 the lecture series on animal physiology in NPTEL. So, we are in section 6 which is blood cells immunity and clotting. So, initially we have dealt with the blood cells in this first lecture in this section and I am just bypassing the immunity section and I am moving on to the clotting and I will come back to the immunity. So, when I was explaining about the different kind of blood cells I told you that there are broadly speaking there are three kinds of blood cells. Red blood cells, white blood cells and the platelets and the red blood cells are the cells which has no nucleus and I explain you how the nucleus kind of gets degenerated during the formation of these cells. And I also mentioned that these red blood cells have a life of 100 to 120 days after which they are engulfed by the macrophages or the white blood cells and they are being destroyed and all the iron and all other thing which makes the hemoglobin molecule is being reabsorbed by the body. So, that was pretty much about the red blood cells and I have not discussed one part which I will be doing in summation once I will be winding up the this whole section is how all these cells have developed. But apart from so among these two three kind of blood cells red blood cell white blood cells and the platelets this third type the platelets they also do not have nucleus, but there is something more interesting about these cells. So, they are not purely really cells they are something they do not have any nucleus other than. So, mark my word there are few invertebrates they have platelets or some other maybe there are some other vertebrates which have platelet with nucleus, but in human being the platelets are not having a nucleus. They are essentially it is something like that they are cellular pieces you can call it suppose there is a huge cell and it kind of you know chopped down into pieces. So, what happens part of the cytoplasm engulfed into a bilipid membrane and those are kind of small vesicle like structure and they are around 3 to 4 micron or I mean long and they are kind of elongated shape kind of cells. It is kind of if you look it under the microscope if you take a blood smear and look it under the microscope it looks more or less like a triangular kind of shape at a low resolution microscope they look like you know like you know this something like this this kind of shape of cells, but these in nucleated or without nucleated nucleus cells are of extreme importance for some one of the very interesting phenomena which is called blood clotting or in other word the repair of the blood vessels. So, while talking about this let us take a simple system simple physical system say for example, you make a pipe. So, say for example, so you see this. So, I roll it down like this something like a pipe structure. So, you could see this is a see through pipe out here. So, say for example, fluid flows through this pipe and it is all sealed all from the top to the bottom. Now, say for example, I you create by some reason a hole is formed. So, whatsoever the fluid flowing through it will start oozing out and eventually that hole will become bigger and bigger and bigger and eventually no fluid can flow this whole thing will kind of you know tear up out into two pieces fine, but if that happens say for example, in your blood vessel then this is a serious problem. The blood won't flow and basically we will die oxygen won't be supplied to all parts of the body and blood will mix up in the outer extracellular space and we will lose all the nutrients and everything will be in a mess. So, and yet we are always prone to injuries you know you fell down what you see essentially is that you fell down. So, blood starts coming out from x y z part of your body and then after sometime it stops and then what you see is that after few days you see a kind of a heart tissue forms there and eventually that is also whites of and you are hell and hearty. So, there is a self-repairing mechanism and this self-repairing mechanism of the blood vessel is initiated by the process called blood clotting which is a very controlled process it has to be regulated at a very the very I should say precise fine tuning why is it so is that if the repair mechanism exceeds certain limit then it will lead to blood clots blood clot means you know globules say for example, the blood is flowing through this these are basically particles these are cells. So, if there is a clot it will form a kind of lumpy like a structure if a huge lump kind of you know gets here this is going to block the flow of the fluid. So, if there is a damage then it has to be repaired. So, there will be some degree of clotting, clotting has to be regulated in a very fine tuned fashion and this whole clotting mechanism one of the central player in this clotting mechanism is the blood cells bloodlets are you can call them the in a simple analogy the tailors of the blood vessels they are just like tailor they go whenever there is stitching is needed or the stitching elements of the blood vessel they go there and stitch the part which is broken. And this whole cascade of clotting is divided into three different stages here first is a vascular stage and I will come to that then there is a platelet movement stage then there is a clotting coagulation state, but it is a chain of reaction which initiates at 0 or the first the exact