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl
RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%
RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%
Diet and/orDrugs
Diet and/orDrugs
DietRetest in 1 yr
0-1 risk factorNo coronary HD0-1 risk factorNo coronary HD
2 or morerisk factors2 or morerisk factors
Risk Factors for CHD• POSITIVE RISK FACTORS:
- Age: Male >45 yr; Female >55 yr or premature menopause.
– Family history of premature CHD(<55 yr for father and <65 yr for mother)
– Current cigarette smoking– Hypertension or on anti-HPN medication
– Low HDL-cholesterol– Diabetes mellitus
• NEGATIVE RISK FACTOR:– High LDL-cholesterol: >60 mg/dl
from NCEP Guidelines
Adults: Cholesterol and HDL*• Total Cholesterol:
Desirable level <200 mg/dlBorderline High 200-239 mg/dl
High >240 mg/dl
• HDL-CholesterolLow <35 mg/dl
* National Cholesterol Education Program
Children of Hypercholesterolemics
T Chol LDL-C Category (mg/dl) (mg/dl)
Acceptable <170 <110Borderline 170-199 110-129High >200 >130
from NCEP Expert Panel on Children and Adolescents
GOOD DAY!