Transcription
Hey guys, it's Medicosis Perfection Ellis, continuing our bleeding and coagulation disorder playlist. In the previous video, we started talking about fibrinolysis. Today, we'll talk about plasminogen and plasmin. We need to destroy the clot and restore the function. With that being said, now let's get started. [Music]
Here are some of my previous videos in this playlist called bleeding and coagulation, so please subscribe and save the playlist. Einstein said, "If you can't explain it simply, you don't understand it well enough." Some people tell me your video sounds like you're talking to little children. That's exactly right, honey. That's exactly right. I mean, look at this guy, look at these like pair of glasses. Why is this side larger than this one? Because it's relative.
Hemostasis is the process of prevention of blood loss by stopping bleeding. Steps of hemostasis: vasoconstriction, the primary hemostasis (the platelets), and the secondary hemostasis (which is the coagulation factors), then fibrinolysis. The first thing that happens after you injure yourself is vasoconstriction. It's a local myogenic spasm; it's automatic; it's awesome. After this, we have primary hemostasis—that platelet plug. First, platelet adhesion thanks to GP 1b and von Willebrand. Then, platelet activation thanks to thromboxane A2 and ADP. This was the release of the platelet granules. ADP will help express this receptor called GP IIb/IIIa. The GP IIb/IIIa is used to fuse with another platelet. And then there is a molecule of fibrinogen here. Fibrinogen will be converted into fibrin in a process called the coagulation cascade or secondary hemostasis. And that's about it.
After we form the clot, and it has done its work and it has run its time, let's destroy this clot and restore function. This is called fibrinolysis, which is the topic of today's video. The secondary hemostasis: we start with fibrin because this is the end goal. It comes from fibrinogen, activated by thrombin, which comes from prothrombin. Prothrombin to thrombin, we need a prothrombinase complex thanks to this committee of two numbers, ten and five, and two words, calcium and phosphate lipid. Extrinsic pathway activated by the tissue factor and has only one coagulation factor called factor VII. The intrinsic pathway activated by the subendothelial collagen and the high molecular weight kininogen and plasma kallikrein and has four factors: XII, XI, IX, and VIII.
Fibrinolysis: "lysis" means to break down. Also, "unasked to beat the crap out of the clot, man." Forgive my language. "He who has a why to live can bear almost any how," said Nietzsche. "He who has a why to fibrinolysis can bear almost any mechanism," said Medicosis. Why fibrinolysis? Why fibrinolysis or thrombolysis? What's the purpose? Because if you leave the clot alone, it will grow and grow and grow until it will include the vessel, until it will press on local structure, and you will suffer; you'll be miserable until you die. So fibrinolysis is actually awesome because after this clot has just blocked the bleeding, now it's time for you to go. #Too much of anything is problematic—something grandma will tell you. Too much listening to your crazy professors, and you will be mad. Now we have our why, fixed in stone, which is to prevent the clot from growing and pressing on the local structure and occluding vessels. Okay, this clot needs to go. What enzyme do you use to break down the clot? We call it plasmin. It's a proteolytic enzyme, which makes sense because fibrin is a protein. If an enzyme degrades or cuts down this fibrin, it's called a proteolytic enzyme—lysis to the protein. Medicine is like a piece of cake, guys.
Then what? Then this clot is broken down into fragments. We break fibrin down into fibrin degradation products, also known as FDPs or fibrin split products. And we break down the fibrinogen into degradation products—also known as fibrinogen degradation products. Why not just break the fibrin? Because if you leave fibrinogen, and there is thrombin, thrombin is going to activate fibrinogen into fibrin, forming another clot. We need to destroy this fibrin and anybody who is related to the fibrin. That's how efficient this fibrinolysis process is. And then what? Will happen to these fragments? They are cleared by the sewage system—the garbage people. The garbage organs are the liver and the… I'm just saying garbage organs not because they are bad; they are awesome, but they deal with garbage. So if you met plasmin in the street and asked him what do you do for a living: "Okay, I digest fibrin into fibrin degradation products. Okay, and that's not enough for me; I also digest fibrinogen because if I leave it alone, it's gonna be fibrin. Digest fibrinogen into fibrin degradation products, or FDPs. Okay, in short, I break down the clot, but this is not enough for me; let's prevent new clot formation. Okay, although just factors V & VIII, also I'll just factor II, which is prothrombin, and factor XII. Why would you digest prothrombin? Because if you leave prothrombin to be activated into thrombin thanks to prothrombinase complex, it's gonna convert fibrinogen into fibrin, and it's not good for me. I have to prevent new clot formation as well as break down the current clot." So all of your actions can be summarized in one word: hypocoagulability. Brilliant.
