Now this figure shows the movement of cholesterol
in the body and it's a little complicated but
I think that you will see some general themes.
Let's consider dietary cholesterol
first. Starting on the right
dietary lipids come into
your digestive system.
This include fats, includes fats soluble vitamins;
it includes cholesterol and related compounds.
These pass through the intestinal
wall into the lymph system actually
where they are packaged up into chylomicrons.
So these very insoluble substances
that I just described
are packaged almost immediately upon
leaving the digestive system.
The chylomicrons are the biggest, fluffiest complexes
that are lipoprotein complexes that
ultimately make into the blood stream.
So these complexes contain the very water
insoluble compounds the fats, the
fat soluble vitamins and the cholesterol.
And chylomicron's job is to get them into
the blood stream where they travel.
And they then go through the blood
stream and hit the tissues.
When the chylomicrons hit the tissues
something happens. Now, you might think that the chylomicrons
they are really big. They are actually the biggest
complexes involved in carrying these things.
You might thing these are associated
with atherosclerosis, they are not.
So these guys are traveling in the blood
stream and they hit the capillaries
where they get stuck; because, they are so big.
And what happens with the capillaries is that
the capillaries have enzymes that literally
peel the inside of the material in the
chylomicron away and eat those nutrients.
So the cells will be taking fat, they will be taking
fat soluble vitamins out of the chylomicrons.
They don't take cholesterol out, by the way,
and the chylomicrons will shrink creating
what are called chylomicron remnants.
Now every thing that you see in green on the
screen is happening in the blood stream.
The chylomicron remnants are at the capillaries
and they become small enough that they
can pass through the capillary.
And when that happens they
travel back to the liver.
And the liver has a receptor that grabs the chylomicron
remnants and it takes all the stuff inside of them
and all that stuff inside of them it has
to package and put it away somewhere.
That includes the fat, a fat
soluble vitamins and the cholesterol.
Well you can see that we start overloading the liver with
some of this stuff and we might have some problems.
And that's why dietary considerations are
important in monitoring cholesterol levels.
Cholesterol and fat, however, are needed by the body
and we have seen in other lectures
how the liver plays a role in
maintaining glucose levels that
are reasonably constant level.
The liver is also involved in maintaining fat
and hopefully cholesterol levels in the same way.
Now this happens through a sensing mechanism
that the liver uses. That is a little complicated.
So let me tell you how this works.
When the liver senses that there is a need in the body
for some of the materials I have just described
it says "Okay, I am gonna package these up".
And it packages it up in the
form of what are called VLDLs.
So the VLDLs released by the liver contain
the fats, the fatty acids and cholesterol.
And what the VLDLs is do they go
back out into the blood stream
where a similar process happen like with
a chylomicrons. The cells grab them
and start taking this away.
Well the VLDLs become the IDLs known as
the intermediate density lipoproteins.
And again cholesterol hasn't been taken out of them.
So the goodies are being taken away.
The lipoprotein complexes are shrinking which is why they
are going from very low density to intermediate density.
And the intermediate density go to the low
density lipoprotein complexes or the LDLs.
Now the LDLs have the highest
concentration of cholesterol.
And the LDLs also are the
most likely to be oxidized
by reactive oxygen species that
are present in the blood stream.
Now reactive oxygen species are the problem.
They are problem; because, they react
without the control of enzymes.
And when you have reactions that are out of
control, unpredictable things can happen.
Well one of the unpredictable things
that can happen is the LDL
can actually get damaged and become
attached to part of an artery.
When that happens the immune system can recognize
that damage LDL as a problem and attack it.
And then more of the immune system can attack it and this
attack can continue and we can create a process what's known
as a foam cell; because, it
looks big and foamy.
Well this can involve the
binding of other LDLs;
because, the immune system is now recognizing all
these LDLs of this complex and this can be the
start of the formation of
an atherosclerotic plaque.
So it's not the cholesterol per se
that's causing the problem.
The cholesterol is more of an indicator of the
problem associated with the LDLs. But nonetheless
the accumulation of LDLs causes this problem.
So the higher a person's LDL level is,
the more likely they are to form atherosclerotic plaque.
They might wonder about the reactive oxygen species.
Where do they come? Well they come from
some normal cellular processes which we can't control.
But there are some things that we can control
that produce the reactive oxygen species.
One of those is smoking cigarettes.
Smoking cigarettes will increase levels
of reactive oxygen species. And increasing
levels of reactive oxygen species
has very detrimental effects on health.
Now we have gotten to the
LDLs and most LDLs of course
don't get oxidize. They actually
make it back to the liver
and this is how the liver
actually does the sensing.
So liver has on its surface, receptors.
And the liver tries to monitor what the
level of concentration of LDLs actually is.
And if the liver senses
that the LDL level is too low,
then the liver knows that the things it has
been sending out need to be increased.
So if it senses too low of a level of LDL
it says "Okay let's put out more VLDLs; because,
everything I am putting out is being eaten."
In the ideal world if the LDL level is high
the liver says "Okay don't put out so much"
and then the LDL level drops
accordingly. So we could see how this system sort of
helps to control itself if it's working properly.
If there are disruptions to the way that
the LDL signal is being perceived
then there can be some pretty significant
problems. Familiar hypercholesterolemia
occurs when a person has
a defective LDL receptor.
Then the liver doesn't get any signal
for example that their LDL level isn't coming
back at all. So the liver as far as it concerned,
"Everything I am putting out is not
coming back. Put out more! Put out more!"
So people who have this genetic disease
tend to have very extremely high levels
of cholesterol and many of them
die before they become teenagers. So
pretty serious consequences associated
with cholesterol metabolism.
Okay, so as I have said, the liver plays a
very important role in modulating lipid levels.
It has limitations of capacity.
So, if you overload the liver
the liver is gonna have a hard time maintaining this and
this is why maintaining and monitoring diet is important.
So the one lipoprotein complex I haven't talked about
it are the HDLs or the high density lipoproteins.
Now the high density lipoproteins interestingly
are what people called the good cholesterol.
So the good cholesterol is involved in
scavenging damage. It's involved in
scavenging cholesterol and things
that haven gotten deposited
along the way that really shouldn't have been
deposited where they were deposited.
Your doctor, if you go to your doctor and check
your cholesterol levels, if your HDL levels are high
your doctor will be happy; because, that means that
a lot of the garbage is being taken care of and
been taken back to the liver
where it needs to be.
So the yin and the yang of cholesterol are LDL is bad,
HDL is good; although, that's quite a simplification.