What are those modifiable risk factors?
Smoking. Try to prevent your patient from smoking or if the patient already started smoking,
to quit the smoking whatever the cessation methodologies might be.
Hypertension, Hyperlipidemia, Diabetes, Metabolic syndrome.
Now, what type of lipidemia? We're gonna go in to further detail
because it's important for you to understand the biochemistry of -- well, maybe, just maybe,
it might be a part of what's known as your hyperlipidemia with acquired,
meaning to say that you're trying to lose weight and you're eating too much.
Or, the fact that you might have genetic issues in which you have no control but you have to be careful.
And so these are things that you need to make sure that you explain to your patient
so that they know how to deal with their particular issue.
So to begin at the top, and here, I want you to understand this to, what's going on in this schematic,
so that you can clearly see as to what is the normal pathophys and biochemistry
of the lipid that we're going to consume,
from our mouth, and it's making a way, all way over to the liver. Okay?
So, here, let's say that you just had a fatty meal, you just had a bratwurst,
you just had a burger from McDonald’s.
So that means that the fatty meal -- I made a stereotype, but there you have it.
So now you just ate a fatty meal.
For effective digestion, as far as your licensing boards are concerned. What would you wanna know?
Sure, you have a little bit of lipase in your mouth. I'm not arguing that.
But in terms of effective digestion of your muscle,
or excuse me, why would you wanna eat your muscle? Fat. Well, would it be in the mouth?
Effective digestion maybe perhaps in the stomach,
well, once again it's going to assist with fat digestion there as well.
You have acids, might then break apart your meats and such if you're consuming them.
But in terms of effective digestion of your lipid, it begins in the duodenum.
Is that clear? Really?
Remember, if I ask you this question which is, this patient has a right upper quadrant pain postprandial,
every time this patient has a meal there's going to be right upper quadrant pain.
What is happening with this patient?
What is the name of the hormone and name of the cell that's responsible for causing this pain after eating a fatty meal?
It's the fact that you're working upon your I-cell, and the I-cell is going to release what, please?
Your CCK. Could that be a question? Sure it can. It can be from phys or could be from path.
But what does that mean to you? What's causing this right upper quadrant pain after eating a fatty meal?
It's the fact that the I-cell releasing cholecystokinin works on the gall bladder which is the pathology.
It might be cholecystitis, isn't it? And the gall bladder contains what? It contains bile.
Why do you require that bile? Now, we get into the effective, effective, effective lipid digestion.
So we have this bile which is then being housed in your gall bladder
which makes its way to the second part of the duodenum. Are you there? Are you with me? Good.
And you see this enterocyte, and so, therefore,
that bile coming into the second part of the duodenum is going to surround the triglycerides.
And when you surround your triglycerides with bile, what does it called?
You call this a myocele. You call this a chylomicron. What do you call this?
You call this a myocele, don't you? So myocele has been formed with emulsification process.
What it's gonna do? It does exactly that. It emulsifies the triglycerides
because a triglyceride can -- can you see those finger-like projections?
Those finger-like projections are the brush border of your duodenum, shall we say.
So you see where it says free fatty acids and glycerol.
That would be the lumen of the duodenum. Are you with me?
And this is now become emulsified with the help of bile.
Then you're going to create these free fatty acids, FFA,
which is then going to make its way through the brush border into the enterocyte. Stop there for a second.
So earlier, with that question that I was trying to post you in terms of,
what was it that caused the pain postprandial? Well, it was the fact that cholecystitis was then aggravated by the hormone
which is being released by the lipid which was making its way down into the duodenum. Clear?
What was the cell that released the CCK? It's called an I-cell, isn't it?
Good. So now, the bile is emulsified, let's get back to normal here, and continue through the biochemical process.
So we're now inside my enterocyte and we're going to now recreate that triglyceride.
We are gonna reesterify, is what it's called. We re-esterified.
Think of this as being, those of you that like X-men, why not?
And there's Nightcrawler. What does he do? He disintegrates. He goes to the wall,
and then he reappears. That's what this is doing. The triglyceride went through the wall.
At first, it became free fatty acid. Amonotype of glycerol, and then it reformed into triglyceride.
Here I am. What are you gonna do with me? You're gonna form a chylomicron, a nascent.
