hey guys it's medicosis perfectionalis where medicine makes perfect sense in the previous video we had an introduction about secondary hemostasis or coagulation today let's talk about the coagulation Cascade the coagulation factors that come from the liver indeed they are beta globulins and let's get started [Music] if you haven't watched my previous videos it means you live under a rock literally these videos are amazing Please Subscribe and save this playlist hemostasis prevention of blood loss by stopping bleeding steps vasal constriction temporary plal plug which is primary hemostasis thanks to plats coagulation which is called secondary hemostasis thanks to coagulation factors fiis to dissolve the clot restore function and restore the blood flow and then regeneration primary hemostasis is balanced on the dynamic harmonious antagonism between the smooth endothelium which wants the blood to flow and thrombocytes which favor thrombosis here is the entire story injury vasal constriction temporary platet plug depending on the type of the trauma if it's very small platelet plug is sufficient if it's larger we need secondary hemostasis also as coagulation also known as the fibrin mesh work to trap the r cell then the clot contracts producing serum and then fibron liasis to destroy the clot and restore blood flow regenerate here is the process of vas of constriction I've explained it in a previous video we start with a trauma then back pressure these muscles contract constricting The Vessel The Vessel by itself constrict it's a local myogenic spasm thromboxane A2 helps the pro constriction substances include serotonin thromboxane A2 epinephrine and fibrinopeptide B the platelet is like the policeman inspecting the gate by the gate I mean the endothelium if everything is nice and secure okay it's calm it's a quiet night everything is fine but if the gate is open and the layer underneath the gate called sub indal Collen is exposed the platelets go mad same thing with this amazing engineer he just goes bananas when he sees cracked wall because it could be something major steps of primary hemostasis platelet adhesion thanks to JP 1B and the vonbrand factor where does the Von vand come from from the platelet and the endothelium then comes here plat activation they activate swell contract and release the granules ADP ADP dependent expression of dp2 b3a receptors and it's a whistleblower it whistles for other ples to come to help PL aggregation thromboxane E2 which is an even bigger whistle blower PL aggregation promotes vasil constriction and Bron Co constriction then platelet aggregation this platelet and this platet will connect together each one has its own gp2 be 3A receptor fien molecules forms in between then primary hemostasis is done secondary hemostasis is to do this the fibrin MW workk then the fiin missw workk traps the red bu cell forming an even bigger and better plug let me explain the coagulation Cascade like your crazy Professor you will never understand the thing but then I'll explain okay so coagulation is we have intrinsic pathway the intrinsic pathway has Factor 12 then it's converted into 12 a then 11 converted into 11 a then after this we have um 10 no no no no no it's not 10 it's I believe it's nine and to 9 a then after nine we have like factor 8 which is activated then this will activate Factor 10 and then we have Factor 10 a this is the intrinsic pathway also there is another pathway called the extrinsic pathway and here we have only one factor it's called Factor 7 Factor 7 is converted into 7 a and then they will activate Factor 10 Factor 10 together with Factor 5 a and some calcium let's add some membrane phospholipid they will help the prothrombin being activated from prothrombin into thrombin and then throm will activate by the way prothombin is factor to thrombin helps activate the fibrinogen oen into fibin and for some reason we call fibrin Factor one and then fibrin will have Factor 13 to stabilize the fibron into stronger better fibers and this is the story of coagulation go to health did you understand the thing no now let's do it the medicosis way so let's start with this nice scientist Mor in 1910 he said the the clot is just the fibrin fibers okay and this fibrin is present in a precursor form called fibrinogen that's I called it fibrogen why gen means Genesis this fibrinogen will cause Genesis of fibin brilliant what does fibin mean I in means protein and fibrin because it's a protein of fibers excellent then to stimulate fibrinogen and converted into the active fibrin you need something called protein of thrombus let's call it protein thrombus so we have thrombin this thrombin is present in a precursor inactivated form called pro thrombin pro means pre it's pre thrombin it will form thrombin since this was the first factor to be discovered and the factor that leads to the real clot which is the fibbr let's call it Factor one what's before it is prothrombin let's call it Factor 2 very interesting after the great scientist Mor ofits we have the modern coagulation Theory we just discovered some reactions here before and some one reaction here after fiber so that's basically it we have these same two steps a Cascade before a fiber and stabilizing Factor after okay so the Cascade will explain this what the flip is fi and stabilizing Factor it was it we discovered it by a chance some patients formed fibrin fibers and they trapped the red blood cells and their bleeding stopped excellent then suddenly out of the blue this fiber Mish workk was destroyed and the patient bled to death what the what yes because these fibrin fibers were unstable you need something to stabilize the fibber into stable stronger fibrant fibers that are irreversible you cannot break it down easily this is called fibrin stabilizing Factor since we discovered all the other factors from 3 to 12 because as you know this is one and this is two so 3 to 12 let's call the fiber and stabilizing factor factor 13 that's brilliant then let's talk about factors 3 to 12 we have two Pathways the intrinsic and the extrinsic this path way is called the common pathway a Cascade is a small waterfall each step is stronger than the preceding one boom boom boom boom boom boom boom boom it allows time and steps for regulation it's not all or none you can regulated if it has several steps and if it had several steps it means that every step is going to be stronger than the one before it this is how you form strong fibbr and fibers and stop the bleeding efficiently that's why secondary hemostasis is way way way more important and more efficient than the stupid platelet plug of primary hemostasis because the platelet didn't have a Cascade so here is the story you injure yourself vas of constriction plate of plug also know as primary hemostasis if it's it's very weak and it's temporary then comes the coagulation Cascade boom boom boom boom boom boom Pro thr and thr fision fiber strong fibrin trap the oral cells boom we're done and then stabilize it with Factor 13 that's why we need a Cascade every step is stronger than the one before it unless there is platelet activation in vain there is blood coagulation there is no platelet activation you cannot form blood coagulation there are only two ways to coagulate but there are tens of ways to bleed oh my goodness this is deep what are the two ways to coagulate you have the intrinsic pathway and the extrinsic pathway two way way to coagulate this is physiology 10 ways to bleed this is pathology here we have intrinsic and extrinsic Pathways what why do we call it intrinsic intrinsic to the blood it's intrinsic to the blood vessel something from within will start the ignition # self-sufficient we depend on factors from within the blood or at least the blood vessel how about you extrinsic no I need something from outside the blood you me like the tissue yeah that works we are dependent on outside factors we are not self-sufficient so extrinsic pathway depends on factors from outside the blood that's why we call it extrinsic intrinsic has more steps it's a longer Cascade if it's a longer Cascade it's going to be stronger that's the whole point of a Cascade boom boom boom boom boom boom boom it's called acceleration it's going to be more efficient yeah it's a longer Cascade extrinsic less steps shorter Cascade therefore it's faster but less efficient here is a question for you when you put blood in a test tube except for the purple one it coagulates using the which pathway is it the end transic pathway the ex transic pathway or both I'll give you 3 seconds go and the answer is the intrinsic pathway because remember the extrinsic wants something from outside the blood for example the tissue but when you put blood in a test tube you don't have tissue it has to be the intrinsic pathway use your prefrontal cortex For Heaven's Sake so here's the old theory fibrin is the clot comes from fibrin oen then we have thrombin comes from prothombin what activates prothombin into thrombin is the prothrombinase complex what's the complex it has four membranes I call it the famous quad quad is like Triad but for four calcium membrane phospholipid Factor five and Factor 10 which one is the most important factor 10 baby this is the best 10 is a very important number that's why the gurus on the internet will write blogs about the 10 ways to lose weight the 10 ways to travel abroad the best 10 places to visit in blank here's a quick monic for you here's fibrin and here's FBR oen this is the president okay will you leave the president alone to rule the country no this is called dictatorship like the country that I came from power corrupts and absolute power corrupts absolutely we need checks and balances let's add a vice president pro thrin Factor two but we need more we need a congressional committee has Factor 10 five calcium and phospho lipid to form the prothrombinase complex the perisan cannot act alone without approval of Congress first let's start with the extrinsic pathway we start from here because this is how history worked fibrin this is the clot it's what galin and hypocrates said then we have fibrinogen then we have thrombin the protein of thrombosis and then prothombin prothombin is going to be activated into thrombin which will convert fibbr into fibin fibin traps the red blood cells what converts prothrombin into thrombin prothrombin is complex the