Chronic metabolic acidosis augments acidification along the inner medullary collecting duct

1986 ◽  
Vol 250 (4) ◽  
pp. F690-F694 ◽  
Author(s):  
H. H. Bengele ◽  
J. H. Schwartz ◽  
E. R. McNamara ◽  
E. A. Alexander
Keyword(s):  
Metabolic Acidosis ◽  
Acid Secretion ◽  
Ammonium Chloride ◽  
Collecting Duct ◽  
Major Site ◽  
Chronic Metabolic Acidosis ◽  
Inner Medullary Collecting Duct ◽  
Titratable Acid ◽  
Arterial Ph ◽  
Medullary Collecting Duct

The inner medullary collecting duct (IMCD) of the rat is a major site of acidification. However, previous micropuncture studies have failed to demonstrate acidification along the terminal IMCD during chronic acid feeding. To more completely evaluate this question we used the microcatheterization method in rats fed ammonium chloride for 3-7 days. Arterial pH was 7.30 +/- 0.015, and PCO2 was set at 40 +/- 0.6 mmHg. The IMCD data were analyzed as a function of IMCD length between 40% and the tip. Equilibrium pH decreased from 6.21 +/- 0.11 to 5.47 +/- 0.03, whereas PCO2 was unchanged (28 +/- 1 mmHg between the deep samples and tip). Bicarbonate delivery decreased from 92 +/- 14 to 10 +/- 1 nmol/min, titratable acid increased from 462 +/- 33 to 762 +/- 40 nmol/min, and ammonium delivery increased from 2,235 +/- 121 to 3,528 +/- 140 nmol/min. Thus estimated net acid increased from 2,638 +/- 134 to 4,303 +/- 161 nmol/min. To determine whether increasing delivery of buffer to the IMCD would stimulate acid secretion in acute acidosis, rats were studied during the infusion of HCl and creatinine. Arterial pH was 7.18 +/- 0.02. IMCD acidification was not increased compared with our previously published studies during HCl infusion [Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F669-F676, 1981]. We conclude that chronic ammonium chloride ingestion stimulates IMCD acidification and that this increase may be an intrinsic modification of the acidification mechanism of the IMCD.

Suppression of acidification along inner medullary collecting duct

1988 ◽  
Vol 255 (2) ◽  
pp. F307-F312 ◽  
Author(s):  
H. H. Bengele ◽  
E. R. McNamara ◽  
J. H. Schwartz ◽  
E. A. Alexander
Keyword(s):  
Acid Secretion ◽  
Collecting Duct ◽  
Respiratory Alkalosis ◽  
Inner Medullary Collecting Duct ◽  
Titratable Acid ◽  
Arterial Ph ◽  
Medullary Collecting Duct ◽  
Collection Sites

The purpose of these experiments was to evaluate the effect of acute respiratory alkalosis (ARA) and chronic bicarbonate drinking (CBD) on inner medullary collecting duct (IMCD) acidification. Microcatheterization was used to measure pH and PCO2, and samples were simultaneously obtained for measurement of bicarbonate, titratable acid (TA), and ammonium. In ten ARA rats (arterial pH was 7.54 +/- 0.02; PCO2 was 20 +/- 1 mmHg), IMCD equilibrium pH was not different (deep pH was 5.65 +/- 0.06 and PCO2 was 20 +/- 1 mmHg; tip pH was 5.54 +/- 0.07 and PCO2 was 22 +/- 1 mmHg). Delivery of bicarbonate, TA, and ammonium also did not differ between collection sites. Thus net acidification along the IMCD was negligible. Nine rats drank NaHCO3 for 5-8 days (pH = 7.48 +/- 0.02) but did not receive NaHCO3 during the experiment so that arterial pH fell to 7.40 +/- 0.01. IMCD equilibrium pH was different at deep (pH was 5.68 +/- 0.06; PCO2 was 32 +/- 1 mmHg) and tip (pH was 5.57 +/- 0.04; PCO2 was 27 +/- 1 mmHg; P less than or equal to 0.05) collection sites. However, only minimal changes in the delivery of bicarbonate, TA, and ammonium were noted, and net acidification along the IMCD was negligible. In ten control rats, net acidification was 219 nmol/min between collection sites (P less than 0.001). We conclude that ARA and CBD abolish acidification along the IMCD. In addition, CBD produces an intrinsic modification along the IMCD, which suppresses acid secretion and persists after acute recovery from alkalemia.

