Voiceover: Okay, so here we have
a blood vessel and it's been injured.
So right now I want to do an overview of hemostasis first.
We want to make sure when an blood vessel's been injured,
that the blood that's flowing through that blood vessel
continues to flow through the blood vessel, and
we try to minimize as much as possible, the amount of blood
that leaks out of the blood vessel at that site of an injury.
And the way we do that is through hemostasis.
And the first part of hemostasis
is making that platelet plug.
And this happens during primary hemostasis.
But it's still kind of weak, so we need to make it stronger.
And the way we make it stronger
is through secondary hemostasis.
And what we do is we get this protein called fibrin.
And we link it up together and we create
this fibrin mesh over the platelet plug.
And this fibrin mesh over the
platelet plug is what we call a clot.
Now, what were to happen if hemostasis were
to continue and nothing were to stop it?
So we'd just get clot after clot after clot after clot.
So you can see that that's a problem.
Now the blood that should be flowing through
is getting backed up behind this clot and
not getting to where it needs to go.
So even though hemostasis is good, if we have
too much clotting, then that can be bad.
So our bodies need a way to make
sure we don't get many clots.
So let me get rid of these clots.
And the way that our bodies do this is through
two processes, called anticoagulation, and thrombolysis.
Anticoagulation is the process that
prevents any clots from forming.
And thrombolysis is the process that
breaks down clots after they've been formed.
And these two processes are what I'm gonna focus on today.
And this tug-of-war between two competing
processes happens a lot in our body.
Our bodies like to maintain a certain equilibrium.
A middle ground, a set point, we have a normal.
On a day to day basis, our bodies
need ways to get back to normal.
Let's take body temperature, for example.
Our bodies like to stay at 98.6 degrees Fahrenheit,
which is about 37 degrees Celsius.
So that's normal, that's where we like to be at.
Of course it's a range, so it can be a little bit higher,
a little bit lower, but nothing too drastic.
But sometimes we can get lower
than that and we can be too cold.
Say it's snowing outside and you don't have a sweater.
And so what our bodies do in order to get our
temperature back up, is we shiver.
Our muscles create heat to get our bodies
back up to the temperature that we like.
Or sometimes our bodies can get too hot.
Say we have a fever, or sick, or
or maybe we're running on a hot day.
And what our bodies do in order to cool ourselves off
and get our temperature back down, is we start sweating.
And that cools us off, and that lets off the extra heat
that we have in our body, and that gets us back to normal.
So let me erase this now.
And let me show you how this is similar to
what's going on in our blood vessels.
So our sub-point, our middle
ground, let's say good blood flow.
And this is important because if we have good blood flow,
then all our tissues are getting what they need.
They're getting oxygen and nutrients
that's carried in our blood.
But sometimes we can have some injury to that blood vessel,
and then we'll start bleeding.
And that goes away from what we
want, which is good blood flow.
And so what we do in response to that to get us back
to having good blood flow, is we go through hemostasis.
And that allows us to make a clot, stop the
bleeding at that injured blood vessel, and
get us back to having good blood flow.
But if we have too much hemostasis or any other
process that causes us to clot, we have too much clotting,
then as we saw before, the clots can block
the blood flow going through that blood vessel.
So the way that we take care of that is
through anticoagulation and thrombolysis.
And with anticoagulation and thrombolysis, we'll
break down any clot and prevent more clots from happening,
and make sure that we have good
blood flow in our blood vessel.
So this is the balance between hemostasis
and anticoagulation and thrombolysis.
Let's go over exactly what our bodies do in order to
prevent any clots or break down clots.
So let's talk about anticoagulation first.
In anticoagulation we want to
prevent any clots from forming.
So we want to prevent hemostasis.
And in hemostasis we can prevent the platelet plug,
or we can prevent making the fibrin mesh.
So let's talk about making the platelet plug first,
and how we prevent primary hemostasis.
So here we have our platelets that
are floating around in our blood.
So we want to make sure we prevent clots from happening.
There's no injured endothelial cells, so we don't need
hemostasis to happen, we don't need platelets to get there.
So our healthy endothelial cells will secrete two molecules.
They both do the same thing.
