 Welcome back to the NPTEL lecture series on animal physiology. So, today we will be initiating the section on blood cells, immunity and clotting. So, we have talked about the cardiovascular system where we have learnt about how the blood is pumped all over the body. Then we talked about the circulation, we talked about the vessels, the arteries, veins and the capillaries and arterioles where all the exchange of different gases takes place and the nutrient take up and disposing of the stuff which has to be thrown out of the body along the capillary network and along the lymphatic vessels. What we have not discussed yet, what are the components which constitute the blood itself, the major other than what are the major fluid or the fluid which helps us to communicate with the rest of the body and the major medium or the major career medium as well as the whole for the immune system. So, overall whenever you see I mean like the broad classification of blood could be like you know you have different kind of blood cells. So, what we will be ensuring in this class, in this first class will be outlining all the different kind of blood cells, how they are formed, what are their functions and where ever the deficiency or excess of those leads to what kind of physiological problem that is what we are going to discuss. So, broadly speaking you could divide the complete blood, let us come back and let us start putting them down on the slides. So, this is the section what we are starting. So, we will be covering three parts the blood cells immunity and clotting. So, just to clarify so the blood. So, this is the part where we will be talking about blood cell classification. So, this is the overall outline which will be dealing today classification function formation related physiological problem. So, these are the headings under which physiological roles. So, these are the broad headings under which we are going to discuss this topic. So, let us go into the classification first. So, the blood could be classified into three different component blood cell classification. So, the major classification falls under red blood cells, these red blood cells gets their red color because of the hemoglobin molecule. And I have discussed this hemoglobin molecule while we talked about in the respiration, while we talked about how the oxygen binds to the hemolecule, hemoiety and it has a porphyrin ring. In the porphyrin ring you have this iron in the center. So, it is something like this. Let me do the classification and I will come back to this. Then you have white blood cells and then you have a very small cells called platelet. So, these platelets are involved these are the smallest of all cells compared to red blood cells. These are involved in blood clotting. So, which is the third part what we will be studying in this particular section. White blood cells is involved in immunity and we will be talking about the classification of the white blood cell. Red blood cells are our oxygen transporter all over the body. Now, these red blood cells what you see here are without nucleus and why they are without nucleus we will be discussing it. These indeed have nucleus. These white blood cells are also called erythrocyte. So, what we will do now? We will talk about overall how this. So, one more thing which we have to discuss is the location where red blood cells are synthesized location of blood cells. So, basically the blood cell is synthesized in the bone marrow something like this structure where is the marrow region somewhere inside deep inside basically the site of synthesis is out here somewhere. So, whenever you hear that for people who are suffering from cancer blood cancer you say bone marrow transplantation. So, basically in other word is that if the marrow material is unable. So, there is a misregulation or because of which production of red blood cells or white blood cells goes in excess red blood cells falls down which leads to cancer like situation of blood cancer or leukemia which is commonly called. There is a time when there are medical options of curing that thing is that if you could transplant another bone marrow to the host from another source which is kind of a very challenging thing or from other from the same part from somewhere else you transplant the bone marrow. So, it is that site where all these blood cells are being formed and it is very tightly regulated phenomena after this the location once we have discussed about location now what I will do what. So, what regulates the synthesis of it. So, first of all what we will be dealing with we will be dealing with the RBC's. So, before I get into the RBC's there are some facts which people need to like it will help you to appreciate the blood better. The blood volume is approximately of the whole body is a approximately 6 to 8 percent of the body weight these are some of the facts which will help you to appreciate. And 1 liter of blood contains approximately 0.46 liter of RBC's in males and 0.41 liter of RBC's in females. It varies and varies according to the physiological status. So, this is basically essentially this value what you see here is essentially called hematocrit. If you see any prescription given in the clinic they say 46 percent hematocrit which is essentially nothing but the red blood cell concentration. So, this is very essential that if you will understand what is hematocrit and how hematocrit is being shown in the complete blood profile when you whenever you take the blood profile. So, next what I will do I will draw the overall control or rather the synthesis and destruction of synthesis and destruction of erythrocyte in adult. And then we will talk about why these erythrocytes or red blood cells are without nucleus adults. So, what I will do I