Acidification adaptation along the inner medullary collecting duct

1988 ◽  
Vol 255 (6) ◽  
pp. F1155-F1159 ◽  
Author(s):  
H. H. Bengele ◽  
E. R. McNamara ◽  
J. H. Schwartz ◽  
E. A. Alexander
Keyword(s):  
Acid Secretion ◽  
Collecting Duct ◽  
Acid Base ◽  
Regular Diet ◽  
Inner Medullary Collecting Duct ◽  
Titratable Acid ◽  
Arterial Ph ◽  
Acid Base Status ◽  
Medullary Collecting Duct ◽  
Additional Support

Chronic acid feeding (ACD) stimulates and chronic alkali (AKL) feeding suppresses acid secretion along the inner medullary collecting duct (IMCD) of the rat. The purpose of these experiments was to determine whether these stimuli produce IMCD acidification adaptation. We tested this hypothesis by acutely changing systemic PCO2 in rats chronically fed ACD or ALK. Microcatheterization was used to measure pH and PCO2 and samples were simultaneously obtained for measurement of bicarbonate, titratable acid (TA), and ammonium. In 10 ACD rats (arterial pH, 7.26 +/- 0.01; PCO2, 88 +/- 1 mmHg) acid secretion along the IMCD was 506 +/- 88 nmol/min. In 10 ALK rats with similar arterial gases (pH, 7.16 +/- 0.02; PCO2, 82 +/- 1 mmHg) IMCD acid secretion was only 284 +/- 57 nmol/min, P less than 0.05. In ACD rats made hypocarbic (pH, 7.26 +/- 0.03; PCO2, 24 +/- 1 mmHg), IMCD acid secretion was 163 +/- 55 nmol/min. These data were compared with previously studied rats eating a regular diet. Acute hypocarbia (pH, 7.54 +/- 0.02; PCO2, 20 +/- 1 mmHg) completely suppressed acid secretion, 4 +/- 23 nmol/min, along the IMCD. We conclude that chronic alterations in acid-base status provide an IMCD "set" where comparable stimuli produce significant differences in IMCD acidification. These data provide additional support for the concept of IMCD acidification adaptation.

Effect of buffer infusion during acute respiratory acidosis

1986 ◽  
Vol 250 (1) ◽  
pp. F115-F119 ◽  
Author(s):  
H. H. Bengele ◽  
J. H. Schwartz ◽  
E. R. McNamara ◽  
E. A. Alexander
Keyword(s):  
Collecting Duct ◽  
Respiratory Acidosis ◽  
Membrane Electrodes ◽  
Proton Secretion ◽  
Inner Medullary Collecting Duct ◽  
Titratable Acid ◽  
Arterial Ph ◽  
Glass Membrane ◽  
Medullary Collecting Duct ◽  
Terminal Nephron

We previously reported that acute respiratory acidosis (ARA) did not stimulate inner medullary collecting duct (IMCD) acidification. It was possible that the failure to find enhanced IMCD acidification was a function of insufficient buffer delivery. To answer this question we studied IMCD acidification in rats with ARA during the infusion of the buffer creatinine. We employed the microcatheterization technique to directly measure pH and PCO2 with glass membrane electrodes and also obtained fluid samples for the measurement of titratable acid and ammonium. Arterial pH was 7.19 +/- 0.01 and PCO2 was 93 +/- 2 mmHg. The IMCD data were analyzed as a function of IMCD length (approximately 6 mm). Equilibrium pH decreased from 5.99 +/- 0.05 to 5.58 +/- 0.02 and PCO2 increased from 71 +/- 11 to 132 +/- 6 mmHg between origin and tip. Bicarbonate delivery decreased from 111 +/- 14 to 38 +/- 2 nmol/min; titratable acid increased from 867 +/- 87 to 1,625 +/- 61 nmol/min, but ammonium delivery did not change along the duct. Thus, estimated net acid increased from 1,772 +/- 155 to 2,709 +/- 88 nmol/min. We conclude that during the presence of increased buffer delivery to the IMCD, rats with ARA markedly increased proton secretion along the terminal nephron.