What's nascent mean? Maybe, think neonatal, neonate. It's a nascent chylomicron.
What kind of apolipoprotein, it'd require? You must memorize ApoB-48.
It's imperative that you know that. The ApoB-48 is now formed a chylomicron.
What's a chylomicron have in it? It has what? It has triglycerides. Good.
What are we trying to get to? What's your objective for this entire illustration?
It's the fact that you have lipid that you're consuming from your mouth, making its way to the liver.
Is that clear? Now, you have a chylomicron. What's the number one method?
What's a preferred method of transport of your lipid? It is through your lymphatics.
Do you see lymphatics?
So there it is, and if you're a dork like I am, then you'll notice that after you eat, and if you're to do an ultrasound,
you can actually see these after -- a lipid-rich meal.
A river of chylomicrons running through lymphatics. Absolutely magnificent.
Now, you find this lymphatic and it's going to make its way eventually where?
Into your thoracic duct, empty into the right atrium. Are you there? Good.
And from the right atrium, where are you gonna enter?
You're going to of course enter your blood vessels. This is important, isn't it? Oh, yeah.
Because inside that blood vessel there are a couple of things that I wish to bring to your attention.
So here, you’ll notice that HDO. What's HDO mean to you?
It's called "good cholesterol," isn't it?
So, that good cholesterol is then going to donate its C-II and E to the nascent chylomicron.
What's nascent mean? Neonatal, baby. Think of it that way.
It's naive. It is now -- you have been knighted. What does that mean?
HDO comes over to chylomicron and says, "Son, you have now been knighted.
I am now imparting unto you C-II and E." Now, you have a mature chylomicron.
Still filled with what please? Triglycerides. Where are you? In your blood vessel.
You're literally in your circulation. Now, that we have a mature chylomicron. What is its objective?
To make its way to the liver. Let's continue. Alright now, there's number two.
Number two says CPL. That means capillary lipoprotein lipase.
CPL is capillary lipoprotein lipase.
Eventually, what are we gonna do here? We're gonna put in -- we're gonna plug in these pathologies.
But if you don't understand the normal first, it makes it quite impossible for you to understand
what's going on with the pathology and you're just memorizing and that's not going to really,
it won't be in your best interest.
So the capillary lipoprotein lipase, you pay attention to lipase,
is then going to take the triglyceride from your chylomicron and extract it. Is that clear?
And that triglyceride then, what's known as your fat muscle. But now, what do you have?
You have an empty chylomicron. You see that chylomicron number 3, it's empty.
It has emptiness syndrome. Oh, my babies has left me. What do you mean?
The triglyceride has been removed by whom? Capillary lipoprotein lipase.
This is the second lipase, actually, from biochemistry that comes into play. Second.
What's the first one? In biochemistry, way back where it says free fatty acids,
that was the lumen of the duodenum, you had your first lipase.
You did? Yes, you did. In biochemistry, you referred to or you learned about pancreatic lipase.
Keep that separate from what we're looking at here in pathology
which is capillary lipoprotein lipase, CPL. Is that clear? Make sure that you understand this well.
Repeat me if you need to so that you're clear about which lipase deals with what.
Here's a third lipase that you learn about in biochemistry.
The third lipase only comes into play, half the fat has been stored.
And so that is referred to as known as hormone-sensitive lipase,
and that's something that you and I will be looking at in endocrinology. Let's continue.
So now that we have an empty chylomicron, what do you need
so that you can be taken up by the liver? It's called an E-receptor.
You take a look at that three. So number three is dealing with what's known as the E-receptor.
Now, let's take number one, let's take number two, let's take number three,
and now that you've understand the flow of this illustration,
you can see how clearly you can understand what's going on with your patient and the presentation.
The first one, number one is abetalipoproteinemia in which you literally are not able to form a proper chylomicron
because apolipoprotein B or ApoB-48 is not present, pathology number one.
Pathology number two, it's the fact that you need to have C-II. Where does C-II come from?
I know that we're speaking a different language but you and I, you and I, right now,
we're seeing eye-to-eye, aren't we?
We have to. and we have to speak the same language, and that's where I'm trying to get you right now.
So, you need C-II, pay attention. That C-II is there to stimulate your CPL.