will give you in a diagrammatical manner that will help you to understand this whole process. Say for example, a situation when there is oxygen in excess in the body. This sends an inhibitory signal to the kidney. So, this is inhibitory signal the first phase. This inhibitory signal sends another inhibitory signal to the bone marrow. Whereas, if the body is having deficiency of oxygen, oxygen is fairly low and there is a positive signal which is being sent to the kidney. From there another positive signal is being sent to the bone marrow. This is done by erythrocyte poetin. These are the factors which are responsible for it. And erythropoetin and there is one more signal which comes from the big organ called liver which we have already covered in the digestive system. Second signal comes from the liver. Now, these two signals what essentially it does is that these are all let me give a mark. These are all positive signals going all the positive signal. Positive signal coming from here. This positive signal is being conveyed by erythropoetin. Erythropoetin tells the bone marrow to start synthesizing the blood especially the red blood cells. Then begins the synthesis process. Synthesis of RBCs. Next page two. And once these are synthesized. So, this is continuing from the previous page from the bone marrow here. So, basically here the red blood cells are forming now. These red blood cells from here moves on to the blood vessels. So, now these are suspended on to the blood vessels. In the blood vessels a life span of these red blood cells is approximately 120 days. They die out after 120 days. Once they die out then these red blood cells have to be distracted. And these are done by couple of process which we will be discussing now. Red cell destruction. So, red cell destruction takes place by phagocytosis by macrophages. So, what does that mean? And this is also called. This is one root by which it they are being destroyed. There is another root where they go to the spleen. And the spleen there are selective. The one which are old they are phagocytized. The old ones and the new ones are being retained or the not that old ones are being retained and put back into the blood vessels. There is a in the spleen there is something called a selective destruction process takes place. So, this is kind of a scanner where if the blood cells are older then they are sent for red blood cell destruction process. And if they are still they have possibility that they can carry on the whole process. Then they are being sent back to the blood vessels. So, if you summarize the whole process it is a very tightly regulated process. So, what essentially is happening is that body is running out of oxygen. Body has a lesser concentration of oxygen. So, automatically there will be a signal which will be sent to the kidney. From the kidney another signal in the form of erythropoietin will be sent to the bone marrow along with certain signals which will be coming from the liver. And the bone marrow will start synthesizing the blood. Then the blood which are synthesized are now channelized to the blood vessels. Now, within the blood vessels they have a life span of 120 days. After 120 days when their ability to carry oxygen is kind of getting dewindled and those have to be distracted. So, in order for the destruction there are two routes. A part of it goes to the spleen. In the spleen there is a selective scanning. The one which are very old and what to be discarded out from the body are being sent for red blood cell destruction. Whereas, some of those which are still active are being retained by the body till they finish their life term. And what exactly happens in the form of destruction is that there is a phagocytosis taking place by the macrophages. So, macrophages are nothing but the white blood cells basically. So, what they do is the way it works if this is a red blood cell then these macrophages will come and they will kind of engulf it inside them something like this. So, if these are the macrophages here you have a red blood cell. So, what they will do essentially is this. This macrophage will engulf this. So, if you go to the next slide it will make more sense. So, it will be something like an event will happen like this. So, now they are entrapping the red blood cell inside it then to the next page explain it. So, eventually what happens here you have the macrophage and you have the red blood cell inside. And then there are series of enzymes which comes and chop it off and this whole process is basically called phagocytosis by the macrophages. So, this is how this is not the only not only the red blood cells which are being processed like that. Anything which body has to break down they are phagocytized like this. They are engulfed inside the white blood cells and then they chop it off using different kind of enzyme different kind of other molecules which are present there. So, this is the overall geometry or overall schematics of the red blood cell formation. But, I told you in the beginning there is something very interesting about red blood cells that red blood cells do not have a nucleus how that happens this is a very interesting thing. So, when the red blood cell starts forming they indeed have a nucleus it starts like this I will tell you the story and then I will draw it. So, that it kind of gets into your understanding properly. So, when the red blood cells are forming. So, there are progenitor cells which leads to the formation of all kind of cells. Same way there are progenitor cells which leads to the formation of the red blood cells. Once the cells are formed they have a nucleus this is all intact. Then what happens as it gets mature like all the organelles inside the cells are forming mitochondria it has