Inner medullary collecting duct function during rebound alkalemia

1987 ◽  
Vol 252 (4) ◽  
pp. F712-F716
Author(s):  
H. H. Bengele ◽  
E. R. McNamara ◽  
J. H. Schwartz ◽  
E. A. Alexander
Keyword(s):  
Collecting Duct ◽  
Acid Excretion ◽  
Acid Base ◽  
Proton Secretion ◽  
Inner Medullary Collecting Duct ◽  
Titratable Acid ◽  
Base Parameters ◽  
Arterial Ph ◽  
Medullary Collecting Duct ◽  
Net Acid Excretion

Rats, made acidemic when fed NH4Cl, become alkalemic with discontinuation of the NH4Cl. This phenomenon has been called rebound metabolic alkalemia (RMA). This study examines the function of the inner medullary collecting duct (IMCD) during RMA. Rats drank only 1.5% NH4Cl for 5 days and then water for 16 h prior to study, yielding an arterial pH = 7.50 +/- 0.01, PCO2 = 39 +/- 1 mmHg, and bicarbonate = 29.5 +/- 1.0 mM. The IMCD data were obtained by microcatheterization from deep (1.5-3.0 mm) and tip (0.2-0.5 mm) samples. Equilibrium pH decreased from 5.92 +/- 0.09 (n = 20) to 5.38 +/- 0.04 (n = 20) and PCO2 increased from 32 +/- 1 to 38 +/- 1 mmHg between deep and tip samples. Bicarbonate delivery decreased from 37 +/- 8 to 7 +/- 1 nmol/min. Titratable acid and ammonium delivery increased from 284 +/- 52 to 347 +/- 62 nmol/min and from 549 +/- 38 to 685 +/- 40 nmol/min, respectively. Calculated net acid excretion increased from 796 +/- 88 to 1,026 +/- 95 nmol/min. Thus during RMA, proton secretion continues along the IMCD, although there is a systemic alkalemia. It appears that factors in addition to systemic acid-base parameters are important in the regulation of proton secretion by the IMCD.

Transepithelial ammonia concentration gradients in inner medulla of the rat

1987 ◽  
Vol 252 (3) ◽  
pp. F491-F500 ◽  
Author(s):  
D. W. Good ◽  
C. R. Caflisch ◽  
T. D. DuBose
Keyword(s):  
Metabolic Acidosis ◽  
Collecting Duct ◽  
Ammonia Concentration ◽  
Loop Of Henle ◽  
Concentration Gradients ◽  
Chronic Metabolic Acidosis ◽  
Inner Medullary Collecting Duct ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Medullary Collecting Duct

Transport of NH3 from loops of Henle to medullary collecting ducts has been proposed to play an important role in renal ammonia excretion. To determine whether transepithelial ammonia concentration gradients capable of driving this transport are present in the inner medulla, micropuncture experiments were performed in control rats and in rats with chronic metabolic acidosis. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations ([NH3]) for base and tip collecting duct, loop of Henle, and vasa recta. In control and acidotic rats, [NH3] in the loop of Henle was significantly greater than [NH3] in the collecting ducts. [NH3] did not differ in loop of Henle and adjacent vasa recta in either group of rats, indicating that NH3 concentration gradients between loop and collecting duct represent NH3 gradients that are present between medullary interstitium and collecting duct. During acidosis, an increase in collecting duct ammonia secretion was associated with an increase in the NH3 concentration difference between loop of Henle and collecting duct but occurred in the absence of a fall in collecting duct pH. The NH3 concentration gradient favoring diffusion of NH3 into the collecting ducts increased during acidosis because [NH3] in the loop of Henle and medullary interstitium increased more than [NH3] in the collecting duct. These findings indicate that transport processes involved in medullary ammonia accumulation play an important role in regulating ammonia secretion into the inner medullary collecting duct in vivo and that a fall in inner medullary collecting duct pH is not necessarily required for ammonia secretion by this segment to increase during chronic metabolic acidosis.

