Lecture 6,9,10: lipids, storage, transport

Question 1

A blood specimen from a patient with suspected appendicitis has a “creamy” layer at the top of the sample after centrifugation. The child was at a birthday party the day before where they ate a burger, chips and drunk a milkshake. They have hyperlipidaemia and an electrophoresis of their lipoproteins indicated the presence of large amounts of chylomicrons. Their lipoprotein lipase activity is low.

Provide an explanation for the creamy appearance of the patient’s plasma.

Answer 1

The ‘creamy’ appearance of their plasma is due to the presence of chylomicrons. They are the least dense lipoproteins and carry dietary fat which will remain present in the blood for 4-6hrs after a meal.

Question 2

Are chylomicrons normally present in a plasma sample taken from a patient who has not eaten for 15hrs? Explain your answer.

Answer 2

No as chylomicrons are usually cleared out by muscles and tissue after 4-6hrs.

Question 3

A blood specimen from a patient with suspected appendicitis has a “creamy” layer at the top of the sample after centrifugation. The child was at a birthday party the day before where they ate a burger, chips and drunk a milkshake. They have hyperlipidaemia and an electrophoresis of their lipoproteins indicated the presence of large amounts of chylomicrons. Their lipoprotein lipase activity is low.

What is the cause of the patient’s high level of chylomicrons?

Answer 3

Sudden increase of dietary fat means more chylomicrons needed for lipid transport. Lack of lipoprotein lipase means no chylomicrons can release lipids so they remain as chylomicrons in the blood.

Question 4

What possible causes could there be for a patient’s low plasma LPL activity?

Answer 4

Genetic mutation that affects chylomicrons’ structure or cofactor ApoC-II. No chylomicrons available for lipids to be broken down by the LPL.

Question 5

A blood specimen from a patient with suspected appendicitis has a “creamy” layer at the top of the sample after centrifugation. The child was at a birthday party the day before where they ate a burger, chips and drunk a milkshake.

Why would their plasma cholesterol level be elevated?

Answer 5

Chylomicrons carry dietary TAGs from the SI to peripheral tissues via the blood. Cholesterol is transported in chylomicrons so more chylomicrons means higher plasma cholesterol.

Question 6

A blood specimen from a patient with suspected appendicitis has a “creamy” layer at the top of the sample after centrifugation. The child was at a birthday party the day before where they ate a burger, chips and drunk a milkshake. They have hyperlipidaemia and an electrophoresis of their lipoproteins indicated the presence of large amounts of chylomicrons. Their lipoprotein lipase activity is low.

Should the patient continue with a low-fat diet throughout their life?

Answer 6

It is likely that they have a large amount of chylomicrons and very low LPL activity due to a genetic mutation to the LPL enzyme. As this can’t be changed, they will naturally have a higher plasma cholesterol than normal. Thus, a low-fat diet is advised to compensate for the higher levels.

Question 7

If a patient has hyperlipidaemia, they would be recommended a low-fat diet in order to reduce their plasma lipid levels.

What are the potential problems of a low-fat diet?

Answer 7

Need for lipid-soluble vitamins (ADEK)

Need TAGs for an alternative source for energy

Question 8

37yrs man with hypercholesterolaemia consumed a lot of food derived from animal sources. Fasting plasma cholesterol=8.5mmol/L, plasma glucose & thyroid function = normal.

Why would this patient be prescribed a diet low in animal fat specifically?

Answer 8

Animal fat has more saturated fats so more saturated FA. Saturated FA causes higher blood cholesterol.

Question 9

37yrs man with hypercholesterolaemia consumed a lot of food derived from animal sources. Fasting plasma cholesterol=8.5mmol/L, plasma glucose & thyroid function = normal. After 3 months of lifestyle modifications, his plasma cholesterol decreased to 7.7mmol/L. Family history shows early heart disease so he was treated with atorvastatin.

What does this drug do and why are lifestyle modifications considered to be an important component of treatment in this case?

Answer 9

Atorvastatin prevents cholesterol production by inhibiting HMG-CoA reductase: lowering plasma cholesterol.

With a family history of early heart disease, lifestyle modifications are important in preventing risk factors of developing hypercholesterolaemia related conditions (coronary heart disease).

Question 10

Why does a cholesterol-free diet not necessarily reduce the plasma cholesterol concentration?

Answer 10

There are pathways that will produce cholesterol without consuming higher levels of cholesterol. AcetylCoA (glycolysis) can be converted into cholesterol.

Question 11

What is the significance of high plasma levels of LDL?

Answer 11

These lipoproteins have the longest half-life so they are more likely to be oxidised. Macrophages engulf them and become foam cells. These cells cause atherosclerosis so there is a higher chance of developing coronary heart disease.

Question 12

How does atorvastatin reduce plasma cholesterol concentration?

Answer 12

Atorvastatin (statins) inhibits HMG-CoA reductase so that less acetylCoA can be converted into cholesterol.

Question 13

What are the possible health benefits of a reduction in plasma cholesterol from 8.5 to 55.5mmol/L in a patient with a family history of early heart disease?

Answer 13

Less cholesterol= less LDLs needed to transport cholesterol.
Less LDLs= less chance of oxidisation= less foam cells
Usually, foam cells accumulate into fatty streak
Fatty streak evolves into atherosclerotic plaque causes angina
Plaque rupture= MI or stroke

Question 14

32yrs male sees his GP requesting to check his plasma cholesterol because his father died at 50yrs from a MI. He has a fasting blood sample for a lipid analysis:
Total serum cholesterol=12mmol/L (3.5-6.5mmol/L)
Serum TAGs=1.0mmol/L (0.7-2.0mmol/L)
Serum Lipoprotein profile= more LDL particles

What type of hyperlipoproteinaemia is this patient likely to be suffering from?

