 Okay. So, good day everybody. So, welcome to our discussion for today. So, our discussion on hematology too will be starting on an introduction to hemostasis. Again, good morning to everybody and I hope everybody has their product with them right now. So, as for your reading assignment, okay, reading assignment or you can just simply follow along when I'm discussing will be your products hematology 2020, the 6th edition. So, please turn to chapter 35 and let us talk about normal hemostasis. Specifically, the one that I'll be discussing for today is found on pages 626 to 627, specifically the overview to hemostasis. So, last time during our orientation, okay, last time during our orientation, I already gave you an overview of the hemostasis. So, we said that hemostasis is very important because it preserves your blood in its proper compartment at a proper face at the, at a proper face at the right time. So, I always tell you that the blood should be in a liquid form or the blood should coagulate, okay, the blood should coagulate at a perfect time, at a perfect place and for the right purpose. So, for this particular discussion on your screen right now, so we're going to talk about hemostasis. So, when we talk about hemostasis in general, this is the process in which, it is the process in which the blood is retained within the vascular system during period of injury or it localizes the reaction involved to the site of injury alone and it will not be a systemic bleeding. So, remember that, take for example, you have your bone, you have your wound. So, we want as much as possible to localize the bleeding on that part so that it can be addressed immediately, it can be stopped immediately by our body, okay. But always remember, okay, always remember that hemostasis doesn't just only is concerned when it comes to our blood being in its liquid form, when it is within our blood vessel but it is also responsible in maintaining coagulation once the blood escaped from your blood vessel. At the same time, just like what I told you last time, our ultimate goal is to stop the bleeding, to address the injury and also for tissue repair to happen and after that we can now re-establish the blood flow but before that happens, fibrenolysis should take place first, okay. So, your hemostasis is a system, okay, a system that is very much important to be maintained within our blood, that's why we call it hemostasis. So, as you all know, your blood, your only liquid connective tissue when inside the blood, there should not be any coagulation. So, it should remain fluid, it should be liquid in state when inside our blood vessel, this is for blood flow to happen, that can yet be delivered, your oxygen been delivered all across your tissue and at the same time, when now your blood is outside your blood vessel, when does your blood escape from your blood vessel? So, this is during injury, okay, this is during injury or during tissue damage whereby there is an involvement of your blood vessel, so once that your blood is outside the blood vessel, it needs to coagulate, okay, it's need to coagulate, so here is the time now where your hemotactic reaction happen, all of your coagulation factors, both all the components of your primary and secondary hemostasis which we are going to talk about in a short while will all be involved, okay, so that is the normal state, your blood being liquid when inside your blood vessel and when outside the blood vessel, it should be coagulating, okay, so to prevent further loss of blood. Now, the problem is that there are some hemostasis abnormality, okay, abnormal mechanism inside our body that may cause the opposite of what I just mentioned to you a while back, so what happened is that, what happened when your blood is inside your blood vessel and it coagulated, then that's the problem now because it would need to thrombosis diseases, okay, thrombosis diseases, so the result of excessive blood formation inside your blood vessel or persistence of blood inside your blood vessel can lead to thrombosis, so they can occlude their blood vessel, therefore your oxygen cannot pass through, your nutrients cannot pass through that organ or that particular part of your body will be deprived of nutrients and it would eventually be damaged or it can even lead to cell death. Now, on the other end of the spectrum, if your blood demand is outside your blood and there's also abnormal mechanism, so sabi datin dapat pag, if it is already outside the blood, then it should be coagulating, but the problem is if that didn't happen, okay, there is no coagulation that happened, bleeding will persist or what we call now these are your hemorrhagic diseases. So the problem here, this type, is that when there are any procoagulant, meaning to say, proteins that favor the coagulation of our blood, like your coagulation factors, if there are procoagulants that are missing, deficient