The cardiovascular system regulates the number of erythrocytes in the bloodstream to ensure optimal oxygen transport. It also prevents over-proliferation of these cells, which helps to maintain blood viscosity and flow rate.

Several factors influence the erythrocyte production rate, with tissue oxygen level being among the most critical. Intense exercise or high altitudes can cause tissue hypoxia, which triggers the kidneys to release more erythropoietin (EPO) into the bloodstream.

EPO then stimulates hematopoietic stem cells in the bone marrow to form proerythroblasts that quickly mature into erythrocytes. This process enhances oxygen delivery to the tissues.

In addition to oxygen uptake efficiency, EPO release is also triggered by a decrease in the number of circulating erythrocytes. For example, a deficiency of vitamins such as B9 and B12 can affect DNA synthesis, leading to improper nuclear maturation of erythroblast cells. As a result, there is the formation of larger, irregular erythrocytes called macrocytes that have a flimsy membrane and are short-lived. In response to short-lived cells, erythrocyte production increases to meet the tissue's oxygen demand.