moment when there is a kind of rupture in the blood vessels. And within 15 to 30 seconds pretty much all the process comes into play. So, but in order to understand this whole process we need to divide it into different compartments. So, phase one phase two phase three, but mind it pretty much all the phases overlap with the other one it is not like that one phase is exclusive and then the second one takes place and then the third one takes place. So, they are all overlap with each other that is something you have to understand it is not something like you know one phase stand alone second phase is stand alone third phase stand alone. There is another thing which you have to understand why I am telling I will giving in the overview because that will help you once I will get in the technical details there are two major component which are involved in this whole process first component is the blood component. The platelets and all those components red blood cells white blood cells which are flowing through it those component are called intrinsic components and it there is another set of components who are not part of the blood they may be part of the vessel like you know endothelial cells or the surrounding tissue and those are called extrinsic factors. So, this is regulated by extrinsic factor and intrinsic factors and these different intrinsic and extrinsic factors are responsible for regulating the different feedback mechanisms which are involved in it controlling the flow of controlling the secretion of different kind of molecules which will regulate this whole process. So, it is a very fine tuned very well organized process starting from the formation of the platelets. So, what we will do now I will give you some of the simple details which is essential for you to you know grasp the topic and then we will go technically one by one at the different stages and I will try to make it as diagrammatic as possible so that it helps you to visualize this in front of you how this whole process is taking place. So, let us first of all get some of the technical details of the platelets itself how the platelet is forming. So, diagrammatically how it looks like how small those are what is the number we are talking about in mind it this is one thing you people wish to kind of retain in your mind that if the half life of a red blood cell is 120 days half life of a platelet is very low very very very low it is almost may be a day or less than that that is the half life of a platelet. We will come to those we will come to those some of those some of those logistical or statistical details which you need to know and the technical aspect of it, but it has to be very clear in your visualization how this whole process of a rupture and what immediately happens what are the cascade of reactions has to be very very clear in your mind. Let us get into the some of the technical details what we are talking about. So, here we are talking about the platelets and the blood clotting. So, in this section so basically what we are trying today so I told you that with if you look at the platelet they look like this something like you know this kind of they do not have any nucleus essentially how they are formed is basically there are huge cells and these huge cells especially what you see is these are basically called thrombocytes from there comes these smaller fragments which forms the platelets and their average diameter is around 4 micron meter and roughly 1 micron meter of the thickness. This is essentially is talking about their size and they are essentially are individual they are the different fragments and their half life is 9 to 12 days sorry this is the total days total total circulation time and at times it could be even a day and each microliter of blood per microliter of blood contains the you can call them as particle hundred. So, this is these are some of the statistics which I would recommend you to remember and some of the disease related to platelets are thrombocytopenia where essentially the platelet count is very low around 80,000 per microliter and automatically such patients have clotting it will be compromised this is one of the major problems that patient faces and then you have thrombocytosis these are the patient whose platelet count goes extremely high per microliter sorry. So, these this is the situation which happens sometime in cancer and some kind of inflammation disorder and all the things. So, if you look at in terms of the number these are fairly high in terms of the number and this number has to be regulated very tightly the number goes up then also there is a problem the number goes down then there is a problem the reason is that your size of your blood vessel or the dimension of your blood vessel is limited and it has a limited degree of elastic feature. So, if the total number of particle goes up as it happens in thrombocytosis automatically the viscosity of the blood increases big time when the viscosity increases the flow reduces. So, automatically if the part of the body needs oxygen at a certain period of time. So, the oxygen will be reaching slowly because the blood has to there are too many particle it is just like you know a muddy water flowing through think of it huge amount of muddy water that flows slowly because the total number of particles are very huge in that situation. Whereas, if