in a particular individual, then okay, what will happen is that there would be an uncontrolled bleeding, so your patient will just bleed and bleed all throughout, there will be severe blood loss, and there will be hemorrhage that will also lead to death. So in a nutshell, it's very important that our blood should be maintained in its liquid form inside the blood vessel and when the blood escaped from your blood vessel, it should be coagulating. So this particular mechanism is very much maintained, did usually, inside our body. So at the very moment that your blood escaped, a lot of your proteins will also ready to be released to favor coagulation, but at the same time, there are also inhibitors that will be secreted so to ensure that your blood, your blood will not be coagulated. Excessively, there will not be thrombus formation or clot formation anywhere in your body. Again, always remember, the clot should happen at the right time, at the right place, and at the right, for the right purpose. Okay, so in addition to that now, okay, when we talk about hemostasis, it's not just a job of your, it's not just the job of your platelets, although platelet is one key player, but platelet is not alone, so for us to be able to understand how hemostasis happen, we will also be talking about today the different key components of hemostasis which are as follow. So there are two general classification of the different components of hemostasis. First are the cellular components and second are the plasma components. So when we talk about cellular components, these are now the cells of your vascular intima. To be more specific, these are your endothelial cells. Okay, this will be part of our discussion in the coming weeks when we will be talking about your vascular intima. Next, we also have your vascular tissue factor bearing cells. So very simple. All of your tissue cells that can produce or that contains your tissue factor is included here. Okay, so they secrete a very important coagulation factor, coagulation factor three, which is your tissue factor. Also favoring your coagulation. And of course, last but definitely not the least, we have your platelets, your platelets being one of the key cellular components for your hemostasis. As for the plasma components, we also have your coagulation proteins. Your coagulation proteins, these are the proteins that favor coagulation. You can also read this in your rodac as pro-coagulant or in other words, they are also called your coagulation proteins meaning to say once that they are present and activated inside your body, they will favor coagulation. At the other end, we also have your fibrolytic proteins. So remember, I told you last time that when it comes to fibrolytic proteins, these are proteins now that will elicit or that will trigger the lysis or that will hasten the clot to be dissolved inside your body. So once the tissue repair is on its way, the clot that has been formed will now have to be lice or now have to be destroyed and be cleared out of your blood vessel. How? That is through the health of your fibrolytic proteins. Now, aside from coagulation proteins and fibrolytic proteins, coagulation, one that promotes coagulation, fibrolytic, the one that the group of proteins that will lice or destroy now or dissolve your clot, we also have your inhibitors. Inhibitors now are the one that inhibits your coagulation proteins. For example, there is a bystander clot formation inside your blood vessel. There is no need for clot formation to happen but it happened. So your inhibitors now will prevent the coagulation from further developing into a stabilized clot. On the other end, you also have your inhibitors for your fibrolytic proteins. What is the purpose of these inhibitors? The inhibitors of your fibrolytic protein. So remember, fibrolytic proteins should only be activated once that tissue repair is about to happen. That is to clear out the clot, that is to clear out the passage of the blood and kung hindi pa tapos, if the repair is not yet done, if the blood vessel is still healing, the clot should remain there. Do not remove the clot if it's not yet time. Take for example, your baking cake in the oven and then you remove it under time. You did not wait for 30 minutes, just remove it after 5 minutes. Of course, that is uncooked. So to be able to inhibit, for you to ensure that it will be cooked, you have to put some inhibitors. For example, the oven cannot be opened until the timer is done. Inside our body, it's also very similar. We have inhibitors that will prevent fibrolytic protein from destroying the clot if it's not yet time to be destroyed. So these mechanisms happen inside our body in a very close and tedious manner so that we will be able to prevent the clot from being destroyed unknowingly. And we'll be able to prevent it from being destroyed na wala pang t-shirt repair na nangyari. So apologies for