Lipids Flashcards
What does a lipoprotein structure consist of
hydrophilic shell - phospholipids and cholesterols
Hydrophobic core - triglyceride and esters
contains specific protein - apolipoprotein
maintains structural integrity
binds to cell receptor, enzyme activators and inhibitors
function and how classification of lipoproteins
main function - fuel delivery
acts as a transport molecule for lipids
made in intestine and liver
classified by density via ultracentrifugation
chylomicrons (highest lipid to protein ratio)
H/LDL
What is a chylomicron
largest and least dense (floats)
-found in intestine
part takes in endogenous pathway - transports DIETARY triglycerides to liver
-hydrolyzed by lipase
-found in blood after a FAT RICH MEAL
What is a VLDL
smaller than chylomircons
low lipid and higher protein - dont float
-most triglycerides
-found in liver
transports dietary and endogenous TRIGR from liver to tissues
-presence can cause turbidity in fasting sample
too much carbohydrates, saturated and trans fats
What are LDLs
smaller than vldl
known an BAD cholesterol can lead to atherosclerosis
even less lipid content - MAJOR cholesterol carrier
found in liver from lipolysis of liver
transports cholesterol from liver to tissues
PROATHEROGENIC
taken up into vessel walls
FOAM CELLS when taken up by macrophages
increases BAD cholesterol
What are HDLs
SMALLEST MOST DENSE
made in liver and intestine
50/50 protein and lipid
reverses cholesterol transport pathway
removes excess cholesterol and returns to liver
LOWERS CHOL - GOOD CHOL
HDL = decreased risk of CVD
Why can you have differences in serum lipid/protein concentrations
Sex - pre/post menopause
Age
Culture/Location
Genetics
Why are lipids analyzed
CVD leading cause of death in Canada
-CVD associated with serum Chol concentration = dyslipidemia
-risk of premature atherosclerosis
➢hypercholesterolemia
➢ hypertriglyceridemia
➢ high levels of LDL cholesterol (hyperbetalipoproteinemia)
➢ low levels of HDL cholesterol (hypoalphalipoproteinemia)
How do we collect sample for cholesterol
person on normal diet fasts 12-14 hrs
serum or heparin plasma
➢ Avoid fluoride/oxalate
➢ Separate ASAP; store at
4˚C or -20˚C
how is cholesterol measured
Conversion of Cholesteryl ester to fatty acid and then to peroxide with esterases and oxidases
use of peroxidase to view color change
➢ Measure absorbance of coloured dye at 540 nm (e.g. AU480)
➢ Absorbance proportional to concentration
RI for total CHOL level that are associated with CVD risk are set by experts
-increased result is associated with increased risk
-needs to be used with other tests to confirm
Health <5.20
High risk >6.20
What is familial hypercholesteromelia
genetic disorder - codominant
-when the exogenous pathway is overwhelmed
-high LDL due to defective LDL receptors = premature CVD
signs : first heart attack as a teenager, tuberous xanthomas (deposits in skin , raised lesions with yellow centers) and corneal arcus (deposits in cornea)
how do you collect triglycerides
fast 12-14 hours
water only
no alcohol 24 hours prior
serum or heparin plasma
store at -4 or -20
use of bacterial lipase, glycerokinase, oxidase and peroxidase for an enzymatic assay sequence where ABs is measured at 520 nm
-abs proportional to concentration
What are the sources of error in triglyceride measurement
endogenous glycerol false increases result can be small in instances of stress or disease but there is an increase nonetheless
➢ glycerol-containing medication
➢ glycerol-coated stoppers
healthy <1.70
high <2-5
how does Hypertriglyceridemia contribute to CVD
not an independent factor for CHD but increased TRIGR, LDL, HDL contribute to CVD risk
Familial Hypertriglyceridemia:
increases in VLDL lipoprotein
complication from pancreatitis
increased dietary triglycerides like chylomicrons can block pancreatic capillaries and can cause ischemia which exposes TRIGR to pancreatic lipase and causes inflammation and pancreatitis
how to treat Hypertriglyceridemia
moderate and severe
moderate hypertriglyceridemia
➢ modify diet
➢ control blood glucose
➢ exercise
➢ weight loss
➢ abstain from alcohol
✓for severe primary hypertriglyceridemia
➢ very-low-fat diet
➢ drug therapy: fibric acid derivatives
Ranges for HDL/LDL
HDLc
<1.3 mmol/L is a risk factor
LDLc
<2.5 mmol/L is optimal 3 is average
>3.0 mmol/L is a risk factor
-if youre a high cvd risk you need to stay under 2
these points can change if there are other factors involved
HDLc: Measurement
selective chemical precipitation
1Precipitate non-HDL lipoproteins (VLDL, LDL) with heparin or dextran sulfate
2. Centrifuge or use polymer-coated beads in magnetic field: VLDL & LDL lipoproteins stay in sediment and HPLc in supernatant
-INTERFERNCE AND INACCURACIES - OLD
can also have a direct homogenous assay
-no precipitation
-use detergents or enzymes to bind non HDL particles so the HDL in sample can be measured - quick
high levels = good
LDLc: measurement
Calculated using Friedewald calculation
LOOK AT CALCULATION
Total CHOL - HDLC -(TRIGR/2.2 (also known as VDL)
-increased - CVD or PAD
-2.2 is a conversion factor to approximate how much VLDL is in the blood mmol/L
-the formula assumes pt is fasting because TRIGR after eating can be very elevated
-can be inaccurate when TRIGR are over 4.5
what encompasses a treatment plan for an increased lipid profile
better diet with no unsat fats, more fibre, and omega 3 fatty acids
Drugs
Statins - HMG COA reductase inhibitors -lipitorm crestor
reduces LDLc
removes bile acids and forces liver to use CHOL in blood to make bile acids
how do you measure Apolipoproteins (A1 and B)
markers for cvd risk
Apo B
➢ Measure protein component of LDL & VLDL lipoproteins
➢ Good indicator of CVD risk
➢ more reliable than LDL measurement
➢ Direct measurement (not calculated)
➢ Not affected by high triglyceride
➢ >0.80 g/L high risk
Apo A1
➢ measure protein component of HDL lipoproteins
Calculate Apo B/A1 ratio (LDL/HDL ratio)
<0.633: no added cardiovascular risk
>0.984: high risk for cardiovascular disease
What is Lp(a): Lipoprotein “Little (a)”
GENETICALLY DETERMINED
can increase CVD risk
not part of routine panel
LDL like
Apoa linked to Apo B by disulphide bond
promotes clot lysis (plasminogen )
competes with plasminogen for fibrin binding sites and promotes clotting
Lpa is proatherogenic
Conc is genetically determined and can explain familial predisposition to premature MI/stroke
-increase with increase in LDL = CVD
-genetic risk for AMI
What is cholesterol
precursor for steroid hormones
Hypertriglyceridemia
not linked directly to CHD but elevated triglycerides with high LDL and low HDL = contribute to risk
-extreme hypertriglyceridemia can lead to pancreatitis
how to measure triglyceride
enzymatic colormeteric assays
hydrolysis and glycerol measurement
-breaking TRIGR into fatty acids
-using peroxidase for a color changing reaction
high levels = CVD risk
very high >5 = pancreatitis
normal - <1.5
high <1.5
how to measure LDLc NOT equation
Homogenous assay
-using detergents
-measures LDL directly in blood and is not affected by high triglyceride level
Ultracentrifugation and precipitation
you used to be able to centrifuge and separate lipoproteins by density and then precipitate out non LDL lipoproteins
