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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

20
Q

Secondary Hypertriglyceridemia

21
Q

Familial combined hyperlipoidaemia

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

25
1. Phlebotomy
Check patient and sample details match
26
2. Correct sample collection tubes
* SST (Biochemistry) * K-EDTA (Haematology) Patient has fasted ([triglyceride] affected and its used for LDL reporting
27
• 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
Triglycerides
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
HDL
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
Calculating LDL Which equation is used?
• Friedewald equation: [LDL Cholesterol] = [Total Cholesterol] – [HDL Cholesterol] - ([Triacylglycerol]/2.2)
31
What are the problems with the Friedewald equation?
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
Additional tests: visually inspecting serum What are these?
A. Normal B. Raised chylomicrons D. Raised chylomicrons and VLDL E. Raised VLDL
33
Lipoprotein A (LpA)
Semi-routine – immunoturbidmetr
33
Lipoprotein A (LpA)
Semi-routine – immunoturbidmetr
34
Apoproteins
ApoB:ApoA1
35
Molecular
APoE and LDL receptor
36
Treatments for hypercholesterolaemia: Statins
* Inhibits HMG-CoA reductase * Decreases intracellular cholesterol – increased uptake from the plasma
37
Treatments for hypercholesterolaemia: Ezetimide
* Inhibiting the absorption of cholesterol * Effective when combined with a statin
38
Treatments for hypercholesterolaemia: Probucol
* Antioxidant effect on LDL * May reduce LDL uptake by macrophages
39
Treatments for hypercholesterolaemia: Ricotinic acid and derivative
* Inhibit fatty acid release from adipocytes * Inhibit VLDL synthesis and secretion
40
Treatments for hypercholesterolaemia: Fish oil
* Inhibit VLDL synthesis and secretion
41
Treatments for hypercholesterolaemia: LDL apheresis
* LDL removed from the blood * Patients who have high LDL despite medication and lifestyle changes
42
Treatments for hypertriglyceridemia Limit fat intake
* \<20g/day
43
Treatments for hypertriglyceridemia: Fibrates
* Upregulate genes involved in lipid metabolism * Reduction in triglycerides and raised HDL
44
Treatments for hypertriglyceridemia: Surgery and exercise
* Gastric banding * Partial gastrectomy * Intestinal bypass * Regular exercise

Medical Biochemistry (10 decks)

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