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Learning outcomes
at the end of this lecture , students should be able to:
• 1.Discuss the metabolism of cholesterol and
triglyceride and state the reference interval of each for
apparently healthy subjects.
• 2.Compare and contrast the five lipoprotein classes
based on chemical makeup and clinical significance.
• 3.List the hyperlipoproteinemias and state the
laboratory findings associated with each.
• 4.Discuss hyperlipidemia and its relation to atheroma
and coronary artery disease.
• 5.List the hypolipoproteinemias and state the
laboratory findings associated with each.
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phospholipids
cholesterol Triglyceride FFA
3
Triglycerides
4
TAG Levels
Normal less than 150 (mg/dL)
Increase in :
1. Cirrhosis or liver damage
2. Diet low in protein and high in carbohydrates
3. Hypothyroidism
4. Nephrotic syndrome
5. Poorly controlled diabetes
5
TAG Levels cont.
Decrease in :
1. Low fat diet
2. Hyperthyroidism
3. Malabsorption syndrome (conditions in which
the small intestine does not absorb fats well)
4. Malnutrition
6
Cholesterol
• Cholesterol is an extremely important
biological molecule that has roles in
membrane structure as well as being a
precursor for the synthesis of the steroid
hormones, bile acids and vitamin D.
• Cholesterol synthesis occurs in the cytoplasm
and microsomes (ER) from acetyl-CoA
7
Cholesterol level
Normal: less than 5mmol/l
Increased with other diseases such as:
• Reduced metabolism due to thyroid problems
• Kidney diseases
• Diabetes particularly when poorly controlled
• Alcohol abuse
• Overweight – this is probably the commonest
cause of high cholesterol levels.
• Smoking, and high blood pressure.
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Cholesterol level cont.
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Metabolism TAG & Cholesterol
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Lipoproteins
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Lipoproteins
lipoprotein is a biochemical assembly that contains •
both protein and lipids.
Core : •
TG, cholesterol ester. •
Surface: •
Phospholipids, free cholesterol, & •
Apo-proteins
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Type Source density Size Function
Transport of dietary TAG
CM Intestine (mainly), cholesterol &
cholesterol esters from the
lowest largest
intestine to the tissues.
• Serum Triglycerides
• Total Cholesterol < 150 → normal
– < 200 → normale 200-499 → High
– 200-239 → Borderline ≥ 500 → Very High
– ≥240 → High
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Laboratory Testing
Electrophoresis :
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ultracentrifugation:
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Metabolism Of Chylomicrons
1- Chylomicrons synthesized in intestine as nascent
chylomicrons. Main components TAG.
2- Take from HDL (apoCII & apoE) to become
mature chylomicrons.
3- In blood vessels, apoCII activate lipoprotein lipase to
hydrolyze TG to FFA go to tissues & glycerol.
4- Chylomicrons become smaller in size and known as
by chylomicron remnants
5- apoE make receptors of liver identifies chylomicron
remnants to be taken up & metabolized to its
comonents.
Metabolism of chylomicrons
Metabolism of VLDL
Synthesized in liver
Nacsnt VLDL (TAG, apo B100) in live
Take from HDL ( apoCII, apo2424E , chlestrol ester).
Mature VLDL (apoCII, apoE, cholesterol ester) in blood
vessels.
In capillaries, apoCII activates lipoprotein lipase to
metabolyze TG to FFA go to tissue & glycerol.
VLDL remnants, (apo B100 ,cholesterol ester) will make
LDL and other part go to liver by apoB100 for compleet
metabolism.
Metabolism of VLDL
LDL Metabolism
LDL is removed by
apoB100 receptors
which are mainly
expressed in the liver
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Metabolism of HDL
Lipoprotein
HDL is secreted in a discoidal
form from the liver and gut.
Cholesterol and
Atherosclerosis, Grundy)
Metabolism of HDL (cont.)
• Excess cholesterol is changed to CE by LCAT and
is taken up by HDL3 that is increased in size to
form HDL2.
• HDL2 carries these CE to the liver.
• The cycle is completed by the re-formation
of HDL3, either after selective delivery of
cholesteryl ester to the liver or by hydrolysis
of HDL2 to phospholipids and TG by hepatic
lipase.
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Metabolism of HDL (cont.)
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Metabolism of HDL
Checking lipids
• Nonfasting lipid panel
• measures HDL and total cholesterol
• Fasting lipid panel
• Measures HDL, total cholesterol and TG.
• LDL cholesterol is calculated: LDL cholesterol =
total cholesterol – (HDL + triglycerides/5)
Dyslipoproteinemias
Definition:
Hyperlipoproteinemias: Presence of raised levels of lipids and/or
lipoproteins in the blood.
Hypolipoproteinemias: Presence of decreased levels of lipids
and/or lipoproteins in the blood.
Common Causes may be:
• Genetic or
• Acquired or secondary.
1-Hyperlipoproteinemias
• Classified according to the “Fredrickson
Classification”.
• Based on the pattern of lipoproteins on
electrophoresis or ultracentrifugation into 5
types
Hyperlipoproteinemia Type I
• has a pure elevation of TAG in chylomicrons.
• exists in two forms:
• Type IA(Familial LPL deficiency)
due to deficiency or abnormal form of LPL
• Type Ib (Familial apoCII deficiency)
• Character:
Increase serum TAG, due to slow clearance of chylomicrons
& VLDL.
Low level of LDL & HDL.
Increase serum Chylomicrons.
No increased risk of coronary heart disease
• Serum appearance: creamy top layer.
Hyperlipoproteinemia type II
It is the most common. Autosomal dominant defect.
.
Hyperlipoproteinemia type II
• Diabetes mellitus.
• Use of drugs such as diuretics, beta blockers and
estrogens.
• Hypothyroidism.
• Renal failure.
• Nephrotic syndrome.
• Alcohol.
• Some rare endocrine disorders and metabolic
disorders.
Hypolipoproteinemias
• Definition: a lack of lipoprotein in the blood
due to genetic or other diseases.
.
Relationship Between Hyperlipidemia & Coronary
Heart Disease
Relationship:
• The higher the levels of blood LDLs, the higher
the risk for coronary heart disease.
• Conversely, the higher the levels of blood HDLs
in, the lower the risk for coronary heart
disease.
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Hyperlipdemia and Atheroma
Definition:
Atheroma is an accumulation of inflammatory cells
(like macrophages), cholesterol, and other lipids in
the inner wall of arteries.
An atheroma can grow to the point where it
narrows or completely occludes a vessel.
This can restrict blood, O2, and other nutrients
needed by tissues and organs of the body to
perform important functions in the body.
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Hyperlipidemia Must be
Remembered as a Controllable
Cause of Coronary Heart Disease,
Especially in The Young