Which of the following is primarily responsible for the physiological change in RBCs during hypoxia?

The physiological change in red blood cells (RBCs) during hypoxia is primarily due to the stimulation of erythropoietin (EPO) production. When oxygen levels are low, the kidneys respond by increasing the synthesis and release of EPO, a hormone that stimulates the bone marrow to produce more RBCs. This process increases the oxygen-carrying capacity of the blood, helping to alleviate the effects of hypoxia.

EPO acts on erythroid progenitor cells in the bone marrow, promoting their survival, proliferation, and differentiation into mature red blood cells. The increase in RBC numbers enhances oxygen transport throughout the body, thereby improving tissue oxygenation, which is crucial in a hypoxic environment.

The other options, while related to RBCs or hematopoiesis, do not serve as the primary mechanism in response to hypoxia. Increased hemoglobin production and enhanced production of stem cells may occur as secondary effects but are not the initial physiological response. Activation of macrophages relates to immune response and does not directly contribute to the increase in RBC production in hypoxic conditions.