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Hey guys, it's Medicosis Perfection Alice. And after talking about hematology for 150 videos, let's talk about erythropoietin. Then let's talk about the platelet disorders, bleeding disorders, and coagulation disorders, only on Medicosis. Thank you for watching, and let's get started. [Music]
Some words of wisdom: Opportunity has spread its wares before you. Step up to the front, select what you want, create your plan, put your plan into action, and follow through with persistence. Capitalistic America will do the rest. Woo!
A small company called Amgen, listen to Napoleon Hill, and develop their biotechnology company. They were a very small company, just a few scientists. They had no CEO; they were raising their own money, like $100,000, which is for a biotech company, nothing. But they perfected their recombinant DNA technology. They knew what they were doing. First, they tried this technology on many things but didn't succeed: interferon for viral disease, growth hormone-releasing factor, hepatitis B vaccine, epidermal growth factor receptors for wound healing, bioengineering indigo color to dye blue jeans—no kidding. However, by 1984, they isolated the gene for EPO, erythropoietin, and launched the first artificial EPO by recombinant DNA technology, and it was a big hit. EPO is the first blockbuster bioengineered product in the history of mankind. They had a dream; they never gave up. They didn't say the little man can't get ahead; they didn't say the big corporation will kill us. They had a dream; they followed through.
I've talked about hematopoiesis before and fetal hematopoiesis in a previous video. So, in the fetal period, three to eight weeks, which is still an embryo, I think, yolk sac is forming the blood cells, then liver, then spleen, then bone marrow, according to these intervals. So, yolk sac, liver, spleen, bone marrow; yolk sac, liver, spleen, bone marrow. Yellow lava, smart bunny, red blood cell production. Fetal period: liver; adult: bone marrow. Hip hop production: fetal liver; adult kidney. EPO, erythropoietin, or hematopoietic or hemopoietic nature. It's a protein. What a protein! The like of protein behind rate and protein secreted by the kidney, mainly cortex or medulla. Cortex? Where exactly? Be precise. The interstitial fibroblasts near the peritubular capillaries? Is that correct? I prefer peritubular capillary endothelial—the peritubular capillary; there's an endothelium lining them. That's where EPO is secreted from, and then liver, prenatal and the perinatal period. Function: primary regulator of RBC production. It stimulates erythropoiesis; it stimulates erythroid progenitor cells. What's the stimulus for EPO secretion? Normally, under like physiologic circumstances: hypoxia, so ischemia, hypoxemia, hemoglobin abnormalities or this hemoglobin, such as CO poisoning and methemoglobinemia. Pathologically, some other tissues and tumors can secrete EPO.
Quick physiology review: This is the kidney; it has endocrine and paracrine function. What are the endocrine functions? Secreting EPO, renin, and the active form of vitamin D, also known as vitamin D3 or calcitriol. Paracrine function: prostaglandin and bradykinin secretion to the near tissue, not to the blood. This is the definition of paracrine. In one of my previous videos, we have talked about polycythemia vera, and I've told you polycythemia could be relative when you lose plasma or absolute, such as polycythemia vera, which is primary or secondary secretion of EPO. It could be an appropriate response to hypoxia, such as COPD, obstructive sleep apnea, high-altitude sickness, CO poisoning, right-to-left shunt, such as cyanotic heart disease. By the way, right-to-left shunt patients are patients who are hypoxic, and when you give them oxygen, they don't improve. That's the definition of right-to-left shunt. Androgens can increase EPO, and maybe this is one of the reasons why men have more red blood cells than women—one of the reasons, not the only reason. Or it could be inappropriate secretion of EPO because of a tumor, such as renal cell carcinoma. Yes, EPO is secreted by the kidney. Renal cell carcinoma is going to have a lot of EPO. Hepatocellular carcinoma, pheochromocytoma, hemangioblastoma. This is called paraneoplastic syndrome.
