The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity

This review focuses on the basolateral membrane mechanisms of H-OH-HCO3 transport in the proximal tubule. The mechanism that has the greatest transport capacity and mediates most of transepithelial H-HCO3 transport is the electrogenic, Na-3HCO3 cotransporter. This transporter has been extensively characterized in the salamander, rat, and rabbit proximal tubule, and has now been found in a number of other epithelia that effect transepithelial NaHCO3 transport. Transporter rate is sensitive to intra- and extracellular [Na], intra- and extracellular [HCO3]/pH, and cell voltage. Adaptations in transporter activity have been demonstrated in chronic metabolic acidosis and alkalosis, chronic respiratory acidosis and alkalosis, and chronic hyperfiltration. In addition to the Na-3HCO3 cotransporter, the basolateral membrane possesses both Na-dependent and -independent Cl-HCO3 exchangers, a H leak, and in the S3 proximal tubule an Na-H antiporter. The role of these H-OH-HCO3 transport mechanisms in transcellular HCO3 and Cl absorption and pHi defense is discussed.

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Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1982.243.4.e265 ◽

1982 ◽

Vol 243 (4) ◽

pp. E265-E271

Author(s):

G. S. Reddy ◽

G. Jones ◽

S. W. Kooh ◽

D. Fraser

Keyword(s):

Vitamin D ◽

Metabolic Acidosis ◽

Rat Kidney ◽

Ion Concentration ◽

Hydroxylase Activity ◽

Renal Metabolism ◽

Dihydroxyvitamin D3 ◽

Hydrogen Ion Concentration ◽

Chronic Metabolic Acidosis ◽

Negative Linear Correlation

Chronic metabolic acidosis had been shown to influence the renal metabolism of 25-hydroxyvitamin D3. Using the isolated perfused rat kidney model, we evaluated the rates of synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in vitamin D-depleted [D(-)] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in vitamin D-replete [D(+)] rats. Metabolic acidosis was induced in both groups of rats by feeding aqueous ammonium chloride for 9 days. Kidneys isolated from D(-) acidotic rats (mean pH, 7.11) exhibited a decreased rate of 1,25(OH)2D3 synthesis (0.79 +/- 0.17 pmol produce . h-1 . g kidney-1) when compared with that (1.27 +/- 0.09) of D(-) nonacidotic (mean pH, 7.33) rats. There was a significant negative linear correlation between the rate of synthesis of 1,25(OH)2D3 and the hydrogen ion concentration of the animal (r = 0.79, P less than 0.005). The rate of synthesis of 24,25(OH)2D3 by the kidneys from D(+) acidotic (mean pH, 7.06) and nonacidotic (mean pH, 7.39) rats did not differ (0.81 +/- 0.21 vs. 0.60 +/- 0.12 pmol product . h-1 . g kidney-1). It is concluded that chronic acidosis suppressed 1-hydroxylase activity, but does not suppress 24-hydroxylase activity.

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Effect of chronic metabolic acidosis on net electrolyte transport in rat colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.6.g1036 ◽

1989 ◽

Vol 256 (6) ◽

pp. G1036-G1040 ◽

Cited By ~ 3

Author(s):

G. M. Feldman

Keyword(s):

