Transcription
Hey guys, it's Medicosis Perfeccion Ellis, one more time continuing our topics about the series of bleeding and coagulation disorders. In the previous video, we have talked about thrombocytes and their clinical significance. Today, I'll talk about thrombopoietin. I n means protein; poesis is the synthesis of cells. Thrombopoietin is the protein that helps synthesis of thrombocytes, aka platelets. So thrombopoietin, also known as TPO—not to be confused with Tim Tebow—is the topic of today's video, and let's get started. [Music]
In a previous video in my hematology playlist, we have discussed EPO (erythropoietin), but today let's talk about TPO. As you know already, your blood consists of plasma and cells. The cells are red blood cells, white blood cells, and platelets. By the way, white blood cells are the only cells that can migrate to the interstitial space. Red blood cells and platelets are confined into the vascular space. And we have talked about the hematopoiesis before; we have the myeloid and the lymphoid. The megakaryocytes, of course, are myeloid. So megakaryoblast, promegakaryocyte, megakaryocytes, and platelets. Who helps promote all of these steps? The great TPO. Platelets, thrombocytes, the cell of thrombus. We only have a decreased number of platelets; this is from Buu site opinion. When you have an increased number of platelets, this is thrombocytosis or thrombocythemia. Platelets are synthesized from the glorious, magnificent megakaryocyte, which are made in the bone marrow. While living, trying to squeeze through sinusoids, they break down into pieces. Each megakaryocyte will give you thousands of platelets. Platelets are pieces; they are not even cells. They have no nucleus; they have no ability to divide. They depend on the ability of the megakaryocytes to divide. They get their granules from the cytoplasm of the megakaryocyte. You don't see platelets on bone marrow biopsy; you see platelets on a peripheral smear. By the same token, you don't see megakaryocytes usually on peripheral smear; you see them on bone marrow biopsy.
TPO is inversely related to bone marrow megakaryocytes, and TPO is inversely related to platelets. When you have lots of megakaryocytes, you will have less TPO, because if you have lots of megakaryocytes, why the flip do you need TPO? This is called negative feedback. Same thing: when you have lots of platelets, you will decrease TPO because I've already have enough; why synthesize more? On the other hand, when you have hypoproliferative thrombocytopenia, you have a decreased number of platelets. When you have a decreased number of platelets, TPO is gonna rise, causing a compensatory increase in thrombosis, trying to increase the platelet count and back to normal. Thrombopoietin, or TPO, is one of the hematopoietic growth factors. EPO increases the number of red blood cells; TPO increases the number of platelets. GM-CSF (granulocyte monocytes manufacture) they increase the number of granulocytes and monocytes. What are the granulocytes? The three famous cells: basophils, neutrophils, eosinophils. Cytokine receptor system include interleukin-1, TNF alpha; they stimulate G-CSF to increase the granulocytes, including neutrophils. Interleukin-5 is in eosinophil production. Interleukin-6 helps in TPO production, willing to increase platelets. Interleukin-7 will help increase the lymphocyte production, because you were wondering the factor that helps those lymphocytes; it's called interleukin-7.
If you'll recall my video on multiple myeloma, osteoblasts a'queen interleukin-6, and interleukin-6 stimulated osteoclasts causing bone resorption. Multiple myeloma can secrete interleukin-6 directly, bypassing the osteoblasts. And if you watch my video about the RANK and the RANK ligand, I have discussed this process in great detail, which was an awesome video, by the way. I have 100+ pages of notes about lymphoma called the Perfeccion Ellis Ultimate Notebook, or pun, with 20 lymphoma cases and 25 bleeding cases. To get them, go to patreon.com/medicosis. Available for a limited time. Thrombopoietin, or TPO, produced by liver and kidney, like EPO. Where exactly in the liver? Parenchymal cells and sinusoidal endothelial cells. Where exactly in the kidney? Proximal convoluted tubule. Produced constitutively by the bone marrow stromal cells, unlike EPO. So EPO is present, is produced by the liver and kidney; TPO, liver and kidney and bone marrow stromal cells. Its receptor is called MPL. So when TPO is going to work, it needs a receptor for this. This receptor is called MPL. This is very important; it promotes proliferation of megakaryocytes, increases their size and number, production of platelets, a reactivity of the platelets, and this is unique to TPO; all this is not present with EPO.
TPO is sufficient but not absolutely necessary for inducing differentiation of bone-marrow progenitor cells towards megakaryocytes. So sufficient but not absolutely necessary. This is a deep philosophical statement. Okay, a necessary condition is a condition that must be present for an event to occur. A sufficient condition is a condition or set of conditions that will produce the event. What the flip does that mean? Translation: if you have TPO alone, by itself, can you order the progenitor cells to becoming megakaryocytes? The answer is absolutely yes, because TPO is sufficient. If you don't have TPO, can you still form megakaryocytes? The answer is yes, why? Because TPO is not absolutely necessary, which means we would love to have it, but even if it's not there, we can still manage, we can still produce those progenitor cells and make them into megakaryocytes. So what are the other things that can promote this process of progenitor cells becoming megakaryocytes? They include GM-CSF, they include interleukin-3, they include interleukin-6, interleukin-11, chemokines, and even EPO. I thought it was for the red blood cells; yet, mainly for the red blood cells, but it can also produce megakaryocytes. TPO is sufficient but not absolutely necessary.
Clinical uses of TPO still under trial. Theoretically, you may give it to patients with ITP, especially if the plasma level is not high. Let me explain this: you would expect that you have ITP, you have immunological destruction of platelets, you'll have a decreased number of platelets, which will lead to an increased number of TPO; increase amount of TPO; negative feedback. However, this is not the vacation in every patient. Some patients with ITP can have a low plasma level of TPO. For these patients, you can give them TPO from outside, and it can help with their symptoms by promoting megakaryocytes into platelets. That's it about TPO. Thank you so much. Please subscribe and join the tribe. Follow me on Facebook. We have cases. Go to patreon.com/medicosis. Get my pun: Perfeccion Ellis Ultimate Notebook about lymphoma + 25 lymphoma cases + 20—sorry, 20 lymphoma cases and 25 bleeding cases at patreon.com/medicosis. This is Medicosis Perfeccion Ellis, where medicine makes perfect sense. Medicine and sense—those don't go together like a Japanese burger.