Transcription
This is probably my last video on hemostasis, the physiology, because we still have to talk about the pathologies, such as the platelet disorders and the hemophilia, Sande, the warfarin, and the heparin, etc.
Today, we'll review hemostasis. It will be a quick video. If you have any problems understanding any of it, please go to my previous videos where I explained the stuff in detail. Now, let's have a quick review on hemostasis, and let's get started. [Music]
What is hemostasis? Stopping the blood loss, and it has many steps: vasoconstriction, then primary hemostasis by platelets, and secondary hemostasis by the coagulation factor, then fibrinolysis is to destroy the clot and restore the function.
Here's the story: You injure yourself because you're stupid, and then vasoconstriction occurs. Temporary platelet plug—this is primary hemostasis. Depending on the type of the trauma, if it's small, we're done. Thank you so much. Thanks for the temporary platelet plug. Fine, we are sufficient. But if it's larger, we need something more; we need the coagulation cascade or the secondary hemostasis to lay down the fibrin mesh work, trapping the red blood cells. Then the clot will contract, producing serum, then fibrinolysis to dissolve the clot and restore the blood flow. Then let's regenerate the tissue, and everything is back to normal. Amazing.
Here is the vasoconstriction after the injury. The tissue is injured, and it will exert back pressure on the blood coming forward, which will decrease the speed of the blood. Then the muscles in the surrounding tissue will contract. Then the vessel itself will contract. This is a local myogenic spasm with the help of local autocoit factors, thromboxane A2, and some nervous reflexes secondary to pain. So the vasoconstriction itself, it's a local mountain experiment. Why do we need the pain? Because the pain is going to be sent to your CNS in order for you to remember this and learn from your mistakes and don't do this again. Okay, don't do it again, like mama tells you.
Vasoconstriction: What are the pro-constriction substances? Serotonin, thromboxane A2, epinephrine, and fibrin peptide B. So when you are running from a tiger in the forest and you hit your finger and you bleed a little, you're not going to feel the bleeding because epinephrine is a powerful pro-constrictor. Your vessel will constrict to the point of occlusion, and you're not going to bleed. After you ran away from the tiger and you're safe, now we realize, "Oh, I'm bleeding from my finger. How come I didn't notice this?" Because epinephrine occluded your vessel, baby. And also epinephrine switched all of the blood from your finger to your viscera because we care more about your brain and your heart than your stupid finger. That's why it's called the fight-or-flight mechanism.
Let's talk about the platelet plug: primary hemostasis, like the policemen who inspects the gate that everything is fine and secure, and the engineer who inspects the wall if everything is normal. Everything is fine. Same thing: Platelet is inspecting the endothelium. If it's normal, okay, everything's fine. But if the gate is open, if the wall is cracked, if the endothelium is injured and the subendothelial collagen is exposed, baby, we have a trouble, baby. The platelets are going to be active. When the platelets notice the injury, they adhere to the tissue, to the subendothelial collagen, especially the von Willebrand factor, and thanks to the GP Ib. GP stands for glycoprotein. Then happens platelet activation. Activation by releasing thromboxane A2 and ATP. ADP will express this receptor called GP IIb/IIIa, and thromboxane A2 will do three stuffs: increase platelet aggregation, vasoconstriction, and bronchoconstriction. Nice. Then platelet aggregation: This platelet is going to meet this platelet thanks to GP IIb/IIIa on every platelet. Fibrinogen molecule happens to be in the middle. This is primary hemostasis. Secondary hemostasis is converting this fibrinogen into fibrin fibers. The fibrin mesh work is going to trap the red blood cell. Now we have a stronger thrombus. I am spitting wisdom all over the place. There are only two ways to coagulate, but there are several ways to bleed. What are the two ways to coagulate? The intrinsic pathway and the extrinsic pathway in the secondary hemostasis. So let's talk about that.
To understand secondary hemostasis and the coagulation cascade, please start from the bottom. Here we have the fibrin. Nice. Comes from fibrinogen. For fibrinogen to become fibrin, we need thrombin. But thrombin is present in a precursor, inactive form called prothrombin. For prothrombin to be thrombin, a complex once this congressional committee agrees on the decision of coagulation, prothrombin is going to be… when fibrinogen is going to be fibrin, and baby, it's going to be done. We'll have a clot to stop the bleeding. Who activates this congressional committee that consists of two numbers and two words? Extrinsic or intrinsic pathways. Let's talk about the extrinsic because it's easier and faster, but less efficient. Tissue factors coming from the tissue to activate factor VII into factor VIIa. Then the intrinsic. The intrinsic has many steps. Intrinsic to what? To the blood vessel. We need something from within the blood vessel, such as the subendothelial collagen, such as the high molecular weight kininogen. They are within the blood as well as the plasma kininogen. They'll activate XII into XIIa. Forget about X because X is here, so skip X. We have XII, XI, skip X, IX, and VIII—the so-called intrinsic pathway. Their end result of the intrinsic or the extrinsic pathway is an activation of factor X, the most important factor, into active form, factor Xa. Factor X, together with V, calcium, and phospholipids, are the Congressional Committee called prothrombinase complex that will activate prothrombin to thrombin to activate fibrinogen to fibrin to lay the clot. The highest number that we have reached was XII, but then we discovered a new factor called fibrin stabilizing factor, so we called it number XIII. It's important for stabilizing this labile fibrin into stable, strong, nice fibers. The difference between intrinsic and the extrinsic pathway was discussed in a previous video, so please go ahead and watch it because I'm not going to do it again.
Now, fibrinolysis: What's the purpose? Now you have a clot. Do you want to have this clot forever? No. It will grow and grow and grow, occlude the vessels till you die. So let's get rid of this clot. Let's dissolve the clot and restore the function. Who will dissolve the clot? A great protein called plasmin. But plasmin is very active, so we put it in an inactive precursor form called plasminogen. In order for plasminogen to become plasmin, we need tPA, which comes from the injured endothelium. Now, the normal, smooth endothelium, the injured endothelium, because life is tough. Urokinase. So the story goes like this: Intrinsic and extrinsic pathways, they activate prothrombin to thrombin, active thrombin, active fibrin. Now we have the fibrin. This is secondary hemostasis. Now let's get rid of this fibrin. Plasminogen to plasmin thanks to tPA. Plasmin will degrade fibrin into fibrinogen degradation products (FDPs) and the stabilized fibrin into D-dimer. Not only this, let's get rid of fibrin and his father, his daddy, fibrinogen, degraded into fibrinogen degradation products. Let's digest factors V and VIII because they are procoagulant and would like to be anticoagulant right now because we are destroying the clot, and let's digest prothrombin and factor XII, the beginning of the intrinsic pathway. What are their regulators, also known as the inhibitors of the process of fibrinolysis? We have three things. So here's one, two, three. First thing: Let's inhibit those tPA and urokinase. This is called plasminogen activator inhibitor because that plasminogen activator is a fancy term for tPA. Plasminogen activator inhibitor is something that will inhibit the tPA, nice, and urokinase. Cool. Now we have plasmin. Let's inhibit the plasmin at this stage by α2-antiplasmin. Then three is to degrade fibrin into fibrin degradation products. Who is going to inhibit this step? Thrombin-activatable fibrinolysis inhibitor. They are fibrosis inhibitors and errors of fibrinolysis that are activated by thrombin. So thrombin will activate this compound. This compound is active. This compound is going to stop the step of plasmin degrading the fibrin.
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