Lipids Flashcards

1
Q

What does a lipoprotein structure consist of

A

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

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2
Q

function and how classification of lipoproteins

A

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

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3
Q

What is a chylomicron

A

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

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4
Q

What is a VLDL

A

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

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5
Q

What are LDLs

A

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

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6
Q

What are HDLs

A

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

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7
Q

Why can you have differences in serum lipid/protein concentrations

A

Sex - pre/post menopause
Age
Culture/Location
Genetics

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8
Q

Why are lipids analyzed

A

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)

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9
Q

How do we collect sample for cholesterol

A

person on normal diet fasts 12-14 hrs

serum or heparin plasma
➢ Avoid fluoride/oxalate
➢ Separate ASAP; store at
4˚C or -20˚C

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10
Q

how is cholesterol measured

A

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

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11
Q

What is familial hypercholesteromelia

A

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)

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12
Q

how do you collect triglycerides

A

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

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13
Q

What are the sources of error in triglyceride measurement

A

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

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14
Q

how does Hypertriglyceridemia contribute to CVD

A

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

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15
Q

how to treat Hypertriglyceridemia
moderate and severe

A

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

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16
Q

Ranges for HDL/LDL

A

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

17
Q

HDLc: Measurement

A

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

18
Q

LDLc: measurement

A

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

19
Q

what encompasses a treatment plan for an increased lipid profile

A

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

20
Q

how do you measure Apolipoproteins (A1 and B)

A

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

21
Q

What is Lp(a): Lipoprotein “Little (a)”

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

22
Q

What is cholesterol

A

precursor for steroid hormones

23
Q

Hypertriglyceridemia

A

not linked directly to CHD but elevated triglycerides with high LDL and low HDL = contribute to risk
-extreme hypertriglyceridemia can lead to pancreatitis

24
Q

how to measure triglyceride

A

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

25
Q

how to measure LDLc NOT equation

A

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