Acute acidosis-induced alteration in bone bicarbonate and phosphate

Abstract

During an acute fall in systemic pH due to a decrease in the concentration of serum bicarbonate ([HCO[Formula: see text]]), metabolic acidosis, there is an influx of hydrogen ions into the mineral phase of bone, buffering the decrement in pH. When bone is cultured in medium modeling acute metabolic acidosis, the influx of hydrogen ions is coupled to an efflux of sodium and potassium and a depletion of mineral carbonate. These ionic fluxes would be expected to neutralize some of the excess hydrogen ions and restore the pH toward normal. Approximately one-third of bone carbonate is located on the hydration shell of apatite, where it is readily accessible to the systemic circulation, whereas the remainder is located in less accessible areas. We hypothesize that the surface of bone would respond to acidosis in a different manner than the interior of bone, with depletion of carbonate preferentially occurring on the bone surface. We utilized a high-resolution scanning ion microprobe with secondary ion mass spectroscopy to localize the changes in bone carbonate, as measured by HCO[Formula: see text], and phosphate and determine their relative contribution to the buffering of hydrogen ions during acute metabolic acidosis. Neonatal mouse calvariae were incubated in control medium (pH ∼7.44, [HCO[Formula: see text]] ∼27 mM) or in medium acidified by a reduction in [HCO[Formula: see text]] (pH ∼7.14, [HCO[Formula: see text]] ∼13). Compared with control, after a 3-h incubation in acidic medium there is a fivefold decrease in surface HCO[Formula: see text] with respect to the carbon-carbon bond (C2) and a threefold decrease in surface HCO[Formula: see text] with respect to the carbon-nitrogen bond (CN) with no change in cross-sectional HCO[Formula: see text]. Compared with control, after a 3-h incubation in acidic medium there is a 10-fold decrease in cross-sectional phosphate with respect to C2 and a 10-fold decrease in cross-sectional phosphate with respect to CN, with no change in surface phosphate. On the bone surface, there is a fourfold depletion of HCO[Formula: see text] in relation to phosphate, and, in cross section, a sevenfold depletion of phosphate in relation to HCO[Formula: see text]. Thus acute hydrogen ion buffering by bone involves preferential dissolution of surface HCO[Formula: see text] and of cross-sectional phosphate.