hey guys it's medicos is perfection animals one more time we have started talking about fibrinolysis in our series about bleeding and coagulation we talked about fibrinolysis and plasminogen and plasmon but today let's talk about the real hero the tissue plasminogen activator or TPA the one that converts plasminogen to plasmin then plasmon will break the fibrin clot and everything will return back to normal hopefully with that being said now let's get started but before we get started where do you think the TPA come from from the endothelium right do you mean the healthy smooth endothelium wrong
from the injured traumatized endothelium life is rough man [Music] so here's just a sample of my previous videos on bleeding and coagulation that's why you need subscribe and save this playlist hemostasis as the stoppage of blood loss or Prevention of blood loss it has many steps vasoconstriction temporary platelet plug or primary hemostasis coagulation or the thrombus the secondary hemostasis then fibrinolysis or as merriam-webster says for analysis or fibrinolysis then regeneration and repair we have talked about vasoconstriction temporal plug in coagulation before and we are now talking about fibrinolysis fibrinolysis fibrin is the protein which is
made of fibres lysis is to break down AKA to beat the crap out of the clot man forgive my language life is rough what's the goal of fibrinolysis what's the why because Friedrich Nietzsche said he who has a why to live can bear almost any how and medic osa says he who has a why to fibrinolysis can bear almost any mechanism fibrinolysis the why why do you do that because if you leave the clot alone it will grow and grow and grow and press on the structure occlude vessels and tell you die too much of
anything is problematic so you better break this clot down after it has done its job and drawn its course fibrinolysis has two types primary and secondary primaries physiology which we are talking about right now we're going to talk about diseases this is secondary fiber and lysis so primary fibrinolysis now we know the why let's discuss the how which enzyme breaks down the clot the great of all time plasmon then what then the clot is broken down into degradation products which are soluble fragments clear by your sewage system liver and kidney where does plasma come from
from plasminogen plasma no gen will give us plasma and we need a protease why because these guys are proteins protease an enzyme that digests protein how does they protease digest plasminogen into plasmid by cleaving the arginine valine bond if you want to be super sophisticated memory this crap what protease are you talking about I'm talking about the great tissue plasminogen activator so we activated plasminogen to plasmin thanks to TPA now what we'll plasmon do a lot digest fibrin into fibrin degradation products they disappear energy into fibrin degradation products all digest 5 & 8 & 2
& 12 5 & 8 2 and 12 if you undescribed plasmon just one word hypo coagula ability if you leave this crazy plasmon free all the time it will degrade every single blood clot in your body you will never form a useful clot even when you injure yourself which will lead to bleeding until you die that's why we need checks and balances put this crazy act of plasma in a precursor in active form called plasma no gen and then we need an enzyme to convert those measures in to plasmin we can regulate this step because
this is the most important step this takes a few days and that's good why because we need time for this fibrin to grow form a nice cloth stop the bleeding and once you stop the bleeding let's break this clot down and regenerate the tissue to maintain or to restore the blood flow and back to normal Plus managin also known as pro fibrin licen which means that the plasma is called fibrin lines let's talk about plays mission plasma no jen is it active yes it's active therefore it's a protein therefore it's made in the liver it's
a zymogen which means it's a pro enzyme the enzyme here being the plasma then what plasminogen floats in the plasma then gets incorporated into the blood clot into the fibrin during the fibrin formation that's why I call it plasma najin ink now this plasma nation which is incorporated in the fibrin is activated by TPA which comes from now the smooth endothelium the injured traumatized endothelium which takes days then plasmon here the crazy active guy degrading fibrin into fibrin tear relation prod degrading fibrinogen into fibrin degradation parts degrading the stabilized fibrin into the d-dimer after the
clot is formed plasminogen which was incorporated into the clot is converted into plasma that turns around and aid the clot as William Shakespeare said Avenue brutus when he killed Julius Caesar if it weren't for TPA many minut clots would clog several small vessels until he died I mean several like millions of clots even though the endo theam is traumatized it can produce the glorious TPA to save our lives Thank You endothelium great news guys I have 50 hematology cases on my patreon page please go to patreon.com/scishow in the kosis and get all of these cases
