A quantitative analysis of renal ammoniagenesis and energy balance: a theoretical approach

1982 ◽  
Vol 60 (12) ◽  
pp. 1431-1435 ◽  
Author(s):  
Mitchell L. Halperin ◽  
Robert L. Jungas ◽  
Carole Pichette ◽  
Marc B. Goldstein
Keyword(s):  
Metabolic Acidosis ◽  
Quantitative Analysis ◽  
Maximum Rate ◽  
Intact Animal ◽  
Maximum Velocity ◽  
Chronic Metabolic Acidosis ◽  
Atp Production ◽  
Ammonium Production ◽  
Substrate Concentrations

Many theories have been proposed to explain the regulation of renal ammoniagenesis during chronic metabolic acidosis but none of these is entirely satisfactory. Since the activity of each of the enzymes in this pathway greatly exceeds the maximum rate of ammonium production in vivo, even when physiological substrate concentrations are used in this calculation, it follows that ammoniagenesis must be inhibited in the intact animal. We shall present a novel hypothesis for the regulation of the maximum rate of ammoniagenesis which emphasizes the fact that ATP is a product of this pathway and that a limited rate of ATP utilization could control its maximum velocity during chronic metabolic acidosis. To test the validity of our hypothesis, a quantitative analysis of the pathways of ATP production and utilization in the kidney will be reviewed. This approach is similar to one already proposed for the regulation of the maximum rate of ketogenesis in the liver.

scholarly journals The kidney of chicken adapts to chronic metabolic acidosis: In vivo and in vitro studies

1982 ◽  
Vol 22 (2) ◽  
pp. 103-111 ◽  
Author(s):  
André G. Craan ◽  
◽  
Guy Lemieux ◽  
Patrick Vinay ◽  
André Gougoux
Keyword(s):  
Metabolic Acidosis ◽  
In Vitro Studies ◽  
Chronic Metabolic Acidosis

Influence of acute hyponatremia on renal ammoniagenesis in dogs with chronic metabolic acidosis

1990 ◽  
Vol 258 (2) ◽  
pp. F328-F332
Author(s):  
M. L. Halperin ◽  
B. C. Ching
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Acidosis ◽  
Chronic Metabolic Acidosis ◽  
Rate Of Oxygen Consumption ◽  
Ammonium Production ◽  
Significant Change ◽  
Acute Hyponatremia ◽  
Rate Of Extraction

The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine.

Intracellular bicarbonate of skeletal muscle under different metabolic states

1976 ◽  
Vol 230 (1) ◽  
pp. 228-232 ◽  
Author(s):  
RN Khuri ◽  
SK Agulian ◽  
KK Bogharian
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Metabolic Alkalosis ◽  
Equilibrium Potential ◽  
Chronic Metabolic Acidosis ◽  
Cell Ph ◽  
Metabolic States ◽  
Na Depletion ◽  
K Depletion

Intracellular bicarbonate of single muscle fibers in vivo was measured by a direct electrometric method simultaneously with the membrane PD in rats under seven different metabolic states. From the measured intracellular bicarbonate values and the PCO2, the bicarbonate equilibrium potential and the intracellular pH were calculated. The mean intracellular [HCO3-] under normal control conditions was 10.3 +/- 0.7 mM (SE). The intracellular bicarbonate fell significantly in both chronic metabolic acidosis and chronic K+ depletion. In contrast, intracellular bicarbonate was elevated in chronic metabolic alkalosis, K+ loading, and Na+ depletion. Taking intracellular pH as an index of the acid-base status of cells, we find that whereas the calculated cell pH decreased along with the cell bicarbonate in both chronic metabolic acidosis and K+ depletion, cell pH increased along with the bicarbonate only in chronic metabolic alkalosis. Cell pH was unchanged in both chronic K+ loading and Na+ depletion.

