Metabolic syndrome. Now, with hyperlipidemia,
we are going to go into further detail because
it is important for you to understand the
biochemistry of well maybe, just maybe, it might
be part of what is known as your hyperlipidemia
with acquired meaning to say that you are
trying to lose weight and you are 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 the things
that you need to make sure that you explain
to your patient so that they know as how to
deal with their particular issue. So to begin
at the top end here, I want you to understand
as to what is going on in the schematic so
that you can clearly see as to what is the
normal pathophys and biochemistry of the lipid
that we are going to consume from our mouth
and it is making their way all way over to
the liver. Here let us say that you just had
a fatty meal. You just had a broad roast, you just had a burger
from McDonalds. So that means that the fatty meal. So, now
you just ate a fatty meal. For effective digestion
as far as your licensing boards are concerned,
what do you want to know? Sure you have a
little bit of lipase in your mouth. I am not
arguing that, but in terms of effective digestion
of your fat would not be in the mouth. The
effective digestion maybe perhaps in the stomach.
Well, once again it is going to assist with
fat digestion there as well. You have acids might
then break apart your meat and such, if you are
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 is
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 is responsible for causing this pain
after eating a fatty meal? It is the fact
that you are working upon your I-cells. And the I-cells are
going to release what please? Your CCK. Could that be a
question? Sure it can. It can be from physio,
it can be from path. What does that mean to
you? What is causing this right upper quadrant
pain after eating a fatty meal? It is the
fact that the I-cell releasing cholecystokinin
works on a gallbladder, which is the pathology.
Might be cholecystitis, isn't it? And gallbladder
contains what? It contains bile. Why do you
require that bile? Now we get into the effective
lipid digestion. We had this bile, which is
then being housed in your gallbladder, which
makes its way to the second part of the duodenum.
Are you there? Are you with me? Good. And do 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 triglyceride with bile,
which is it called? You call this a micelle.
You call this as a color micron. What do you
call this? You call this as a micelle, don't
you? So micelle has been formed with emulsification
process. What is it going to do? It does exactly that
it emulsifies the triglycerides because the
triglyceride can, you can see those finger-like
projections. Those finger-like projections are
the brush border of your duodenum, shall we
say. You see where's the free fatty acids in glycerol
that would be the lumen of the duodenum. Are you
with me? And this has now become emulsified
with the help of bile. Then you are going
to create this free fatty acids, FFA, which is then
going to make its way through the brush border
into the enterocyte, stop there for a second.
Earlier with the question that I was trying
to post you in terms of what was it that caused
the pain postprandial? It is the fact that
cholecystitis was then aggravated by the hormone,
which is being released by the lipid, which
was making its way down into duodenum. Clear?
What was the cell that released CCK? It's called the
I-cell, isn't it? The bile that is emulsified
get back to normal here and continue through
the biochemical process
So we're now inside my enterocyte, we are going
to now recreate the triglyceride. We are going
to reesterify what is called? When you reesterify,
think of this as being X-men. What does he
do? It disintegrates. He goes through the
wall and then he reappears. That is what
this is doing. The triglyceride went through
the wall. It first became free fatty acid
or monothioglycerol and then it reformed into
triglyceride. Here I am. What are you going to do with me?
You are going to form a chylomicron nascent.
What does nascent mean? Baby, neonatal. It
is nascent chylomicron. What kind of apolipoprotein
do you require? You must memorize apo B-48.
It is imperative that you know that. The apo
B-48 has now formed a chylomicron. What does
a chylomicron have in it? It has triglycerides.
What we are trying to get to? What is your
objective for this entire illustration? It
is a fact that you have lipid that you're consuming
from your mouth making its way to the
liver. Is that clear? So now you have a chylomicron.
What is the number 1 method, what is the preferred
method of transport of every lipid? It is
through your lymphatics. You see lymphatics.
So there it is. If you are doc like I am,
then you will notice that after you eat and
if you were to do ultrasound, you can actually
see after a lipid-rich meal, a river of chylomicrons
running through your lymphatics absolutely
magnificent. You find these lymphatics that
is going to make its way eventually where? Into thoracic
duct, empty into right atrium. Are you there? Good.
And from the right atrium, where are you going to enter?
You are going of course
enter your blood vessels. This is important,
isn't it? Inside the blood vessel, there are
couple of things that I wish to bring to your
attention. Here you will notice that HDL.
What does HDL mean to you? It is 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 nascent means?
Neonatal, baby. Think of in that way.
