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OK, should be able to hear and see me guys. Um Hi everyone. My name is Para, I'm the second year and got some heme for you this afternoon. Gonna do some red blood cells and white blood cells. Um Any questions throughout just put them in the chat. Yeah, just confirm if you can if you can see and hear me but it's quite, there's quite a lot to get through in an hour. So I'm gonna go fairly at pace. Um But yeah, any questions put them in the chat. So this is what we're gonna go through. Um We're gonna start off with hemopoiesis then erythropoiesis and anemia before moving on to some white blood cell stuff and white cell abnormalities. OK. Safe. Um He hemopoiesis. So it's a big like scary word. It looks, it looks confusing, but essentially what it means is just generating blood cells. So, hemopoiesis is the process by which we make our blood cells and it all starts from this really powerful cell called the multipotent hematopoietic stem cell or HS C. And the HSC gives rise to all of these different kinds of blood cells that we can see. So, from your basophils and your T cells, all of them come from your HSC S and the HSE S, they have two very important characteristics that allows them to do that. So firstly, they can self renew, meaning that they can divide and become more hematopoietic stem cells. Um So they can basically self replenish or they can differentiate to mature progeny. And what that means is basically, they can differentiate and divide and become more and more specialized to become any of these final products. So, where does hemopoiesis happen? Um Different places throughout the uh throughout gestation, it starts off in the yolk sac at about three weeks. Um And here we generate the H SDS and then at 6 to 8 weeks, your liver picks up and maintains and expands the hematophytic stem cells. And the liver is the main source of the blood until shortly before birth. So, your bone marrow, which is what we can typically think of as making blood starts at about 10 weeks gestation and but it doesn't become the main source until, until the liver um until just before birth. Um And in what bones does it happen? Or in Children, it's almost all of them. And in adults, it's um mostly the pelvis vertebrae and the sternum. Ok. So it's a pretty complicated process as you saw from the diagram. So it needs to be regulated by a bunch of growth factors. Um And these growth factors are glycoprotein hormones which bind to the cell surface receptors. Um and different growth factors regulate different sort of arms of the hemopoiesis um pathway. So, for example, IPO or erythropoietin is the hormone that regulates erythropoiesis or our generation of red blood cells. Whereas G CSF, which is granulocyte colony stimulating factor and GMCSF which is granulocyte monocyte colony stimulating factor, those regulate the product, the generation of granulocytes and monocytes respectively. Um And I'll talk about what those are in a in a second cytokines also play a role. And then tipo thrombin, that's the equivalent for um thrombocytes or platelets. OK. So functions and lifespans of the different blood cells. Um I'm gonna go through this in more detail anyway. But um this is just here for your reference. Um And also, yeah, full blood count. So someone's gonna go through this in much more detail in terms of the Practicals, but I thought I'd include it anyway, because it's really important for him. So your full blood count is probably one of the most important investigations that we do in medicine. Um And it can tell us a lot of information. So for example, your white blood cell count, how many white blood cells there are in a given volume of blood. Obviously, the red cell count. Hb the hemoglobin concentration, hematocrit is also called the packed cell volume. And it's basically the proportion of the blood that is made up of red blood cells. Then you've got your M CV, which is basically the average volume of the red red cells, your MC H, which is how much mass of hemoglobin is in each red cell on average. And then the MC HC, there's the mean concentration of hemoglobin in each of the red cells and then your platelet counts the number of platelets. Um but yeah, make sure you know the the units as well. I'd say because they, they tend to love asking questions where you've got to work with weird and wonderful units. So keep that in mind. OK. So erythropoiesis is the specific part of hemopoiesis where we're making red cells or erythrocytes. Um And if I just go back to this slide of the diagram, you can see it starts off with a hematopoietic stem cell and then we go to something called the common myeloid progenitor. Now, this diagram shows it going straight to the erythrocyte, but it's a little bit more complicated than that. Um From our common myeloid progenitor, we then get all of these different blast cells. Now, don't worry too much about knowing the names of the cells because you don't need to know that it's more about the general gist of what happens. So, from your common myeloid progenitor, you your cell differentiates to become a pro erythroblast and then an early, then intermediate and then late erythroblast. And this all happens in the bone marrow. Um But what's important to know is that as you go through that process, your cell, it gets smaller, but also your nucleus is getting smaller. So if you think of a mature red blood cell, it doesn't have a nucleus, right? Um But it does start off with one and so the nucleus gets smaller and smaller and smaller until from your late erythroblast, the nucleus is expelled. So we get rid of the nucleus and that all happens in the bone marrow and then your cell is now in your peripheral blood. So just in the circulation um and it starts as a reticulocyte, which is a type of polychromatic red blood cell. And what that means is when we stain our blood with a specific, a special stain called methylene blue. Um The reticulocytes, they stain sort of bluish purplish and that's because they have a high RNA content. Whereas your mature red blood cells, they don't have RNA. So they just s stay in red. Um And that's what it says here. So your RNA content increases then decreases. So as you go from your common myeloid progenitor to your um polychromatic red blood cell or your reticulocyte, the RNA content rises. But then from your reticulocyte, which is your sort of penultimate step to your mature red blood cell, the RNA content falls. And so that's a way for us to differentiate between reticulocytes and mature cells is when we stain them with methylene blue, we can see that the immature or reticulocytes have RNA. Um and then also it says, so you lose the self renewal and the lineage plasticity, what that means is that as you go from an HSC down the steps to a mature cell, you lose that capacity to self renew and you also lose the ability to become different kinds of cells. So an HSE can become loads of kinds of cells. Uh Common myeloid progenitor can become even fewer cells. And then uh a mature red blood cell can't become any other type of cell. So that's what it means by the lineage plasticity force. OK. So this is just a diagram to just to explain what I just said. Don't need to know the names again, but just appreciate the fact that the cell gets smaller and the nucleus gets smaller as well until it's ex expelled. And then in the blood cell, in the peripheral blood, you go from your reticulocyte to your red cell mature, which lasts for about 100 and 20 days. So, erythropoesis, it's requires a lot of things to happen. Iron is needed to make the hemoglobin for our red cells. We also need folic acid and B12. Um And we need that for DNA synthesis. So, because erythropoiesis involves lots of cell divisions before your a cell device, the DNA needs to duplicate, right. So that when you your both of your divided cells have the complete set of DNA. Um And so there's a lot of DNA synthesis that needs to happen in erythropoesis. So you need folic acid and B12 for that. And then like I said, you need erythropoietin as well, which stimulates the bone marrow activity. So, moving on to iron, he homeostasis. So our body does, she doesn't have a dedicated way of excreting iron. Um and that's can be quite dangerous because if excess iron builds up in our body, then that can cause a lot of damage to our organs. And an example of a condition where that happens is hemochromatosis. So you might have heard of that where sort of excess iron builds up and that causes damage. And so because we don't want that to happen, but we don't have a way of excreting iron. We have to have this very special uh homeostatic homeostatic mechanism to control the amount of iron in our body. So let's break it down. You start off in your liver, which is where your iron is stored. And in the liver, your iron is stored as ferritin. So it's basically iron as a, as a protein which which contains iron and that's how we store store it. Um And when we have a lot of ferritin, we our liver produces this protein called hepcidin. And hepcidin essentially blocks the release of the storage iron into the circulation, but it also blocks the absorption of iron from the gut. And so this controls the amount of iron that's in our circulation. Hence, to prevent that iron build up um an iron is transferred at, when the iron that does get into our plasma, it's bound to a protein called transferrin. And transferrin is the protein that basically carries iron to the sites that it needs to go to for its functions. So.