it goes low say for example, the thrombocytopenia where your platelet count has gone down. So, in that situation the problem is that if there is a damage blood vessel damage then the total number of platelet which has to reach to that spot will be less and there would not be any significant backup coming. So, automatically such patients are prone to excess blood loss. So, these are the two extreme situations and now what we will do I will enumerate all the different functions of platelets. Let us get into the functions of platelets among the functions. So, basically it is a transporting it transports all the important all the important clotting molecules. This is the major function by this time it is very clear to you people and then apart from it it is it forms a patch at the site of blood vessel damage. This is the second major function third major function it has it is it has an active contraction after clot formation. In other word what that essentially means is that once the clot is formed after sometime once the whole repairing of the vessel has taken place then it has to be retracted back the clot has to retract back it has to be moved out otherwise you will always see say for example, you have a cut here after the cut is kind of repaired and the clot has to be you know moved out it has to be thrown out of the system otherwise there will be always a scar out there. So, this scar has to be moved out. So, that is called a clot retraction process. So, these are the three major functions which is which is very very tightly regulated with a optimal number of platelets in your body and which are regulated by a cascade of chemical reactions what we are going to talk now. So, let us talk about I told you in the beginning which is a cascade of three step reaction. So, now what we will do I will enumerate first of all I will enumerate all the three different states which are involved in the clotting and then we will pick up one step after another and we will discuss what exactly happens in those state. So, now I was talking about the stages steps or in step one basically is your. So, this whole so that is one step is called the vascular phase phase one phase two is little at phase which is phase two and there is a third phase which is called coagulation phase which is the coagulation phase these are the three phases which are involved in the whole process of hemostasis. So, this whole process is called hemostasis essentially what does that mean is that hemostasis means cessation of bleeding HEMO hemostasis where basically if you break this word heima means blood in Greek heima in blood and stasis halting the blood the leakage of the blood. So, now what we will do we will start with the vascular phase what really vascular phase is about. So, in order to explain the vascular phase I will again take this analogy which will help you write this paper. So, I roll this paper. So, this is imagine this is a blood vessel now say for example, there is a leakage somewhere or imagine somewhere. So, if there is a leakage here. So, essentially what happens as more and more pressure goes the leak the leaky spot goes becomes bigger or something like this. So, imagine this is the vessel and you have a kind of leak here. So, essentially this is how it works inanimate object like this this leak goes on increasing and eventually this leaky thing becomes this big and then this big likewise this thing increases. But in the case of blood vessels there is something called a phenomena called vascular spasm takes place whenever there is a damage what vascular spasm means essentially what vascular spasm means say for example, we have to take an extreme example to explain this. So, if this is the blood vessel imagine this is your blood vessel through the blood is flowing through now if there is a cut something like this I am cutting it into two pieces. So, this is the part of the vessel and this is the other part of the vessel. So, what happens is that under this situation these sites these two sites become narrows down. So, the diameter of these two ends damaged end becomes narrowed something like this and if you look at it they become narrowing down the diameter here is more and diameter here is less. And this process is a inherent tendency of the smooth muscles which are forming the blood vessels along with the endothelial covering. So, they contract like this and this contraction process. So, essentially if I have to draw this it will be something like this. So, imagine this is your this is your blood vessel fine. So, now there is say for example, you create a cut out here. So, then what will happen this vessel this is the vascular spasm situation. So, here the diameter if you look at diameters out here this is all same, but the diameter here is reduced. This reduction is diameter at time. So, imagine if this vessel is like you know some say if the thickness of this vessel is the cross section of this vessel is same as say for example, out say 20 microns or say 30 micron. So, at that level there is a significant reduction out here and this whole change is called vascular spasm. This is a very very critical step in the formation of the vascular phase. This is part of the next thing what happens in this is that this is regulated by the endothelial cells endothelial cells contracts. As I was telling you and expose the underlying