Answer 14

Type IIa. High levels of LDL particles in blood probably means LDL receptors are defective.

Question 15

What classes of lipoprotein are present in the serum from a fasting blood sample taken from a normal individual?

Answer 15

VLDL
IDl
LDL
HDL

Not chylomicrons as they are only present up until 4-6hrs after a meal.

Question 16

Lipoproteins can be classed into 5 classifications:
-chylomicrons
-VLDL
-IDL
-VDL
-HDL
What are each of their functions?

Answer 16

Chylomicrons: dietary TAGs from SI–> MSK + adipose
VLDL: TAGs from liver –> adipose (store)
IDL & LDL: Transports cholesterol from liver–> tissues
HDL: transports excess cholesterol from tissues–> liver

Question 17

List all 3 symptoms a patient with hypercholesterolaemia would experience.

Answer 17

Tendon Xanthoma
Corneal arcus
Xanthelasma

Question 18

Other than consuming a high cholesterol diet, outline 2 pathways the body has to produce cholesterol.

Answer 18

1. AcetylCoA –HMG-CoA reductase–> cholesterol

2. AcetylCoA via carbohydrate metabolism.

Question 19

32yrs male sees his GP requesting to check his plasma cholesterol because his father died at 50yrs from a MI. He has a fasting blood sample for a lipid analysis:
Total serum cholesterol=12mmol/L (3.5-6.5mmol/L)
Serum TAGs=1.0mmol/L (0.7-2.0mmol/L)
Serum Lipoprotein profile= more LDL particles

What are 3 treatment options?

Answer 19

Statins (atorvastatin)
Low fat diet (especially in saturated animal fats)
Bile acid sequestrants (acts like dietary fibre) so liver produces more bile salts from cholesterol.

Question 20

58yrs man suffering from angina resulting from oxidised LDL lipoprotein particles leads to developing atherosclerosis in his left anterior descending coronary artery.

By what mechanism is the non-oxidised LDL normally taken up by the liver and peripheral tissues?

Answer 20

Receptor mediated endocytosis

Question 21

Cholesterol and cholesterol esters are transported around the body by lipoprotein particles.

Which class of lipoprotein particle typically contains the greatest proportion of these metabolites?

Answer 21

LDL as their main function is to transport cholesterol from the liver to tissues.

Question 22

A healthy 56yrs man has his total plasma cholesterol measured as part of a free NHS health check.

What plasma concentration of this metabolite is considered normal for a healthy adult?

Answer 22

Less than 5mmol/L for total cholesterol concentration.

Question 23

22yrs woman has premature coronary heart disease, cerebellar ataxia, neurosensory hearing loss and proliferative retinopathy. Further investigations show she has a rare disorder of apoA-1 deficiency.

What process would this deficiency directly inhibit?

Answer 23

HDL synthesis. Deduce this from knowing that HDL plays a part in preventing early heart disease by removing cholesterol from tissues.

Question 24

72yrs man suffers from angina caused by atherosclerotic plaques in his coronary arteries. He has high levels of LDL in his blood. LDL’s longer half-life makes them more susceptible to oxidative damage.

How does oxidative damage to the lipoproteins lead to atherosclerosis?

Answer 24

Macrophages engulf them as they are now harmful. Macrophages become foam cells and they lead to fatty streak formation.
The fatty streaks can evolve into atherosclerotic plaques
which narrow the artery lumen and causes angina.

Question 25

As part of aa routine NHS health check, a 47yrs woman is found to have a plasma HDL level below normal range.
What is the normal function of this type of lipoprotein?

Answer 25

They transport excess cholesterol from tissues to the liver to be converted into bile salts.

Question 26

60yrs man attends his GP surgery for a health check. The GP is pleased to see that his HDL-Cholesterol level is 1.5mmol/L (>1mmol/L).

Why is this test result considered beneficial in reducing the risk of CVD?

Answer 26

HDL are lipoproteins that transport excess cholesterol from tissues to the liver to be converted into bile salts. Having higher HDLs means that less cholesterol needs to be transported by LDLs. This decreases amount of foam cells created from macrophages so less fatty streaks=less atherosclerotic plaques= less risk of CVD.

Question 27

10yrs girl referred to paeds unit due to recurring severe abdominal pain. Total plasma cholesterol= 19mmol/L (<5mmol/L) and further investigations uncover she has familial hypercholesterolaemia due to LDL receptor gene mutation.

Which sign is likely to be observed in this patient as a result of her condition?

Answer 27

Corneal arcus
Tendon Xanthoma
Xathelasma

Question 28

As part of a routine NHS health check, a 56yrs man id found to have a total plasma cholesterol level of 15mM (<5mmol/L). Majority of cholesterol is transported around the body, in lipoprotein particles, in cholesterol ester form.

Which enzyme catalyses the formation of these esters?

Answer 28

LCAT= Lecithin Cholesterol Acyltransferase

Question 29

An 18yrs girl has gained 12kg in weight over past 6 months after eating a tub of ice cream every evening whilst watching TV. The fat in her diet has been transported to her adipose tissue by chylomicrons.

Which enzyme located on the muscle capillary walls and adipose tissue facilitates the release of FA from this type of lipoprotein particle?

Answer 29

Lipoprotein lipase.