Current time:0:00Total duration:10:51
0 energy points
During primary hemostasis, a platelet plug is formed to rapidly stop the initial bleeding after injury. Learn about the different steps involved in primary hemostasis: vasoconstriction, platelet adhesion, activation and degranulation, platelet aggregation. Created by Gricelda Gomez.
Video transcript
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.