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Title

Month 3 Week 3 Clin Med Lipid Disorders T3

Description

Month 3 Week 3 Clin Med Lipid Disorders T3

Total Cards

Subject

Medical

Level

Graduate

Created

11/12/2018

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Term

Epidemiology of lipid disorders

Definition

• Research over the past 4 decades has consistently shown the burden of dyslipidemia to be very high in terms of morbidity, mortality, and medical costs.
• Dyslipidemia is an important major risk factor for coronary heart disease (CHD), which is the leading cause of death in the United States.
• The World Health Organization estimates that dyslipidemia is associated with more than half of global cases of ischemic heart disease and more than 4 million deaths per year.
• American Heart Association estimates that more than 100 million Americans–one third of all Americans–have total cholesterol levels in excess of 200 mg/dL, which is considered a moderately high level
• 34 million adult Americans have levels greater than 240 mg/dL, which is considered a high level necessitating treatment.
• Most (80%) lipid disorders are related to diet and lifestyle.
• Familial disorders (20%) are important as well.

Term

The five major lipoproteins

Definition

chylomicrons, very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein, high density lipoprotein

Term

Chylomicrons

Definition

very large particles that carry dietary lipid. They are associated with a variety of apolipoproteins, including A-I, A-II, A-IV, B- 48, C-I, C-II, C-III, and E

Term

Very low density lipoprotein

Definition

particles carry endogenous triglycerides and to a lesser degree cholesterol. The major apolipoproteins associated with VLDL are B-100, C-I, C-II, C-III, and E

Term

Intermediate density lipoprotein (IDL)

Definition

particles carry cholesterol esters and triglycerides. It is associated with apolipoproteins B-100, C-III, and E

Term

High density lipoprotein (HDL)

Definition

particles carry cholesterol esters. These particles are associated with apolipoproteins (apo) A-I, A-II, C-I, C-II, C-III, D, and E

Term

Lipid Metabolism

Definition

• Chylomicrons are processed by lipoprotein lipase (LPL), which is activated by apoC-II, and release free fatty acids to be absorbed by muscle and fat.
• Remaining chylomicron remnant is removed from the circulation by the liver.
• Requires apoE as ligand for receptors within the liver.
• Chylomicrons and chylomicron remnants should be largely absent from the blood after a 12-hour fast.
• Except in patients with derangements in chylomicron metabolism.

Term

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Definition

So these are the two important pathways that I'm going to discuss for the lipid metabolism. So you have the exogenous pathway. And then, later on, in my slides, I'm going to talk about the endogenous pathway.

So as you see, this exogenous pathway, the reason it's called as exogenous is because it takes place in the gut, which is in the intestines. Whereas when you talk about the endogenous pathway, it primarily takes place in the liver.

So in regards for this exogenous pathway, what happens is that when any person ingests any fatty meal, it's going to be broken down by the lipoprotein lipase. And as a result, the free fatty acids are going to be released. The free fatty acids are going to be converted into triglycerides and the cholesterol esters. And they'll be packaged into this chylomicron.

Now it's important for the functionality of this chylomicron that it should carry these apoproteins on the surface. So you have apo B-48. You have an apo A on here. You have an apo C-II, apo C-III, and then you have the apo E.

Now what happens is that this chylomicron particle is going to be acted upon by the lipoprotein lipase. Now for the lipoprotein lipase activation, this apo C plays the major role. So what this lipoprotein lipase does is that it breaks this chylomicron. And it releases the free fatty acids. It releases the apo A. It releases the apo C-II and C-III. And all you're left with is basically a chylomicron remnant.

Now this chylomicron remnant, in order to be removed from the circulation, it needs to be taken out by the liver. And for it to be taken out by the liver, it needs assistance of the apo E. The easiest way to remember these apo proteins would be the apo E, "E" for elimination. That means that for this chylomicron remnant to be removed from the system, it needs apo E. So it needs to be eliminated with the help of apo E.

So going to our next diagram, we're going to talk about the endogenous pathway. So when we say the "endogenous pathway," we're basically signifying that we we'll be talking about the lipid metabolism that happens within the liver.

So what happens in the liver? So in the liver, there is formation of the nascent VLDL. So the term "nascent" by itself means that it's still premature. It needs to be matured. So this nascent VLDL is going to carry an apo B-100, and it's going to carry the apo E.

So what happens here is that the nascent VLDL is going to get the cholesterol esters. It's going to get the apo A, the apo C-II, the C-III, and E. And this it's going to get from the catabolism of the HDL particle, which is basically a separate pathway, which we are not going to discuss too much in detail. But I do want to highlight here that this is from where these apoproteins come. And as a result, what happens is the nascent VLDL then gets converted into a mature VLDL.

Now this mature VLDL, as you see, carry on its surface an apo C-III. Now as we discussed before, the apo C is important for the activation of the lipoprotein lipase as in the endogenous pathway. So what happens is that the apo C is going to activate this lipoprotein lipase. And what this lipoprotein lipase is going to do is that it's going to act on this mature VLDL. And it's going to release all this, the phospholipids, the fatty acids, the apo E, the apo C. And all these are going to help in the formation of the HDL particle.

And what you are going to be left with is basically a VLDL remnant. Another name for a VLDL remnant is the IDL that we discussed within the lipoprotein section itself. And for this VLDL remnant to be taken out back into circulation, it needs the apo E. As I mentioned before, "E" for elimination. So it needs apo E to be removed from circulation. And apart from that, what happens is that this VLDL remnant could be acted upon by the hepatic lipase and could then be converted into LDL

Term