A model of proximal tubular bicarbonate absorption

1985 ◽  
Vol 248 (2) ◽  
pp. F272-F281 ◽  
Author(s):  
R. J. Alpern ◽  
F. C. Rector
Keyword(s):  
Extracellular Fluid ◽  
High Plasma ◽  
Bicarbonate Concentration ◽  
Solvent Interactions ◽  
Proton Secretion ◽  
Plasma Bicarbonate ◽  
Flow Dependence ◽  
Model Predictions ◽  
Proximal Tubular ◽  
Luminal Flow

A model is presented that utilizes determinants of acidification defined from microperfusion studies in the rat to stimulate the effect on absolute bicarbonate absorption along the entire proximal convoluted tubule. Net bicarbonate absorption is considered to consist of active transcellular proton secretion in parallel with passive paracellular bicarbonate diffusion. The rate of proton secretion is calculated as a function of luminal bicarbonate concentration using Michaelis-Menten kinetics. The K1/2 is modified by luminal flow rate and the Vmax by peritubular bicarbonate concentration. Solute-solvent interactions and axial heterogeneity are also included as determinants of proton secretion rate. The model demonstrates that a given percentage stimulation or inhibition of active proton secretion leads to a much smaller effect on absolute proximal bicarbonate absorption along the entire tubular length. This blunting of the stimulation or inhibition is greatest when filtered bicarbonate load is limited by decreases in glomerular filtration rate or plasma bicarbonate concentration. In addition, the model shows that flow dependence is greater at low plasma bicarbonate concentrations, whereas the effect of extracellular fluid volume expansion is greater at high plasma bicarbonate concentrations. Agreement between the model predictions and the results of free-flow micropuncture studies from our laboratory is good with the exception of the effect of raising plasma bicarbonate concentration. This discrepancy is resolvable by allowing the effect of peritubular pH to increase along the length of the tubule, a hypothesis that requires verification.

Flow dependence of proximal tubular bicarbonate absorption

1983 ◽  
Vol 245 (4) ◽  
pp. F478-F484 ◽  
Author(s):  
R. J. Alpern ◽  
M. G. Cogan ◽  
F. C. Rector
Keyword(s):  
Flow Rate ◽  
Concentration Profile ◽  
Concentration Gradients ◽  
Bicarbonate Concentration ◽  
Proton Secretion ◽  
Flow Dependence ◽  
Proximal Tubular ◽  
Convoluted Tubules ◽  
Stimulation Of

Rat proximal convoluted tubules were microperfused in vivo to examine the effect of flow rate on bicarbonate absorption. When tubules were perfused with 25 mM bicarbonate, increases in perfusion rate from 15 to 33 to 49 nl/min caused bicarbonate absorption to increase from 105 +/- 4 to 176 +/- 8 to 209 +/- 7 pmol X mm-1 X min-1, respectively. Only 15% of this stimulation could be attributed to a flow-induced increase in the measured axial luminal bicarbonate concentration profile. In addition, effects of flow on passive bicarbonate diffusion or convection could not account for the observed stimulation. When tubules were perfused with 58 mM bicarbonate (a concentration previously shown to achieve maximal rates of proton secretion), increasing flow rate from 15 to 49 nl/min did not stimulate bicarbonate absorption. Thus, when examined as a function of mean luminal bicarbonate concentration, increases in flow increased the rate of proton secretion without affecting the maximal rate. The data are most consistent with flow-dependent stimulation of bicarbonate absorption, secondary to flow-dependent changes in luminal bicarbonate concentration, occurring by two mechanisms: 1) flow-dependent increases in the measured axial luminal bicarbonate concentration profile and 2) flow-dependent decreases in radial luminal bicarbonate concentration gradients.

Influence of plasma bicarbonate concentration and pH on citrate excretion

1964 ◽  
Vol 206 (4) ◽  
pp. 875-882 ◽  
Author(s):  
David P. Simpson
Keyword(s):  
Linear Relationship ◽  
Metabolic Alkalosis ◽  
High Plasma ◽  
Alkaline Ph ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Close Relationship ◽  
Base Balance

Citrate excretion has been studied in dogs under various conditions of acid-base balance in order to determine which factors are responsible for the increased citrate clearance present in metabolic alkalosis. A close relationship, significantly modified by systemic pH, was found between plasma bicarbonate concentration and citrate clearance. In the presence of an alkaline plasma pH, there was a linear relationship between changes in plasma bicarbonate concentration and changes in citrate clearance. Other experiments also demonstrated the influence of plasma bicarbonate concentration on citrate clearance at alkaline pH. Under acidotic conditions citrate clearances were low and changes in plasma bicarbonate concentration had little effect on citrate excretion. A change in plasma pH from an acidotic to an alkalotic state, with a constant plasma bicarbonate concentration, produced an increase in citrate clearance. Thus the coexistence in metabolic alkalosis of high plasma bicarbonate concentration and high plasma pH results in a markedly increased citrate clearance.

Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption

1963 ◽  
Vol 205 (4) ◽  
pp. 693-696 ◽  
Author(s):  
James R. Clapp ◽  
John F. Watson ◽  
Robert W. Berliner
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Intravenous Administration ◽  
Distal Portion ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
Carbonic Anhydrase Inhibition ◽  
Before And After ◽  
Proximal Tubular

Samples of fluid from the proximal tubule were collected for the measurement of pH and bicarbonate concentration before and after the administration of acetazolamide (Diamox). Samples collected before acetazolamide were consistently more acid than plasma with the most acid samples coming from the more distal portion of the proximal tubule. After the intravenous administration of acetazolamide, the pH and bicarbonate concentration were consistently higher than in plasma. Bicarbonate concentrations as high as 2.8 times that in plasma were observed. The rise in proximal tubular fluid bicarbonate concentration after acetazolamide is presumably due to a reduction in the rate of bicarbonate reabsorption out of proportion to any impairment in proximal tubular fluid volume reduction.

Effect of luminal bicarbonate concentration on proximal acidification in the rat

1982 ◽  
Vol 243 (1) ◽  
pp. F53-F59 ◽  
Author(s):  
R. J. Alpern ◽  
M. G. Cogan ◽  
F. C. Rector
Keyword(s):  
Partial Saturation ◽  
Bicarbonate Concentration ◽  
Proton Secretion ◽  
Saturation Kinetics ◽  
Proximal Tubular ◽  
Convoluted Tubules ◽  
Proximal Convoluted Tubules

The effect of luminal bicarbonate concentration on proximal tubular acidification was studied. Rat proximal convoluted tubules were perfused in vivo with solutions of varying bicarbonate concentration, and bicarbonate absorption was measured using microcalorimetry. Bicarbonate absorption was found to increase linearly with mean luminal bicarbonate concentrations up to 45 mM, but above this level it showed evidence of partial saturation. Bicarbonate permeability was measured and found to be 2.6 +/- 0.3 x 10(-7) cm2/s. Using this permeability, net bicarbonate absorption could be divided into two parallel components, both sensitive to luminal bicarbonate concentration: 1) proton secretion and 2) a passive bicarbonate leak. Proton secretion, when examined as a function of luminal bicarbonate concentration, exhibited saturation kinetics with an apparent Km of 16 mM and a Vmax of 200 pmol . mm-1 . min-1.

Flow dependence of bicarbonate transport in the early (S1) proximal convoluted tubule

1988 ◽  
Vol 254 (6) ◽  
pp. F851-F855 ◽  
Author(s):  
F. Y. Liu ◽  
M. G. Cogan
Keyword(s):  
Wistar Rat ◽  
Proximal Convoluted Tubule ◽  
Bicarbonate Transport ◽  
Bicarbonate Concentration ◽  
Perfusion Rate ◽  
Proton Secretion ◽  
Pump Rate ◽  
Luminal Perfusion ◽  
Luminal Flow

We previously found, using an in vivo microperfusion pump rate of 30 nl/min, that proton secretion in the early (S1) proximal convoluted tubule (PCT) of the Munich-Wistar rat exhibited saturation kinetics. The maximal transport capacity was very high, approximately 500–600 peq.mm-1.min-1. The present studies assessed the change in early PCT acidification kinetics in response to an increase in microperfusion rate to 45 nl/min. First, bicarbonate permeability in the early PCT was measured and was found to be flow dependent. Proton secretion was then calculated using perfusate bicarbonate concentrations from 8 to 100 mM. Saturation of early proximal acidification (Vmax) still occurred at approximately 500–600 peq.mm-1.min-1, but the bicarbonate concentration effecting half-maximal acidification (apparent Km) decreased (from approximately 11 mM at 30 nl/min perfusion rate to less than 6 mM at 45 nl/min). By increasing luminal perfusion rate further to 60 nl/min at constant luminal bicarbonate concentration (25 mM), we confirmed that luminal flow rate did not affect the maximal level of acidification. Similar flow-dependent changes in acidification kinetics in the late PCT were also found, as has been previously shown. In conclusion, although an increase in luminal flow increased bicarbonate permeability and apparent affinity for substrate transport, there was no effect on maximal acidification rate in the early PCT.

