Transcription
Hey guys, it's Medicosis Perfection Ellis. This is video number 12 in our series about bleeding and coagulation disorders. In the previous two videos, we have talked about primary hemostasis. Today, let's talk about secondary hemostasis, also known as coagulation. So let's get started. [Music]
Here are the previous videos, so make sure to save this playlist. Hemostasis: Hema means blood; stasis means stable; it is prevention of blood loss or stopping bleeding. Steps of hemostasis: vasoconstriction, temporarily; platelet plug; primary hemostasis; thanks to platelets; coagulation, also known as secondary hemostasis; thanks to coagulation factors; fibrinolysis, resolve the clot and restore the normal blood flow; then regenerate and repair the tissue. Primary hemostasis is balanced on the dynamic harmonious antagonism between the smooth endothelium, which wants blood flow, and thrombocytes, which favor clotting.
Here is the scenario: injury, vasoconstriction, temporary platelet plug. And depending on the type of trauma, if it's a very small platelet plug, is sufficient; we're done. This is primary hemostasis. Thank you so much. If it's larger, we need secondary hemostasis, the coagulation to form fibrin meshwork. The fibrin meshwork will trap the red blood cells, then the clot contracts and serum is produced. Fibrinolysis to restore the blood flow and destroy the clot, and then regeneration.
First step is vasoconstriction. We've talked about it before. Trauma; then the surrounding tissue will exert a back pressure; the muscles surrounding this injury will contract, forcing this vessel to constrict. The vasoconstriction itself is a local myogenic expansion, independent of nerves; local due to contractile factors and some nervous reflexes will help, but the process itself is myogenic. It's like the heart; it has automaticity. Yes, the vagus can slow it down; the sympathetic fibers can speed it up, but the heart itself is autonomous; same concept: vasoconstriction. We have some factors that are pro-constrictions: serotonin, thromboxane A2, epinephrine, and fibrin peptide B.
Like the police who checks the security gate that's safe and secure, and the layer underneath the gate is not exposed; everything is fine. And the engineer inspecting the building that walls are not cracked; what's behind the wall is not exposed; everything is fine. When the stuff is cracked and the underneath, the sub-endothelial collagen starts to be exposed: baby, we have a problem.
In a quick review of primary hemostasis: here is normal intact endothelium; sub-endothelial collagen is not exposed; then injury happens; endothelium is damaged and injured; the sub-endothelium is exposed; platelets will start to swell and form pseudopods, so that they can adhere or roll over and adhere. Platelet adhesion thanks to GP1b and the von Willebrand factor, which is produced from the endothelium and the platelet. Then platelet activation: more swelling; they contract and release granules, which is ADP, von Willebrand factor, and then thromboxane A2.
What are the functions of ADP? ADP helps express GPIIb/IIIa receptor and the conformational change activation. That thromboxane A2 helps with platelet aggregation, vasoconstriction, and bronchoconstriction. ADP expresses the receptor and also helps with platelet aggregation. Thromboxane A2 has more function; that's why it's a whistle plus platelet aggregation. We have a platelet and another platelet, thanks to the whistles, and then we have GPIIb/IIIa here, GPIIb/IIIa here on the other platelet; the fibrinogen molecules is in between; it will be converted into fibrin fibers. This fibrin fibers will help bridge the gap, and those two platelets will fuse together and with the fibrin fibers. Now the red blood cells are coming to be trapped here, and we have a strong meshwork. What helps this is the coagulation cascade. What starts this procoagulation is the platelet factor 3; one of the platelet granules is it alpha or dense alpha? Then we have platelet fusion, thanks to that fibrinogen being converted into fibrin. The coagulation cascade is going on here, and coagulation cascade is called the secondary hemostasis. Then the fibrin is formed from fibrinogen; we have a strong meshwork trapping red blood cells, forming a strong plug. The platelet plug is temporary; the coagulation is relatively permanent; the platelet plug is weak; the coagulation is strong.
Now, brief history lesson about the coagulation cascade. Let's start with the father of Medicine, Hippocrates. He said, "I see some fibers here in the blood vessel; what are these? I have no idea; I'll just call them fibers." Then Galen comes in and calls it thrombus, but he didn't have a clue: why does blood clot outside the body but not inside the vessel? I don't know. Then comes William Hewson: Eureka! The blood can clot; coagulation is king. We have more understanding of the process of coagulation; we called this dude the father of hematology. Then the 1880s: we understood that we have procoagulants and anticoagulants; we will call this thrombin and we call this antithrombin. Then Morawitz's flood spiro hypothesis in 1910. What did Morawitz say? The coagulation is nothing but fibrin fibers; these fibers are formed from a precursor called fibrinogen; thrombin converts this fibrinogen into strong fibrin fibers; thrombin is formed from a precursor called prothrombin. So fibrin is formed from a precursor called fibrinogen, and thrombin is formed from a precursor called prothrombin. What does fibrinogen mean? It means it will help genesis of fibrin. Fibrinogen. What does prothrombin mean? Pro here doesn't mean a professional; it means before, before thrombin, because prothrombin is a precursor for thrombin. So in the early 20th century, this is all of coagulation; no intrinsic or extrinsic nonsense; this is it. Coagulation is nothing but fibrin fibers that trap the red blood cells. Fibrin is present in a precursor, inactivated form, called fibrinogen. In order for this fibrinogen, the inactive, to become fibrin, the active, we need thrombin, the protein of thrombosis. But the thrombin is also present in a precursor, inactivated form, called prothrombin. So we have here the prothrombin being converted into thrombin, and there is something here that's very complicated; has many items and many members; we'll call the thrombin a complex. Prothrombinase because ase means an enzyme, and prothrombinase because it will convert the prothrombin into something else, something better.