basement membrane to the bloodstream the important part is that this part underlying the basement membrane to the bloodstream. Because this is where another next set of reactions starts to take place in the vascular spasm phase. So, what essentially happens is this than this endothelial cell lining cell lining secret certain compounds which includes your ADP tissue factor and endothelins. These are the different factors which are secreted endothelins. These are the different factors which are being secreted at that point and there is one more thing what happens at this phase. These two zones these two zones becomes fairly sticky. So, in other word if I have to again take the paper analogy out here which will help you to understand. So, these two ends start to secret certain things which makes it fairly more sticky. So, they try to you know glue together it is just like there is we put some glue and they started to glue together slowly. So, these are some of the reactions which takes place in the endothelial phase and what we will do now I will just put them in a drawing in a diagram. So, that from there we could graduate to the next level which is the which is essentially the platelet phase because as soon as there is. So, for example, the if imagine these are the blood cells which are moving these the blue ones are the blood cells which are traveling along it and this imagine that the direction of this things like this. So, as soon as there is a damage here so these cells are coming out and this is what is the blood is flowing out. So, at this stage certain things happens and this is I will put it diagrammatically that will help you to appreciate what exactly happens at that point. So, if I have to draw it really in terms of. So, now I will put all the cells in place likewise these are the endothelial cells of the basement membrane and something like this these are the nucleus these are the cells all over the place and this is the blood vessels. Now, I am putting all the cellular structures in place and this is the basement membrane and this is the zone where this is the zone cut edge of blood vessel. Here you have the upper part of the blood vessels and here you have the endothelial cells out here likewise and here you have the interstitial fluid on this side interstitial fluid and these are endothelins this is what essentially happens. So, as soon as there is a breakage here the platelet starts to come out at this zone because they are the smallest one. So, now in the blue you see the platelets all over the place these are the blue cells are the platelets and platelets tries to aggregate at this spot. So, these are the platelets so what is happening is that they are aggregating at the site of injury while they are aggregating simultaneously from the platelet as well as from the surrounding there is secretion of certain factors and the secretion could take place either from these cells what I am just shedding in red now from these cells as well as from these cells as well as from these cells what I circulate put the circle this leads to the secretion of ADP thrombax in A 2 thrombax in A 2 calcium and platelet factors. So, at the site of injury these are the different compounds which are being secreted out and the next phase comes is the platelet phase. So, and mind it these are all happening like now fraction of a moment like within 15 seconds of the injury the platelet is started to accumulate at the site as I was drawing with all the blue cells what do you see those are accumulating at that spot and that initiates the platelet phase. So, there is a overlapping and mind it the vascular phase is continuing because it is still there are secretion of chemicals which will continue for few more hours. So, it is not as I was telling in the beginning it is not a water tight compound phase 1 phase 2 phase 3 no phase 1 phase 2 and then there is a phase 3 they are all overlap over one another. So, now we will diagrammatically show the platelet phase the phase 2 coming back to the slides. So, now we are into the platelet phase. So, platelet phase is shown by first is first reaction is platelet adhesion as I told you that at that site at the site of injury there is an adhesive sticky situation. Then this form platelet aggregation because of the adhesion platelet aggregation and the third phase is forming platelet plug these are the three things which happens at that phase and apart from it as I was enumerating there are secretion of a bunch of compounds which takes place which includes ADP, calcium thrombaxan A2 and you have PDGF platelet derived growth factors and you have the calcium ions and you have few other clotting factors. These are the different factors which are secreted at this phase and apart from it the there are few other compounds which are secreted which basically limit the formation of platelet plug which includes preventing excess platelet plug and why it is important I will just explain is done by molecules like prostacycline, prostacycline and prostacycline. And few other inhibitory molecules which includes sometime serotonin and few other molecules which are known. So, the essentially what happens if the plug is becomes. So, again I will take this paper example if the plug becomes too sticky out there. So, what will happen the blood would not be able to flow from this site to this