so as we stated in our previous video regulation of red blood cell production and destruction is going to be very key because it can so dramatically impact the viscosity of blood and consequently how much taxing there is on the heart to pump that blood through out the vasculature so when we look at red blood cells if we don't have enough red blood cells this will lead to tissue hypoxia meaning you're not meeting the oxygen demand of the tissues so you're not supplying enough oxygen for proper aerobic respiration and again too many red blood cells you have too high viscosity now interestingly enough we make over 2 million red blood cells per second that also means that there's about 2 million red blood cells being destroyed within the spleen now what initiates red blood cell production well it's initiated by a condition called hypoxia so low oxygen at the tissues and this is specifically gauged by the kidneys because the kidneys get almost 25 percent of the cardiac output at any given minute so within the kidneys you have specialized cells that have a protein called hypoxia inducible factor number one or hif1 for short this is a transcription factor that is activated under hypoxic conditions and what it activates transcription factors turn on genes it will turn on a specific gene within the kidneys within the cells of the kidneys and the name of the gene is erythropoietin or epo for short now whenever you see a lowercase letter that's the gene whenever you see an upper case that's the protein that is made so we turn on the epo gene and consequently start cranking out and we start secreting the hormone which is a protein erythropoietin into circulation so this is not a hormone that we make before we need it and then release it we make it as we need it and this was probably the reason why working on this home hormone originally was so complicated because it's not like you have vast amounts of erythropoietin being stored so this erythropoietin targets cells within the bone marrow and the target primarily is that uncommitted undifferentiated metapolitic stem cell it also does some of the intermediate cells so the not so well ones that are already committed but bottom line is it turns on the process of urethropoesis that is the making specifically of red blood cells now the textbook goes into the various intermediates myeloid cells and that those are details you don't need to know the one detail that i do expect you to know is that you will release immature red blood cells and they actually are spherical because they haven't completely destroyed the nucleus there's still some nuclear fragments left over and these immature red blood cells aren't going to work as well as the biconcave shaped mature red blood cells so we call these cells reticulocytes so since we're always making red blood cells you're always going to have some reticulocytes flowing around but somebody who is hypoxic might have an elevated level now over the course of the next 24 to 48 hours those reticulocytes will completely remove the nuclear fragments will have a biconcave shape and their diameter is actually just slightly larger than capillaries so they actually have to be flexible to squeeze through the capillary single file again an optimization for rapid gas exchange so after the 24 to 48 hours you have a mature red blood cell now once you're no longer hypoxic this hypoxia inducible factor shuts off you stop releasing erythropoietin you stop promoting erythropoiesis okay now testosterone can help enhance the release of erythropoietin and this explains why males tend to have a higher a red blood cell count erythropoietin can also cause those intermediates to rapidly mature ordinarily it takes about 15 days to go from a hematopoietic stem cell to a mature red blood cell but you could accelerate that with the presence of erythropoietin now typically red blood cells last for about four months or 120 days after that point the the elastic and compliant properties of the cytoskeletal elements prevent red blood cells to very effectively squeeze through the capillaries and so these red blood cells are shown to pasture that's where the spleen comes in breaks down the globins into amino acids reincorporating that into other proteins the iron can be recycled it could be transferred back to the liver uh for storage uh and by the way the the protein that transfers the iron in blood is called transferrin while the protein that stores iron in the liver this is known as ferritin the heme again is also recycled some of it as we had mentioned earlier does get converted by the liver into bilirubin and elevated levels can be indicated with the presence of jaundice now given their small size red blood cells are about anywhere from i've seen ranges eight to ten so let's just say about nine micrometers so they're on the smaller side for red blood cells or for cells in general they are highly susceptible to osmotic stresses now in an isotonic solution your red blood cells have this beautiful biconcave shape however in a hypertonic solution where water rushes out you have this crenation and this disrupts that very high surface area to volume ratio that is so important for rapid gas exchange and of course in a hypotonic solution where water rushes in you get that spherical shape again the distance so if you think about the distance if this oxygen was here it's a much larger distance for that oxygen to diffuse in order to go into plasma so it's going to be much much much more inefficient so when we look at the various disorders with erythropoiesis the first condition that we're going to talk about is polycythemia vera so this is actually primary polycythemia vera this is usually associated with a bone marrow cancer that leads to excessive red blood cell production so we're not carefully balancing production with destruction and this results in an increase in blood viscosity higher resistance so the heart has to pump that blood which now has the consistency of molasses pump it significantly harder in the heart hypertrophies and eventually will fail in secondary polycythemia vera in this condition you have red blood cell production due to a hypoxic condition so when you go to a higher elevation the percentage of oxygen is the same but the overall amounts the gradients that we have are much less steep so we're not getting as much oxygen to our tissues as a consequence of this we start to release erythropoietin to produce a higher red blood cell count so somebody who lives in a higher elevation will have a higher visc higher viscosity to their blood because they have more red blood cell production to sort of counteract the lower amount of oxygen in their environment and this leads us to this concept of blood doping blood doping comes in many forms you can actually remove some of your blood wait a couple weeks and then re-inject it again with some preservatives to increase your red blood cell and therefore your oxygen carrying capacity alternatively you could inject artificial levels of erythropoietin to promote red blood cell production so this increase in red blood cell production helps with endurance so activities that require a sustained amount of oxygen can be benefited by this type of blood doping alternatively you might have athletes that train at higher elevations when their competitions are at sea level and so that increases their red blood cells so in order to produce red blood cells we're going to need lots of nutrients because we're making lots of hemoglobin protein so those nutrients could come in the form of carbohydrates or fats you're going to need lots of amino acids so you need to have protein in your diet to make those globin chains you need to have iron okay you need to have trace amounts of you know minerals in general and you need to have certain vitamins so for example vitamin b9 or folate and vitamin b12 are very important for red blood cell development and maturation if you have insufficiencies in these two b vitamins this can cause an abnormal red blood cell development in the absence of b9 and b12 you will produce larger red blood cells and in the absence of iron you actually will produce smaller red blood cells the larger red blood cells won't be able to fit through capillaries and the rate of diffusion will be significantly slower while with smaller red blood cells they can fit through capillaries all fine but the amount of oxygen they're delivering is going to be significantly lower so we see some of these foods that are iron rich b9 and b12 rich to alter our diets to increase the raw materials that you need for red blood cell production