Transcription
Hey guys, it's Medicos. Is perfection elsewhere? Medicine makes perfect sense. We are continuing our series about bleeding and coagulation. In the previous video, we had a quick review about hereditary angioedema. They all talked about the famous antithrombin 3, produced by the great liver, and it's really antithrombin; it hates thrombosis. Now let's get started. [Music]
Here are some of my previous videos in my bleeding and coagulation playlist, so please subscribe and save this playlist; otherwise, there is no hope for you. As you know, there you have procoagulation factors and anticoagulation mechanisms. So the anti-clotting or anticoagulation factors are the great smooth endothelium. It provides a smooth, non-thrombogenic surface. It helps in vasodilation; when the vessel is larger, it makes it harder for platelets to aggregate because there is more surface area. It secretes endothelial-derived ways to die later, such as nitric oxide, which causes vasodilation and inhibits platelet aggregation. It secretes heparin-like molecules, such as heparin sulfate, which stimulates antithrombin 3 (which is the topic of today's video) and neutralizes the crazy activated serine proteases, such as prothrombin and all of this crazy stuff. It synthesizes prostaglandin I2, also known as prostacyclin, which keeps the blood cycling by vasodilation and decreased platelet aggregation. It expresses thrombomodulin, which modulates the thrombin from being procoagulation to being anticoagulation, which is amazing. It produces TPA, which converts plasminogen to plasmin to destroy the clot and restore the function called fibrinolysis.
What are the other anti-clotting mechanisms? You have heparin. Heparin? Do we have heparin in our bodies? Yes, all of you right now you have heparin in your body. Oh, really? Yep. It's a glycosaminoglycan. It stimulates antithrombin 3. Then antithrombin 3 inactivates the serine proteases, such as 9, 10, 11, and 12. Heparin-like molecules are floating around. Protein C, protein S—those are the brakes of the coagulation process. Protein C and protein S are vitamin K-dependent. Protein S is a cofactor of protein C. Both of them will inactivate factor 5 and factor 8 in the intrinsic coagulation pathway. So it goes like this: you go to the liver; the liver has vitamin K in it; and the liver will synthesize this vitamin K-dependent factor, as well as protein S. Then protein C and then they will inactivate factor 5 and factor 8 in the intrinsic coagulation cascade. The liver inactivates the activated clotting factors. Who secretes all of your coagulation factors 1 through 13? Liver. Yet most of them? Okay. So when the liver finds them floating in the plasma and they are activated when they are not supposed to be active, the liver, like a mature person, takes responsibility for its action and starts inactivating those activated coagulation factors. The liver takes responsibility for its action. I wish politicians would learn from the liver. My goodness.
I've talked about the arachidonic acid pathway in a previous video, but in brief: membrane phospholipid things—phospholipids. It—do we have the arachidonic acid? Prostaglandin G2, thanks to the cyclooxygenase. And here we have the thromboxane synthase and prostacyclin synthase. If you are in the platelet and you want to clot, okay, go ahead. Thromboxane synthase produced thromboxane A2, which vasoconstricts and increases platelet aggregation. If you are the smooth endothelium and you have a vested interest in the blood fluidity and in the normal laminar flow of the blood, secrete prostacyclin to keep the blood cycling, why? Vasodilation and preventing platelet aggregation, i.e., anticoagulation.
So here are the anti-clotting mechanisms and the pro-clotting mechanisms. Let's talk about the pro-clotting first: thromboxane A2, the tissue factor which activates the extrinsic pathway, the subendothelial collagen which activates the intrinsic pathway, as well as help activate the platelet during primary hemostasis. Actually, ADP, which is part of the platelet granules, von Willebrand factor, platelets, activated endothelium, and coagulation factors. The anti-clotting factors or anti-clotting mechanisms include the smooth endothelium—it's smooth and vasodilator—nitrous oxide or nitric oxide, heparin sulfate, prostaglandin I2, thrombomodulin, TPA, tPA for fibrinolysis, excellent. Thank you, endothelium. Heparin, heparin-like molecules, protein C, protein S, and the liver inactivates the crazy over-activated coagulation factors because it takes responsibility for its actions. Heparin stimulates antithrombin 3. This is the topic of today's video. Now let's get started.