What does CPL stand for? Capillary, not pancreatic, and it's definitely not hormone sensitive.
Is that clear?
At the capillary lipoprotein lipase. That C-II exists to stimulate that CPL.
What if you're deficient of C-II? Your lipoprotein lipase isn't working.
If that isn't working, oh my goodness, we're accumulating in your patient.
Tons of chylomicron. What's chylomicron mean to you in terms of presentation of your patient?
Is it triglycerides or cholesterol? Good. Triglycerides.
Your patient is going to have triglyceride levels out the wazoo.
In other words, it'll be ridiculously elevated. Even 150 is high. 300 is really high.
Thousands is what I'm talking about with triglyceride, not a good thing. Is it clear?
That's pathology number two.
Pathology number three, I would like for you to take that capital E at the E-receptor and you see the horizontal lines,
how many horizontal lines do you see with that capital E? 1, 2, 3. Good.
There are three lines. So, therefore, type III.
We'll talk about this coming up in a table, not to worry.
All I am doing here is introducing concepts here and plugging in relevant pathologies.
So type III, what's known as hyperlipoproteinemia is actually missing your E-receptor.
So guess what. You cannot properly pick up your chylomicron remnant into your liver.
It's called remnant-removal disease, but another name that you wanna know for this is called familial dysbetalipoproteinemia.
Here we go. Pathology 1, 2, and 3, spent a little bit of time here.
Everything that you need to know about these pathologies begins with the understanding the biochem,
the phys, and then eventually, the disease processes.
Now, if that was from the mouth to the liver, what are we gonna do next?
We're gonna take this lipid and we're going to then deliver it to the tissues.
What tissues? Let me ask you something. I want you to picture adrenocortex. Are you there?
Close your eyes. Adrenocortex. What are the layers? G, F, and R.
What are they? Glomerulosa, fasciculata, reticularis. Interesting.
Tell me about that fasciculata. What are you producing with fasciculata?
I do believe it's called cortisol. Good. If it's cortisol that you're producing,
how in the world do you even begin the synthesis of your aldosterone glomerulosa? Cortisol.
Fasciculata. Sex steroids. Reticularis. Fasciculata, reticularis, and glomerulosa on the superficial side.
How do you even begin the process of synthesizing those hormones?
It begins with the process of cholesterol being cholesterol.
Being properly delivered to the tissue. Not triglycerides.
Where does cholesterol like to live? What kind of package does cholesterol like to be in?
It likes to be in LDL. Are we clear about the target?
What you have here in your tissue is going to be -- see where number one is? That number one represents LDL receptors.
Those LDL receptors represent what target tissue that you are referring to?
That target tissue, as an example that I just gave you, was your adrenal cortex.
Now, before we get to that, take a look at the liver.
So, from the liver, we're going to then deliver triglycerides at first into circulation.
We're going to through a number of processes in which the triglycerides
then becomes your cholesterol that is being properly delivered to the tissue. Let's begin.
So from the liver is where we are, and just like we began in the previous discussion,
where we looked at your chylomicron, right? Chylomicron. Where did they come from?
The enterocyte, right?
What did they require for the formation of a chylomicron, it was ApoB-48. Good.
Here, the triglycerides being delivered by -- versus VLDL.
That VLDL is what is going to then transport your triglyceride. Okay
Now, you see where this ApoB100?
How important is that? Ridiculously important ApoB100 is a component that is required for proper VLDL formation.
What does it contain? Triglycerides.
Now, this is at first, a precursor with nascent VLDL. It's young. It's a baby.
What was it that then matured chylomicron ?
Son, you have been knighted. Who knighted that particular baby?
Vessel or package. It was called HDL. Here, you have it here again.
You see where this HDL. HDL is going to then also implant or deliver C-II
and E here as well to VLDL. You form a proper and mature VLDL.
In the meantime, you will see an exchange of what's known as CETP.
All that is part of biochemistry that we do not have time to go through
but it's important that you understand their proper to change between VLDL and HDL.
So, now they we're in -- where am I now? You're in your circulation.
Where did VLDL come from? It came from the liver.
Keep this separate please from your chylomicron that we discussed earlier.