You have been united. What does
that mean? HDL comes over to chylomicron and
says "Son, you have now been united. I am now
importing onto you C-II and E." And now you
have a mature chylomicron, still filled with
what please? Triglycerides. Where are you? In your
blood vessel. Literally in your circulation.
So now then we have matured chylomicrons what
is the objective? To make its way to the liver.
Let us continue. Alright now, here's number 2.
Number 2 says CPL, that means capillary lipoprotein
lipase. CPL is capillary lipoprotein lipase.
Eventually, what you are going to do here?
We are going to plug in this pathology. But
if we don't understand the normal first, it
makes it quite impossible for you to understand
what is going on with the pathology. You're just
memorizing and 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 the triglycerides what is known
as your fat muscle. But now what do you know?
You have an empty chylomicron. You see the
chylomicron number 3. It is empty. It has emptiness syndrome.
"Oh! my baby 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 they
come into play second. Second. Who is the first one?
In biochemistry way back versus free fatty
acids. Those need lumen of the duodenum. You
had your first lipase. You did, you see it in biochemistry
you referred to or you learned about pancreatic
lipase. Keep that separate from what we are
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 are clear about
which lipase deals with what. There is the
third lipase, which you learned about in biochemistry.
The third lipase only comes into play after
the fat has been stored. And so that it is referred
to what's known as hormone-sensitive lipase and that is
something that you and I will be looking at
in endocrinology. Let us continue. So now that
we have an empty chylomicron, what you need
so that you can be taken up by the liver?
It is called an E-receptor. You take a look
at that 3. So number 3 is dealing with what is known as
the E-receptor. Now let us take number 1, let us
take number 2, let us take number 3. And now that you have
understand the flow of this illustration,
you can see how clearly you can understand
what is going on with your patient and the
The first one, number 1 is abetalipoproteinemia
in which you literally are not able to form
a proper chylomicron because apolipoprotein
B or apo B-48 is not present, pathology number 1.
Pathology number 2, it is the fact that you need
to have C-II. Where does the C-II come from?
I know that we speak in different language,
but you and I right now, we are seeing
eye-to-eye only. We have to and we have to
speak the same language and that is where
I am trying to get you right now. So you need
C-II, pay attention. That C-II is there to
stimulate your CPL. What CPL stand for?
Capillary not pancreatic and it is definitely not
hormone sensitive. Is that clear? The capillary
lipoprotein lipase. If that C-II exists to
stimulate that CPL. What if there's deficient
of C-II? The lipoprotein lipase isn’t working.
If that is not working, oh! my goodness, we
are accumulating in your patient, tons of
chylomicron. What does chylomicron mean to
you in terms of presentation of your patient?
Is that triglycerides or cholesterol? Good. Triglycerides.
So your patient is going to have triglyceride
levels, it will be ridiculously elevated.
Even 150 is high, 300 is really high, 1000s
is what I am talking about, triglyceride, not
a good thing. Is that clear? That is pathology
number 2. Pathology number 3, I would like for you to take
that E-receptor and you see the horizontal
line. How many horizontal lines you see with
that E? One, two, three good. So there are
three lines. Therefore, type III. We talk
about this coming up on a table, not to worry,
all I am doing here is introducing concepts
here and pluging in relevant pathologies. So
type III, what's known as hyperlipoproteinemia,
is actually missing your E-receptor. So guess
what, you cannot properly take up your chylomicron
remnant into your liver. It is called remnant
removal disease but another name that you want to know
for this is called familial dysbetalipoproteinemia.
Here were go. Pathology 1, 2, and 3, spend
a little bit of time here everything that
you need to know about these pathologies begins
with understanding the biochem, the phys and
then eventually the disease processes.
Now if that was from the mouth to the liver,
what are we going to do next? We are going
to take this lipid and we are going to then
deliver to the tissues. What tissues? May I ask you something?
Could you picture adrenal cortex, close your
eyes. Adrenal cortex, what are the layers?
G, F, and R. What are they? Glomerulosa, fasciculata,
reticularis, interesting. Tell me about the
fasciculata. What is producing fasciculata?
I do believe it is called cortisol. Good.
If it is cortisol that you are 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,
meaning properly delivered to the tissue,
not triglycerides. What is cholesterol like
to live? What kind of package does cholesterol
like to be in? It likes to be in LDL. Are
you clear about the target? What you have
here in your tissue is going to, we see what number 1 is.
That number 1 represents LDL receptors. Those LDL receptors represent
what target tissue that you are referring
to? 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.