some of them are really difficult they cover bleeding and coagulation disorders by the way plasminogen to plasmin thanks to TPA or REO kinase plasmon will turn around and activate the TPN euro kinase which will convert plasminogen to plasmin which will activate TPA which will like to propose an into plasma acting in its self-interest plasminogen to plasmin thanks to thrombin TPA euro kinase factors 1112 and collector in the free plasma here will convert fibrinogen to fibrin fibrin into fibrin degradation products fibrinogen into fibrin degradation products stabilized fiber into the d-dimer who will inhibit this crazy guy
alpha to enter plasma alpha 2 macroglobulin any free plasma and please remember 3 free not incorporated free plasmon will bind the alpha 2 anti plasmin when it binds the alpha to enter plasmin they destroy the plasma here is the full story have the intrinsic and the extrinsic coagulation pathways activating the prothrombin is complex which will activate for thrombin into thrombin and 25 million into fibrin fire is being stabilized by factor 13 into the active stabilized fibrin thanks to cross-linking now that's secondary hemostasis let's go to fibrinolysis we have the plasma no gen gets incorporated while
we are forming the freakin clot it's incorporated within the fibrin fibers then the TPA comes from the injured endothelium or the uro kinase which comes from the liver okay I think into plasma plasma no convert fibrin into the degradation products and fibrinogen into fibrin degradation products and the stabilized fibrin into d-dimer's also all digest factors 5 & 8 2 and 12 both plasma no Jen and TPA bind to fibrin which I called they get incorporated into fibrin forming a ternary complex this will help plasminogen activation into plasma please don't forget this ternary complex and by
the way ternary means 3 albert einstein said if you can't explain simply he don't understand it well enough so let's explain simply there are two types of plasminogen activators we have the tissue type plasminogen activator or TPA which is the topic of today's video and the gyro kinase type was made an activator or the UPA which was first discovered in human urine yikes for the last time TPA activates plasminogen to plasmin where was the plasminogen it was incorporated into the fibrin fibers together with the TPA and the vibrant we have three structures plasminogen TPA and
fibrin they will combine together forming the ternary complex will activate first magenta plasma plasma and will degrade the fibrin into fibrin degradation products the fibration fibrin degradation products the stabilized fiber into the dimer if you knock out TPA and your kinase genes from the mice or rat let's knock the TPA out now plasma is not gonna get activated the clot is never will never get destroyed this will lead to spontaneous deposition of extensive fibrin mesh work no wonder because nobody is destroying this fibrin the positive feedback loop as plasmon degrades the fibrin so here's plasminogen
to plasmin plasma degrades the fibrin the c-terminus on the fibrin gets exposed this c-terminus contains lisen residue that binds plasma node and TPA converted into plasma the grace fibrin the licen residue is exposed TPA plasmon degraded fibrin more fiber lines it's more fibrinolysis more fiber Isis there are two types postman is an activator TPA and UPA also we have recombinant TPA which is made through their recombinant DNA technology and we have the strip to kinase which comes from bacteria TPA drugs drugs that contain TPA streptokinase which comes from bacteria it's less effective usually used outside
of the United States so some nuts will say because of the big corporations the big pharmaceutical corporations are keeping them out for that week they can sell us more expensive drugs shut up in the next video I'll tell you why this person is an idiot alteplase rather plays connect to place those are the recombinant tissue plasminogen activators clinical uses of GPA will be discussed in detail in the next video but for now remember they are clot lacing drugs the layman will call it open heart surgery the sophisticated we'll call it coronary artery bypass graft this
will increase TPA level in your plasma for some reason which will convert plasminogen to plasmin more fibrinolysis will end and bleeding in the next video we'll talk about clinical uses of TPA but for now let me leave you with a question what's the antidote for TPA let's say that you're a crazy doctor you gave too much tp8 of the patient and now the patient is bleeding how would you reverse that what's the antidote this is the first question second question what are the contraindications of TPA use please subscribe and hit the bell to get notifications
because subscriptions don't mean anything anymore follow me on Facebook and Instagram get all of my notes and my cases in my Pilate Dropbox links when you go to patreon.com/scishow thank you so much for watching this is mythical sister fiction a loss for medicine makes perfect sense until next time be safe stay happy and study hard
