Effects of in vivo and in vitro production of lactic acid on ionized, protein-bound, and complex-bound calcium in blood.

We have studied, both in vitro and in vivo, the quantitative effects of lactic acid production on concentrations of ionized calcium, bound calcium, pH, bicarbonate, and albumin. To do so, we examined the effects of addition of aqueous solutions of either hydrochloric acid, lactic acid, or lithium lactate to blood; we studied in vitro accumulation by storing blood sealed in tubes at room temperature for 5 h, then exposing the blood to air; and we induced in vivo production of lactic acid in healthy individuals who climbed stairs for 10 min. Lactic acid evidently affects the ionized, protein-bound, and complex-bound calcium concentrations in the following ways: (a) hydrogen ions from lactic acid bind to protein, which decreases protein-bound calcium; (b) lactate chelates calcium ions from free ionized calcium and protein-bound calcium about equally; and (c) the loss of a millimole of bicarbonate, either by exposure of blood to air or by respiratory alkalosis, results in the release of about 7 mumol of calcium ions, which re-equilibrate with both the protein-bound and ionized calcium. Because lactate apparently removes calcium ions directly from albumin, our study indicates that protein-bound calcium readily provides calcium ions that buffer changes in the concentration of ionized calcium.