31P-NMR in vivo measurement of renal intracellular pH: effects of acidosis and K+ depletion in rats

1986 ◽  
Vol 251 (5) ◽  
pp. F904-F910 ◽  
Author(s):  
W. R. Adam ◽  
A. P. Koretsky ◽  
M. W. Weiner
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Respiratory Acidosis ◽  
Resonance Spectroscopy ◽  
Ph Effects ◽  
Potassium Depletion ◽  
Chronic Metabolic Acidosis ◽  
Arterial Blood ◽  
Blood Ph

Renal intracellular pH (pHi) was measured in vivo from the chemical shift (sigma) of inorganic phosphate (Pi), obtained by 31P-nuclear magnetic resonance spectroscopy (NMR). pH was calculated from the difference between sigma Pi and sigma alpha-ATP. Changes of sigma Pi closely correlated with changes of sigma monophosphoesters; this supports the hypothesis that the pH determined from sigma Pi represents pHi. Renal pH in control rats was 7.39 +/- 0.04 (n = 8). This is higher than pHi of muscle and brain in vivo, suggesting that renal Na-H antiporter activity raises renal pHi. To examine the relationship between renal pH and ammoniagenesis, rats were subjected to acute (less than 24 h) and chronic (4-7 days) metabolic acidosis, acute (20 min) and chronic (6-8 days) respiratory acidosis, and dietary potassium depletion (7-21 days). Acute metabolic and respiratory acidosis produced acidification of renal pHi. Chronic metabolic acidosis (arterial blood pH, 7.26 +/- 0.02) lowered renal pHi to 7.30 +/- 0.02, but chronic respiratory acidosis (arterial blood pH, 7.30 +/- 0.05) was not associated with renal acidosis (pH, 7.40 +/- 0.04). At a similar level of blood pH, pHi was higher in chronic metabolic acidosis than in acute metabolic acidosis, suggesting an adaptive process that raises pHi. Potassium depletion (arterial blood pH, 7.44 +/- 0.05) was associated with a marked renal acidosis (renal pH, 7.17 +/- 0.02). There was a direct relationship between renal pH and cardiac K+. Rapid partial repletion with KCl (1 mmol) significantly increased renal pHi from 7.14 +/- 0.03 to 7.31 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats

2014 ◽  
Vol 306 (5) ◽  
pp. F517-F524 ◽  
Author(s):  
Jürg A. Gasser ◽  
Henry N. Hulter ◽  
Peter Imboden ◽  
Reto Krapf
Keyword(s):  
Metabolic Acidosis ◽  
Bone Resorption ◽  
Bone Mass ◽  
Cortical Bone ◽  
Bone Microarchitecture ◽  
Chronic Metabolic Acidosis ◽  
Ovx Rats ◽  
Cortical Bone Mass ◽  
Trabecular Number

Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3−]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk ( week 10: intact normal +2.1 ± 0.9% vs. intact acidosis −3.6 ± 1.2%, P < 0.001), an effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number.

Determinants of ammonia entry along the rat proximal tubule during chronic metabolic acidosis

1989 ◽  
Vol 256 (6) ◽  
pp. F1104-F1110 ◽  
Author(s):  
E. E. Simon ◽  
C. Merli ◽  
J. Herndon ◽  
E. J. Cragoe ◽  
L. L. Hamm
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Significant Inhibition ◽  
Perfusion Rate ◽  
Chronic Metabolic Acidosis ◽  
Bicarbonate Reabsorption ◽  
Rate Dependent ◽  
Rat Proximal Tubule

The technique of in vivo microperfusion was used to examine the determinants of ammonia entry along the rat proximal tubule under conditions of chronic metabolic acidosis (CMA). When perfused with a 5 mM bicarbonate-containing perfusate, collected fluid ammonia concentrations remained constant with increasing flow rate and thus ammonia entry was highly flow-rate dependent. Ammonia entry was also flow-rate dependent using a 25 mM bicarbonate perfusate but entry reached a plateau as perfusion rate increased. Also, ammonia entry tended to be lower at all perfusion rates with the 25 mM perfusate compared with the 5 mM bicarbonate perfusate, but this was most evident at the highest perfusion rate (45 nl/min). The decline in ammonia entry was associated with increasing collected fluid bicarbonate concentrations, suggesting that there was inhibition of diffusion trapping of ammonia. The effects of Na+-H+ exchange inhibition on ammonia entry were examined using the amiloride analogue, 5-(N-ethyl-N-isopropyl)amiloride. With a 25 mM bicarbonate-containing perfusate, the amiloride analogue caused a significant decrease in bicarbonate reabsorption but a nonsignificant decrease in ammonia entry associated with a significant rise in collected fluid bicarbonate concentration. When the potential effects of decreased diffusion trapping of ammonia were eliminated with 12 and 5 mM bicarbonate-containing perfusates, the analogue had no effect on ammonia entry despite significant inhibition of bicarbonate reabsorption. Thus ammonia entry in CMA is moderately affected by tubule fluid pH but is highly flow-rate dependent. There were no effects of inhibition of Na+-H+ exchange above those expected from inhibition of diffusion trapping of ammonia.

