Diffusion of Gases Out of the Distal Nephron-Segment in Man. I. Nh3*

Abstract

Physiologic variation in rate of urine flow in mammals is ascribed principally to reabsorption from distal tubules and collecting ducts of a varying quantity of nearly solute-free water (1-4). Water reabsorption is brought about by bulk flow or diffusion (5-8) incited by the difference in osmotic pressure between the luminal contents and the hypertonic fluid of the adjacent renal medullary interstitium, a process promoted by the action of endogenous vasopressin upon the permeability of the intervening membranes (7, 9). Elaboration of urine much less than maximally dilute increases the osmolality of luminal fluid as it progresses down the most distal portion of the nephron; the result must be to raise the diffusion pressure of all substances dissolved in luminal fluid.Two highly diffusible substances, the gases NH3 and CO2, are present in solution in luminal fluid together with their hydrated forms NH4OH and H2CO3, in turn in equilibrium, so as to constitute two buffer systems, with the ionized species NH4+ and HCO3-, respectively. If, as a result of the reabsorption of solute-free water, these gases are reabsorbed by diffusion, the existence and magnitude of the process should be reflected in alterations in the acid-base composition of voided urine no less than by changes in the rate of excretion of total ammonia and total carbon 1962-63. dioxide. Examination of the effects of water diuresis in normal man upon these various parameters has provided indirect evidence that the gases NH3 and CO2 do in fact diffuse out of the nephron's lumen during antidiuresis (10-12).1 This communication presents evidence that the rate of urinary ammonia excretion is largely determined by factors affecting the net diffusion of the free base NH3 into the distal portion of the nephron; the evidence further indicates that some NH3, having diffused into the lumen, subsequently diffuses back into the renal interstitium as a result of reabsorption of water from the lumen. METHODSExperimental design. Subjects were 12 healthy adult male volunteers whose rate of urinary flow was caused to vary between 1 ml per minute and the physiologic ceiling by controlled water-drinking. Serial, timed urine collections were made at intervals of about 12 minutes by voluntary emptying of the bladder. The individual experiments, generally comprising 20 or more collections, were begun about 8 a.m. in subjects who fasted overnight and remained upright during and for at least an hour before the experiment. When alkaline or mark-1 "Ammonia" means total ammonia. NH, includes NH4OH when ratios of the buffer species are in question, and HCO3 includes anhydrous CO, in the analagous context. NH4, is not considered a form of buffered H' except that "total H`" excretion includes NH,+.It has been inferred from experiments on toad bladder and other membranes (5) that vasopressin promotes osmotic movement of water out of the nephron by hydraulic flow through pores rather than by diffusion. The facts about the toad bladder are disputed (8), and there is no direct info...

Renal Adaptation to a High Potassium Intake

“…phosphate, creatinine or organic acids; rate of urine flow or urinary ionic strength (17,18). Furthermore the decrease is not the result of an increase in net acid excretion.…”

The effect of uncomplicated potassium depletion on urine acidification

“…The pH of an acid urine increases as urine flow rate is increased (16,17)8 and potassium depletion is known to result in a defect in water reabsorption (19,20). This possible explanation for the rise in urine pH observed during potassium deficiency had not been considered in any of the previous investigations, however, it was specifically excluded in this study.…”

Renal ammoniagenesis in an early stage of metabolic acidosis in man.

“…An inverse correlation between urinary ammonia excretion and urine pH was detected (11,22,23); furthermore, an increase in urine flow per se caused an increased ammonia excretion (12,24). It is poorly understood if, and to what extent, these factors are able to stimulate renal ammonia production.…”