From the liver, we are going to then deliver,
triglycerdies at first into circulation. We
are going to go through a number of processes
in which that triglycerides then becomes your
cholesterol that is being properly delivered
to the tissue. Let us begin. From the liver
is where we are and just like we began in the
previous discussion where we looked at your
chylomicron, where do they
come from? The enterocyte right? What did
you require for formation of your chylomicron?
It was apo B-48. Good. Here the triglyceride
is being delivered by TC versus VLDL. That
VLDL is what is going to then transport your
triglyceride. TC versus apo B-100 how important
is that? Ridiculously important. Apo B-100
is a component that is required for proper
VLDL formation. What does it contain? Triglycerides.
This is, at first, a precursor, a nascent VLDL.
It is young. It is a baby. What was it that
then matured chylomicron? Son, you have been
united. Who united that particular baby vessel
or package? It was called HDL. You have it
here again. TC versus HDL. HDL is going to
then also implant or deliver C-II and E here
as well to VLDL to form a proper immature
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 is important that you understand
the proper exchange between VLDL and HDL.
Where am I now? Your inner circulation. Where
do 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 is
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
is a scavenger of cholesterol. What do we
call HDL? We call HDL good cholesterol. What
is the magic number that you want to know
for HDL? It is 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 will scavenge the cholesterol
specifically in the blood vessels and such. Let's continue.
Now that we have VLDL what does it contain?
Triglycerides. So I will ask you this question.
What does the tissue require for proper synthesis
of your cell membrane if a tissue required
let us say production of your cortisol or if it's done in your
gonads, you needed to produce what? Testosterone,
estrogen. It was not triglycerides that you
were delivering. It is the fact that you are
delivering your cholesterol. What are you going
to do now? Quickly we are going to go through
intermediates. So there are not enough capillary
lipoprotein lipase, CPL. You taking the triglyceride
and you are forming IDL. What does IDL mean
to you? Intermediate density lipoprotein. And this
IDL eventually is going to form your LDL right
now for pathology purposes, we are going to
keep things simple. At this point for all
effective discussion, we have taken triglycerides
from the liver and delivered to the tissue
in the form of LDL. Now that LDL receptor,
what if it is deficient? This is not good.
In the previous discussion, we looked at where
the E-receptor was deficient. What is that
called? E-receptor. I showed you how many lines?
Three horizontal lines that were a kind of
hypolipoproteinemia 1, 2, 3, and you have 3 horizontal
lines to form an E. In this case if you have
an LDL receptor deficiency, you all must know
that this is a type II hypolipoproteinemia.
If this is a type II hypolipoproteinemia, another
name for this is called, well before you even
memorize this which you should be doing to begin
with, LDL is being accumulated in your circulation.
What does LDL contain? It contains cholesterol.
So, therefore, if cholesterol is being elevated,
what do you call this when you have LDL receptor
deficiency? Here you have, number 1, familial hypercholesterolemia
type II. To repeat E at three, type III, you remember
the other name for that. It was called familial
dysbetalipoproteinemia. I don't care how
you do this, but you must memorize the type
E or of type III, which is the E receptor
deficiency. It is called familial dysbetalipoprotenemia.
Here we have familial hypercholesterolemia.
What was type I? Type I in the previous
discussion was the fact that you are missing
capillary lipoprotein lipase. What did you
require to stimulate the capillary lipoprotein
lipase? C-II. So if C-II in lipoprotein lipase
aren't present, what would be 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? You see how it is important
that you pay attention normal so that as you
plug in the pathology all of these has come
to life. Let us take a look at number 2. Once again
bottom line is this, there was accumulation
of type IV, accumulation of VLDL. VLDL has
one, two, three, four 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 I say
that is the following. Of all these hyperlipoproteinemias,
which one seems to be a little bit more common?
Once again in the United States, what is
an epidemic? Obesity is an epidemic. What
does that mean to you? Large amounts of lipids.
What kind of lipid? Most are triglycerides
and its mostly VLDL that is accumulating.
Later on, in endocrinology, when we talk about
diabetes mellitus and if there was enough insulin,
we will understand that those patients who are
obese and you have insulin resistance that
that patient is going to have accumulation
of increased VLDL. Take a look of this. What
type of hyperlipoproteinemia is this? Type IV.
Not to worry. All of this we are going
to repeat over and over again. At this point,
we are just giving you two schematics of which,
how your patient and our bodies really handles
and manages the lipid that is coming through
our entire body either from the mouth or from
the liver to the tissue. Let us continue.
Now to summarize everything we just talked