 Right? So again, good morning to everybody. Welcome to our discussion on hematology 2. So last meeting on our last video, we talk about your, we talk about an overview on your hemostasis. Now, we're going to talk about your megahariocytopoasis. So your megahariocytopoasis will be a two-part discussion for today. So a two-part discussion and I divided it will be first talking about platelet production, the megahariocytopoasis part, the production of your megahariocyte and your platelet shedding. And the second part of our discussion will be talking about your platelets alone. So your platelets alone meaning to say we're going to talk about the ultrastructure and also the function of your platelet. Now let's get started with our discussion. So first and foremost, let's talk about your megahariocytopoasis. Some of you are wondering through, is there a difference if I call it megahariocytopoasis or megahariopoasis? There's none. I just wanted you guys to get familiar with the megahariocytopoasis because I guess you are much familiar with the megahariopoasis, but nonetheless, both of them are the same. Now moving forward, megahariocytopoasis is actually the production and the development of megahariocytes. Let me just reiterate that part first. This isn't the production of platelets yet. This is the production of your megahariocytes. I have to clarify that part because later on, we'll be talking about your platelet shedding and platelet shedding is known to be your thrombocytopoasis. This is now the actual production of your platelets and they are now being shed into your bloodstream. Now, again, your megahariocytopoasis happens, of course, none other than you're in your bone marrow. Similarly, just like your hematopoasis, your megahariocytopoasis also happens within your bone marrow. Let's just have a quick review. You're seeing a diagram of the hematopoietic stem cell, your pluripotent stem cell. During your hematology one, you already talked about leukocytopoasis, your leukopoasis, or your erythropoasis. Now we're going to talk about in more detail, your megahariocytopoasis. Last time, during our orientation, one of the few questions I asked you guys is that from what progenitor cell did your megahariocyte came from? There are actually two lineage that we all know. The common myeloid progenitor, let me just pull out my laser, your common myeloid progenitor and your common lymphoid progenitor. Between the two, your common lymphoid progenitor only give rise to three types of cell, your T cell, your B cell, and your natural killer cells, which are to be discussed in our immunology serology discussion. Now let's focus our attention to the common myeloid progenitor. Your common myeloid progenitor give rise to almost, not to almost, it will give rise to all of your granulocytes together with your monocytes or your macrophage. It will also give rise to your erythrocytes and most importantly will give rise now to your megahariocyte that will also produce now your platelet. Now let's focus our attention to your megahariocyte erythrocyte progenitor. Remember that your common myeloid progenitor is being influenced by a lot of your interlukin. In this particular part, when it comes to your common myeloid progenitor, it will commit itself to become a megahariocyte erythrocyte progenitor. Remember that your CFUGMM will influence your common myeloid progenitor, now that it will now start to differentiate and to commit, excuse me, one moment please. Now moving back, your megahariocyte erythrocyte progenitor will now commit itself to either produce your platelets or to produce your erythrocytes. So depending on the hormone that will be produced, so if it is an EPO, your erythropoietin, it will be committing to become, it will be influenced and it will eventually commit to produce erythrocytes. If your thrombopoietin is the one that is produced then it will be influenced, therefore will commit to produce your platelet. Remember that your hematopoietic stem cell, ladies and gentlemen, can make copies of themselves to maintain the stem cell pool and they do possess the ability to generate cells of all lineage. That's why we call it pluripotential. So this stem cell give rise to multipotent myeloid and lymphoid progenitor cells. We say multipotent because they can become a granulocyte, a monocyte, a basophil, eosinophil, megahariocyte, erythrocyte. Even your lymphoid progenitor is also considered to be a multipotent. Why? Because it can become your T cell, your B cell or your NT cell. So ultimately the progenitor cells are restricted only to specific lineage. So that's why I have to clarify and reiterate to you the difference between the common lymphoid and the common myeloid progenitor. So with appropriate cytokine stimulus, appropriate hormone, stimulus, the committed progenitor cell will undergo proliferation to a recognizable precursor of that specific cell they committed to become. Similarly in our life, if you want to become a medical technologist in the future, you commit to yourself with all the stimulus, the academic, and also extracurricular stimulus that will help you proliferate, that will help you differentiate to a recognizable meditech in the future. Similarly to your megahariocyte, that's also what happened. They will also differentiate and mature and therefore become a mature end stage cell. So this stem cell and progenitor cell, always remember, cannot be morphologically differentiated. What I'm trying to say is that lahat sila magtapa mukha. Let's say in English, all of your progenitor cell, including your hematopoetics stem