Dietary K+ restriction upregulates total and Sch-28080-sensitive bicarbonate absorption in rat tIMCD

1998 ◽  
Vol 275 (4) ◽  
pp. F543-F549 ◽  
Author(s):  
Susan M. Wall ◽  
Pramod Mehta ◽  
Thomas D. DuBose
Keyword(s):  
Metabolic Acidosis ◽  
Treatment Group ◽  
Acid Secretion ◽  
Collecting Duct ◽  
Terminal Segment ◽  
Deficient Diet ◽  
Chronic Metabolic Acidosis ◽  
Future Studies ◽  
Medullary Collecting Duct

In tubules from the terminal segment of the inner medullary collecting duct (tIMCD) from rats with chronic metabolic acidosis, our laboratory has shown that bicarbonate absorption ( J tCO2) is inhibited by removal of K+ from the luminal fluid or by the addition of Sch-28080 to the perfusate. The present study asked whether total and/or Sch-28080-sensitive J tCO2 is regulated by changes in systemic K+ homeostasis. Rat tIMCD tubules were perfused in vitro in symmetrical,[Formula: see text]/CO2-buffered solutions containing 10 mM KCl + 6 mM NH4Cl. Total and Sch-28080-sensitive J tCO2 were measured in rats with varying K+intake. In K+-replete rats, baseline J tCO2was 2.1 ± 0.3 pmol ⋅ mm−1 ⋅ min−1( n = 6). In rats fed a K+-deficient diet for 3 days, J tCO2 was 5.4 ± 0.7 pmol ⋅ mm−1 ⋅ min−1( n = 16, P < 0.05). To determine the mechanism for the increase in [Formula: see text]absorption observed with K+restriction, the Sch-28080-sensitive component of J tCO2 was measured in each treatment group. Following the addition of Sch-28080 (10 μM) to the perfusate, a 40% reduction in J tCO2 was observed in K+-restricted rats. J tCO2 was not reduced following the addition of Sch-28080 in rats with normal K+ intake. Because Sch-28080-sensitive J tCO2 was increased in K+-restricted rats, Sch-28080-sensitive J tCO2 was studied further in tIMCD tubules from rats in this treatment group. In K+-restricted rats, J tCO2 decreased by 20% following the addition of 5 mM ouabain to the perfusate. This ouabain-induced decline in J tCO2 was observed both in the presence and in the absence of Sch-28080. We conclude that total and Sch-28080-sensitive net acid secretion is increased with dietary K+restriction. However, since ∼50% of J tCO2 is insensitive to both Sch-28080 and ouabain, future studies will be necessary to define other mechanisms of luminal acidification in the rat tIMCD.

scholarly journals Carbonic anhydrase II and IV mRNA in rabbit nephron segments: stimulation during metabolic acidosis

1998 ◽  
Vol 274 (2) ◽  
pp. F259-F267 ◽  
Author(s):  
Shuichi Tsuruoka ◽  
Ann M. Kittelberger ◽  
George J. Schwartz
Keyword(s):  
Metabolic Acidosis ◽  
Carbonic Anhydrase ◽  
Mrna Expression ◽  
Collecting Duct ◽  
Proximal Tubules ◽  
Rabbit Kidney ◽  
Rt Pcr ◽  
Chronic Metabolic Acidosis ◽  
Nephron Segments ◽  
Medullary Collecting Duct

