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Medical Biochemistry > Blood lipids > Flashcards

Blood lipids Flashcards

1
Q

What are the major groups of lipids?

A

Fatty acids

  • Long Carbon chain with COOL
  • Metabolic fuels stored as triglycerides

Cholesterol

  • Diet and liver
  • Essential component of cell membranes

Triglycerides

  • Glycerol backbone with 3 fatty acid residues
  • Energy source

Lipoproteins

  • Lipid and apoprotein
  • Solubility
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2
Q

How do you transport insoluble lipids into the hydrophilic environment of the blood?

A

Marry them to a protein! (Apoprotein)

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3
Q

Multifunctional protein:

A
  • Maintain structural integrity of the lipoproteins
  • Regulate enzymes acting on lipoproteins
  • Receptor recognition

Defects cause dyslipidaemia

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4
Q

Lipoproteins: Lipid and an apoprotein

What are the three roles:

A
  1. Interorgan fuel
  2. Distribution
  3. Maintain cholesterol pool
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5
Q

What determines the lipoprotein class?

A

The apoprotein determines the lipoprotein class

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6
Q

What is the function of chylomicrons?

A

Main carrier of dietary triglycerides

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7
Q

What is the function of VLDL?

A

Main carrier of endogenously produced triglycerides

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8
Q

What is the function of LDL?

A

Main carrier of cholesterol

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9
Q

What is the function of HDL?

A

Protective

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10
Q

Draw a table of composition, major apolipoproteins, mean diameter and density of:

  • Chylomicrons
  • VLDL
  • LDL
  • HDL
A
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11
Q

Exogenous pathway- chylomicrons

A
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12
Q

Exogenous pathway VLDL

A
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13
Q

Endogenous pathway- LDL

A
  • LDL receptor binds to apoB100
  • Its expression is regulated by intracellular cholesterol concentrations
  • Mediates cellular uptake of intact LDL
  • Mutations can result in severe inherited forms of hypercholesterolemia
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14
Q

HDL

A
  • HDL is involved in the reverse transport of cholesterol
  • Mops up free cholesterol
  • Binds to Scavenger receptor type B1 (SRB1) on hepatocytes
  • Cholesterol excretion via bile
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15
Q

What is dyslipidaemia?

A

Abnormally elevated levels of lipids and/or lipoproteins within the blood

• WHO (Fredrickson) classification for primary hyperlipidaemia

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16
Q

Draw a tree of primary hypercholesterolaemia

A
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17
Q

Draw a tree of secondary hypercholesterolaemia

A
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18
Q

Familial hypercholesterolaemia

A
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19
Q

Primary Hypertriglyceridemia

A
20
Q

Secondary Hypertriglyceridemia

A
21
Q

Familial combined hyperlipoidaemia

A
22
Q

What are atheroma’s?

A

Atheromas – lipid rich lumps in the inner lining of arteries

23
Q

Describe atherosclerosis

A
  • 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
24
Q

Laboratory tests

A
25
Q
  1. Phlebotomy
A

Check patient and sample details match

26
Q
  1. Correct sample collection tubes
A
  • SST (Biochemistry)
  • K-EDTA (Haematology) Patient has fasted ([triglyceride] affected and its used for LDL reporting
27
Q
A

• Enzymatic assay

Three-stages:

Stage 1: Stage 1: Cholesterol esters + H2O (Cholesterol esterase)→Cholesterol + Fatty Acids

Stage 2: Cholesterol + O2 (cholesterol oxidase) → Cholest-4-en-3-one + H2O2

Stage 3: Hydrogen peroxide reacts with phenol and peroxidase to oxidise colourless 4-aminophenazone

  • Colour intensity of the product is directly proportional to the cholesterol concentration
  • Normal range: <5 mmol/L
28
Q

Triglycerides

A

Enzymatic assay Four-stages:

Stage 1: Triglycerides + 3H2O (lipase_ →Glycerol + Fatty Acids

Stage 2: Glycerol + ATP (glycerol kinase) →Glycerol-3-phosphate + ADP

Stage 3: Glycerol-3-phosphate (glycerophosphate oxidase) → Dihydroxyacetone phosphate + H2O2

Stage 4: Hydrogen peroxide reacts with phenol and peroxidase to oxidise colourless 4- aminophenazone

  • Colour intensity of the product is directly proportional to the triglyceride concentration
  • Normal range: 0.8-1.9 mmol/L Lipase Glycerol Kinase
29
Q

HDL

A

Enzymatic assay Three-stages:

Stage 1: Cholesterol ester (esterase-PEG)→ Cholesterol + Fatty Acids

Stage 2: HDL-Cholesterol (oxidase-PEG) →Delta-4-cholestenone + H2O

Stage 3: Hydrogen peroxide reacts with phenol and peroxidase to oxidise colourless 4- aminophenazone

  • Colour intensity of the product is directly proportional to the HDL concentration
  • Normal range: >1.20 mmol/L
30
Q

Calculating LDL

Which equation is used?

A

• Friedewald equation:

[LDL Cholesterol] = [Total Cholesterol] – [HDL Cholesterol] - ([Triacylglycerol]/2.2)

31
Q

What are the problems with the Friedewald equation?

A

Problems:

  • Assumes most circulating triglycerides are in VLDL
  • Assumes that the triglyceride : VLDL ratio is 5:1
  • Should not be used when triglyceride concentration >4.52 mmol/L

Normal range: <3.0 mmol/L

32
Q

Additional tests: visually inspecting serum

What are these?

A

A. Normal

B. Raised chylomicrons

D. Raised chylomicrons and VLDL

E. Raised VLDL

33
Q

Lipoprotein A (LpA)

A

Semi-routine – immunoturbidmetr

33
Q

Lipoprotein A (LpA)

A

Semi-routine – immunoturbidmetr

34
Q

Apoproteins

A

ApoB:ApoA1

35
Q

Molecular

A

APoE and LDL receptor

36
Q

Treatments for hypercholesterolaemia:

Statins

A
  • Inhibits HMG-CoA reductase
  • Decreases intracellular cholesterol – increased uptake from the plasma
37
Q

Treatments for hypercholesterolaemia:

Ezetimide

A
  • Inhibiting the absorption of cholesterol
  • Effective when combined with a statin
38
Q

Treatments for hypercholesterolaemia:

Probucol

A
  • Antioxidant effect on LDL
  • May reduce LDL uptake by macrophages
39
Q

Treatments for hypercholesterolaemia:

Ricotinic acid and derivative

A
  • Inhibit fatty acid release from adipocytes
  • Inhibit VLDL synthesis and secretion
40
Q

Treatments for hypercholesterolaemia:

Fish oil

A
  • Inhibit VLDL synthesis and secretion
41
Q

Treatments for hypercholesterolaemia:

LDL apheresis

A
  • LDL removed from the blood
  • Patients who have high LDL despite medication and lifestyle changes
42
Q

Treatments for hypertriglyceridemia

Limit fat intake

A
  • <20g/day
43
Q

Treatments for hypertriglyceridemia:

Fibrates

A
  • Upregulate genes involved in lipid metabolism
  • Reduction in triglycerides and raised HDL
44
Q

Treatments for hypertriglyceridemia:

Surgery and exercise

A
  • Gastric banding
  • Partial gastrectomy
  • Intestinal bypass
  • Regular exercise

Medical Biochemistry (10 decks)

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