cell, all of them looks the same. They are morphologically indistinguishable. So all of them look like the same cell. So how do we differentiate them later on? We'll be talking about that shortly. So since we cannot classify them by their appearances, by their morphologic appearance, what we use now are your CD. I mentioned it immediately, your CD or your cluster of differentiation. So your cluster of differentiations, these are protein markers specific to a specific type of cell. But think for example, you have identical triplets. So these are three individuals, all look the same, but there are distinguishing marks that will enable you to identify who is this person. If this is A, B, or C. So similarly, with the use of your cluster of differentiation or your CD proteins, we're also able to classify them. That is only through CD or cluster of differentiation. Never through morphological or microscopic differentiation. So let us note that I wrote down our discussion to your megacaryocyte. Remember that your megacaryocyte of poesis happen in your bone marrow and most of your megacaryocyte. The differentiating in your mature megacaryocyte usually are localized in the abluminal or the non-blood surface of the sinusoid lining in the telial cells. So as you can see, they are not within the blood surface. So they are just near or they are localized. They are residing on the lining of your endothelial cell. This is in preparation for their bupid into the blood stream. They just reside near so that at any given time, once that they are ready to shed the platelets, they can already deliver it directly to the blood. Directly to your blood. So since we're already talking about your megacaryocyte to poesis, let's talk about now the progenitor cells of your megacaryocyte. So when we say progenitor cell of your megacaryocyte again, similarly to your hematopoietic stem cell, they are indistinguishable. So there are three stages of megacaryocyte progenitor. So from your megacaryocyte eretrocyte progenitor, remember it will become your CFUGMM will give rise to your megacaryocyte eretrocyte progenitor. So once that there are cytokines like your megacaryocyte colony-stimulating factor or your MEG-CSF together with your interleukin-3, now with also the influence of your thrombopoietin, your CFUGMM will now be differentiating into becoming your burst forming unit megacaryocyte or your BFU megacaryocyte. Your BFU megacaryocyte is capable of producing or proliferating into forming hundreds of BFU. That's why you call it BFU because these are burst forming units. They can undergo mitosis. So eventually this burst forming unit will eventually become now your colony forming unit megacaryocyte. Your colony forming megacaryocyte, your CFU will now form a differentiated and a more mature megacaryocyte. Remember that in your BFU meg and your CFU meg, burst forming unit megacaryocyte and colony forming megacaryocyte, both of them are still capable of the normal mitosis. I say normal mitosis because once that your CFU and your BFU meg become now your LD CFU megacaryocyte or your light density colony forming unit megacaryocyte, it is no longer capable of the normal mitosis. It is only capable of endo mitosis. Before I explain to you guys what is endo mitosis, remember that your BFU meg CFU meg and your LD CFU meg, all of them looks the same. They cannot be differentiated from one or the other. All of them looks the same. You guys might look at it as something smaller, but your BFU meg, these are actually all BFU megs. These are all BFU megs. These are all CFU megs. We are just trying to give you an idea how much, how much mitotic activity do they have. So your BFU meg can form hundreds of BFU megs and then it will differentiate to become your CFU meg and then it will become your LD CFU meg. So again, between among the three, LD CFU meg is the one not capable of normal mitosis, not capable of normal mitosis. What is it capable of? It is capable of what? It is capable of endo mitosis. So what is endo mitosis? So let me explain what endo mitosis is. Endo mitosis is a form of mitosis that lacks your telophase and your cytokinesis. So as you all know, your mitosis has four important phases, your prophase, metaphase, anaphase, and telophase. So those are the five phases or the phases of your mitosis. Now when it comes to endo mitosis, it is not similar to the usual one that our cells underwent every now and then because your endo mitosis lacks your telophase. So there is no cytokinesis, there is no cell separation, there is no production of two daughter cells. Instead what happened is that your megacaryocyte just continually just continue to grow. Your megacaryte will just continue to grow. Your megacaryocyte will employ their multiple DNA copies. The DNA will continually replicate and the nucleus will continually enlarge. But at the same time, it will also synthesize abundant cytoplasm. Magproduce abundant cytoplasm because ultimately that is where your platelet will come from. So in a more technical aspect, remember that you have your gata one or it stands for your globine transcription factor one and your FOG gene, which is a friend of gata, a friend of gata one. That's why it is FOG one. So what happened is that these two are the one that facilitates or ensure your mitosis. But once that it enters your LBCFU peg, your gata one and your FOG one will now start to slow down being expressed in your cell. Once that nawala or these two are no longer expressed, the one that will be expressed now, the one that will control the mitosis inside your megacaryocyte are your RNX1 or your RNX1 gene. This is a gene that will now initiate your endomitosis. So once that your RNX1 is the one responsible for the mitosis, it will become now your endomitosis. Endomitosis in the sense that there will no longer be cell division. There is technically a cell division and I hope you get me guys now. But there is no longer a telophase and a cytokinesis part in the cell division that's happening. And that is what we call your endomitosis. Where do we see endomitosis? We see that in your LD CFU meg of the three megacaryocyte progenitor. Three megacarycyte progenitor. Again, reiterate to everybody the stages are your BFU meg, your CFU meg, and your LD CFU meg. So your BFU meg is the least mature one of the three progenitor, meaning to say, ito yung pinakabata, least differentiated, followed by your colony farming unit megacaryocyte, which has at this time, since this is still normal mitosis, it's still deployed. It produces deployed. It participates still in your normal mitosis until we go to your LD CFU meg, which is the one more mature of them all. Among the three, your LD CFU meg is the most mature. Aside from that, your LD CFU meg, aside being the most mature progenitor of your megacaryocyte, it also loses its capacity to divide. Again, that is your endo mitosis. That is your endo mitosis. It lacks your telophase and your cytokinesis. So there is no separation now of your daughters. So all of these three, again, resembles like a small lymphocyte in your bone marrow. If you prepare a bone marrow, a bone marrow smear. So remember that all of these three that we're discussing cannot be differentiated morphologically. That's why we're saying that these are morphologically indistinguishable from one another. Now, the question is, sir, how do we identify them now? So the way to identify them is through immunologic test or cytokemical state. I guess you guys are familiar with cytokemical stain from your histopathology last semester and also hematology one, specifically when you talk about your white blood cells. When you did talk about your white blood cells. So there are immunological tests that uses your flow cytometry that will allow us to identify what specific cell are we dealing. So there are different markers that we can use. So you can use your MPL. You can use your MPL, your CD34, CD41, CD42, your PF4, your platelet factor 4, your vaudeville brand factor, and your fibrelogen. So as you can see, as you can see guys, the bar that you can see meaning to say the marker is present in that particular specific. The marker is present on that specific type of cell. So now I want you guys just to focus first on your BFU meg until your LDCFU meg because they are indistinguishable morphologically. So like for example, you look at the microscope. You will not know if this is BFU meg, CFU meg, or LDFU meg unless you look at the microscope. Unless you look at the microscope. Now how are we going to differentiate BFU meg? BFU meg can be differentiated because it does have all of them. So let me just try to erase the high things that I did. So here, how do we differentiate your BFU meg from all the others? Remember that when you use MPL, all of them does have MPL. So check. They do have MPL meaning to say we cannot use MPL to differentiate them because they all have the same. Now when we talk about CD4, that's also problematic because all of them does contain CD34. So we cannot differentiate that. We cannot differentiate the three using that. Now we can differentiate your BFU meg from your CFU meg and your LDCFU meg using your CD34. Why? Because your BFU meg do not contain your CD41. So if the cell contains MPL, CD34, but does not have your CD41, that means that it is a BFU megacarouside. Now let's go to another story. How about CFU meg and LDCFU meg? Sure. If we're going to do immunologic test, if we're going to do immunologic test, they're almost the same. They're almost the same. So how will I be able to differentiate one from the other? To answer your question, the ultimate differentiating factor between your CFU meg and your LDFU meg is to identify if there is endometosis or not. If there is no endometosis, walang endometosis, then that is probably your CFU clinical carouside. But if it has, okay, if it has your endometosis going on, then that will give you an idea now that what you're looking at, what you're seeing or what you are counting are your LDCFU megacarouside. So again, please remember how to differentiate them. Your BFU meg can be differentiated using your CD41 between the two CFU meg and LDCFU meg, how to differentiate them by identifying which one has your endometosis. Okay? Which one has your endometosis? So please, again, remember that. Okay? And do not forget that in our succeeding discussion. Now, okay, we are finished talking about the non-identifiable stages of megacarouside progenitor, which are your BFU meg, your CFU meg, and your LDCFU meg. So do not forget that, do not forget these three. So these are the first three progenitors of your megacarouside. After that comes now your morphologically identifiable. When we say morphologically identified, we can now identify them under the microscope, okay? So we have your MK1, your MK2, and your MK3. Your MK1, also known as your megacarouside blast, your MK2, your pro megacarouside, excuse me, okay? So again, we have your MK1, your megacarouside blast, and then your MK2, your pro megacarouside, okay, your pro megacarouside. And now finally, okay, we also have your blast that is your megacarouside, which is the mature one now, okay? So to further give