I'm going to begin with an overview of hemostasis first.
I'm drawing an endothelial cell
and the purpose of hemostasis is
to stop any bleeding right away
when there's injury to the endothelial cell.
The way we do this is first we make a platelet plug.
And this is the goal of primary hemostasis.
And then in order to make that stronger,
what we do is we link fibrin together
on top of that platelet plug
and make a mesh
and this is what makes the platelet plug stronger.
And this is what we accomplish,
this is what we do in secondary hemostasis.
And when we have primary and secondary working together
And we form this mesh with the platelet plug,
this is called a clot.
Right now I'm just going to focus on primary hemostasis.
I'm going to put the endothelial cell
up to the right and to the side
so that we remember that we're focusing
on the platelet plug.
I'm going to bring in another endothelial cell
that we'll work with
and I'm going to cause some damage,
cause some injury,
and see what we do, what our bodies do
in order to stop that bleeding.
The first step in primary hemostasis
is vasoconstriction.
What we want to do
is clamp down the smooth muscle cells
in the blood vessel.
want to clamp down and make the hole
that blood is flowing through smaller.
So I'm drying it right now
and you can see that the hole
that the blood can flow through is smaller.
And this is going to decrease
the amount of blood that we lose.
The way I like to think about it is
say we're on a bridge and we're driving,
and all of a sudden half the bridge
on one side collapses.
In order to stop any cars from falling off
or limiting the amount of damage,
the police come right away
and they slow down traffic,
and they also probably cut down lanes
so they go from four to two
in order to make sure that the cars don't fall off.
So that's what the blood vessels are doing.
We do vasoconstriction in two ways.
One is just a nerve reflex.
It's like a knee jerk reaction.
We have some injury and then all of a sudden
our nerves tell our smooth muscle cells to contract.
A second way we do it
is by this blue molecule called endothelin.
And it's secreted from the endothelial cells
and acts on the smooth muscle cells in the blood vessel
and causes vasoconstriction,
it causes the smooth muscle cells to contract.
But in order to know how endothelin does this,
we need to talk about healthy endothelial cells
and what healthy blood vessels do.
So normally in a healthy blood vessel,
we're secreting all three molecules.
The green molecules are nitric oxide and prostacyclin.
And these are vasodilators
and endothelium like I mentioned
is a vasoconstrictor.
And they kind of play a tug-of-war with each other.
The endothelial cells are always secreting these substances,
but vasodilation always tends to win out
in healthy blood vessels
and that makes sense because we want to
make sure that blood is flowing through.
But what happens during an injury to our blood vessels
is that we lose the amount of nitric oxide
and prostacyclin that we make.
So endothelium wins over
because there's no more nitric oxide
and prostacyclin.
So we're going to get vasoconstriction.
And now, after vasoconstriction,
we get platelet adhesion meaning
we need the platelets to stick to the site of injury.
We need the platelets to get there.
In order to understand how the platelets do that,
let's talk a little bit more about the platelets.
I'm going to draw a platelet
and normally they're not square
and normally they're not that big.
But I just want to make sure that we get a good picture
of what's going on.
So platelets are normally flowing around in our blood
with red blood cells,
and they carry around these two granules they're called,
and I like to think of them as sacs
or sort of like backpacks on a camping trip.
You carry around a lot of things in your backpack
on that camping trip,
and you may not use any of it,
but you carry it around just in case you might need it.
That's how these granules work in these platelets.
I want to talk about two receptors also.
The platelets have more receptors,
but there are two key ones
that are important for primary hemostasis.
The blue and the purple receptors that I'm drawing,
they're both glycoproteins,
but that's such a long name,
so I'm just going to refer to them
as the second part of their name
and I'm also going to write everything
that we're talking about on the side,
sort of like a scorecard,
and that way keep track of all the
molecules and receptors that are important
for primary hemostasis.
