 If we know how RBCs are produced and destroyed, we can easily understand what can lead to anemia or decreased red cell mass. To maintain normal oxygen carrying capacity, body should maintain normal RBC count. So, let us consider this as normal RBC count. Obviously, this is only a schematic diagram. But if this is normal RBC pool, some of these RBCs are regularly being destroyed. So, it is a loss of RBCs, right? And we know that RBCs are destroyed mostly in a spleen that is known as extravascular hemolysis which contributes to 90% of lysis of RBCs and 10% is intravascular. The numbers which are destroyed are replaced by production from bone marrow. So, there is a gain of RBCs from bone marrow. This is production, right? So, if we see this scheme, anemia will occur if cell destruction increases, right? So, there is increase in cell destruction will lead to decrease in this pool or there is decrease in cell production. So, gain will decrease and with that also will lead to decrease in this pool. Now, in some diseases, there can be a combination of both of these causes. Other is there can be direct loss of blood. So, again it will decrease the red cell mass. Okay, now let us go into details of each of these causes. What are these causes? Either there is decreased production of cells or increased destruction of cells or there can be blood loss. Now, let us consider decreased production of cells. Now, this scheme, the stages of erythropoiesis, there is hematopoietic stem cells which is capable of producing all other hemat cells that is WBCs, RBCs and platelets. Then there are progenitor cells which are capable of producing only a few lineages like maybe only RBC and platelets. Then it becomes further committed and this shows that blast cells becoming mature into RBCs. Each stage requires either growth factors or there are certain raw materials required for the process to continue efficiently. So, this production of cells can be affected at any of these stages. Like anemia can occur if anything directly affects the reserve pool of hematopoietic stem cells or progenitor cells. Now, it could be a genetic abnormality or it can be an immune attack by T cells. This occurs in aplastic anemia. It can also be caused by marrow infiltration. That means, occupation of marrow spaces by some other cells or fibrosis of marrow. So, that will directly affect these stages. Now, going to other stages if there is a deficiency of erythropoietin. We know that erythropoietin is produced from kidneys. So, if there is a chronic kidney failure that will lead to deficiency of erythropoietin. In these cases, red cell mass will reduce but whatever RBCs are produced will be of normal morphology. That is, they will have normal size. So, they will be normalcytic and they will have normal concentration of hemoglobin in them. That is, they will be normalchromic. But since total number will be less, anemia will occur. So, these are essentially normalcytic, normalchromic, high-toproliferative anemia. But if production is affected because of nutritional deficiency, it will affect the morphology of anemia also. For example, if vitamin B12 and follic acid deficiency occurs, RBCs don't mature and big nucleated blast cells enter into circulation. These big cells are known as macrosites. But since these are also immature blast cells, they are also known as megaloplasts. Similarly, decrease in iron deficiency or decrease in iron uptake by precursor cells as occurs in anemia of chronic inflammation. It will cause decreased hemoglobin synthesis and has decreased RBC production. Now, amount of hemoglobin and size of RBCs are highly interrelated. When amount of synthesized hemoglobin decreases, size of RBC also decreases. These small cells with less hemoglobin are known as microcytes. And since hemoglobin is also less, the color of the RBC will also be less. So, they are known as hypochromic. Now, amino acids are also required for hemoglobin synthesis. So, protein deficiency will also lead to decrease in RBC production. So, basically we saw that anemia occurring due to decreased production of cells is known as hypo-proliferative anemia. Then it will be associated with decreased reticulocyte count. Why? Because the number of RBC which are being produced are less. So, less reticulocytes will be released into circulation. So, in hypo-proliferative anemias, we will have less RBC count. And third, they may or may not affect morphology of cells. That is, they may be either of normalcytic, normochromic type or macrocytic as in vitamin B12 deficiency or maybe microcytic hypochromic type also. Okay, before we finish off, we will just touch upon next cause of anemia that is chronic blood loss, where the spool will decrease because of blood loss. Now, in chronic blood loss, there is more demand than usual for synthesis of RBCs. Since RBCs are lost more than usual. So, the demand for nutrients required for production of RBCs is also more. This ultimately leads to iron deficiency anemia. So, nutrients will be less. So, chronic blood loss ultimately leads to hypo-proliferative type of anemia known as iron deficiency anemia.