The role of pH in altering serum ionized calcium concentration

Although parathormone primarily determines normal ionized serum calcium concentration [Ca++] over the long term, it has little impact in the acute situation. Nonhormonal changes in [Ca++] have been related to acute changes in serum pH, but these have been believed small. With use of an experimental model of acute pancreatitis, we measured changes in [Ca++] and related them to changes in other serum constituents known to affect it. All 18 animals studied experienced a decrease in total serum calcium concentration [CaT]. Changes in [CaT] correlated only with changes in protein-bound calcium concentration [CaP] (r = 0.98, p less than or equal to 0.0005). They did not correlate independently with changes in albumin, globulin, or total protein concentration. [CaP] varied as a function of albumin, globulin, and phosphate concentration and pH according to the equation: [CaP] = 17.9 +/- 0.89 [albumin] = 0.68 [globulin] - 2.5 pH + 0.12 [phosphate]. Calculated values for [CaP], when this equation was used, correlated strongly with observed values for [CaP] (r = 0.81, p less than or equal to 0.0005). Measured [Ca++] increased in the animals early during pancreatitis and then returned to baseline levels. A few animals experienced ionized hypocalcemia. [Ca++] correlated only with changes in pH (r = 0.87, p less than or equal to 0.02). The calculated response slope was delta [Ca++]/delta pH = -2.9. It is concluded that pH has a greater effect on [Ca++] than previously recognized. The major determinant of [CaT] during periods of rapid physiologic change appears to be [CaP] while that for [Ca++] is pH.