quad the committee it has 10 five calcium and phosphor liid don't ever forget that what is the extrinsic pathway extrinsic pathway can you um tell us your story of course I'm extrinsic which means I need something from outside of me from outside of the blood and the blood vessel even tissue yeah the tissue works fine why do you need something from the outside I'll tell you my friend because what's the evidence that you are bleeding and you need coagulation how is the tissue an Evidence think think if there is a trauma and here's the tissue and here's the blood vessel the only way by which this tissue is going to be in contact with the blood directly is only when you have a trauma you have pierced through the tissue and this vessel wall and the endothelium and now the blood is going to be in contact with the tissue factor which means there has to be a trauma which means let's work in order to form a clot brilliant so what factor are you looking for it's called the tissue Factor the factor from the tissue it's it's it can't be easier it's it's very easy tissue Factor we call it tissue thromboplastin I mean look at the name i n means protein plast means creation thrombo means thrombosis it's the protein that creates the thrombus wonderful or tissue phospholipid it comes from the tissue phospholipid so we call it TPL okay so let's do it again we have a trauma the tissue factors comes in contact with the blood the blood has Factor seven yes indeed when tissue Factor comes in contact with Factor 7 it means that there's a trauma then Factor 7 is going to activate into Factor 7A a for active then it's going to activate the famous Factor 10 the hero into 10 a 10 a together with five phospholipid and calcium is going to form a prothrombinase complex prothrombinase will convert the pro thrombin into thrombin to converting the fibbr Engen into fibrin trap the rot cells boom we're done extrinsic pathway is done it's fast but it's less efficient as the extrinsic pathway is starting to work the intrinsic is also working but it takes longer because we have more steps and more Cascade longer Cascade so intrinsic pathway please tell us your whole story in detail I'm intrinsic so I need something from within us by that you mean I mean something from within the blood vessel will the sub endothal collagen work yeah it's part of the dead gum basement membrane it's part of the blood vessel it works so when you injure your tissue the sub indal collagen is exposed so so this is an evidence that there is a trauma it's an evidence that you are bleeding it's an Evidence enough for me in order to work and start the Cascade in order to form fiber Mish work to stop this bleeding wonderful so please work I start with Factor 12 Then I then Factor 11 then after this I have Factor n then I have factor 8 why do we call them these names because we discovered them like from here to here we discovered Factor seven for the extrinsic and another factor for the intrinsic we called it factor eight then we discovered more factors we have nine so we have 8 9 10 is here so skip 10 11 12 8 9 11 12 we have two before 10 and 2 after 10 8 9 11 12 let's do the whole intrinsic pathway we have sub indal collagen exposed activate 12 then activates 11 skip 10 activate nine and have the eight vonbrand factor is part of factor eight this is important this will activate Factor 10 into 10 a and 10 is the hero together with calcium phospholipid and Factor 5 we have two factors and two substances or you can say two numbers and two words then we have the the prothombin a complex the quad the committee to convert prothrombin into thrombin to convert fibrine into fibrin fibrin traps theed blood cells boom we have a clot baby so let me tell you the whole story you injure yourself the platelets start to work then comes the coagulation Cascade we start with the extrinsic the tissue factor which is in the tissue came in contact with the blood which is in the vessel I.E there is a trauma it's very easy like it's self there's a trauma fine tissue Factor activates Factor 7 into 7 a converting 10 into 10 a at the same time the intrinsic is working like mad but it takes time because it's a longer Cascade however it's more efficient it's more has more steps we start with the sub indal collagen then you have two factors after 10 and two factors before 10 let's activate 10 into 10 a villa brand factor which came from the plate let and the endothelium is part of factor 10 okay 10 10 a together with five we have two numbers and two words prothrombin is complex prothombin into thrombin fibrin into fibrin but we need to stabilize this fibin by another Factor since we are done with these factors the last name was 12 let's call it Factor 13 the fibrin stabilizing Factor it converts the fibbr from being labile to a more stable fibin this is called crosslinking this my friends is why we need a Cascade boom boom boom boom boom boom boom fibrin let's have some fun remember the most important factor yes Factor 10 in the common pathway standing in between the intrinsic and extrinsic pathway so here is lonel Messi and here we have the four factors why four factors because we have two factors before 10 8 9 then we have 