The Influence of Extracellular Fluid Volume on the Renal Bicarbonate Threshold. A Study of Two Children with Lowe's Syndrome

Abstract

ExtractThis study on the renal acid-base balance in two slightly acidotic patients with Lowe's syndrome was undertaken to demonstrate the influence of extracellular fluid volume on the renal bicarbonate threshold. The clinical observation of chronic dehydration in both patients lead to the hypothesis that a low plasma volume might account for a relative compensation of metabolic acidosis in these patients and, conversely, that volume expansion might unmask a more severe acidosis.The ability to excrete an acid urine was established by measuring the response to acute NH,Cl loading. Optimal response was seen three to four hours after NH,C1 was given. Both patients were able to excrete acid urine with a p H of 5.5 at blood total CO, content below 18.5 mmoles/l. The excretion rates for titratable acidity (TA) and for ammonium rose after NH,C1 administration to values within normal range (table I). The excretion rate of T A in one patient attained normal limits after correction for the low GFR, which on repeated examinations was 25-30 % of normal.The renal bicarbonate threshold was determined by infusions of increasing amounts of NaHCO,. The infusion rates were kept constant a t 1.4 ml/min/m2 during the first study undertaken in each patient, and 5.6 ml/min/m2 during the second. With low infusion rates, plasma volume, determined by the radioisotope dilution technique, was 57.8 ml/kg in Patient C.St. and 54.5 ml/kg in Patient M. B.; during high infusion rates it was 63.6 ml/kg in Patient C. St. and 64.9 ml/kg in Patient M. B.Plasma volume was thus expanded 10 and 19 %, respectively, from one study to the next. During low rates of infusion, the renal bicarbonate threshold in both patients was 21 mmoles/l (tables I1 and I11 and fig. 2) ; during high infusion rates it was 17.5 mmoles/l (tables I V and V and fig. 2). During low infusion rates, the bicarbonate thresholds were decreased, in comparison with the normal for age, 22-24 mmoles/l, and with the normal for weight, 21.5-22.5 mmoles/l. After expansion of extracellular fluid volume, the renal bicarbonate threshold decreased by 3.5 mmoles/l. SpeculationThe renal bicarbonate threshold can be decreased by volume expansion. In patients with Lowe's syndrome, chronic dehydration may compensate in part for the decreased renal bicarbonate threshold.

Hypokalemia, a Factor Influencing Renal Bicarbonate Reabsorption: Continued Studies on the Regulatory Mechanisms Governing Renal Handling of Acid-Base in Children

“…Since plasma volume or ECF volume has been shown to be indirectly related to renal bicarbonate threshold [11,14], it was crucial for the present studies to relate only kalemia to renal bicarbonate threshold, when plasma or ECF volumes were identical or were slightly changed to have an opposite effect than kalemia might have had. The reported situations fulfill these criteria.…”

“…Blood pH status, urine CO 2 content and bicarbonate, serum electrolytes, and inulin levels were determined as described earlier [14].…”

“…Experimental evidence had been advanced that the alkalosis is due to an increased proximal tubular bicarbonate reabsorption [11]. In earlier studies in two patients with Lowe's syndrome, a relative volume contraction was found to influence acid-base equilibrium [14]; in man, plasma volume was shown to be inversely related to renal bicarbonate threshold. In patients with hypokalemic alkalosis, ECF volume may play a major role in the genesis of the disorder, as it probably did in the patients treated with massive doses of sodium penicillin by Brunner and Frick [3].…”

“…This state is best achieved by determination of renal bicarbonate threshold, which arbitrarily describes the plasma level of HCO 3~ in millimoles per liter at which a urinary excretion rate of 0.02 mmoles HCO3/IOO ml GFR occurs. It can be determined in bicarbonate titration studies [14]. When it was not possible to perform bicarbonate titration studies, a simplified method of estimating renal bicarbonate threshold was used instead.…”

Renal Acid-Base Titration Studies in Infants with and without Metabolic Acidosis in the Postneonatal Period

“…Several factors may influence the excretion and reabsorption of bicarbonate and thus the renal bicarbonate threshold, e.g., ( I ) activity of carbonic anhydrase [36]; (2) alterations in renal metabolism and in kinetics of enzyme reactions [20]; ( 3 ) disturbances in potassium balance [24]; (4) morphologic glomerulotubular imbalance [5, 81 ; ( 5 ) changes in extracellular volume [16,21,26,27,371.…”