Transcription
It's Medicos is perfection. Else, once again continuing our series about bleeding and coagulation disorders. In the previous videos, we have started talking about fibrinolysis. In the last video, we talked about streptokinase. So, they will talk about urokinase-type plasminogen activator, also known as urokinase or uPA. With that being said, now let's get started. [Music]
Hemostasis has many steps, and we are still stuck in step number four. Urokinase and TPA will activate plasminogen to plasmin. Plasmin will go back and activate tPA, urokinase to form more plasmin; plasminogen to plasmin via thrombin, tPA, urokinase, 11, 12, and collector. And so, urokinase is here; it activates plasminogen to plasmin. Then, plasmin will degrade fibrin to fibrin degradation products and the stabilized fibrin into the D-dimer. 50 hematology cases are waiting for you when you go to patreon.com/scishow Sirs. They cover topics like bleeding and coagulation disorders. Here's the whole story: intrinsic and extrinsic pathway activating prothrombin to thrombin, fibrinogen to fibrin. Plasminogen gets incorporated into the fibrin fibers. tPA, urokinase activation into plasma, and this takes days. Fibrin is degrading to degradation products, fibrinogen to degradation products, and the stabilized fibrin into freakin' D-dimer.
Let's use the KISS principle and keep it simple, stupid. We have two types of plasminogen activators: tPA and uPA. The tissue-type plasminogen activator, which comes from the tissue, precisely the injured endothelial, and urokinase-type plasminogen activator, which was first isolated from human urine. It can also be produced from cultured fetal kidney cells. It's also present in the blood and in many extracellular matrix locations. This is very important; pay attention. Leave the phone. Two types of plasminogen: plasminogen incorporated in the fibrin and the freely circulating plasminogen. When you activate this, you get localized fibrinolysis, which is desirable. When you activate this, you get systemic lytic state; you get fibrinolysis all over the body. This increases the risk of bleeding. This is not a good thing. Therefore, tPA drugs are divided into two groups: the superior, great group of alteplase, reteplase, tenecteplase. This group, of course, is going to be more expensive, no kidding. And the non-fibrin-specific plasminogen activator, such as the garbage streptokinase, the trash, and the ugly urokinase.
Urokinase-type plasminogen activator, uPA, present in the urine, yep, and blood. It better be in the blood because fibrinolysis occurs in the blood. Hello, it's a serine protease. It better damn well be protease because plasminogen is a protein. In order to break down this protein, you need a freaking protease. PAI-1 and PAI-2, plasminogen activator inhibitor one and two, are gonna inhibit this urokinase. Some god is gonna come after you. Urokinase activates both the fibrin-specific plasminogen and the nonspecific plasminogen. So, this will lead to systemic lytic state, increasing your risk of bleeding, which is not fun. Please don't forget radical prostatectomies. Surgical removal of the prostate gland releases urokinase. Remember, urokinase is related to the urine. So, prostate is very close. Increased fibrinolysis because you have lots of uPA, and this uPA is gonna activate plasminogen to plasmin. Plasmin increases fibrinolysis, and you will bleed.
When we talked about tPA, tPA was administered through two routes: locally through a catheter or systemically through intravenous injection. Not anymore. Urokinase. We tried so many times to administer systemically, but we failed. Until this moment, the only method of administrating this crazy urokinase is through the catheter-directed chemical thrombolysis of the clot. Hashtag pocket baby. So, if this is your vein and this is a DVT, a clot, please introduce a catheter and cover it with a chemical, in this case, urokinase. And this urokinase, it works like tPA; it will convert plasminogen into the active plasmin. And plasmin is gonna destroy the clot. Clinical uses of urokinase: please think like a plumber. Catheter-directed thrombolysis. Okay, so let's say the patient has DVT. Introduce a catheter, cover it with urokinase, and poke the clot. Restoration of flow in the IV catheter. Now we're talking in vitro. We have something outside of the body. You know, the catheters, they get clogged all of the time. 25% of cancers get blocked by blood clots and fibrin, etc. So, to clear the catheter and make it brand new, poke the clot again. Introduce urokinase into the catheter. This is called catheter clearance, not to be confused with JCPenney clearance. This corporation is gonna go out of business. Suit life is rough, man. So, we use urokinase for DVT, PE, peripheral arterial disease, and myocardial infarction. In other words, poke the clot. So, poke the patient, poke the clot, basically. Urokinase is just like the drain cleaner that you pour down the kitchen sink to unclog it. Remember, I told you to think like a plumber. This guy works for uPA, not to be confused with UPS.
Now here's a little pearl for you: urokinase advantages over tPA. Here you have the tPA, tissue plasminogen activator, break down every single dadgum clot in your body: the useful and the harmful, the good, the bad, and the ugly. The goods, such as hemostasis after trauma. You injured your finger; you need a clot, so that's good, that's useful. tPA, now under my watch, I destroy everything, and it destroyed the harmful. Thank you, tPA. Such as MI and DVT. uPA somewhat better; breakdown only the harmful clots, MI and DVT. uPA is not incorporated in the fibrin. Remember the ternary complex: plasminogen and tPA and fibrin. tPA, not uPA. But again, don't forget alteplase will kick urokinase's butt. But that's it for today. Thank you so much, and forget to subscribe. Follow me on Facebook and Instagram. Get my notes, get my cases by going to patreon.com. Now for the coasters to receive my bloody Dropbox. Thanks. Thank you for watching. Be safe, stay happy, and study hard. This is Medicos is perfection elsewhere. Medicine makes perfect sense.