ExtractThe present observations were undertaken to establish the response of children to the acute administration of ammonium chloride, in order to provide a basis for identifying and interpreting abnormalities in the mechanisms involved in renal acid base regulation. Fifty-eight normal children aged 4 to 13 years were studied before and for 5 hours following administration of ammonium chloride. Group A, consisting of 23 children, received 75 mEq/m2 body surface area or 2.75 mEq/kg body weight. Group B, consisting of 35 children, received 150 mEq/mZ, or 5.45 mEq/kg.Values for serum electrolytes, urea, creatinine, osmolality and acid-base parameters in children in Groups A and B are shown in tables I and 111. Urinary pH and rates of excretion of titratable acid and ammonium are shown in tables I1 and IV. The relations between blood tCO, and urinary concentration of H+, rate of excretion of titratable acid, and rate of excretion of ammonium for all subjects are shown in figures 1-3. Progressively lower values of pH were observed over the entire range of tCO, studied. During control periods, an inverse correlation was present between tCO, and rates of excretion of both titratable acid and ammonium. At levels of tCO, below 22.5 mmoles/l, the rate of excretion of TA and ammonium became constant, with mean rates of excretion of 52 pEqlminl 1.73 m2 (range, f 2 SD, 33 to 71), and 73 pEqlminll.73 m2 (46 to loo), respectively.These data are interpreted as demonstrating the importance of the blood tCO, or, more precisely, the concentratibn of bicarbonate in glomerular filtrate in urinary acidification mechanisms as well as in control of excretion of bicarbonate. Assessment of renal acidifying mechanisms requires administration of sufficient ammonium chloride or other acidifying substance to depress blood tCO, to levels well below the renal threshold.The physiologic validity of the hydrogen ion clearance index must be questioned, since correcting rates of excretion of hydrogen ion for concentration of total CO, in blood presumes that there is a fixed relation between these two measurements. In figure 4, urinary excretion of total hydrogen ion is plotted as a function of blood tCO,. Hydrogen ion excretion, negligible at tCO, levels of 26 or more, increases steadily as tCO, falls to values below the threshold. The rate of excretion then reaches maximal levels, despite further reduction in blood tCO,. Thus, the hydrogen ion clearance index is valid only over the range of blood tCO, in which there is a linear relationship with rate of excretion of hydrogen ion. Renal acidification mechanisms should be evaluated with blood tCO, several millimoles below the threshold, assuring a maximal response and permitting direct comparison with normals. In subjects with a normal bicarbonate threshold, blood tCO, should be depressed at least to 17-18 mmoles/l in infants and 20-21 mmoles/l in older children. If an abnormal bicarbonate threshold is present the dose must be adjusted accordingly.
SpeculationThese studies suggest that both the con...