you their identifiable or their distinguishable characteristic, so let's go on. Your MK1 or your megacarouside blast, they contain your, you can see plasma blebs, blunt projections, okay, sorry for the typographical error. So they have plasma blebs, blunt projectors, okay? So their plasma blebs or these are blunt projections from the margin that resembles your platelet, okay? At the same time, you can already see your demarcation system. So this is very important. Your demarcation system, these are like lines, okay? If this is your cell, okay? These are already lines, okay? Or cutouts. It looks like cutouts within the cytoplasm and that will now be shed off as a mature platelet, okay? A mature platelet. So there, you have cutouts or these are demarcation lines. Yan matatanggal, okay? Kapag nag shed off yan, that is now an entire platelet, okay? So aside from that, we also have your MK2 or your pro megacarouside. So they have lobulate nucleus. So aside from, they do have lobulate nucleus. So you have to see lobulation on their nucleus already, okay? And lastly, okay? Lastly, we have your MK3 or your megacarouside. Intensely, they are observable by having your intensely lobulated nucleus already. So between the two, you can differentiate pro megacarouside from megacarouside depending on the lobulation and their nucleus. Aside from that, if you're reading your product, the latest edition, you can also differentiate them and you can specifically identify your megacarouside by identifying the ploidy level, okay, the ploidy level using your propodium iodide, okay? Using your propodium iodide. So this is what we use, okay? This is what we use so that you'll be able to what? You'll be able to identify your platelets or rather, your megacarouside. Now, okay? To give you a summary, okay? So remember, so this is a terminal megacarouside differentiation stage. So we can differentiate them according to their diameter. But most importantly, what I want you guys to remember when it comes to the difference to the megacarouside differentiation stages, your MK-123, when it comes to my tosis, all of that, MK-123, it's already absent. When it comes to endometosis, in your megacario blast, it's still present, okay? And it will end at your pro megacarouside or your MK-2, okay? And already absent in your MK-3, in your MK-3. And lastly, your demarcation system is present in all of them. Similarly with your alpha granules and also your dense granules. Much about your alpha dense granules in your demarcation system once we reach your ultra, the platelet ultra structure. Now, we're nearing the end of our discussion. So now that we already know, there are three progenitor cells of your megacarouside, your BFUMeg, CFUMeg, LDCFUMeg. Once they enter a different, a distinguishable stages, we can now call them as your MK-1, your megacario blast, your pro megacarouside and your megacarouside. Now, we will now talk about your megacarouside. So this is not the end of your megacarouside to poesis. Your megacarouside is the largest cell in the bone marrow. So we have less than 0.5% of all, we have less than 0.5% megacarouside of all bone marrow cells. So, with multiple chromosome copies because of their polyploid, because of their polyploid, we can reach up until 128 ploidy, 128 ploidy, again, because of endo, mitosis. So we can identify them, okay, we can study them using your bone marrow aspirate and stain them using your right gym sustain. And when we measure it, it's around 30 to 50 micrometer. So their nucleus is multi-lubulated, intensely-lubulated. Because this is already your MK3, your megacarouside. So, when you're looking under the microscope, you can see around 2 to 4 megacarouside per 10 times LPO, okay, per LPO field. So 2 to 4 megacarouside per LPO. So, that's now how your megacarouside are produced. So from the hematopoietic stem cell, okay, from the hematopoietic stem cell, it becomes your CFU GEMM. Influenced by your TPO, your megacarouside-stimulating factor, colony-stimulating factor. And then your interleukin 3, becoming now your BFU meg, CFU meg, LDCFU meg. And then, becoming now your megacarouside pro-megacarouside. And then eventually your megacarouside, which we have now like this, okay? This is now your megacarouside, okay? This is now your megacarouside. Now, once your megacarouside are mature enough, okay? Sabi natin kanina, they will be residing on the endothelial lining of your bone marrow. They will now be ready for platelet shedding. Okay? Your platelet shedding, also known as thrombocytopoiesis. Your thrombocytopoiesis are your platelet shedding as you can see here on your picture. Okay, this is your megacarouside. And this one, okay, a pro-platelet projection. Okay, a pro-platelet projection. As you can see, they are now releasing. Okay, they are now shedding. Rather, they are now shedding your platelet. So, one megacarouside, okay, one megacarouside can produce around 2,000 to 4,000 platelets. So, maybe you're wondering how are they being released or how they are being shed. That is through your demarcation or your demarcation system, the one that I'm talking about moments ago. So, your demarcation system are like cutouts in the cytoplasm that will be where your platelets shed or be released. So, they undergo fragment the cytoplasm of your megacarouside undergo fragmentation where your platelets are now being released. Now, the platelets are formed at the end of your pro-platelets and are released by micro tubular action. Okay, I'll show, I think I have a picture later. I think I was able to delete the picture here. Here na