In the meantime, what you also find from the intestine,
it's important for you in biochemistry as well, is some of your long chain fatty acids, your LCAT.
So, all of this is then going to allow you to properly form your HDL, and what you know about HDL?
HDL is a scavenger. Scavenger of what? It's a scavenger of cholesterol. What do we call HDL?
We call HDL, good cholesterol. What is the magic number that you wanna know for HDL?
It's called 50, remember that. Why? Because if your patient has an HDL less than 50,
not a good thing, so you want HDL to be on the higher side because it was scavenged the cholesterols,
specifically premium blood vessels and such.
Let's continue. So now you have VLDL. What does it contain? Triglycerides.
So, let me ask you this question. What did the tissue require for proper synthesis of your cell membrane if a tissue required,
let's say, a production of your cortisol or -- gonads, you needed to produce what?
Testosterone and estrogen.
It was in triglycerides that you were delivering. It's the fact that you're delivering your cholesterol.
So, what you're gonna do now? Now, quickly you're going to then go through intermediates.
So, there now you have capillary lipoprotein lipase, CPL.
You're taking out the triglyceride and you're forming IDL. What does IDL mean to you?
Intermediate density lipoprotein. In this IDL, eventually is going to form your LDL right now for pathology purposes.
We're going to keep things simple.
So at this point, for all effective discussion, we've taken triglycerides from the liver
and delivered to the tissue in the form of LDL.
Now, that LDL receptor, what if it was deficient? Wow, this is not good.
In the previous discussion, we looked at where the E-receptor was deficient. What's that called?
E-receptor. I showed you how many lines? Three horizontal lines.
That was what kind of hyperlipoproteinemia?
1, 2, 3. You need three horizontal lines to form a capital E.
In this case, if you have an LDL receptor deficiency, you all must know that this is a type II hyperlipoproteinemia.
If this is a type II hyperlipoproteinemia another name for this is called,
well, before you even memorize this, which you shouldn't be doing to begin with,
LDL is being accumulated in your circulation. What does LDL contain?
It contains cholesterol and so therefore, if cholesterol is being elevated,
what would you call this when you have LDL receptor deficiency?
There you have it. Number one, familial hypercholesterolemia type II. To repeat, E had three, types III.
Remember the other name for that? It was called familiar dysbetalipoproteinemia.
I don't care how you do this but you must memorize that type E or type III which is the E-receptor deficiency.
It's called familial dysbetalipoproteinemia. Here we have familial hypercholesterolemia.
What was type I? Type I in a previous discussion was the fact that you're missing capillary lipoprotein lipase.
What is your required to stimulate the capillary lipoprotein lipase? C-II.
So if C-II and lipoprotein lipase aren't present, what are you accumulating in your patient? Good.
Tons of chylomicron. What does chylomicron contain? Tons of triglycerides.
So, what might you call? Type I hypertriglyceridemia, is that clear?
Do you see as to how it's important? It's important that you pay attention normal
so that as you plugged in the pathology, all of this is coming to life.
Now, let's take a look at number 2. You see number 2.
Number two, once again the bottom line is this -- there's an accumulation of type IV.
Accumulation of the VLDL. VLDL has 1, 2, 3, 4 letters in it.
Thus, accumulation of VLDL, which also contains triglyceride, will be a type IV hyperlipoproteinemia,
and this may either be primary or secondary hypertriglyceridemia. Is that clear?
And how important is this? Very. The reason to say that is the following, of all this hyperlipoproteinemia,
which one seems to be a little bit more common?
Well, once again, in the United States, what's an epidemic? Obesity is an epidemic. Obesity.
What does that mean to you? Large amounts of lipid. What kind of lipid?
Lots of triglycerides, and it's mostly VLDL that is accumulating.
Later on, in endocrinology, when we talk about diabetes mellitus.
There isn't enough insulin, we'll understand that those patients, who are obese and you have insulin resistance,
that that patient is going to have accumulation of increase of VLDL.
Take a look at this. What type of hyperlipoproteinemia is this? Type IV. Okay.
Not to worry, all of this we're going to repeat over and over again.
At this point, we're just giving you two schematics of which how your patient
and our bodies really handles and manages a lipid that's coming through our entire body
either from the mouth or from the liver to the tissue. Let's continue.