Expansion of interstitial fluid is required for full restitution of blood volume after hemorrhage.

Dogs with splenectomy and intact adrenals and adrenalectomized-splenectomized dogs infused with cortisol at a physiologically increased rate restored plasma volume and protein and demonstrated early extracellular hyperosmolality. In contrast, adrenalectomized-splenectomized dogs infused with cortisol at a basal rate did not restore volume or protein after a transient initial phase and did not demonstrate extracellular hyperosmolality. From the foregoing evidence, it is postulated that the second state of restitution of blood volume following hemorrhage proceeds as follows: 1) Hemorrhage and the subsequent increase in plasma cortisol concentration lead to an increase in extracellular osmolality. An osmotic shift of intracellular fluid to the interstitium ensues. 2) The small increase in interstitial fluid volume results in a relatively large increase in interstitial hydrostatic pressure (because of the low compliance of the interstitium), thus accelerating lymphatic movement of interstitial protein to the vascular system. This movement results in a reequilibration of extracellular fluid toward the plasma. 3) The osmotically active agents mobilized by cortisol and hemorrhage do not appear to be glucose, sodium, or potassium. 4) There may be an adrenal factor other than cortisol that is necessary for full restitution of blood volume with 24 hours after hemorrhage.