that quick commercial. Aside from the components of your hemostasis being classified as cellular components and plasma components, we can further classify them according to where they belong. So some belong to your primary hemostasis, some belong to your secondary hemostasis, and now your fibrolysis. So these are the processes of your hemostasis. So let's first talk about your primary hemostasis. So when we talk about primary hemostasis, primary hemostasis is usually activated by small injuries to blood vessels. So primary hemostasis is very rapid yet short lived response. So this is just like a first aid scenario inside our body. So it is very rapid, once there is a small injury in the blood vessel, it is the first one to be activated, but it is short lived. So what are the components of your primary hemostasis? So the components are your vascular system, starting off from the smallest blood vessel that we have, which are your what? Which are your capillaries, also included here are your arteries, and of course your veins as well. So what important thing that I want you guys to remember is that the main component responsible for the primary hemostasis specifically for your vascular system are your vascular intima. Your vascular intima or your endothelium, or as product one to call it, your endothelial cells. So when we say endothelial cell, endothelium, and vascular intima, which is the innermost layer of your blood vessel, vascular intima, which are all made up of your endothelium, that is component that is part of your primary hemostasis. At the same time, we also include your platelets, okay? We also include your platelets. So let's have a quick quen to how does it happen. So for example, how does your primary hemostasis happen? So as you all know, once there is a small injury, the vascular system would contract to seal the wound, and that is the initial hemotactic response that is your vasoconstriction. So remember that people, the initial hemostatic response of our body, specifically our vascular system, is your vasoconstriction. Vasoconstriction helps so that we can seal the wound, we can seal the wound and prevent further or excessive loss of blood, but that will not be enough. Why? Because we also need to have your platelet plug. So your platelet plug, okay? Your platelet plug is, of course, made up of your platelet that fill the open space of your wound, so that is to form your platelet plug. So remember that the innermost vascular lining of your blood vessel, your vascular intima, are aligned by your endothelial cells. So aside from your endothelial cells, you also have your supporting structures for your endothelial cells like your internal elastic lamina, your elastin and your collagen, which in return, once exposed, once your platelet are exposed to elastin and collagen, they will be activated. Once they are activated, they will adhere to the site of injury. So as you can see here, your platelets now started to adhere to the wound or to the blood vessel wound. Aside from that, I also want you guys to remember that on your subendothelial, remember that your blood vessel has layers, right? Your vascular, your adventisha, your adventisha, the outermost layer of your blood vessel, okay? And the innermost layer of your blood vessel also interacts. So you have your subendothelial connective tissue containing your collagen, your fibroblast, okay? And also smooth muscle and your artery. These are your arteries. If it's just your veins, these are only your collagen and fibroblast. Sir, why is your fibroblast important? Your fibroblast is important when it comes to the repair part of your blood vessel. So they are the one that will produce new set of cells that will close the blood vessel, okay? But to summarize everything that I just mentioned about primary hemostasis and what once that there is a small injury and the blood vessel, a rapid and a short response called your primary hemostasis will take place. Again, the key player of this or your vascular system and your platelet, how does they prevent your bleeding? They prevent bleeding by first sealing, okay? The wound, how do they seal the wound by the initial hemostatic response, which is your vasoconstriction? And afterwards platelet will fill in the gap or will fill in now the open space coming from your wound producing a platelet plug. And your platelet plug in other books, you can read it as your primary hemostatic plug, okay? Your primary hemostatic plug. Your primary hemostatic plug ladies and gentlemen are mainly made up of your platelets alone, okay? Let me repeat that. It is only your platelet. Why? Because we are still in the primary hemostasis. So, meaning sir, there is a more advanced or a better, a more advanced or a secondary response after your primary. Yes, that's very correct. Your primary hemostasis is the first aid. It is the first thing that would happen followed by your