Antithrombin 3 also has antithrombin heparin cofactor. You can write it this way: antithrombin 3, and here AT stands for antithrombin, not angiotensin. Okay. It's an alpha globulin. You know proteins; we have globulin, we have albumin, and we have three types of globulin: we have the alpha globulin, the beta globulin such as your coagulation factors, and the gamma globulin such as your immunoglobulins or antibodies. But this antithrombin 3 is an alpha globulin. Excellent. It's a serpin, not to be confused with the serpent. What is a serpin? Serpin is an inhibitor of the serine protease. Oh, okay. This is very sophisticated stuff. It inactivates the serine proteases, such as 9, 10, 11, and 12. It binds thrombin and blocks its effect. No kidding. If the name is antithrombin, okay, it's going to bind to thrombin and block its effect, and it's also going to inhibit the serine protease. Heparin on its own is useless, but heparin when it binds to the antithrombin 3—now antithrombin 3—it's super energetic, has a 10x boost, and antithrombin 3 is going to bind thrombin to block its effects. It's going to inhibit all of the serine proteases, and it's going to be anticoagulation big-time. And here is the prothrombin, thrombin converting fibrinogen into fibrin. Antithrombin 3 is antithrombin, as well as inactivating those serine proteases.
"A woman without her man is nothing." The sentence can make ladies angry. Never make a lady angry. So let's punctuate: "A woman without her man is nothing." Same thing: antithrombin 3 without heparin is nothing. Heparin takes all the credit for what? For nothing, actually. Antithrombin 3 is the hero; it's doing all the job. I think this should change. Hey, it's 2019. It's time to recognize antithrombin 3 for the hero he is. I have 50 hematology cases that are available only for a limited number of students. Go to patreon.com/scishowsis because these are just awesome. I'm just telling you. And if you have watched my previous video about cases on Hodgkin's lymphoma, I had 10 cases on how to tackle lymphoma in one video. These are the same style; they go step by step so that you can understand all of the stuff about bleeding and coagulation.
Fibrin fibers as anticoagulants? What the what? You mean the fibrin fibers, which are the exact clot, can act as an anticoagulant? Yes, indeed. Okay. Prothrombin is converting to thrombin; we know that thanks to the prothrombinase complex. You know that congressional committee? We had two numbers: we had factor 10 and we had factor 5; and we had two words: we had the phospholipid and we had the calcium. Those were the committee that activated prothrombin to thrombin. Okay, 90% of that thrombin becomes adsorbed or incorporated or attached into the fibrin fibers, so we will call it from being inked. So here is—here are the fibers of the fibrin; here are the red blood cells with the central pallor; and here is the thrombin, the protein of thrombosis. It's incorporated into the fibrin fibers. Why do we do that? Because if the act of thrombin is left to float freely in the blood, it will go around causing clots everywhere because it's active. And notice I said thrombin, not prothrombin, because I don't mind prothrombin falling around; it's prothrombin; it's not active. But now if it's activated into thrombin, it's going to cause clots everywhere. Prothrombin? Don't worry about it. Why don't worry about it? Because for prothrombin to be activated into thrombin, you have to have the prothrombinase complex; you have to have the intrinsic and/or the extrinsic pathway active, which will not happen unless there is a real trauma. So prothrombin falling around, no big deal. But thrombin floating around in its active form, it's going to convert fibrinogen to fibrin, and you will have clots in your brain, in your heart, in your legs, everywhere, and yes, in your genitalia. So now the picture is complete.
What are the anti-clotting mechanisms? The smooth endothelium, heparin which stimulates antithrombin, heparin-like molecules such as heparin sulfate, protein C, protein S, liver inactivates the activated coagulation factors. Antithrombin 3 is antithrombin, and it inactivates the serine proteases factors 9, 10, 11, 12. Fibrin fibers incorporate the thrombin within so that it's not left freely to float around causing clots in your genitalia as well as everywhere. Thank you so much for watching. Subscribe, hit the bell, smash like, follow me on Facebook and Instagram, get all of my notes, cases. Support this channel on Patreon; I'll give you my Dropbox links, which are bloody because we're talking about bleeding and coagulation. Thank you for watching. This is Medicos, perfectionist. Be safe, stay happy, and study hard.