everything it has mitochondria and plus mu radiculum it has nucleus it has all the cytoplasmic component. Then at a specific point of time there is an expression of a particular enzyme and that particular enzyme with respect to other cell as compared to the other cell is expressed higher in these red blood cells. And when this concentration goes up that particular enzyme chop off the nuclear membrane get rid of all the DNA and get rid of most of the organelles inside the cell. Then almost but like it has the ability when to chop off the membrane of the cell itself. But it does not do so because it is concentration falls down and due to that process then the cell is nothing but it has the bilipine membrane and a fluid field cavity which is filled with in the case of red blood cell it is filled with this hemo molecules hemoglobin. So, if you have a globulin protein on which you have the hemoity and this is how the red blood cells are being formed. So, then I will tell you that which is that enzymes let us get back to the schematics of it. So, RBC red blood cell formation the first step is. So, these are the progenitor cell these are the progenitor cell or the one which will form red blood cells RBC formation. So, here the RBCs are formed lot of RBCs out here these are the RBCs most premature RBCs they are in the maturation phase. So, they have all the organelles like bilipate membrane nucleus mitochondria likewise all the organelles they are all present then what happens. So, here is the nucleus with the DNA and everything as they are maturing during maturation of RBC at a specific point of time it is very very tightly regulated. So, if this this is showing time. So, it is very specific time a particular enzyme. So, that enzyme remains at a basal level but at a specific time there is a sharp peak of that particular enzyme and it falls down like this. And this particular enzyme is called 15 locks. Locks stand for lipoxygenase 15 lipoxygenase this enzyme generally remain in the basal level if this blue color is showing it is in the basal level during maturation but there is a specific point when there is a sharp peak of this enzyme and it falls down like this. So, when there is a sharp peak during that time what this what is essentially is happening a let me represent lipoxygenase molecule like this lot of lipoxygenase in the green color green dots are the lipoxygenase and what they do generally what they essentially do is that they start chopping of this. They even have the ability to chop of the main membrane but they chop of all other organelles. So, what is left after this at the end of the maturity is biconcave red blood cells without. So, it is a structure is almost like if you see the three dimensional structure it is a biconcave structure and it has absolutely no organelle left in it. So, what you essentially see is a bilipid membrane which remain intact like this here is the bilipid membrane out here with if you go back to your first membrane class what you have dealt with something like this. So, and this whole fluid this whole cavity is filled with these heme proteins which are like this these are like this are global in protein and on that you have this iron center the green one showing the irons which each one of the heme molecule has the ability to bind to 4 oxygen. So, it is something like this 4 sides. So, essentially that green stands for kindly look for the structure of the porphyrin I am just drawing the skeleton of it but if you go online you will see the structure of the porphyrin pretty much in every. So, and here you have. So, this is how this is sitting surrounded by the globulin protein this is basically the blow up of this image and this is the one which is the ability to carry the oxygen. So, if you look at this structure is one more thing which will come. So, basically there are 4 oxygen molecules which are coming to bind to this. So, if you logically think of it the last major protein which is synthesized by the red blood cell is hemoglobin because that is which is in highest concentration. This particular process or this kind of event is seen in the body in physiology in only 2 places is a very fantastic well regulated mechanism. The other place where you see this slide digression is in the formation of the lens cells lens of the eyes. So, those lens of the eyes think of it all the light process through the lens people think it is the inanimate thing actually lens cells are nothing they exactly follow the same pattern if I draw that it is. So, if you just go back and see the structure of the eye it is something like this. So, you have this lens. So, what lens is because all the light all the light passes through it without any problem they passes through it because this lens structure is formed by individual cells which are arranged like this and none of these structures have any nucleus they have no nucleus in the case of lens they are filled with a fluid kind of gelatinous protein called crystalline. So, this is how the lens cells are formed and whenever the and what is cataract this I did not discuss I am just coming since cataract is cells either start dying out or the crystalline protein which is present inside those cells are folded wrongly that start like their folding pattern changes and they started occluding the path of light. So, what we essentially do is that we remove this lens and put an artificial lens out there, but this is the same thing the reason why I brought you back to the lens brought you to lens is that this is exactly the same mechanism by which red blood cells are formed. They follow the same enzyme 15 lipoxygenase and 15 lipoxygenase has this ability and there are some profound implication of this because there are pharmacologists who are trying to use this 