secondary hemostasis. Secondary hemostasis will now be activated once that the primary hemostasis response is not enough. How would that be or when are the times that it's going to happen? First, when your secondary hemostasis will be activated by a large injury, large injuries to your blood vessel. Like, for example, there is really a big wound, okay? Your blood vessel was caught. So, lots of blood will be coming out or will be, lots of blood will be, will escape your blood vessel. So, when it comes to your secondary hemostasis, this is activated again by a large injury of your blood vessels. This is a delayed response, okay? But the good thing about this is that it is a long-term response, okay? It is a long-term response. So, the following components of your secondary hemostasis are as follow. So, components are your coagulation factors, your coagulation inhibitors. So, your coagulation factors are those that promote coagulation. We also call this your procoagulance and your coagulation inhibitors. Obviously, these are their inhibitors. So, to prevent any unwanted clot formation inside your blood vessels, okay? So, to prevent any unwanted blood, to prevent any unwanted clot formation in the body, they're also coagulation inhibitors, okay? Coagulation inhibitors that are also found in your blood. So, to prevent any unwanted coagulation, okay? Any coagulation. So, with that, okay, let's also talk about how does the secondary hemostasis happen. So, the secondary hemostasis happened by the interaction of your coagulation factors. So, to produce fibrin clot, okay? Your fibrin clot, which is what we call now your secondary hemostatic clot. Remember that in the primary hemostasis, the end product there will be a platelet clot, a platelet clot that will prevent bleeding. That is your primary hemostatic clot. And now, for your secondary hemostasis, we have now the interaction of your coagulation factor. So, I'll part this. I won't be discussing the coagulation factors yet because we will be discussing that around the fifth week before the fifth week of our discussion. And we will also be talking about the coagulation cascade, okay? It is a pathway in which your proteins are activated simultaneously one after the other to produce now your fibrin clot. Remember that your fibrin clot is from the activation of your factor one or your fibrinogen. Fibrinogen becoming your fibrin, okay? Your fibrinogen now becoming your fibrin. And the ultimate protein, okay, or the ultimate enzyme that we want to produce there is your thrombin. Thrombin now will be the one to convert your fibrinogen to fibrin, paking it now or producing now a fibrin clot. So, as you can see, once that the secondary hemostatic clot happened, okay, it needs to be stabilized. And it will be stabilized by your factor 13, which is now your fibrin stabilization. So, if you guys can see, no, if you guys can see your screen right now, initially, okay, initially, once that there is a damage here, okay, the first thing that will always happen will be your primary hemostasis. The first line of defense in your blood vessel is your endothelium or your vascular system and then your platelets. Once that it will not, once that their effort is not enough, that's the time that the secondary hemostasis will be activated. These are now your coagulation factor. Your coagulation factor will form your fibrin clot. The one that you see here like a mesh surrounding the blood vessels, the platelets and the red blood cells, okay, these are your, this is your fibrin clot. But your fibrin clot needs to be further stabilized as to prevent it from breaking, okay, that is now through the help of your factor 13. Okay, that is now through the help of your factor 13. You guys don't worry because will be, this is just an overview of hemostasis. In the coming days after your mega-choreocytopoiesis will be discussing the components of your primary and your secondary hemostasis and talk about more about how they happen and what are the other neat and gritty details about these processes. And finally, we also have your fibrenolysis. Now, in your fibrenolysis, remember that this is now the final stage of coagulation. Fibrenolysis will only happen once that the wound is sealed and now we are ready to repair the blood vessels. So this is the final stage of coagulation. So as you can see, there will now be thrombolysis. Thrombolysis or your fibrinolysis is one and the same. As you can see, there are a lot of proteins, okay, there are a lot of proteins that will digest your fibrin clot. So the digestion of your fibrin clot keeps the vascular system free of deposited fibrin or fibrin clot. Why? Number one, deposited fibrin and fibrin clot will clog your blood vessel, okay? Barado ang ating blood vessel if the fibrin will not be removed. Aside from that, fibrin and fibrin and fibrin clot, okay? Your fibrin or your fibrin clot can also