site. So, in order to ensure that the blood continues to flow maybe at a slower velocity at that point because it is kind of you know lesser amount of blood will move because it will slow down because the diameter has reduced down. But, if it is become too sticky and there are too many plugs of platelet starts forming and automatically what will happen is that that the blood flow will be interrupted for longer. So, you have to ensure that this whole process of plugging in. So, adhesion, aggregation, plug formation has to be very tightly regulated. If there is a little error in that then there will be a problem and this is the hallmark of the body. It is a very smart machine it is one of the it is build with probably some of the most smartest material you can ever think of on the floor of earth and it just very tightly regulated. As soon as that plug formation and still these are some of the mysteries what really determine that this much sufficient plug has formed. What is that feedback loop to say we do not need to recruit any more platelets out there because you are recruiting platelet at the site of injury. So, now who says that I do not need more platelet these are falls under the most beautiful area biology called the signal transduction or signal processing or feedback loops. So, there is a inbuilt feedback loop which says that we do not need any more of the platelets out there fine. Now, we can proceed with the phase three of the game which is the clotting factor or the clotting phase or coagulation phase which is what you call that. So, now from there we will move on to the coagulation phase and this is the coagulation phase here we will be talking about almost 12 different clotting factors and how they regulate this process. So, in this clotting the coagulation phase or the clotting phase there are two sets of chemical reactions which are involved. One is called extrinsic reaction the other one is called intrinsic reaction. Intrinsic reaction are the ones which are carried out by the blood cells as I was mentioning in the beginning of the talk by the platelets and all other cells which are involved the blood cells blood vessel is involved in this whole thing. All the blood components are secreting factors they regulate the intrinsic pathway and then there is an extrinsic pathway which is regulated by the vessels around or the surrounding tissue or the endothelial cells which is not component of the blood it is just forming the vessel those are called extrinsic pathways. So, these two pathways merge at one point and results in the whole clotting process and that is what we are going to regulate and what are the regulatory mechanism which says clotting is done no further clotting is needed otherwise there will be blood aggregation and the flow the dynamics of flow of blood will be hindered. So, now what we will do in the coagulation phase will diagrammatically see the extrinsic factor and the intrinsic factor how they are regulating this whole process of clotting and then what I will do I will put a table for you with of all the factors and the regular names and where they are being produced. Let us move on to the phase three of it which is the clotting phase or the coagulation phase the coagulation phase in the coagulation phase. So, this is what essentially happens I will again redraw what I was drawing the just the last diagram while I was drawing the injury site that will help you to understand it much better these are the different cells which are forming the basement cells if you follow the previous diagram and this is the site where the let me redraw it that will help you to sorry for this mix up fine. So, here is the basement layer the basement layer and here is the injury site. So, I am just putting the injury site like this with the cross this is the injury site and these are the cells of the blood vessels which are forming the blood vessels likewise and we will draw the endothelial cells and then we will again make the platelet plug and from there we will initiate the process of. So, here you have the endothelial cells which I am drawing now these are the EC endothelial cell endothelial cell basement cells now. So, this is the site now what you see essentially here are lot of platelets and when the platelets move at the injury site they change their shape they become more circular from triangular they become more and more circular and more and more spherical because they have to accommodate in large number and as we know the spheres does it better in terms of the maximum number of spheres could be accommodated in one spot. So, this is where the plug has to be formed. So, now the two pathways this starts to function. So, on my right what we will do on this right we will be talking about the intrinsic pathway on the left we will talk about the extrinsic pathway extrinsic and the red will show the extrinsic with red and intrinsic with blue. So, the first thing intrinsic means these are all coming from the platelets. So, platelets or other blood vessels which are involved in it. So, the first thing happens is activated pro enzymes usually factor 12 activated pro enzyme which is also called factor 12. So, there are 12 different factors I was telling you this particular factor reacts with platelet factor P F factor 3 P F 3 platelet factor 3 and further a reaction with calcium leading and further