The cardiovascular system regulates erythrocyte numbers for optimal oxygen transport. It also prevents erythrocyte over-proliferation, maintaining blood viscosity and flow rate. Tissue oxygen level is one of the critical factors that determines the rate of erythrocyte production. Intense exercise or high altitudes affect the quantity of oxygen intake, resulting in tissue hypoxia. Kidneys detect this oxygen shortage and increase the amount of erythropoietin, or EPO, released in the blood. EPO triggers the hematopoietic stem cells in the bone marrow to form proerythroblasts — which quickly mature to form the erythrocytes, enhancing the oxygen delivery to tissues. Besides oxygen uptake efficiency, EPO release is also triggered by the decrease in the number of circulating erythrocytes. For example, a deficiency of vitamins like B9 and B12 affects DNA synthesis, leading to improper nuclear maturation of the erythroblast cells. Such blast cells form larger, irregular erythrocytes called macrocytes, with a flimsy membrane, which can transport oxygen but are short-lived. Due to the short lifespan, erythrocyte production increases to meet the tissue oxygen demand.