If you leave plasmin free all the time, it will degrade every single blood clot in your body into hypocoagulability until you bleed. You form the clot; boom, the clot is gone. You injure yourself; you want to stop the bleeding, and no, no, plasmin is here. Okay, but this is not the case, why? Because there are checks and balances on the plasmin. Okay, so plasmin is not free all the time. In fact, it's present in a precursor, inactivated form called plasminogen, which will cause genesis to plasmin. It makes perfect sense. Who will activate plasminogen to plasmin? Several factors, including the great tPA—tissue plasminogen activator. Plasminogen activator because it's going to activate the plasminogen. Tissue because it comes from the tissue, specifically from the injured, traumatized endothelium. So now I get it. First, you have plasminogen. tPA, coming from the injured endothelium, is going to activate plasminogen. Plasmin now. Plasmin will break down the fibrin into fibrin degradation products, and it will break down the fibrinogen into fibrin degradation products. Awesome. But this plasmin is not just free all the time because it comes from plasminogen, and for plasminogen to become plasmin, you better have a trauma because tPA comes from the injured endothelium, and this process takes days, in fact, which is very wise. Why? Because let's say that the injured endothelium secretes tPA, and instantaneously plasminogen was converted into plasmin instantaneously; you will break the clot and you'll bleed to death as if coagulation was not there, which is nonsense. Now you know everything you need to know about plasmin. But I'm interested in his father, the plasminogen. The profibrinolysin and the plasmin is the fibrinolysin because it's going to lyse the fibrin. So plasminogen: who makes you? I'm a protein; I come from… I come from the liver. Okay, as simple as that. Okay, why are you a protein? Because I'm an active guy; I'm gonna produce plasmin. Anything that's active in your body is freaking protein, hello. And also a zymogen, which means a proenzyme. Zymogen—something that will generate an enzyme, the enzyme here being the plasmin. Okay, then what? Plasminogen floats around in the plasma and gets incorporated, gets trapped, gets adsorbed into the blood clot during its formation. #Plasminogen Inc. Prothrombin to thrombin. Okay, we're forming the clot; it's called secondary hemostasis. Please go on converting fibrinogen into fibrin. At that moment, plasminogen is being incorporated among the fibrin, among the clot, until tPA arrives and activates plasminogen by converting it into plasmin, which takes days. Now plasmin is active; it's gonna degrade fibrin into fibrin split products, and it will degrade fibrinogen into fibrinogen split products. Amazing. So once the clot is formed, this plasminogen, which is incorporated into the clot, is going to be converted into the plasmin, which turns around and eats the clot. As William Shakespeare said, "Et tu, Brute?" when he killed Julius Caesar. If you haven't read William Shakespeare, there is no hope for you. Yeah, keep reading capital and medical words of wisdom because I can't help myself.
If it weren't for tPA, many minute clots would clog several small vessels all over your body. Without tPA, you will have millions of clots in your brain, your legs, your heart, your GI tract, and even your genitalia. So you should be grateful that you have tPA. Plasminogen to plasmin thanks to tPA. What else? Urokinase. Urokinase: "uro" means urine, and kinase—okay, you know biochemistry—kinase is going to play with a phosphate. "Uro" because it was isolated from human urine. Ill. Okay, now we have plasmin. Plasmin, acting in its self-interest, is going to activate tPA to produce more plasmin; it's gonna activate urokinase to convert plasminogen to plasmin, producing more plasmin. This is called acting in your self-interest; there is nothing wrong with that. Okay, so fibrin is stabilized and destabilized fibrin thanks to cross-linking by the great fibrin stabilizing factor, also known as factor XIII. Cool. And you know that plasminogen is converted into plasmin thanks to tPA and urokinase, but there are other members that activate this: factor XIIa, factor XIa, and kallikrein. We prepare the dinner—being the clot—then we clean the table—called fibrinolysis. Prepare the dinner, then clean the table; that's every mother's dream come true. Plasmin: what will plasmin do? It will cut down and destroy this fibrin into fibrin degradation products, and it will destroy the stabilized fibrin into D-dimer. The end product of fibrin destruction is the fibrin degradation products, also known as fibrin split products, also known as FDP. The end product of stabilized fibrin destruction is the D-dimer. Don't ever forget that. If those guys are going to activate plasminogen to plasmin, who will inhibit plasmin? Because plasmin can be crazy; too much plasmin is too bad. We have the α2-antiplasmin and the α2-macroglobulin, not to be confused with the β2-microglobulin in multiple myeloma. Watch my video on multiple myeloma to know what the flip I'm talking about.
So here is a quick summary: extrinsic pathway thanks to tissue factor; intrinsic pathway activated by subendothelial collagen, high molecular weight kininogen, and plasma kallikrein. Both of them will activate the prothrombinase complex to convert prothrombin into thrombin. Thrombin will convert fibrinogen into fibrin. Once the fibrin is being formed, plasminogen is being incorporated into the fibrin clot. tPA, which comes from the endothelium—the injured endothelium—and urokinase—this process takes days—are going to be converted into plasmin. Plasmin will turn around to destroy the clot at which plasminogen is incorporated. Plasmin now is active; degrades fibrin to fibrin degradation products; degrades fibrinogen into fibrin degradation products; digests factor V and VIII; digests prothrombin and factor XII. Plasmin did an awesome job. Thank you, plasmin. Also, if you stabilize some fibrin, I'm gonna degrade it into a D-dimer. Bahahaha. Those fibrin degradation products are gonna inhibit thrombin because if you have enough fibrin degradation products, why the flip will you produce new ones? Because if you leave thrombin free, it's gonna act, refibrinating fibrin. Fibrinolysis has plasminogen Inc. Plasminogen Inc. becomes plasmin, becomes degradation products. So it's a negative feedback to inhibit thrombin to prevent new fibrin degradation process because too much of anything is bad for you.
Next video, we'll talk about tPA, the tissue plasminogen activator, and the inhibitors of the tPA. Don't forget to subscribe, follow me on Facebook and Instagram, support this channel, get the cases, get the notes by going to patreon.com/letmeDakota. You guys are awesome. Thank you for watching. Be safe, stay happy, and study hard. This is Medicosis Perfection Ellis, where medicine makes perfect sense. Medicine and sense—two words that don't come together like airline service.