The Pnh3 of Renal Tubular Cells*

Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled. As anticipated, the ammonium concentration (TFNHO3 was significantly higher in proximal tubule fluid during acidosis, and ammonium delivery to end proximal sites increased from 19.4±2.3 to 34.0±3.2 pmol/min (P < 0.001). Although chronic acidosis did not affect TFNW at the beginning of the distal tubule, ammonium delivery to the end of the distal tubule increased from 5.72±0.97 to 9.88±0.97 pmol/min. In both control and acidotic groups ammonium delivery was lower (P < 0.001) to end distal sites than to end proximal sites, indicating net loss in the intervening segment. This loss was greater during chronic metabolic acidosis (23.9±33 vs. 13.6±2.0 pmol/min in controls, P < 0.025). In both groups net entry of ammonia, in similar amounts, occurred along the distal tubule (P < 0.05). In situ pH averaged 6.80±0.05 at end proximal tubule sites and fell to 6.54±0.08 at the beginning of the distal tubule (P < 0.005). Chronic metabolic acidosis did not affect these measurements. The calculated free ammonia at the end of the proximal tubule rose from 93±2.2 to 21±9 iM (P < 0.005) during chronic metabolic acidosis, and was also higher at beginning distal sites during acidosis (8.8±2.4 vs.2.7±0.7 uM in controls, P < 0.05). In both groups ammonia values for the beginning distal tubule fluid were lower than for end proximal tubule fluid. Thus, loss of ammonium in the loop segment is enhanced by chronic metabolic acidosis. Distal entry of ammonia is markedly less than along the proximal tubule and does not change in chronic metabolic acidosis, and ammonia permeabilities for the proximal and distal segments of surface nephrons seem different.

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of individual superficial nephron segments to ammonium handling in chronic metabolic acidosis in the rat. Evidence for ammonia disequilibrium in the renal cortex.

Simon¹,

Martin²,

Buerkert³

1985

“…Moreover, renal utilization of ammonia precursors, mainly glutamine, in these circumstances is unexplored so far. A number of investigations carried out in animals with acute metabolic acidosis provided conflicting results that also depended on species differences (14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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

Tizianello¹,

Garibotto²,

Robaudo³

et al. 1982

A B S T R A C T Total renal ammonia production and ammonia precursor utilization were evaluated in patients under normal acid-base balance and in patients with 24-h NH4C1 acidosis by measuring (a) ammonia excreted with urine and that added to renal venous blood, and (b) amino acid exchange across the kidney. In 24-h acidosis not only urinary ammonia excretion is increased, but also total ammonia production is augmented (P < 0.005) in comparison with controls. By evaluating the individual role of acid-base parameters, urine pH and urine flow in influencing renal ammonia production, it was shown that the degree of acidosis and urine flow are likely major factors stimulating ammoniagenesis. Both urine pH and urine flow are determinant in the preferential shift of ammonia into urine. In 1-d acidosis, renal extraction of glutamine was not increased and the total ammonia produced/ glutamine N extracted ratio was higher than in controls (P < 0.005) and was inversely correlated with the log of arterial bicarbonate concentration (P < 0.001). In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P < 0.001). These data indicate that at the early stages of metabolic acidosis, in spite of a brisk increase in ammonia production, the mechanisms responsible for the increased glutamine use, which are operative in chronic acidosis, are not activated and other ammonia precursors, besides glutamine, are probably used for ammonia production.

“…Normally the concentration of arterial ammonia is very low (13)(14)(15). In our experiments the quantities of 15NH4Cl infused are by no means tracer amounts relative to the normal arterial load of ammonia.…”

Section: Resultsmentioning

confidence: 63%

Pathways of Ammonia Metabolism in the Intact Functioning Kidney of the Dog*

Stone¹,

Pitts²

1967

Summary. Studies in which 15N-labeled precursors of urinary ammonia were infused into the artery of an intact functioning kidney of an acidotic dog have led to the following conclusions: Preformed ammonia and ammonia derived from the amide nitrogen of plasma glutamine are added directly to urine without significant incorporation into amino acid intermediates of renal tissue. Thus, reductive amination of a-ketoglutarate to form glutamate does not occur to an appreciable extent nor is there significant transfer of the amide nitrogen of glutamine to the corresponding keto acids to form glutamate, aspartate, alanine, or glycine. The enzyme system "glutaminase II" may participate to a significant extent in the metabolism of glutamine by forming aspartate and alanine by direct transamination of oxalacetate and pyruvate and liberating the amide nitrogen as ammonia. Renal alanine exists as a well mixed pool derived in roughly equal amounts from filtered and reabsorbed plasma alanine and newly synthesized alanine. The alanine pool of tubular cells does not equilibrate with the alanine of peritubular capillary blood. Transfer of the nitrogen of alanine to a-ketoglutarate and subsequent oxidative deamination of the resulting glutamate can account for the ammonia formed from alanine. Glycine is not an important intermediate in renal nitrogen metabolism. IntroductionIf an ammonia-generating enzyme cannot be