addition of clotting factors C F stands for clotting factor 8 and clotting factor 9 clotting factor 8 and clotting factor 9 further with clotting factor 10 activator complex initiates the reaction and this eventually leads here the common pathway comes again the role of factor 10. So, factor 10 activator complex comes here and that factor 10 activator complex leads to the formation or the activation of the factor 10. So, now here this is the part which is the common pathway from here it is all common from the left and once I come to the extrinsic from the extrinsic side you will realize that common pathway. So, factor 10 activated. So, again to summarize so activated pro enzyme factor 12 secreted by the platelet reaction with platelet factor 3 and calcium it leads to formation of clotting factor and the reaction of clotting factor 8 and 9 activates something called platelet 10 activating factor and activating platelet the factor 10. Now, factor 10 simultaneously what is happening from this damage tissues out here from this tissue damage and endothelial cells and the basement cells this secret something called tissue factor. So, on that side you saw the you saw the platelet clotting factors or the platelet factors on the other side you say tissue factor 3 this tissue factor 3 so on react with calcium then clotting factor 7 then that goes to factor 7 tissue factor complex and then this activates to factor 10. So, now the common pathway starts. So, if you look at it on your left on the extrinsic pathway and the intrinsic pathway and the source of extrinsic pathway are all the damage tissues out here and the source of intrinsic pathway are all the platelets which are present here and these are the platelets. So, now there are series of reaction taking at this stage which I am putting in green now. So, that activates something called pro thrombinase this pro thrombinase leads to a reaction of pro thrombin to thrombin pro thrombin to thrombin and this thrombin then leads to the conversion of fibrinogen to fibrin and this fibrin is the one which essentially forms the clot and coming back while summarizing the whole process. So, when you are kind of creating a stitching. So, you need thread to stitch. So, the thread component in this game is the fibrin there is a fibrin thread which forms a mesh work like this you see consider these my fingers as fibrin but they do not get activated till there is this thrombin coming into play which breaks down the fibrinogen to fibrin that conversion and thrombin never gets activated because it remains in a pro thrombin state till it gets thrombinase and thrombinase never get activated till factor 10 comes into play and factor 10 would not get activated till both extrinsic pathways from factor like tissue factor 7 from the extrinsic pathway factor 10 activating complex from the intrinsic pathway comes and activated. So, this whole cascade is a function of injury if by chance this cascade gets activated all by itself we would not be alive because all our bloods will start getting clotting in the vessel and blood on flow. So, you realize that this has to be very very temporally very tightly regulated if there is a little problem in this whole thing there will be some serious issues will be facing now let us look at anyway I will be enumerating all these factors what I have just drawn for you people and let us talk about some of the control pathways which are controlling this whole process coming back to the slides. So, slides let me go to a fresh slide to explain this is. So, if you look at it. So, there are different the different feedback loops which are involved in it and these are control some of these are controlled by the calcium, vitamin K and will be coming to that all these different factors and apart from it there are certain other factors which needs to be talked about is called heparin these are the one which are controlling the feedback control of blood clotting feedback control of blood clotting. This is done by heparin thrombomodulin H R O M B O thrombomodulin this is done by protein C. So, these are the ones which are this heparin is being released by Bacophil and I will be coming to Bacophil while I will be talking about the white blood cells these are part of that. So, they basically ensure that you know this whole is basically it is it prevents clotting. So, if you see there are there are vacutiners where the blood is being collected they are called heparinized. So, what you essentially do on the on the glass you coat heparin and if you collect the blood the blood would not clot. So, blood clotting could be prevented if you have the heparin because heparin does not promote the clotting of the blood. So, you need these factors to be present there which ensures, but they get activated once the clotting process gets initiated. So, they are the kind of the control check points which ensures that the blood does not get clotted up excessively. So, that the blobs start forming and the blood cannot flow. So, there is this heparin which is produced by the Bacophil. Then you have thrombomodulin this thrombomodulin is secreted by the endothelial cell secreted by endothelial cells and this essentially also ensures that the blood clotting does not you know continue like forever it has to be. So, they restricts clotting that is their role these are the ones which are