cause, okay? Can also cause, ayo, nabangkit ko na, deposition, okay? Deposition of clot inside your body that will cause clogging, okay? So your fibrinolysis occurs when your plasminogen is converted to plasmine. So plasminogen is zymogen, meaning to say an inactive enzyme. So once that it is activated, okay? Once that it is activated by your thrombine, it will now be converted to plasmine, okay? So your plasmine will now be the one that will lyse your fibrin clot, okay? It will lyse your fibrin clot. Remember that the cleaving or the digestion of your fibrin clot is very important, okay? It's very important. So under normal circumstances, your plasminogen is just a part of any clot, okay? As to, ayo, because of the tendency of your fibrin clot to absorb plasminogen from the plasma. So when the time is right, okay? When the time is right, when your plasminogen activators perform their function, your plasminogen now will be converted to plasmine and your plasmine now will start to clean up, will start to digest your clot while leaving time for tissue repair to happen and re-establishing the blood flow, okay? Re-establishing the blood flow. So how does your fibrinolysis happen? So first, release of tissue plasminogen activators and then the plasminogen will be converted to plasmine. Now your plasmine will degrade or digest your fibrin converting them, okay, to fibrin degradation products. Your fibrin degradation products will be talking about that on the latter part of our rheumatology too. But hopefully you understood the concept of hemostasis. So from primary hemostasis, so let's have a quick review lang mo, from primary hemostasis, okay? So in primary hemostasis, what's the first thing that happened? Okay, the first thing that happened, if there any injury in your blood vessel, it will first, the initial hemostatic response, it will lead to what? It will lead to vasoconstriction. So after vasoconstriction, okay, your platelets now will be exposed to your collagen and your elastin. It will attach to that, okay? And then it will now fill up the gap or the wound as to prevent bleeding. If that's not enough, your secondary hemostasis will be activated. And how it is activated, it is through the activation of your coagulation factors. Coagulation factors that will lead to the formation of your fibrin clot. Now once your fibrin clot is produced, okay? Once that your fibrin clot is produced, it will remain there for as long as it is needed. But let us assume that the task is already finished. We will now be entering the final stage of your coagulation, which is your fibrinolysis. And in your fibrinolysis, a protein called your plasmidogen will be converted, will be activated to become your plasmidogen. Your blood to become your plasmid and your plasmid will further convert to your fibrin. Okay? Or your fibrin clot to their degradation products. Okay? Your fibrin degradation product and will now re-establish your blood flow. So I prepared a very, very quick picture here. So when there's injury, okay, there will be vasoconstriction. And at the same time, platelets, okay, will adhere to the wound, will fill up the gap. So that is primary hemostasis. If this once is not enough, okay, your coagulation factors, okay, your platelet plug will not be enough. Your coagulation factors will be activated, forming now your fibrin clot. Okay? Once that's finished, repair is on its way. We need to re-establish the blood flow. Fibrinolysis now will happen. So remember, guys, okay, remember, guys, few things. You should be able to remember the three important stages of hemostasis. Your primary secondary hemostasis and your fibrinolysis. Second, what are the different cellular and plasma components belonging to your primary hemostasis. Your secondary hemostasis and your fibrinolysis. Finally, I also want you to remember what three things, okay, before we end this particular part of our discussion. What is the initial hemostatic response that is vasoconstriction? Okay, second, what is the primary, what is the other name of your primary hemostatic plug that is your platelet plug? Okay, that is your platelet plug. And finally, what do you call the secondary hemostatic plug that is your fibrin clot? What stabilizes your fibrin clot that is your activated factor 13? So I hope our discussion about hemostasis is clear. So again, the ultimate purpose of this is to maintain the blood inside your blood vessel as fluid with no coagulation. If it is outside your blood already, it needs to coagulate. And of course, let's also not forget your fibrinolysis. Again, let me remind everybody to please read on pages 626 to 627, only the overview of hemostasis paragraph, okay. So with that, thank you so much for listening, everyone. So there is a second video right after this. We'll be talking about your mega-choreocytopoeages. So I'll see you on the next video. Thank you so much and have a great day.