The role of the kidney in blood volume regulation: the kidney as a regulator of the hematocrit

The kidney plays a pivotal role in the regulation of blood volume by controlling the plasma volume and red blood cell (RBC) mass. Further, it is proposed that the kidney coordinates the relative volumes of these 2 blood components and in so doing regulates the hematocrit. This novel function as proposed is a functional concept whereby the kidney does not simply produce erythropoietin, but that the kidney regulates the hematocrit is termed the critmeter function. The kidney is unique in that it can indirectly report on blood volume as a tissue oxygen signal. It is proposed that the kidneys detect small changes in tissue oxygen tension for erythropoietin production at the critmeter, a functional unit of marginal oxygen tension within the kidneys. As the production of erythropoietin is modulated by angiotensin II, the renin-angiotensin system entrains the production of erythropoietin as part of the effector signals of the feedback loop of blood volume regulation. Collectively, the consideration of these points generates a paradigm shift in our understanding of blood volume regulation in that the role of the kidney may be expanded from simply "producing" erythropoietin to regulating the hematocrit. Further, this concept broadens the scope of the traditionally identified effector mechanisms of plasma volume regulation to include the modulation of erythropoietin production and hence RBC mass. The inclusion of both plasma volume and RBC mass as factors targeted by the effector signals recapitulates that whole blood volume is sensed and reported in the afferent signals. In summary, distinct sensing and effector mechanisms for regulating the volume of the two components of whole blood (plasma and red cell mass) are recognized. The coupling of the regulation of these 2 components of blood volume is highlighted.