Plasma calcium regulation associated with induced hypocalcemia and hypercalcemia

The plasma calcium level is one of the most precisely regulated constants of the internal environment, and the large reservoir of calcium in the skeleton is primarily responsible for this homeostasis. The experiments presented in this thesis were designed to study quantitatively the regulation of plasma calcium. Acute hypocalcemia was induced by continuous intravenous EDTA infusion (a calcium chelating agent) at a known rate, and hypercalcemia was induced by intravenous calcium gluconate infusion. The rate used in most cases was 10 mg. calcium per kg. for one hour. Both mobilization and storage of calcium appeared to depend on equilibrium with a labile calcium storage pool in bone. The rate of storage or mobilization was shown to be proportional to the amount of blood coming in contact with this labile pool in bone (bone blood flow), and the plasma/bone difference in Ca++ activity. Bone blood flow was measured using the Pick Principle for calcium storage, and it was calculated to be 6.46 ± 0.60% of the cardiac output (14 dogs). The extracellular fluid calcium was also estimated and found to be 15.73 ± 0.72 mg/kg (14 dogs), corresponding to an extracellular fluid volume of approximately 20% of body weight. Less than 5% of the injected calcium was excreted in the urine. The labile calcium storage pool in bone was estimated from the changes in the bone-blood equilibrium after calcium was injected, and was found to be 2 - 5 times greater than the extracellular calcium. The net loss of calcium from the plasma after calcium injection, which is assumed to equal the rate at which calcium is used for bone mineralization less calcium released by resorption, was estimated as 1 - 2 mg. Ca/kg/hr. or 0.15 - 0.35% of the total bone calcium per day. The methods described provide a means of assessing quantitatively the factors involved in acute regulation of the plasma calcium level.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat