Understanding Blood Lipids Lecture

Blood Lipids Lecture Notes

• Blood lipids are essential for cellular structure and metabolic pathways, providing energy storage as well as structural components of cells.
• Lecture aims include understanding lipid biochemistry and metabolism, describing lipid disorders, outlining the role of clinical biochemistry labs in analyzing blood lipids, and explaining dyslipidaemia treatment.

Preparation

• Slides contain chemical structures of cholesterol, a free fatty acid, a triglyceride, and a phospholipid.
• Active revision is recommended involving eating pizza after the lecture.

Aim and Objectives

• The lecture's aim is to introduce blood lipids.
• Students will be able to understand lipid biochemistry and metabolism.
• Lipid disorders and clinical diseases will be described.
• The role of clinical biochemistry labs in blood lipid analysis will be examined.
• Treatment options for dyslipidaemia will be explained.

Essential to Life!

• Lipids have diverse roles in bodily functions, including cell structure maintenance and energy storage.

Major Groups of Lipids

• Fatty acids are metabolic fuels, stored as triglycerides, and have long carbon chains with a carboxyl group.
• Triglycerides are energy sources with glycerol backbones and three fatty acid residues.
• Cholesterol is essential for cell membrane components, prevalent in diet and liver.
• Lipoproteins combine lipids with apoproteins for solubility and transport.

Apoproteins

• Apoproteins are multifunctional proteins that transport insoluble lipids into the blood's hydrophilic environment.
• Apoproteins maintain lipoprotein structure, regulate enzymes acting on lipoproteins, and facilitate receptor recognition.
• Defects in apoproteins can cause dyslipidemias.
• Specific apoproteins are associated with different parts of the body (e.g., intestines, liver, macrophages).

Lipoproteins

• Lipoproteins are complexes of lipids and apoproteins crucial for lipid transport within the body.
• Lipoproteins are responsible for interorgan fuel, distribution, and cholesterol pool maintenance.

Key Lipoprotein Classes

• Chylomicrons transport dietary triglycerides.
• VLDL transports endogenously produced triglycerides.
• LDL transports cholesterol.
• HDL is involved in cholesterol reverse transport.

Exogenous Pathway - Chylomicrons

• Chylomicrons originate in the intestines and carry dietary triglycerides through the lymphatic system.
• Lipoprotein lipase (LPL) breaks down triglycerides into fatty acids for cellular use.
• Chylomicron remnants are cleared by the liver.

Endogenous Pathway - VLDL

• VLDL originates in the liver and carries endogenously produced triglycerides.
• LPL breaks down VLDL triglycerides into fatty acids.

Endogenous Pathway - LDL

• LDL delivers cholesterol to peripheral tissues.
• LDL receptors on cells remove LDL cholesterol for cellular use.

Endogenous Pathway - HDL

• HDL is involved in reverse cholesterol transport, removing excess cholesterol from peripheral tissues.
• HDL delivers cholesterol to the liver for excretion.

Key Lipoprotein Classes (Table Summary)

Chylomicrons: Triglyceride rich; large; low density; carry dietary triglycerides.
VLDL: Triglyceride rich; medium size; low density; carry endogenous triglycerides LDL: Cholesterol rich; medium size; low density; deliver cholesterol to cells HDL: Protein rich; small; high density; remove cholesterol from cells

Dyslipidaemia

• Elevated lipid levels; clinical manifestations often involve elevated LDL and triglycerides.
• WHO/Fredrickson classification details types of hyperlipidaemias, including phenotype, lipoprotein, elevated levels, increased lipid fraction, and plasma appearance.

Classification - Hypercholesterolaemia

• Primary and secondary hypercholesterolaemia are categorized.
• Causes of primary hypercholesterolaemia include familial hypercholesterolaemia and autosomal recessive hypercholesterolaemia.
• Secondary hypercholesterolaemia can be linked to diabetes, renal diseases, anorexia, and liver disease.

Classification - Hypertriglyceridaemia

• Primary and secondary hypertriglyceridaemia subtypes are categorized.
• Primary causes include familial combined hyperlipidemia, lipoprotein lipase deficiency, and familial endogenous hypertriglyceridemia.
• Secondary causes involve pancreatitis, systemic lupus erythematosus (SLE), alcohol use, and pregnancy.

Familial Combined Hyperlipidemia

• Autosomal dominant inheritance; overproduction of VLDL; elevated triglycerides and cholesterol.

Atheroma and Atherosclerosis

• Atheroma is a lipid-rich lump in artery walls that results in atherosclerosis.
• Pathogenesis starts with injury to blood vessels and cholesterol deposition.

Laboratory Tests

• Patient history, family history, physical examination, and laboratory tests are crucial for diagnosis.
• Blood tests (e.g., cholesterol, triglycerides, HDL) are part of the assessment protocol.

Specimen Requirements

• Phlebotomy checks and proper sample collection procedures are critical steps, e.g., proper collection tubes (SST for biochemistry, K-EDTA for hematology).

Laboratory Techniques (Total Cholesterol)

• Enzymatic assay for cholesterol measurement involves three stages: cholesterol esterase, cholesterol oxidase, and hydrogen peroxide reaction with a colour reagent.

Laboratory Techniques (Triglycerides)

• Four-stage enzymatic assay for triglyceride measurement: lipase, glycerol kinase, glycerol phosphate oxidase, oxidation of colourless amine reagent.

Laboratory Techniques (HDL)

• Three-stage enzymatic assay for HDL measurement: cholesterol esterase, HDL-cholesterol oxidase, hydrogen peroxide-colour reagent reaction.

Calculating LDL

• Friedewald equation calculates LDL cholesterol using total cholesterol, HDL cholesterol, and triglyceride values.
• Important to note that the Friedewald equation has limitations regarding accuracy. It is typically unsuitable for high triglyceride (>4.52 mmol/L) levels.

Additional Tests

• Visual inspection of serum for lipoproteins
• Semi-routine measurement of lipoprotein A (Lp(a)) by immunoturbidimetry
• Apoprotein analysis (e.g., Apo B, Apo A1)
• Molecular tests for APOE and LDL receptor genetic variations.

Treatment - Hypercholesterolaemia

• Statins inhibit HMG-CoA reductase to lower intracellular cholesterol levels.
• Ezetimibe inhibits cholesterol absorption.
• Probucol has antioxidant effects on LDL.

Treatment - Hypercholesterolaemia (other methods)

• Nicotinic acid and derivatives inhibit fatty acid release from adipocytes and VLDL secretion.
• Fish oil inhibits VLDL synthesis.
• LDL apheresis removes LDL from the blood.

Treatment – Hypertriglyceridaemia

• Limiting fat intake (<20g/day) is a primary treatment approach.
• Fibrates upregulate lipid metabolism-related genes, reduce triglycerides, and increase HDL levels.
• Surgery and exercise (including gastric banding, partial gastrectomy, and intestinal bypass) can reduce triglycerides and improve lipid profiles.

This quiz focuses on the essential role of blood lipids in cellular structure and energy metabolism. It covers lipid biochemistry, disorders, clinical analysis, and treatment of dyslipidaemia. Students will engage with chemical structures and the clinical significance of lipid levels in health.