11 12 all of these are part of the intrinsic pathway when 10 is in the middle everybody is surrounding him to protect him because he is a public figure one of medo's fans commented on one of my videos he said if I had a million YouTube accounts you would have a million subscribers thank you dear his name is I hate Ronaldo okay I'm old school so I assume this is his real name because who am I to judge why would anybody hide his identity on the internet thank you my friend and this video is just for you enjoy so let's do it from scratch okay we start from here what's the clot the clot is fibin so let's do fibin then the fibrin comes from fibrin oen fibrin oen is also known as Factor one because it's the factor just before the fibin from fibbr to fibbr we need the protein of thrombos thrombosis the famous thrombin protein of thrombin to activate fibrogen into an active fibron Pro thrombin comes from prothombin which is pre thrombin prothrombin is an active thrombin is active this is called Factor 2 very nice here we have the prothrombinase complex also known as prothrombin activating complex it has four members who's the most important guy Messi 10 and we have also five those are two numbers we need two words calcium baby not just calcium charged calcium ionized calcium because the only form of active calcium in your body is the ionized one no one has ever had tiany because of the non ionized calcium it's always the ionized because it's the one that's active the non-ionized calcium is garbage just put it in some bone give you some like kind of a matrix or something strong give it a context and that's it but the physi logically active one that makes symptoms such as muscle contraction or blood coagulation is the active charge Cales the fourth member is the membrane phospholipid or some phospho lipids so in order to activate 10 into 10 a we need two Pathways let's start with the extrinsic pathway extrinsic pathway I need something from the tissue from the extrinsic something from outside of me it's called the tissue factor it's also known as tissue thromboplastin this will activate the only factor that we have here which is Factor 7 into Factor 7 a 7 a will convert 10 into 10 a we're done with the extrinsic pathway very well done let's go to the craziest one intrinsic pathway intrinsic pathway we have two before 10 and two after 10 because 10 is messy is the most important public figure we need to protect it put two guards in front two guards in the back let's start eight and N before Messi and and 111 12 after Messi so we have 12 into 12 a 11 into 11 a and you know all of this garbage what activates Factor 12 yes indeed the sub endothal Cen something from within the vessel now pause the video bring a sheet of paper and try to do it yourself you will never forget it forever let's have some pneumonic time as you know F engine is the president proin is the vice president that's why this is Factor one and this is Factor 2 here we have the the Congressional committee and here we have the intrinsic which is the Senate why the Senators are old the intrinsic pathway is very slow it takes time to grow gray hair okay it's slow but they are more efficient they are old and they have experience then the House of Representative those are young guys okay just young kids they are fast they don't know what they are talking about however they are less efficient why because they are young and it's a shorter Cascade what's the most important factor 10 and this is how you teach coagulation Cascade let's do it for the last time here we have the extrinsic pathway the extrinsic pathway has two before 10 two after 10 boom 10 10 a and we are done the rest is history the extrinsic pathway the shorter one only has seven so let's have some fun okay everything here is two letters this extrinsic pathway needs the tissue factor is two letters and we measure it using the PT test Prothrombin time and the drug that inhibits this pathway is warrin actually warrin inhibits both Pathways but it's better measured by the PT test nice let's go to the intrinsic pathway the longer one everything here is three letters it's activated by the sub indal collagen the test for it is the PT and Hein inhibits this pathway actually heprin can inhibit More Than This pathway but it's better measured by the PTT from here to here is called the common pathway and if you are confused between PTT and PT just remember PT has two letters it has to be the shorter pathway which is the extrinsic one PTT has longer letters some people write it like this a PTT it has to be the longer pathway quiz time I've told you that blood coagulates in vitro which means in the test tube via the intrinsic pathway but how come how is that possible since there is no subendothelial collagen in the test tube how are you going to coagulate using the intrinsic pathway let me know in the comment section in the next video we'll talk about fibrine and the tissue plasminogen activator which destroys the clot and restores function thank you for watching don't forget to subscribe support this channel on patreon to get all of my notes thanks for watching and as always be safe stay happy and study hard medicosis Perfection h