And here is the great slide of hematopoiesis. We have myeloid and lymphoid. These are the red blood cells. EPO stimulates their genesis and creation. These are the white blood cells. GM-CSF, granulocyte monocyte colony-stimulating factor, stimulates the colony of those cells. Then TPO stimulates platelet creation. On your exam, sometimes the diagnosis of the case is iron deficiency anemia, but the patient has thrombocytosis, and students go crazy. No, there is nothing to be crazy about. I'll tell you why. In iron deficiency anemia, you have less iron. If you have less iron, you have less heme. If you have less heme, you have less hemoglobin, because I've told you before that hemoglobin, the nice hemoglobin, is heme, that's called hemoglobin, so it's heme and globin, and the heme is iron and protoporphyrin. Okay? When you have less iron, you will have less heme; when you have less heme, you will have less hemoglobin, and this is the definition of anemia, or one of the definitions. When you have anemia, the kidney is going to sense that, "Oh, I need to secrete more EPO." More EPO is secreted. By the way, EPO is very similar to TPO, thrombopoietin. The bone marrow is deceived; it's fooled. It starts secreting lots of platelets as if TPO was high, when in fact only EPO was high. Fool me once, shame on you; fool me twice, shame on me.
What's the mechanism of action of the great erythropoietin? Erythropoietin binds to the receptor called the erythropoietin receptor, duh. Then JAK2 kinase kicks into gear; it starts working and stimulates other pathways, such as STAT pathway, PI3K, and MAPK, which are beyond the scope of this video. Then the stimulation of these pathways will lead to proliferation of red blood cells, differentiation, proliferation, and survival of erythroid cells to produce mature, nice-looking red blood cells without a nucleus. That's why conditions such as polycythemia vera, essential thrombocytosis, primary myelofibrosis have JAK2 kinase mutation. They don't need EPO to stimulate production of red blood cells. JAK2 kinase mutation by itself will bypass the EPO and secrete lots of red blood cells. That's why in polycythemia vera, EPO is decreased. This is called negative feedback.
Now we have talked about the natural EPO that's in your body, but now we have exogenous EPO, also known as artificial EPO, also known as recombinant human EPO, also known as erythropoiesis-stimulating agent, or ESA. We have two types: Epoetin alfa and Epoetin beta. What are their uses? We have some medical uses and we have some surreptitious uses that are secret medical uses: anemia in chronic kidney disease—yes, because in chronic kidney disease, the kidney is bad; it does not secrete EPO, so giving EPO from outside can help, which makes sense. Anemia in MDS, anemia in cancer patients receiving chemotherapy, rarely used in orthostatic hypotension to maintain the volume. Surreptitious use, on the other hand, by professional athletes—actually, they are not professional; they are cheating; that's why we call them sob athletes. And the reason goes like this: At least EPO doesn't waste my testes. Okay, this guy is brilliant, a philosopher. Is this your standard? But you know what? The athlete is right, because side effects of EPO do not include problems with testes. Problems with EPO include myocardial infarction, stroke, venous thromboembolism, tumor recurrence. And to keep the side effects of EPO treatment at minimum, don't let the hemoglobin concentration rise above 12. Keep it between like less than 10, 10 to 12; don't raise it more than 12. And to be extra safe, keep it below 10.
Now let me tell you about anabolic steroids, also known as testosterone. Some athletes try to cheat by injecting themselves with this kind of stuff. What does testosterone do? Like masculinity, muscles. But then there's a problem. This testosterone is now in your body. Do you think the anterior pituitary will secrete FSH and LH when testosterone is already there? There is no way; no way it's going to secrete FSH and LH. And FSH and LH are food for testes, so your testes will become teeny tiny; you can't even see them, even though you are taking testosterone. Your testes are so tiny. This is called negative feedback. And by the way, do you know the ancient Greek philosophers? They included Socrates, Democritus, and yes, Testicles. He was a very deep thinker. So don't listen to these gem experts giving you extra stuff as supplements or as injections or as the snow train—like, naturally just build your body. Okay? It'll take longer, so what?
And here is my word of wisdom: It's better for you to be slightly overweight than to quote perform at the gym—no pun intended. Now let me know in the comment section what are the tumors that secrete EPO. Try to list as many as possible. Thank you so much for watching. Please don't forget to subscribe, and you can follow me on Patreon. Try to join this medical revolution and education and follow me on Patreon. Go to patreon.com/scishow. So I have lots of good stuff there: You have notes, we have PDFs, we have post notes, art notes, audio notes, etc., and even cases. So go to patreon.com/scishowcosis. And until next time, be safe, stay happy, and study hard.