Metabolic Acidosis ◽

Distal Colon ◽

Distal Segment ◽

Proximal Colon ◽

Electrolyte Transport ◽

Rat Colon ◽

Chronic Metabolic Acidosis ◽

In Situ Perfusion ◽

Arterial Blood ◽

Acute Correction

Rats fed NH4Cl (5 meq.100 g body wt-1.day-1) for one week developed chronic metabolic acidosis and had an arterial blood pH and plasma HCO3- concentration of 7.27 +2- 0.02 and 16.2 +/- 0.8 meq/l, respectively; control animals had values of 7.36 +/- 0.01 and 22.4 +/- 0.5 meq/l, respectively. Net electrolyte transport was measured in proximal and distal colonic segments by in situ perfusion. In proximal colon, chronic metabolic acidosis increased HCO3- absorption from 3.3 +/- 0.8 to 6.4 +/- 0.6 mu eq.min-1.g-1 but did not alter Na+ absorption. In distal colon, although Na+ transport was unaffected, chronic acidosis reduced HCO3- secretion from -6.9 +/- 0.8 to -4.4 +/- 0.7 mu eq.min-1.g-1 and increased voltage from -18.9 +/- 2.0 to -51.1 +/- 4.2 mV. To evaluate the dependence of these effects on altered arterial pH and HCO3- concentration, NaHCO3 was infused intravenously, raising pH and HCO3- concentration to 7.53 +/- 0.04 and 23.9 +/- 1.7 meq/l, respectively. Although acute correction of chronic metabolic acidosis reduced HCO3- absorption in proximal colon, it did not affect HCO3- secretion or voltage in the distal segment, suggesting that proximal and distal colon respond differently to chronic metabolic acidosis. These results also suggest that chronic metabolic acidosis alters the mechanisms of ion transport in distal colon.

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

Kidney International ◽

10.1038/ki.1982.142 ◽

1982 ◽

Vol 22 (2) ◽

pp. 103-111 ◽

Cited By ~ 23

Author(s):

André G. Craan ◽

◽

Guy Lemieux ◽

Patrick Vinay ◽

André Gougoux

Keyword(s):

Metabolic Acidosis ◽

In Vitro Studies ◽

Chronic Metabolic Acidosis

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Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(96)90029-3 ◽

1996 ◽

Vol 27 (1) ◽

pp. 42-47 ◽

Cited By ~ 37

Author(s):

Gheun-Ho Kim ◽

Jin Suk Han ◽

Yon Su Kim ◽

Kwon Wook Joo ◽

Suhnggwon Kim ◽

...

Keyword(s):

Metabolic Acidosis ◽

Anion Gap ◽

Chronic Metabolic Acidosis ◽

Urine Acidification ◽

Osmolal Gap

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Management of Chronic Metabolic Acidosis

Metabolic Acidosis ◽

10.1007/978-1-4939-3463-8_14 ◽

2016 ◽

pp. 145-153 ◽

Cited By ~ 1

Author(s):

Donald E. Wesson

Keyword(s):

Metabolic Acidosis ◽

Chronic Metabolic Acidosis

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Adaptive changes in renal acidification in response to chronic respiratory acidosis

AJP Renal Physiology ◽

10.1152/ajprenal.1985.248.4.f492 ◽

1985 ◽

Vol 248 (4) ◽

pp. F492-F499 ◽

Cited By ~ 1

Author(s):

R. L. Tannen ◽

B. Hamid

Keyword(s):

Metabolic Acidosis ◽

Proton Transport ◽

Respiratory Acidosis ◽

Hydrogen Ion ◽

Distal Nephron ◽

Urine Ph ◽

Chronic Metabolic Acidosis ◽

Adaptive Changes ◽

Secretory Capacity

To examine whether chronic respiratory acidosis results in adaptive changes in renal acidification, rats were housed for 3 days in an environmental chamber with an ambient CO2 content of 10% and their kidneys were perfused in vitro according to two protocols. To assess hydrogen ion secretory capacity of the distal nephron, perfusions were carried out with a low bicarbonate concentration, in the absence of ammoniagenic substrate, and with saturating quantities of the buffer creatinine. Under these conditions, the titration of creatinine at a pH less than 6.0 (TA pH 6.0) reflects the H+ secretory capacity of a discrete functional segment of the distal nephron. Kidneys from rats with chronic respiratory acidosis exhibited a significantly lower urine pH and higher rate of TA pH 6.0 than controls perfused in this fashion, indicative of an adaptive increase in the distal nephron capacity for proton transport. This adaptation was comparable with that reported previously for rats exposed to chronic metabolic acidosis. Furthermore, evidence of adaptation persisted in the presence of amiloride (10(-5) M), suggesting that it reflects, at least in part, a sodium-independent mechanism of proton transport. Hydrogen ion secretion by the proximal nephron was assessed by performing standard bicarbonate titration curves with kidneys from rats with chronic respiratory acidosis, chronic metabolic acidosis, and controls using a perfusate equilibrated with 95% O2/5% CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

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