The first thing that they do is that they do
prevent platelets from getting to the
endothelial cells, from sticking to them.
So they kind of block the platelets from getting close.
And the other thing that they do is they act
on the smooth muscle cells of the blood
vessel, and they cause vasodilation.
And that's important because we want to make sure
that our blood vessels stay open and
blood is able to flow through smoothly.
These two molecules are called, one of them is
called prostacyclin, and this is a peptide.
And the other one is a chemical called nitric oxide.
So now let's talk about secondary
hemostasis and how we prevent that.
In secondary hemostasis, let me scroll over, we make
the fibrin mesh to make that platelet plug stronger.
Which again, in this case we don't need because there's
no injury, and so we don't need to make the clot.
And the way we make that fibrin mesh is
we activate the coagulation cascade.
So here we have our clotting
factors, the family of proteins.
And ultimately when we activate the coagulation cascade,
what we'll end up with is getting thrombin.
The fibrin linking up on top of the platelet
plug is what creates that fibrin mesh and
makes the platelet plug stronger.
So the way that our bodies, our blood vessels
prevent secondary hemostasis is through two different
molecules so that endothelial cells,
the same cells that are lining the inner wall of the
blood vessels, and these are the same cells that are making
prostacyclin and nitric oxide, what we just talked about.
It makes two molecules.
One of them is called heparin-like molecule.
And this molecule is on the surface of the endothelial cell,
communicating with the blood.
And what this molecule does is, it interacts with
another protein that's already floating around in our blood.
This protein is called anti-thrombin III.
So you can see, in hemostasis we have
thrombin and we want to make a clot.
And now in anticoagulation, we have
anti-thrombin III, and we want to prevent a clot.
So what will happen is anti-thrombin III
will interact with this heparin-like molecule.
And when anti-thrombin III interacts with
heparin-like molecule, what it'll
do is it'll inactivate thrombin.
So it'll prevent thrombin from making fibrin
from fibrinogen, and it will also inactivate
a coagulation factor, coagulation factor X.
And the second molecule that our endothelial cells
have on the surface of their cells that's communicating with
the blood, is a protein called thrombomodulin.
"Thrombo," again, means clot, and "modulin" is modulate.
So, to change or alter.
So we said thrombin is what gets fibrin from fibrinogen.
But what thrombomodulin will do is if there's thrombin
floating around in our blood and we want to make sure that
we don't clot too much, is it'll get thrombin and
it'll change what thrombin actually
normally does, which is make a clot.
So that it is actually working in anticoagulation.
But it's not just thrombin and thrombomodulin
that works in anticoagulation.
When we have thrombin and thrombomodulin
working together and interacting with each other, then now
protein C, with the help of protein S will get activated.
And once it's activated, It'll interact with
the thrombin/thrombomodulin complex.
Those three things help with anticoagulation.
The way that it helps with anticoagulation is that it
inactivates two specific coagulation factors.
Coagulation factor V, and inhibits coagulation factor VIII.
So now that we've covered anticoagulation,
let's talk a little more now about thrombolysis.
So like I said in thrombolysis we're
breaking down the clot that we already made.
So the way that we're able to break down that clot
is with this protein called plasmin.
I like to think of it as, like a little shark
floating around waiting to break down those clots.
So I'm gonna draw it like this, like a little saw.
And this protein is called plasmin.
And what plasmin will do is it will
break down fibrin and fibrinogen.
But plasmin isn't floating around in our blood all the time,
or else we wouldn't be able to clot at all, because plasmin
would be breaking down fibrin and fibrinogen all the time.
So we want to make sure that we can
have plasmin whenever we need it.
And we need plasmin whenever we don't want to make a clot
or whenever we don't need to make a clot.
And so we get plasmin from plasminogen.
And just like fibrinogen, plasminogen is
made with just an extra piece of protein.
And the way we get plasmin from plasminogen is
through our healthy endothelial cells again.
Our endothelial cells will release
and secrete plasminogen activator.
And this tissue plasminogen activator will
take off that extra piece of protein
from plasminogen and make plasmin.
So now let's zoom out and take a look at the entire picture
of how anticoagulation and thrombolysis works.