Factors Concerned in the Circulatory Failure of Adrenal Insufficiency.

An increase in the packed cell volume of the blood is a typical finding in the crisis of adrenal insufficiency. Swingle, Vars and Parkins (1), by direct and indirect (dye method) measurements of blood and plasma volumes, demonstrated that a reduced plasma volume was the main cause of the increase in the relative volume of red cells. In a series of papers, Swingle and his coworkers (2, 3, 4, 5) postulated the importance of impairment of capillary tone and consequent increase in capillary permeability to protein as an independent factor in the causation of reduced plasma volume and of circulatory failure in crisis. On the other hand, Loeb (6, 7) and Harrop (8, 9) focused their attention on the changes in the elimination of sodium and potassium by the kidneys and on the changes in electrolyte content of the blood and their logical consequences upon the body fluids. A net loss of sodium could cause a depletion of the plasma volume either by carrying away an equivalent volume of extracellular fluid or simultaneously causing a shift of water from the extracellular to the intracellular compartment because of the reduction in effective osmotic pressure of the extracellular fluid. A net retention of potassium might be expected to have a similar net effect, namely, a shift of fluid from the extracellular to the intracellular compartments. According to Harrison and Darrow (10), "Shifts in body fluids do not play a deciding role in the genesis of symptoms following adrenalectomy in the rat." Others, however, have found that slight hydration of muscle does occur in the rat (10) and in the dog (11, 12, 13) in adrenal insufficiency, being more pronounced in the latter animal. If the plasma volume were diminished as a result of any or all of these aberrations in the regulation of electrolytes, it should be accompanied by a decrease in the interstitial fluid (extracellular tissue fluid). And, indeed, since interstitial fluid is considered to be a labile reservoir for the plasma volume, one might even expect a greater relative change in the interstitial volume than in the plasma volume. On the other hand, if decreased capillary tone and increased capillary permeability to protein were the only important factors in the reduction of plasma volume, the volume of interstitial fluid should show a concomitant increase. If both electrolytes and capillary factors were important and independent consequences of adrenal insufficiency, the changes in interstitial fluid might well be very variable. The interstitial fluid volume might sometimes increase and sometimes decrease. If the permeability of capillaries to protein increased as a result of changes in electrolytes, e.g. a change in ratio of sodium to potassium, a decrease in the interstitial fluid volume should be the rule, but it might be very variable in extent. A study of interstitial fluid volumes in adrenal insufficiency produced under different circumstances might thus throw some light on the relative importance of the various factors which have been postulated. So far, the only study of the interstitial fluid of the body as a whole in adrenal insufficiency is that of Harrop (9) on one adrenalectomized dog, which showed a striking decrease, supporting the importance of the electrolyte changes in the production of crisis. In the present study, we have measured the plasma volume by the blue dye T 1824 and the interstitial fluid by sulfocyanate in adrenalectomized dogs during adequate maintenance with hormone and during crisis after deprivation of hormone. We have also watched for evidence of still another factor in the circulatory failure of crisis, namely, impairment of the function of the heart. Cleghorn and his coworkers have stressed the importance of cardiac failure in adrenal insufficiency in cats, in dogs, and in patients with Addison's disease (14, 15). It may occur in the absence of hemoconcentration or changes in the electrolyte pattern of the blood and quite apart from