lang. This one, okay, this is your pro-platelet. It's an extension. It's like an extension of the cytoplasm where your platelets are being shed. Excuse me. Where your platelets are being shed off. Where your platelets are being shed off. So, your thrombocytopoiesis leaves behind a megacarouside nuclei to be consumed by your bone marrow macrophage. So, remember, okay, like what I was mentioning tanina, okay, like what I was mentioning tanina, your megacarouside even though they do not divide, okay, even if they do not physically divide, they grow their platelet, they grow their cytoplasm because that is where your platelet would come from. Now, the cytoplasm will completely be fragmented and all will become platelet. Around 2,000 to 4,000 platelet will be produced. Leaving us now in noclius, that is exposed and will now be consumed and engulfed by your macrophages, okay, your macrophages. Now, remember, the pro-platelet, the one that I showed you tanina, that is a pseudo-podial extension, okay, a pseudo-podial extension of your megacarouside where your platelets are being released, okay. Now, we finish your megacarouside, we finish, they already undergo thrombocytopoesis or platelet shedding. Now, for the last part of the discussion, let's talk about your platelets or commonly known as your thrombocytes. These are inocliated cells. The only they are inocliated cells, okay. They are inocliated cell, so they are around 2.5 micrometer, so when it comes to their mean platelet volume that is around 8 to 10 femtoliter, so they are the normal range or the reference value for your platelet in a normal individual that is 150 to 400 times 10 to the 9 10 times 10 to the 9 power per litter. It's slightly lower at both sexes over 65 years old and your platelets are technically higher in women. So 30% of your platelets or one third of your platelets are found in your spleen. They are deposited in your spleen and two thirds of your platelets are circulating. So one third or 30% are stored in your spleen that is your resting platelets and two thirds or 70% of your platelets are circulating platelets. Okay, they are circulating platelets. Again, the 30% that is yours that is your resting platelets this are your circulating platelets. So platelets per oil immersion field in your peripheral blood smear a normal one normal when you look at it under the microscope it would have around 7 to 21 7 to 21 platelets per oil immersion field. So your platelets are the one that could trigger your primary hemostasis your primary hemostasis remember your primary hemostatic is your platelet blood. Okay, now to end our discussion let's just talk about a few things before we end this discussion and that is about the different hormones and cytokines of your mega cario cytokines of your mega cario cytokines So the first one are the one that in the most important hormone in your mega cario cytokinesis because they induce stem cell differentiation they induce proliferation and platelet release and these are your drogopoietin ladies and gentlemen are found in your kidney similarly with your erythropoietin although they are also found in your liver and in your smooth so kidney, liver and smooth muscle majority are coming from your liver now it circulates in your plasma your drogopoietin circulates in your plasma and for individuals that has problem producing drogopoietin and would now lead to drogopoietin there's a recombinant drogopoietin that can be used so that as a therapy we can trigger or we can elicit a production of platelets in those patient so aside from that aside from drogopoietin I also mentioned some cytokines a while back and these are your interleukin 3 that is involved for the early differentiation of your stem cell remember your megakaryocyte colony forming colony stimulating factor or your MEG-CSF your MEG-CSF together with your interleukin 3 and your TPO they allow the differentiation of your stem cell to become your BFU megakaryocyte aside from that we also have your interleukin 6 and interleukin 11 to enhance endometosis remember what Jean was responsible for endometosis that is your run X1 your run X1 so endometosis and then eventually megakaryocyte maturation and platelet release and platelet release so finally finally I already showed you this ano na I already showed you this picture a while back this is how we different this are the different hormones and cytokines that control your megakaryocyte so remember your TPO interleukin 3, 6 and 11 so interleukin 3 and TPO is for the differentiation of your progenitors BFU meg until LDCF for the differentiation of your megakaryocyte we have TPO interleukin 3 and interleukin 11 for late maturation your TPO interleukin 6 and interleukin 11 for trombocytopoiesis the platelet shedding we only need your interleukin 6 and interleukin 11 so with that thank you so much everyone for listening so I hope you have an idea now how your megakaryocyte to poiesis is happening inside our body now for the second part of our discussion on our next meeting we will be talking about the ultra structure of your platelets with that thank you so much for listening so if you have any questions or gratification please send me a message through TLC or through my email and I'll be happy to answer you as soon as I can so thank you so much for listening with that thank you so much you can now leave the platform and do not forget to read your book okay to read your book so that you'll be able to have an idea of the entire context of what we just discussed today so again thank you so much and I'll see you on our next discussion goodbye