45. LIPID PROFILE TESTS

Introduction

Lipid Profile Tests are a group of blood tests that help evaluate the levels of various lipids (fats) in the bloodstream. These include cholesterol, triglycerides, HDL (High-Density Lipoprotein), and LDL (Low-Density Lipoprotein). Lipid profiles are essential in assessing the risk of cardiovascular diseases, atherosclerosis, and metabolic disorders.


Lipoproteins

Lipoproteins are complexes of lipids and proteins that serve as transport vehicles for lipids in the bloodstream. Since lipids are water-insoluble, they must be carried in plasma by lipoproteins to reach various tissues for utilization, storage, or energy production.

Structure of Lipoproteins

A typical lipoprotein consists of:

  • Core: Non-polar lipids such as triglycerides and cholesterol esters.
  • Surface Coat: Polar phospholipids, cholesterol, and apoproteins.

This structure makes lipoproteins soluble in aqueous plasma and suitable for lipid transport.


Classification of Lipoproteins

Based on density and electrophoretic mobility, human plasma lipoproteins are classified into five major classes:

  1. Chylomicrons: Formed in the intestine; transport dietary (exogenous) triglycerides to tissues. They have the highest lipid (99%) and lowest protein content (1%).
  2. VLDL (Very Low-Density Lipoproteins): Synthesized in the liver; transport endogenous triglycerides to peripheral tissues.
  3. LDL (Low-Density Lipoproteins): Derived from VLDL in circulation; transport cholesterol from liver to tissues (“bad cholesterol”).
  4. HDL (High-Density Lipoproteins): Synthesized in liver; transport cholesterol from tissues back to liver (“good cholesterol”).
  5. Free Fatty Acids–Albumin Complex: Free fatty acids are transported bound to albumin in plasma.

Composition of Lipoproteins

Lipoproteins contain lipids (triglycerides, cholesterol, phospholipids) and proteins known as apoproteins. The proportion of these components varies across different lipoprotein types.

Major Apoproteins:

  • Apo A (A-I, A-II): Found in HDL; activates LCAT (Lecithin-Cholesterol Acyltransferase).
  • Apo B (B-48, B-100): Present in LDL and VLDL; essential for lipid transport and receptor recognition.
  • Apo C (C-I, C-II, C-III): Regulates lipoprotein lipase.
  • Apo E: Involved in receptor recognition in liver; important for LDL metabolism.

Functions of Lipoproteins

  • Chylomicrons: Transport dietary triglycerides from intestine to liver.
  • VLDL: Carry triglycerides synthesized in the liver to extrahepatic tissues.
  • LDL: Deliver cholesterol to peripheral tissues; elevated levels increase risk of atherosclerosis.
  • HDL: Collect cholesterol from tissues and transport it to the liver for excretion (“reverse cholesterol transport”).

Apolipoproteins also function as enzyme activators, receptor ligands, and structural components of lipoproteins.


Determination of Serum Lipids

Lipid profile tests typically include:

  • Total Cholesterol
  • HDL Cholesterol
  • LDL Cholesterol
  • Triglycerides

These parameters help assess the risk of coronary heart disease and lipid metabolism disorders.


Total Serum Cholesterol

Enzymatic Method – Principle

Cholesterol esters in serum are hydrolyzed by cholesterol esterase to free cholesterol, which is then oxidized by cholesterol oxidase producing hydrogen peroxide (H2O2). In the presence of peroxidase, H2O2 reacts with 4-aminoantipyrine and phenol to form a red quinoneimine dye measurable at 500 nm.

The colour intensity is directly proportional to the cholesterol concentration.

Reagents Used:

  • Cholesterol Ester Hydrolase
  • Cholesterol Oxidase
  • Horseradish Peroxidase
  • Phenol and 4-Aminoantipyrine
  • Phosphate Buffer (pH 6.7)

Reference Values:

  • Normal Range: 150–220 mg/dL
  • High levels: Hypercholesterolemia (risk of atherosclerosis, hypothyroidism, diabetes)
  • Low levels: Hypocholesterolemia (seen in hyperthyroidism, liver disease, malnutrition)

HDL Cholesterol

HDL (High-Density Lipoprotein) cholesterol is considered “good cholesterol” because it removes cholesterol from tissues and transports it to the liver for metabolism and excretion.

Principle:

HDL is separated from other lipoproteins by precipitating VLDL and LDL using polyvalent anions (like heparin or dextran sulfate) and divalent cations (Mg2+ or Mn2+). The HDL cholesterol is measured enzymatically in the supernatant.

Reference Values:

  • Males: 40–50 mg/dL
  • Females: 50–60 mg/dL

Higher HDL levels reduce the risk of heart disease.


LDL Cholesterol

LDL (Low-Density Lipoprotein) cholesterol is termed “bad cholesterol” because high levels promote cholesterol deposition in arteries, increasing the risk of heart disease.

Calculation (Friedewald Formula):

LDL Cholesterol = Total Cholesterol – (HDL Cholesterol + (Triglycerides ÷ 5))

Reference Range:

  • Optimal: <100 mg/dL
  • Borderline High: 130–159 mg/dL
  • High Risk: ≥160 mg/dL

Interpretation:

A high LDL/HDL ratio indicates a greater risk of coronary artery disease. The ideal ratio should be below 3.0.


Serum Triglycerides

Triglycerides are the main form of stored fat in the body. Elevated levels are associated with obesity, diabetes, liver disease, and cardiovascular disorders.

Enzymatic Method – Principle

Triglycerides are hydrolyzed by lipase into glycerol and free fatty acids. Glycerol is phosphorylated to glycerol-1-phosphate, which is then oxidized to form hydrogen peroxide. The H2O2 reacts with a chromogen in the presence of peroxidase, producing a coloured compound measurable spectrophotometrically.

Reference Values:

  • Normal: 40–150 mg/dL
  • Borderline High: 150–199 mg/dL
  • High: ≥200 mg/dL

Increased triglycerides (hypertriglyceridemia) may occur after fatty meals, in diabetes, nephrotic syndrome, and alcohol abuse. Low values are seen in abetalipoproteinemia and malnutrition.


Clinical Significance of Lipid Profile Tests

  • Assess risk of atherosclerosis and coronary artery disease.
  • Monitor treatment response in lipid-lowering therapy.
  • Detect metabolic conditions like diabetes mellitus, hypothyroidism, and nephrotic syndrome.
  • Helps in early diagnosis and prevention of heart disease.

Summary Table: Lipid Profile Components

ParameterNormal Range (mg/dL)Clinical Significance of Increased LevelClinical Significance of Decreased Level
Total Cholesterol150–220Atherosclerosis, hypothyroidism, diabetesLiver disease, malnutrition
HDL Cholesterol40–60Cardioprotective (higher = better)Heart disease risk, smoking, obesity
LDL Cholesterol70–130Coronary artery disease, hyperlipidemiaHyperthyroidism
Triglycerides40–150Diabetes, obesity, nephrotic syndromeAbetalipoproteinemia, malnutrition

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