Investigation of hyperlipidaemia

Dr. S Homathy

Properties of lipids

• Hydrophobic

• High-energy food

• For cell membranes, steroid hormones

• Some lipids essentially exogenous

Lipo-protein structure

• Fat globule in water• Central hydrophobic core

TriglyceridesEsterified cholesterol

• Outer shellApoproteinsPhospholipidsNon-esterified cholesterol

Types of lipo-proteins

• High density (HDL)

• Low density (LDL)

• Very low density (VLDL)

• Intermediate density (IDL)

• Chylomicrons

Primary Functions

• HDL -Cholesterol from tissue to liver

• LDL -Cholesterol to tissue

• VLDL -Endogenous triglycerides

• IDL -Transient form

• Chylomicron -Exogenous triglycerides

Broad basedly …

• HDL = GOOD Cholesterol

• LDL = BAD Cholesterol

Composition of lipoproteins

• HDL -50% proteins

• LDL -55% Cholesterol

• VLDL -55% Triglycerides

• Chylomicron -90% Triglycerides

Apoproteins in lipoproteins

• HDL - A, C, E

• LDL - B

• VLDL - B, C, E.

• Chylomicron - A, B, (C, E.)

Electrophoretic mobility of lipoproteins

• HDL - alpha

• LDL - beta

• VLDL - pre-beta

• Chylomicron - origin

Reference method for measurement of lipoproteins

• ULTRA CENTRIFUGATION

• Lipo protein floatation rate measured in Svedberg units

Laboratory investigations

• Serum total cholesterol

• Serum lipid profile

• Apo lipoprotein levels

• Lipid electrophoresis

• Special tests –geno typing

Total cholesterol

• Usually fasting

• Non-fasting accaptable for screening

• <200 mg/dl (5.2 mmol/l) is desirable.

• >200 mg/dl (5.2 mmol/l) proceed to a lipid profile.

Secondary causes of hyperlipidaemia

• Diabetes mellitus

• Hypothyroidism

• Nephrotic syndrome

• Obstrucive jaundice

• Alcohol abuse (Tg)

Lipid Profile

• Fast for 10 – 12 hours.• Normal lipid diet, constant weight• Not on drug affecting lipids (OCP)• Not on lipid lowering drugs unless being

monitored.• No stress (3 months after MI)• Standardised collection procedure

Overnight serum

• Observe after keeping fasted serum in a test tube at 4C for 18 hours.

• Milky layer on top -chylomicrons

• Turbid serum -VLDL

• Clear -Normal / LDL

Lipid profile

• Measure Total Cholesterol

HDL Cholesterol

Triglycerides

• Calculate LDL Cholesterol

Cardiac risk ratio

Friedewald formula

• Total cholesterol = HDL + LDL + VLDL

• VLDL = Tg(in mg/dl) / 5

= Tg (in mmol/l) / 2.2

• Formula not valid if Triglycerides are > 400 mg/dl (4.5 mmol/l)

Cardiac risk ratio

• Total cholesterol / HDL cholesterol

• > 5 is unfavourable

• Apo A1 / Apo B ratio

Interpretation

• Total Cholesterol

<200 Desirable

200-239 Borderline high

240 High

LDL Cholesterol

<100 Optimal

100-129 Near normal or

above normal

130-159 Border line high

160-189 High

190 Very high

<40 Low

>60 High

HDL Cholesterol

Triglicerides

<150 Normal

150-199 Borderline high

200-499 High

500 Very high

Apolipoprotein levels

• Apolipoprotein A 1- reflects HDL

• Apolipoprotein B - reflects LDL

• Apolipoprotein a - independent risk factor for

MI

Lipid electrophoresis

• Serum electrophoresis is done

• Stain with a lipid staining dye

• Fredrickson’s Classification based on this.

Fredrickson’s classification of hyperlipidaemia

• Type Pattern LipoproteinsI origin chylomicronsII a b-lipoprotein LDLII b pre b & b VLDL + LDLIII broad b IDLIV pre-b VLDLV origin & pre b Chylo + VLDL

Special tests

• Apo E genotyping

using PCR technique

Conversion factors

• Cholesterol mg/dl / 38.6 = mmol/l

• Triglyceride mg/dl / 88.5 = mmol/l

Summary

• Screening test Total Cholesterol

• Confirming test Lipid profile

• Phenotyping Lipid electrophoresis

• Geno typing PCR technology

• Monitoring tests Lipid profile