So the blue receptor is glycoprotein 1b
and the purple receptor is glycoprotein 2b3a.
We'll just refer to them as 1b, 2b3a.
Now in order for platelets to find the site of injury,
we have to talk about normal platelets first
and their interaction with endothelial cells.
Normally platelets don't adhere or stick
to endothelial cells,
and this has to do with nitric oxide and prostacyclin.
The two substances that we had already mentioned
that are secreted by healthy endothelial cells.
And what they do in addition to causing
vasodilation to the smooth muscle cells,
is they kind of block the platelets
from sticking to the endothelial cells.
Like we mentioned,
when there's injury to the endothelial cell,
then there's less nitric oxide and less prostacyclin
that will block platelets from
getting closer to the endothelial cell.
So now that there's less nitric oxide and prostacyclin,
platelets are going to get closer to the site of injury
because there's nothing blocking it from going there.
In addition to that,
we also have this glue,
this molecule that provides the link
to the site of injury and to the platelet.
This glue is called von Willebrand factor.
I wish there was a better way to remember that.
It's a long name.
And we'll just refer to it as VWF.
And this VWF is normally floating around in our blood,
but it also gets secreted from endothelial cells
at the site of injury specifically.
And when von Willebrand factor comes into contact
with the site of injury,
it binds to subentothelial collagen.
Collagen is a substance that provides structure
to the blood vessels,
and it normally doesn't have contact
to blood or to platelets.
So at this injury,
von Willebrand factor binds tightly to the collagen
and on the other side it binds to
the Gp1b receptor on the platelets.
And so the platelet is ready to bind von Willebrand factor
when there's a site of injury.
So now that it binds,
once it's bound,
the platelet actually gets activated
and that's when we begin the next step,
activation and degranulation.
So when the platelet gets activated it changes shape.
So I'm erasing the platelet now,
so that I can change the shape of it.
And it also does many other things.
One of them is the Gp2b3a receptor
is a confirmation that is normally inactive.
So it is not able to bind properly.
And so after activation it changes shapes
so that it's able to bind.
And then the sacs,
the granules that I mentioned that are inside the platelets,
now they become of use
and that's when degranulation happens.
These sacs, these granules,
get released into the blood.
One of them is called the alpha granule
and in the alpha granule
we have two substances that we already know about.
One of them is fibrinogen
which we will be using in secondary hemostasis,
and the other one is von Willebrand factor.
And in the dense granule,
which I like to think of it as dense,
and so it has more,
and so this one has three substances,
three molecules.
And since we're thinking of them as backpacks or sacs,
it also helps me remember what's in the dense granule.
In the dense granule, in the dense sac,
we have serotonin, ADP, and calcium.
And the way I remember what the three molecules do,
I think of past, present, and future.
So serotonin is released,
and it's a constrictor of the smooth muscle cells
and so I think of that as past,
because that's what we did in the past,
but now it's going to do it again.
And ADP is present.
ADP activates platelets and promotes aggregation.
So ADP is what we need now,
in order to get the platelets to clump together.
And then calcium is the future,
because calcium is needed for secondary hemostasis.
That's the next part, make stabilizing that platelet plug.
The third thing that an activated platelet does
is secrete thromboxane A2.
Thromboxane A2 is actually the
exact opposite of prostacyclin,
and it's made by the same enzyme.
And thromboxane also plays a tug-of-war
with prostacyclin.
It acts on smooth muscle cells
to cause vasoconstriction,
and it also causes more platelets to activate,
and helps with aggregation.
And so the final step,
platelet aggregation,
is mediated primarily through Gp2b3a,
And it's not until an activated platelet
actually causes the 2b3a receptor
to change to a shape
that allows it to bind to fibrinogen.
Because 2b3a on the platelet binds fibrinogen
and it's through fibrinogen binding
many 2b3a receptors from many platelets
that creates the clumping and the platelet plug
that we get at the end of primary hemostasis.