Carbonic anhydrase (CA) facilitates renal bicarbonate reabsorption and acid excretion. Cytosolic CA II catalyzes the buffering of intracellular hydroxyl ions by CO2, whereas membrane-bound CA IV catalyzes the dehydration of carbonic acid generated from the secretion of protons. Although CA II and IV are expressed in rabbit kidney, it is not entirely clear which segments express which isoforms. It was the purpose of this study to characterize the expression of CA II and CA IV mRNAs by specific segments of the nephron using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and to determine the effect of chronic metabolic acidosis on CA expression by those segments. Individual nephron segments (usually 1–2 mm) were isolated by microdissection and subjected to RT-PCR. Amplification was performed simultaneously for CA IV, CA II, and malate dehydrogenase (MDH), a housekeeping gene. The intensities of the PCR products were quantitated by densitometry. CA IV mRNA was expressed by S1 and S2 proximal tubules and by outer medullary collecting duct from inner stripe (OMCDi) and outer stripe and initial inner medullary collecting duct (IMCDi). CA II mRNA was expressed by S1, S2, and S3 proximal tubules, thin descending limb, connecting segment (CNT), and all collecting duct segments. Acid loading induced CA IV mRNA expression in S1 and S2 proximal tubules and in OMCDi and IMCDi. CA II mRNA was induced by acidosis in all three proximal segments and nearly all distal segments beginning with CNT. No upregulation of MDH mRNA expression occurred. These adaptive increases in CA II and IV mRNAs are potentially important in the kidney’s adaptation to chronic metabolic acidosis.

Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis

2006 ◽  
Vol 290 (2) ◽  
pp. F397-F408 ◽  
Author(s):  
Ramanathan M. Seshadri ◽  
Janet D. Klein ◽  
Shelley Kozlowski ◽  
Jeff M. Sands ◽  
Young-Hee Kim ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Protein Expression ◽  
Mrna Expression ◽  
Collecting Duct ◽  
Broad Band ◽  
Ammonia Excretion ◽  
Intercalated Cells ◽  
Outer Medulla ◽  
Chronic Metabolic Acidosis ◽  
Medullary Collecting Duct

Chronic metabolic acidosis induces dramatic increases in net acid excretion that are predominantly due to increases in urinary ammonia excretion. The current study examines whether this increase is associated with changes in the expression of the renal ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). Chronic metabolic acidosis was induced in Sprague-Dawley rats by HCl ingestion for 1 wk; control animals were pair-fed. After 1 wk, metabolic acidosis had developed, and urinary ammonia excretion increased significantly. Rhcg protein expression was increased in both the outer medulla and the base of the inner medulla. Intercalated cells in the outer medullary collecting duct (OMCD) and in the inner medullary collecting duct (IMCD) in acid-loaded animals protruded into the tubule lumen and had a sharp, discrete band of apical Rhcg immunoreactivity, compared with a flatter cell profile and a broad band of apical immunolabel in control kidneys. In addition, basolateral Rhcg immunoreactivity was observed in both control and acidotic kidneys. Cortical Rhcg protein expression and immunoreactivity were not detectably altered. Rhcg mRNA expression was not significantly altered in the cortex, outer medulla, or inner medulla by chronic metabolic acidosis. Rhbg protein and mRNA expression were unchanged in the cortex, outer and inner medulla, and no changes in Rhbg immunolabel were evident in these regions. We conclude that chronic metabolic acidosis increases Rhcg protein expression in intercalated cells in the OMCD and in the IMCD, where it is likely to mediate an important role in the increased urinary ammonia excretion.

scholarly journals A mathematical model of the inner medullary collecting duct of the rat: acid/base transport

1998 ◽  
Vol 274 (5) ◽  
pp. F856-F867 ◽  
Author(s):  
Alan M. Weinstein
Keyword(s):  
Mathematical Model ◽  
Acid Secretion ◽  
Collecting Duct ◽  
Model Calculations ◽  
Principal Mode ◽  
Inner Medullary Collecting Duct ◽  
Tubule Lumen ◽  
Nephron Segment ◽  
The Face ◽  
Medullary Collecting Duct

