The Role of the Extracellular Fluid

The importance of the blood volume in maintaining a normal circulation is now well recognized. The circulation will fail if the volume of blood becomes too small to fill the vascular system adequately. In general, the quantity of blood in the vascular bed is of more significance in maintaining a normal cardiac output than is the proportion of red cells to plasma. Because the volume of plasma can be increased or decreased with relative rapidity, the body uses this means to maintain a comparatively constant blood volume. A decrease in the volume of the circulating red blood cells is normally compensated by an increase in plasma volume; and conversely, an increase in the volume of the circulating red cells is compensated by a decrease in plasma volume. B.ecause a constant blood volume is dependent upon these compensatory adjustments in the plasma volume, a knowledge of the factors controlling the plasma volume is of both theoretical and practical importance. If the arterial pressure, the venous pressure, and the volume of the circulating red cells remain relatively constant, the plasma volume increases and decreases as the amount of circulating plasma protein is increased or decreased. Thus, the injection of a concentrated protein solution causes a temporary rise in plasma volume (1); and the removal of plasma protein causes a temporary decrease in plasma volume, even though the fluid lost in the removal of the protein is replaced by an equal quantity of physiological saline solution (2). The changes in plasma volume produced by varying the amount of circulating plasma protein are not permanent in normal subjects because the body is able to add protein to the blood stream or remove it. When the blood volume is raised by the addition of protein, the body withdraws protein from the circulation. When the volume is decreased by lowering the quantity of circulating protein, the body adds protein to the blood stream (3). Ebert, Stead, and Gibson (2) studied the changes in the plasma volume of normal subjects after venesection. Immediately after the removal of approximately one-fifth of the blood volume, hemodilution occurred, presumably because of the lowering of venous and capillary pressures. It has since been demonstrated (4) that the pooling of comparable quantities of blood in the extremities by tourniquets does cause a significant decrease in venous pressure. That this initial hemodilution was caused by adding to the blood stream fluid which contained little protein was shown by the parallel fall in plasma protein concentration and hematocrit reading. After one to two hours, no further fall in protein concentration occurred, though the hematocrit reading continued to decrease. This indicated that protein was being added to the blood stream. The return of the blood volume to normal was not appreciably hastened by giving physiological saline solution to replace the blood removed. Most of the saline left the blood stream and did not return to it until the quantity of circulating protein had increased. In the normal subject, there seemed to be enough available fluid to accomplish the initial phase of dilution, and after that time, a further increase in plasma volume was dependent on the addition of protein to the blood stream. Later experiments (5) demonstrated that after venesection, the blood volume could be immediately brought back to normal by replacing the removed blood by an equal volume of fluid containing albumin. These data demonstrated that in a normal subject, with a relatively constant arterial pressure, the amount of circulating plasma protein determined the size of the plasma volume and that a lowering of the quantity of circulating protein caused a decrease in plasma volume and served as a stimulus to the body for the production of plasma protein. The above data suggested that patients with nephrosis and nutritional edema would have a very small plasma volume because of the striking de-