Bushinsky David A, Smith Susan B, Gavrilov Konstantin L, Gavrilov Leonid F, Li Jianwei, Levi-Setti Riccardo
Nephrology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Am J Physiol Renal Physiol. 2002 Nov;283(5):F1091-7. doi: 10.1152/ajprenal.00155.2002.
During an acute fall in systemic pH due to a decrease in the concentration of serum bicarbonate ([HCO(3)(-)]), 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(3)(-), 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 approximately 7.44, [HCO(3)(-)] approximately 27 mM) or in medium acidified by a reduction in [HCO(3)(-)] (pH approximately 7.14, [HCO(3)(-)] approximately 13). Compared with control, after a 3-h incubation in acidic medium there is a fivefold decrease in surface HCO(3)(-) with respect to the carbon-carbon bond (C(2)) and a threefold decrease in surface HCO(3)(-) with respect to the carbon-nitrogen bond (CN) with no change in cross-sectional HCO(3)(-). Compared with control, after a 3-h incubation in acidic medium there is a 10-fold decrease in cross-sectional phosphate with respect to C(2) 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(3)(-) in relation to phosphate, and, in cross section, a sevenfold depletion of phosphate in relation to HCO(3)(-). Thus acute hydrogen ion buffering by bone involves preferential dissolution of surface HCO(3)(-) and of cross-sectional phosphate.
由于血清碳酸氢盐（[HCO₃⁻]）浓度降低导致全身pH值急性下降，即发生代谢性酸中毒时，氢离子会流入骨的矿质相，缓冲pH值的下降。当将骨置于模拟急性代谢性酸中毒的培养基中培养时，氢离子的流入与钠和钾的流出以及矿质碳酸盐的消耗相关联。预计这些离子通量会中和部分过量的氢离子，并使pH值恢复正常。大约三分之一的骨碳酸盐位于磷灰石的水化层上，在那里它很容易进入体循环，而其余部分则位于较难进入的区域。我们假设骨表面对酸中毒的反应方式与骨内部不同，碳酸盐的消耗优先发生在骨表面。我们使用配备二次离子质谱的高分辨率扫描离子微探针来定位骨碳酸盐的变化（通过HCO₃⁻测量）以及磷酸盐，并确定它们在急性代谢性酸中毒期间对氢离子缓冲的相对贡献。将新生小鼠颅骨在对照培养基（pH约7.44，[HCO₃⁻]约27 mM）或通过降低[HCO₃⁻]酸化的培养基（pH约7.14，[HCO₃⁻]约13）中孵育。与对照相比，在酸性培养基中孵育3小时后，相对于碳 - 碳键（C₂），表面HCO₃⁻下降了五倍，相对于碳 - 氮键（CN），表面HCO₃⁻下降了三倍，而横截面HCO₃⁻没有变化。与对照相比，在酸性培养基中孵育3小时后，相对于C₂，横截面磷酸盐下降了10倍，相对于CN，横截面磷酸盐下降了10倍，而表面磷酸盐没有变化。在骨表面，HCO₃⁻相对于磷酸盐减少了四倍，在横截面中，磷酸盐相对于HCO₃⁻减少了七倍。因此，骨对急性氢离子的缓冲涉及表面HCO₃⁻和横截面磷酸盐的优先溶解。
