29. Blood lipids

4/12/2025

Name the major groups of lipids

• Fatty acids

• Triglycerides

• Phospholipids

• Cholesterol

• Lipoproteins

Why do we do lipid analysis?

• To measure future cardiovascular risk

  • Elevated LDL levels are associated with atherosclerosis

• To measure patient response to lipid lowering drugs

  • To determine if drugs such as statins are working and reducing the patients cholesterol levels

• Assist in the diagnosis of pancreatitis

  • High triglycerides in blood stream can cause pancreatitis

What are lipoproteins?

A particle made of lipids and aporoteins that transports the hydrophobic lipids through the blood stream

What are the two pathways of lipid transport?

• Exogenous

• Endogenous

Summarise the exogenous pathway of lipid transport

• Epithelial cells of small intestine absorb free fatty acids, monoacylglycerols and cholesterol

• Microsomal triglyceride transfer proteins (MTP) packages these lipids as chylomicrons

• When the lipids reach the tissue, lipases remove triglycerides from the chylomicrons retaining their cholesterol resulting in chylomicron remnants

• The liver breaks down the chylomicron remnants

  • Cholesterol from chylomicron remnant is secreted into the small intestine or packaged into VLDL

VLDL

Very low density lipoprotein

LDL

Low density lipoprotein

IDL

Intermediate density lipoprotein

Summarise the endogenous pathway of lipid transport

• Microsomal triacylglycerol transfer protein packages triglycerides and cholesterol into VLDL

• VLDL transports triglycerides to tissues

• VLDL becomes IDL in respiring tissue

• IDL becomes LDL by the removal of remaining triglycerides and cholesterol

• LDL deposits cholesterol into cells

• LDL becomes HDL

• HDL will carry cholesterol from cells to the liver to be eliminated

LDL

Bad cholesterol

HDL

Good cholesterol

Order the lipoproteins from largest to smallest

• Chylomicrons

• VLDL

• LDL

• HDL

Major Apoprotein of chylomicrons

B₄₈

Major apoprotein of VLDL

B₁₀₀

Major apoprotein of LDL

B₁₀₀

Major apoproteins of HDL

A₁, A₂

Function of chylomicrons

Main carrier of dietary triglycerides

Function of VLDL?

Main carrier of endogenously produced triglycerides

Function of LDL

Main carrier of cholesterol

Main function of HDL

Cardio protective, carries cholesterol back to liver

Lipid that makes up most of chylomicron

Triglyceride

Lipid that makes up most of VLDL

Triglyceride

Lipid that makes up most of LDL

Cholesterol

Lipid that makes up most of HDL

Phospholipid (25%) and protein (55%)

What is the collection tube to test for lipids in blood?

SST- yellow top tube

• Serum separator tube

What is total cholesterol?

Both HDL and LDL

When testing a patient for triacylglycerols what should we ensure?

• The patient has fasted

• Because concentration of triacylglycerol concentration is greatly affected by meals

  • If patient hasn’t fasted we cannot accurately calculate LDL using the friedewald equation

What does tiracylglycerol test measure?

Amount of glycerol released by lipids

When cholesterol transported by HDL to liver what is it converted to?

Bile acids and then excreted

What does low levels of HDL in the serum indicate?

Increased risk of cardiovascular disease

How is LDL measured?

Using the friedewald equation:

[Total cholesterol ] - [HDL] - ([Triacylglycerol] / 2.2)

When should the friedewald equation not be used?

when tiglyceride concentration is greater than 4.52mmol/L

What are the assumptions of the friedewald equation?

• Most circulating triglycerides are in VLDL

• That the triglyceride: VLDL ratio is 5:1

What causes familial hypercholesterolaemia?

A defect with the LDL receptor

Symptom of familial hypercholesterolaemia

Tendon xanthomas/ xanthomas

What are xanthomas?

Cholesterol deposits

Cause of familial combined hyperlipidaemia

Over production of VLDL with increased triglycerides

What are atheromas?

Lipid rich lumps in the inner lining of arteries

How does atherosclerosis develop?

• Injury to the blood vessel

• Movement of cholesterol into the subendothelium and media of the artery

• Monocyte infiltration and the conversion to foam cells

• Rupture of the atherosclerotic plaque

What are the specimen requirements for lipid lab test?

1. Phlebotomy need to check that the patient and sample details match

2. Correct sample collection tubes (for biochemistry: SST- yellow), K-EDTA (Haematology: purple)

3. Ensure patient has fasted because this affects triglyceride concentration which is used to report LDL levels

Minimum acceptance criteria for lab tests

• Full name

• patient DOB

• NHS number (or another unique identifier)

Technique used to measure: Total cholesterol, Triglycerides and HDL?

• Enzymatic assay which is automatic and performed on an analyser

• The colour intensity of the product is directly proportional to lipid being measured

What are the additional tests that can be done to test blood lipids?

• Visually inspect the serum

• Immunoassay for Lipoprotein A

• Use of molecular techniques to identify APoE and the presence of LDL receptor

What does the image show?

Normal serum

What does the image show?

Raised chylomicrons

What does the image show?

Raised chylomicrons and VLDL

What does the image show?

Raised VLDL

Treatment for hypercholesteraemia

• Statins

• Ezetimide

• Probucol

• Ricotinic acid

• Fish oil

• LDL aphress

Why can statins be used to treat hypercholesterolaemia?

• Inhibits the enzyme involved in the synthesis of cholesterol

• Decreases intracellular cholesterol causing an increased intake from the plasma

Why can ezitimide be used to treat hypercholesterolaemia?

• Inhibits absorption of cholesterol

• Most effective when combined with a statin

Why can probucol be used to treat hypercholesterolaemia?

• Has an antioxidant effect on LDL

• Which may reduce LDL uptake by macrophages

  • Decreasing atherosclerosis, the formation of and atheroma and progression of atherosclerosis

Why can Ricotinic acid be used to treat hypercholesterolaemia?

• Inhibits fatty acid release from adipocytes

• Inhibits VLDL synthesis and secretion

Why can fish oil be used to treat hypercholesterolaemia?

Inhibits the synthesis and secretion of VLDL

When is LDL aphresis be used to treat hypercholesterolaemia?

• LDL is removed from the blood

• Used for patients

• who have high LDL even after using medication and changing their lifestyle

What are the treatments for hypertriglyceridaemia?

• Limit fat intake

• Fibrates (upregulate genes involved in lipid metabolism to reduce triglycerides and raise HDL)

• Surgery (intestinal bypass, gastric banding )

• Regular exercise