After this, Morawitz did a very important thing; he died. So since this is fibrin and fibrinogen, we cannot call it a factor, so because it's, it's the entire goal. When I say the goal is to be successful, so success is the goal. What are the factors that lead to success? We have one to three factors that will lead to success; we cannot say that success is a factor; no, success is the end result. Same thing here; fibrin is not a coagulation factor; fibrin is the end result. What's before fibrin? Fibrinogen; let's call it factor I, boom. What's before fibrinogen? Thrombin, which comes from prothrombin; let's call it factor II, boom. That's how we got the number; because if you listen to your professor, they start with factor XII. What the flip? Like from factor XII to factor, like I, and then after this factor XIII? What? But if you understand history, you will know what you're talking about.
Modern coagulation theory, the nonsense, the intrinsic and the extrinsic and all of this complicated stuff; we added something before this and something after Morawitz, and this is that's it. What's before these two steps? We have a cascade, factors III to XII. There is no such thing as factor VI. We discovered something; we, like, suspected that it was an important part of coagulation, and we call this factor VI, then we realize it has nothing to do with coagulation, so we just drop the number; that's why we don't have any factor VI, but every other number from I to XIII has a coagulation factor; it has a number, which is a Roman numeral, and it has a name. Okay, now you have told us what's before this, these two steps, the cascade; so what comes after it? Factor XIII. We discovered it absolutely by chance, because some patients had a problem after going through all of this cascade and the extrinsic pathway and the intrinsic pathway, forming thrombin, converting fibrinogen into fibrin; these fibrin fibers are trapping the red blood cells; then suddenly, out of the blue, these patients will bleed and die. What? After forming this strong, these strong vibrant fibers that are trapping the red blood cells, forming the secondary strong coagulation fibrin plug, they will bleed and die? Yes, because this fibrin is unstable. Oh, what do you mean unstable? Do you mean that there is something that should stabilize the fibrin? Yes, let's call it fibrin stabilizing factor. Okay, we need a name, done. We need a number; okay, since we have discovered factor XII, let's give it the next number, factor XIII. Check; we have a name, check, and a number, check. That's why we call it factor XIII.
What the flip does a cascade mean? A cascade literally means a small waterfall or a zigzag, okay, or a series of reactions; zigzag falling, a rushing forth, zig-zig-zig; a series of steps; this step is stronger than this one, and this one is stronger than this one, as it moves on; it gains strength, it gains momentum, it gains gravity, it gains traction; this is called acceleration, the change in velocity over change in time; hashtag gravity. That's why the velocity of water here is greater than the velocity of water up here; makes perfect sense. If you have studied biochemistry before, you know that everything in biochemistry is a cascade, a series of reactions; we start with glucose, then by glucokinase, we have glucose-6-phosphate, then another reaction, another reaction, of the reaction, until we're done with glycolysis. Why have a cascade in the first place? Because each step is stronger than the preceding one; hashtag acceleration, hashtag momentum, hashtag traction. This allows time and more steps, which allows for regulation. Instead of having just one step, let's say glucose here and boom ATP here, how would you regulate this? It's just one step; it will happen suddenly in just a fraction of a second; in one step you cannot regulate it, but when you have one, two, three, four, five, six steps, if you wanna regulate it, you can regulate it here, you can regulate it here, you can regulate it here; one of them will be stronger than the others; we call it the rate-limiting step. This is different from all-or-none; this is a cascade; every step is stronger than the preceding one; that's why we have a coagulation cascade to make a strong fibrin; every step is stronger than the preceding one. So we have step here, factor XII, then factor XI, then factor IX, VIII, X, V, boom-boom-boom-boom, fibrin.
So here is the whole story: you injure yourself, then vasoconstriction, then platelet plug, also known as primary hemostasis, then the coagulation cascade, boom-boom-boom-boom-boom-boom-boom; personal number five, original, vibrant, strong because of a cascade. Unless there is platelet activation, in vain there is blood coagulation. First we have to have platelet plug before we have coagulation; without platelet activation, it's impossible to have blood coagulation; take it to the bank. So Medicosis, words of wisdom: there are only two ways to coagulate, but there are tens of ways to bleed. What does that mean? I'll tell you in the next video. Thank you so much for watching. To get my bloody Dropbox links that contain all of my notes, go to patreon.com/medicosis. Don't forget to subscribe and hit the bell; subscription doesn't mean anything if you didn't hit the bell. Go to Facebook for some cases and Instagram for some notes. Thanks a lot for watching; until next time, be safe, stay happy, and study hard. Medicosis Perfection Ellis.