15 lipoxygenase or this mechanism they are trying to figure out whether this could be used for against cancer could we make could we program a cell that it get rid of all the all the organ that kind of you know it is metabolic activity goes down all of a sudden could we could we really master that pathway by which cell is following this wonderful thing, but again mind it this does not happen in any other cell these are the two very different kind of cell types in our body and they all originate from the same cell, but they follow a different root for of course, different purpose and different reasons. So, as you are seeing this there are some of the things which are which are very important here for us to understand one of the major thing is that you hear about people suffering from anemia. So, in other words that they lack red blood cells. So, that happens when that one of the reason for formation of anemia could be when your iron metabolism is being compromised. So, this essentially brings us to the fact that iron metabolism is extremely essential for the formation of the red blood cells. So, iron has to be absorbed at different level without the absorption of iron the formation of the hemoglobin or the hemoiety is being you know is challenged. And so, automatically if there are less number of hemoglobin your oxygen concentration goes down because your total number of oxygen which needed to be bound is reduced, because they do not have any binding site. So, next what we will do is that we will come back to the iron metabolism and how iron is being regulated. So, this let me go back to the iron what are the different roots of iron being regulated. So, again what I will do essentially is that I will show it diagrammatically that will help you to appreciate this process much better. So, there are different molecules in our body which helps in binding to iron one of them are is called transferent. This is coming from different sources this transferent come from extra vascular they are not in the vascular or not in the blood vessel extra vascular transferent. Then you have ferritin molecule which are present in which are continuously getting transferent changes ferritin. Then this is coming to the blood vessel then you have the hemoity which is when it gets broken down as I told you then the iron is being absorbed by the liver especially in the. So, we have to ensure that none of the iron is being lost they are all being absorbed by the body. Then you have these macrophages I showed you the macrophages what they do is when they chop off the red blood cells this iron is being absorbed by the blood. So, basically what happen is this there is a something called hemo cedrine to ferritin. These are the conversion which are taking place and this iron is being reabsorbed by the body. This is which is being which is being basically eaten away by the erythrocytes these are the erythrocytes. These are the WVCs which are being which eats away the old erythrocytes and apart from it along the digestive system there are different sources from where different zones from where all this iron is being assimilated. So, this is so basically what is highlighting feature is this iron absorption and redistribution in the body. So, what essentially that means is this that whenever red blood cells are being broken down the old red blood cells are being broken down by the WVCs the iron is being stripped off and sent to the blood vessels or to the liver where the synthesis of the from there it is being sent to the bone marrow where the synthesis takes place. Same way from the food what we are eating along the digestive tract iron is being taken out for the blood formation and apart from it liver have a significant storage of it in different form of different. So, basically the way iron moves in the body is that it does not generally does not move freely it is kind of bound to certain protein and which are called sederophores mostly. So, you see transfer in hemo sederine ferritine these are the different molecules which bind to the iron and keep the iron intact in the body. So, this has to be really regulated very thoroughly in order to ensure that the RBC formation remain intact. So, this is the overall I wish to talk to you about RBC few other details which I will be coming up in the next class we will be talking about the immunity briefly about the immunity and then we will go to the clotting. Clotting process where basically we will be talking about if there is a rupture in the blood vessel how that rupture is being meant it is just like you know you have a hole in a cloth you just ensure that you stitch it and get it back. So, these are the things which I will be discussing in this section. So, this is the first class where we talked about the summarize we talked about the different the classification of the different blood cells red blood cell white blood cell platelets their functions red blood cells involved in the oxygen as oxygen carrier double white blood cells in the immunity and the platelets in the blood clotting. Then we talked about the location in the bone marrow and then from there we talked about how the RBC is being formed especially in terms of the shooting of an enzyme called 15 lipoxygenase for a very brief span of time during which all the organelles and the nucleus is being destroyed in the RBC's and which is the same mechanism which is follows in the length cells of your eyes and then we talked about how iron has to be taken back by the different organelles of the body by the different organs of the body in order to ensure that the RBC formation goes on uninterrupted. So, I will close in here and in the next class we will talk about the immunity forward and we will talk about the blood clotting. Thank you.