Primary hemostasis | Advanced hematologic system physiology | Health & Medicine | Khan Academy

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.

49 comments

  1. THIS VIDEO IS ABSOLUTELY AMAZING!!!! I actually am understanding!! 😀 THANK YOU KHAN ACADEMY!! 😀

  2. The alpha granules contain fibronectin, not fibrinogen – fibrinogen itself has to be activated by thrombin to become FIBRIN and is stickier – it polymerises with other fibrins and stuff, and only binds to fibronectin when mediated by factor VIII.

    Fibronectin… don't polymerise, they bind to fibrin when Factor VIII comes into play and catalyse the process (factor VIII stabilises fibrin and 'contracts' it, closing up wounds),

    Fibronectin mainly binds cell membranes through connecting with integrin molecules, which means it binds cells to cells. Platelets basically start working on long term healing the moment the are activated, but is relatively inefficient until fibroblast cells come in and form huge amounts of connective tissue etc.

  3. I don't understand the purpose if vasoconstriction as a result of damage to collagen. Wouldn't this cause more blood to be lost?

  4. for the last part of this video, isn't it fibrin instead of fibrinogen? i thought fibrinogen needs to be converted to fibrin and then it can form cross-linked mesh?

  5. It is a very good video but please, please, please stop moving the cursor around when you are not writing! You wiggle it around and shake it constantly, it is distracting and annoying. I would quit watching this video except it was assigned by my instructor.

  6. I don't know why people are complaining about the voice over. I thought it was perfect. She was talking like an actual person does when they are talking to you. And personally, that helps me listen better.
    Would people rather it be completely monotone? To each their own I suppose.

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