A mathematical model of the inner medullary collecting duct (IMCD) of the rat has been developed that is suitable for simulating luminal buffer titration and ammonia secretion by this nephron segment. Luminal proton secretion has been assigned to an H-K-ATPase, which has been represented by adapting the kinetic model of the gastric enzyme by Brzezinski et al. (P. Brzezinski, B. G. Malmstrom, P. Lorentzon, and B. Wallmark. Biochim. Biophys. Acta 942: 215–219, 1988). In shifting to a 2 H+:1 ATP stoichiometry, the model enzyme can acidify the tubule lumen ∼3 pH units below that of the cytosol, when luminal K+ is in abundance. Peritubular base exit is a combination of ammonia recycling and[Formula: see text] flux (either via[Formula: see text] exchange or via a Cl− channel). Ammonia recycling involves[Formula: see text] uptake on the Na-K-ATPase followed by diffusive NH3 exit [S. M. Wall. Am. J. Physiol. 270 ( Renal Physiol. 39): F432–F439, 1996]; model calculations suggest that this is the principal mode of base exit. By virtue of this mechanism, the model also suggests that realistic elevations in peritubular K+ concentration will compromise IMCD acid secretion. Although ammonia recycling is insensitive to carbonic anhydrase (CA) inhibition, the base exit linked to [Formula: see text] flux provides a CA-sensitive component to acid secretion. In model simulations, it is observed that increased luminal NaCl entry increases ammonia cycling but decreases peritubular [Formula: see text]exchange (due to increased cell Cl−). This parallel system of peritubular base exit stabilizes acid secretion in the face of variable Na+ reabsorption.

H(+)-K(+)-ATPase mediates net acid secretion in rat terminal inner medullary collecting duct

1996 ◽  
Vol 271 (5) ◽  
pp. F1037-F1044 ◽  
Author(s):  
S. M. Wall ◽  
A. V. Truong ◽  
T. D. DuBose
Keyword(s):  
Acid Secretion ◽  
Collecting Duct ◽  
Specific Inhibitor ◽  
Co2 Absorption ◽  
Atpase Inhibitor ◽  
Inner Medullary Collecting Duct ◽  
Total Ammonia ◽  
Medullary Collecting Duct ◽  
Atpase Inhibition

Studies in our laboratory have demonstrated total CO2 absorption (JtCO2) and total ammonia secretion in the terminal inner medullary collecting duct (tIMCD) perfused in vitro. The purpose of the present study was to determine whether the H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) participates in proton secretion or JtCO2 in this segment. Tubules from the middle third of the tIMCD were dissected from rats with chronic metabolic acidosis (300 mM NH4Cl, 3-4 days in drinking water) and perfused in vitro. Perfusate and bath were symmetrical solutions containing 5 mM KCl, 6 mM NH4Cl, and 25 mM NaHCO3. Bafilomycin A1 (5 nM), a specific inhibitor of the H(+)-ATPase, did not affect JtCO2 compared with baseline (JtCO2, 3.0 +/- 1.0 and 3.0 +/- 0.8; n = 6, P = not significant) or with time controls (n = 4). With removal of luminal K+, JtCO2 fell from 2.8 +/- 0.6 to 1.6 +/- 0.4 pmol.mm-1.min-1 (n = 5, P < 0.05). To further evaluate K(+)-sensitive JtCO2, the effect of H(+)-K(+)-ATPase inhibition on JtCO2 was explored using the specific H(+)-K(+)-ATPase inhibitor, Sch-28080. Addition of 10 microM Sch-28080 to the luminal perfusate decreased JtCO2 (2.7 +/- 0.4 to 1.4 +/- 0.5 pmol.mm-1. min-1; n = 5, P < 0.05) but did not alter transepithelial membrane potential. Thus luminal Sch-28080 addition, as well as luminal K+ removal, limits apical H+ exit or OH-/HCO3- entry. These results demonstrate that net acid secretion is mediated by the H(+)-K(+)-ATPase in the tIMCD.

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