involved in restricting the clotting process. Now, what I will do I will just enumerate all the all the different factors which are involved there. So, you have these factors 1 factor 2 factor 3 factor 4 factor 5 factor 6 sorry factor 6 different factors which are involved in this. So, this is a protein. So, p stands for protein these are all pretty much protein factor 3 is a lipoprotein factor 4 is an iron which is basically calcium iron which is factor 4 factor 5 is a protein which is basically proaxylirin proaxylirin proaxylirin proaxylirin and this one is fibrinogen this one is a pro thrombin this lipoprotein is a tissue factor. So, fibrinogen is produced by the liver see how all these things are regulated then this is also produced by liver in the presence of vitamin K this tissue factor is produced by the damage tissues then your calcium is being produced by the bone and the platelets and of course, you get it from the diet then you have proaxylirin produced by liver and platelets produced by both then you have factors 5 that factor 6. So, factor 6 this basically I mean in old literature you will find which is this is no longer being used this is kind of redundant one in the old literature you will find factor 6 then we move on to factor 7 factor 7 is essentially it is also a protein it is called proconvertine pro this is produced by liver and this is also an extrinsic in the extrinsic path I am just leaving it for you guys to look at which is extrinsic which is the intrinsic and you have the factor 8 factor 8 is called A H F this is also protein by the way anti-hemophilic factor anti-hemophilic factor this anti-hemophilic factor is produced by the platelets and endothelial cells endothelial cells then you have factor 9 which is plasma thrombo-plastin factor which is again a protein plasma thrombo-plastin factor this is produced by the liver in the presence of vitamin K vitamin K plays a very critical role in most of them this is your factor 9 then you have factor 10 this is also called this is also protein but there is a special name for this this is called Stuart pro or factor pro factor and factor this is also produced by the liver in the presence of vitamin K then you have factor 11 which is also a protein this is in short this is called PTA or plasma thrombo-plastin and this is also produced by the liver and this is essentially an intrinsic factor and then you have the last which is the factor 12 which is called fibrin stabilizing factor which is produced by the livers and the platelets. So if you essentially look at all the different factors which are involved in it it is a fairly big list of 12 different factors and many more understanding we are gaining with more and more research on the blood and the blood factors which are involved in this whole process but what is essential to understand is that it is a very very tightly regulated process where platelets endothelial cells liver blood calcium damage tissue everybody plays a very critical role and it is very very tightly regulated little bit of here and there in this whole game could lead to severe problems in our body. So the overall understanding in summary what I expect you to understand the nature of the platelet cells they are formed in case of human being of course they are formed by breakage away breaking away from a bigger cell from a mega karyocyte mega means huge karyocyte cell from mega karyocyte they form a small triangular kind of you know shape which changes their morphology when they reach to other the wounded side or the side where the blood vessel gets ruptured and they have a certain optimal number in our body if the number goes up the blood viscosity will go up and that such thing happens in extreme inflammation like cancer and other situation and if the level goes down then there is a chance will be become hemophilic we would not be able to prevent the blood loss because there would not be any stitching mechanism out there or the stitching mechanism will be inefficient. Then we talked about the three phases by the stitching of the ruptured blood vessel takes place we talked about the first phase which is the vascular phase and we talked about the platelet phase and then we talked about the coagulation of the clotting phase and all and within the clotting phase we talk and in the vascular phase initially we talked about the vascular spasm how the innate nature of the tissue kind of helps it to you know glue together and we ensure when we talked about the factors which prevent the complete gluing it should not be a blockage like this it should be slightly like this something like this and then eventually the blood vessels again expands up and becomes like this original. So, the vascular spasm then we talked about the migration of the platelet cells and their adhesion and everything out there and ensuring that there should not be too much adhesion and aggregation and you know the formation of the stitching and then we talked about the clotting where we talked about the intrinsic pathway extrinsic pathway and we and finally we enumerated all the different factors including from factor 1 to factor 12 which are involved in this whole clotting process. So, kindly go through it carefully it is a it is a very straightforward thing, but you have to kind of visualize through day to day example how that is happening thanks a lot.