DIFFUSION OF GASES OUT OF THE DISTAL NEPHRON-SEGMENT IN MAN. I. NH3*

Abstract
Urinary excretion of total ammonia regularly rises, irrespective of initial urinary pH, when urine flow of healthy men is caused to rise from around 1 ml per minute to the physiologic ceiling by water-drinking. The absolute increase during diuresis is considerably greater in acid than in alkaline urine; the percentile increase is greatest for the highest urinary pH range (neutral to alkaline), decreasing progressively as urinary pH declines. When urinary pH does not exceed 6.4 during water diuresis, the increase of ammonia excretion is accompanied by a decrease, approximately chemically equivalent, in the rate of excretion of residual titratable acid. The equivalence supports the view that the rate of elimination of ammonia in the urine is governed by the amount of net diffusion of NH3 out of the renal parenchyma into the fluid passing through the lumen of the distal portion of the nephron, since enhanced net diffusion of NH3 into the lumen as urinary flow increases will diminish H+-excretion by converting H+ to NH4+ while simultaneously increasing total ammonia excretion. Urinary pH varies with urinary flow rate, tending always to approach 6.6 at 37[degree]C as flow rises. When the pH of low-flow urine is 6.0 or less, it is about 0.5 to 1.0 pH U as flow rate rises from 1 ml per minute to its ceiling. Less than 20% of the change can be ascribed to the physiocochemical effect of dilution; the remainder appears to be due entirely to increased net diffusion of NH3 into luminal fluid. Urinary concentration of free-base NH3 is little affected when the flow rate of neutral to alkaline urine rises above about 4 to 7 ml per minute, or the flow rate of acid urine above about 2 ml per minute, to and well beyond the physiologic ceiling of water diuresis. The findings are incompatible with impermeability to NH3 of the terminal nephron-segment, where water reabsorption is completed, and indicate equilibration under these conditions of [NH3] of the luminal fluid with that of the adjacent interstitial water. Semiquantitative treatment of the data provides evidence, reinforced by more direct published data, indicating that NH3, after diffusing to equilibrium in the acidified luminal fluid of the distal nephron-segment, subsequently diffuses out of the terminal nephron-segment as a result of and in proportion to osmotic reabsorption of "solute -free water.".