Regulation of renal ammoniagenesis in the dog with chronic metabolic acidosis: effect of a glutamine load

1985 ◽  
Vol 249 (5) ◽  
pp. F745-F752 ◽  
Author(s):  
A. Gougoux ◽  
P. Vinay ◽  
M. L. Halperin
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Acidosis ◽  
Amino Acid ◽  
Metabolic Changes ◽  
Glutamine Metabolism ◽  
Chronic Metabolic Acidosis ◽  
Atp Production ◽  
Amino Acid Release ◽  
Renal Oxygen Consumption ◽  
Acid Release

We recently emphasized that ATP is an obligatory product of renal glutamine metabolism and that all cells must remain in ATP balance. Based on this, we suggested that the maximum rate of renal ammoniagenesis in dogs with chronic metabolic acidosis may be limited by the rate of ATP utilization in the kidney. Since a large infusion of glutamine led to a twofold increase in renal ammoniagenesis in acidotic dogs, we wished to evaluate the renal metabolic changes that permitted this increment within the constraints of renal ATP balance. A large glutamine infusion did not lead to an augmented rate of ATP hydrolysis because renal oxygen consumption was not increased. Two major metabolic changes could explain this stimulation while maintaining ATP balance: first, ATP production from lactate by the kidney was decreased following the glutamine infusion; second, the metabolic fate of glutamine was changed so that more ammonium per ATP was synthesized (i.e., the rates of amino acid release into the renal vein were markedly enhanced, and gluconeogenesis was now a quantitatively significant process). 3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, when infused with glutamine, apparently decreased the calculated rate of gluconeogenesis as expected; however, ammonium production did not decline, because the rate of amino acid release increased further, as did the rate of oxygen consumption. Therefore, a large glutamine infusion increased renal ammoniagenesis in dogs with chronic metabolic acidosis while maintaining ATP balance, because ATP production from other substrates was decreased and because the fate of glutamine metabolism was altered in that less ATP was formed per glutamine utilized.

scholarly journals In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis

1994 ◽  
Vol 46 (6) ◽  
pp. 1705-1712 ◽  
Author(s):  
Saâd Maniar ◽  
Denise Laouari ◽  
Michèle Dechaux ◽  
Véronique Motel ◽  
Jean-Pierre Yvert ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Metabolic Acidosis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Chronic Metabolic Acidosis

scholarly journals The effects of chronic metabolic acidosis on liver and muscle glutamine metabolism in the dog in vivo

1982 ◽  
Vol 202 (1) ◽  
pp. 271-273 ◽  
Author(s):  
Adrian Fine
Keyword(s):  
Metabolic Acidosis ◽  
Glutamine Metabolism ◽  
Hepatic Extraction ◽  
Chronic Metabolic Acidosis ◽  
Glutamine Production

1. Chronic HCl acidosis was induced in dogs. 2. Hepatic extraction of glutamine fell compared with normal animals. 3. Muscle glutamine production was unchanged in acidosis. 4. The results are discussed in relation to inter-organ glutamine metabolism in acidosis in vivo.

scholarly journals Measurements of the turnover rate of glutamine in normal and acidotic rats

1983 ◽  
Vol 210 (1) ◽  
pp. 277-280 ◽  
Author(s):  
E J Squires ◽  
J T Brosnan
Keyword(s):  
Metabolic Acidosis ◽  
Turnover Rate ◽  
Whole Body ◽  
Constant Infusion ◽  
Chronic Metabolic Acidosis

The turnover of glutamine was measured in rats with [1-14C]glutamine. Rates of turnover measured by constant infusion of the label were 130 mumol/h per 100g body wt. in control rats and were not changed in chronic metabolic acidosis. These rates of turnover of whole-body glutamine were about 13-26% of the rate of net glutamine release into the bloodstream, indicating that the bulk of glutamine turnover in vivo is concerned with intracellular processes rather than inter-organ fluxes.

Sign in / Sign up

Export Citation Format

Share Document