Steroid modulation of response of plasma bicarbonate concentration to NH4Cl loading: gamma distribution analysis

1983 ◽  
Vol 61 (6) ◽  
pp. 641-646 ◽  
Author(s):  
David Z. Levine ◽  
Robert A. McLeod ◽  
S. Raman
Keyword(s):  
Base Composition ◽  
Dynamic Assessment ◽  
Extracellular Fluid ◽  
Distribution Analysis ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Fluid Compartment ◽  
Acid Load ◽  
Continuous Dynamic

Studies have been carried out in awake chronically cannulated adrenalectomized rats subjected to steroid replacement protocols. Our objective was to determine the effects of mineralocorticoid or glucocorticoid or combined replacement on acid–base composition of the extracellular fluid compartment in response to an acute ammonium chloride acid load. We obtained six blood samples from each animal over a 26-h period and, with the help of a specially derived mathematical model, we were able to obtain a continuous dynamic assessment of changes of plasma bicarbonate concentration during induction and recovery of the metabolic acidosis. Assessment of minimum values for plasma bicarbonate concentration, time to reach the minima, and time for 90% recovery showed that dexamethasone did not exert as much protection as aldosterone. The approach we have used, in a sense being a continuous display of plasma bicarbonate concentration, should be useful in further exploring the nature of the interrelations between acid production, net acid excretion, and the resultant plasma acid–base composition.

Acidification is inhibited in late proximal convoluted tubule during chronic metabolic alkalosis

1987 ◽  
Vol 253 (1) ◽  
pp. F89-F94
Author(s):  
F. Y. Liu ◽  
M. G. Cogan
Keyword(s):  
Flow Rate ◽  
Metabolic Alkalosis ◽  
Extracellular Volume ◽  
Proximal Convoluted Tubule ◽  
Bicarbonate Transport ◽  
Bicarbonate Concentration ◽  
Passive Components ◽  
Proton Secretion ◽  
Flow Dependence

In vivo microperfusion was used to assess the changes in the active and passive components of bicarbonate absorption in the rat late proximal tubule during chronic metabolic alkalosis. In tubules perfused with 40 mM bicarbonate, net bicarbonate absorption was inhibited and normal flow dependence was attenuated during alkalosis, compared with values in normal tubules perfused with 40 or even 25 mM bicarbonate concentrations. Under all conditions, bicarbonate back leak was small and contributed little to alterations in net bicarbonate transport, even though bicarbonate permeability was reduced by approximately 75% during chronic metabolic alkalosis and was flow dependent. Suppression of net bicarbonate absorption during chronic metabolic alkalosis was instead attributable to inhibition of proton secretion as a function of both luminal bicarbonate concentration and flow rate. At the highest level of bicarbonate delivery to yield maximal acidification rates, proton secretion during alkalosis was diminished by 38% (from 216 +/- 15 to 133 +/- 10 peq X mm-1 X min-1, P less than 0.001). In conclusion, despite extracellular volume contraction, potassium deficiency, and reduction in bicarbonate permeability during chronic metabolic alkalosis, net bicarbonate absorption in the late proximal convoluted tubule is depressed as a function of luminal bicarbonate concentration and flow rate because acidification is inhibited by hyperbicarbonatemia/alkalemia.

Glomerular-tubular balance for bicarbonate in the dog

1975 ◽  
Vol 228 (1) ◽  
pp. 98-106 ◽  
Author(s):  
CM Bennett ◽  
PD Springberg ◽  
NR Falkinburg
Keyword(s):  
Functional Relationship ◽  
Potassium Concentration ◽  
Extracellular Fluid ◽  
High Protein Diet ◽  
Plasma Potassium ◽  
Absolute Rate ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
The Absolute

Previous work that apparently showed a functional relationship between GFR and maximum bicarbonate reabsorption was done at a time when the effects on the latter of several factors (PCO2, plasma potassium concentration, and extracellular fluid volume expansion) were not recognized. The present study re-examines this relationship, while controlling these factors. In 14 hydropenic dogs, bicarbonate reabsorption per unt GFR increased linearly with increases in plasma bicarbonate concentration. At any level of plasma bicarbonate concentration,the absolute rate of bicarbonate reabsorption was functionally related to the GFR. In six volume-expanded dogs, bicarbonate reabsorption remained stable at 20-22 mmol/liter GFR as plasma bicarbonate was raised to greater than 40mM. The absolute rate of bicarbonate reabsorption increased with large increases in GFR induced by methylprednisolone and high-protein diet. In a third group of dogs, bicarbonate reabsorption varied directly with increases in GFR, while plasma bicarbonate concentration was held relatively constant above the threshold. We conclude there is a close functional relationship between the absolute rate of bicarbonate reabsorption and GFR in individual dogs.

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