Role of organic anions in renal response to dietary acid and base loads

Bicarbonate is formed when organic anions are oxidized systemically. Therefore, changes in organic anion excretion can affect systemic acid-base balance. To assess the role of organic anions in urinary acid-base excretion, we measured urinary excretion in control rats, NaHCO3-loaded rats, and NH4Cl-loaded rats. Total organic anions were measured by the titration method of Van Slyke. As expected, NaHCO3 loading increased urine pH and decreased net acid excretion (NH4+ + titratable acid - HCO3-), whereas NH4Cl loading had the opposite effect. Organic anion excretion was increased in response to NaHCO3 loading and decreased in response to NH4Cl loading. We quantified the overall effect of organic ion plus inorganic buffer ion excretion on acid-base balance. The amounts of organic anions excreted by all animals in this study were greater than the amounts of NH4+, HCO3-, or titratable acidity excreted. In addition, in response to acid and alkali loading, changes in urinary organic anion excretion were 40-50% as large as changes in net acid excretion. We conclude that, in rats, regulation of organic anion excretion can contribute importantly to the overall renal response to acid-base disturbances.

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Role of citrate excretion in acid-base balance in diuretic-induced alkalosis in the rat

AJP Renal Physiology ◽

10.1152/ajprenal.1985.248.6.f796 ◽

1985 ◽

Vol 248 (6) ◽

pp. F796-F803 ◽

Cited By ~ 1

Author(s):

A. M. Kaufman ◽

C. Brod-Miller ◽

T. Kahn

Keyword(s):

Base Line ◽

Acid Excretion ◽

Acid Base Balance ◽

Bicarbonate Concentration ◽

Acid Base ◽

Plasma Bicarbonate ◽

Base Balance ◽

Furosemide Administration ◽

Net Acid Excretion

Studies were performed to assess the role of changes in the excretion of citrate, a metabolic precursor of bicarbonate, in acid-base balance in diuretic-induced metabolic alkalosis. Rats on a low-chloride diet with sodium sulfate added were studied during a base-line period, 3 days of furosemide administration, and 4 days post-furosemide. During the period of furosemide administration, net acid excretion and plasma bicarbonate concentration increased. In the post-furosemide period, net acid excretion remained higher than base line but plasma bicarbonate concentration did not increase further. Citrate excretion was significantly higher in the post-furosemide period than in base line. Studies substituting sodium neutral phosphate or sodium bicarbonate for dietary sodium sulfate demonstrated greater increases in net acid excretion post-furosemide and, again, no increase in plasma bicarbonate concentration during this period. Citrate excretion was greater than in the sulfate group. The increment in citrate excretion was proportional to the base “load,” defined with respect to changes in net acid excretion and/or dietary bicarbonate. Thus, in these studies alterations of base excretion in the form of citrate play an important role in acid-base balance during diuretic-induced metabolic alkalosis.

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Impact of hydrogen ion on fasting ketogenesis: feedback regulation of acid production

AJP Renal Physiology ◽

10.1152/ajprenal.1982.242.3.f238 ◽

1982 ◽

Vol 242 (3) ◽

pp. F238-F245 ◽

Cited By ~ 2

Author(s):

V. L. Hood ◽

E. Danforth ◽

E. S. Horton ◽

R. L. Tannen

Keyword(s):

Acid Production ◽

Metabolic Regulation ◽

Feedback Regulation ◽

Hydrogen Ion ◽

Acid Excretion ◽

Acid Base Balance ◽

Acid Base ◽

Urine Ph ◽

Ion Production ◽

Base Balance

To determine whether acid-base balance regulates hydrogen ion production, seven obese volunteers were given NaHCO3 and NH4Cl (2 mmol.kg-1.day-1) during two separate 7-day fasts. On days 5-7 plasma bicarbonate was lower in the NH4Cl fasts (14.0 +/- 1.4 mM) than in the NaHCO3 fasts (18.3 +/- 1.1 mM), while urine pH and net acid excretion did not differ. Acid production (acid excretion minus intake) was greater by 204 mmol/day in the NaHCO3 fasts (274 +/- 16 mmol/day) than in the NH4Cl fasts (70 +/- 19 mmol/day). Ketoacid excretion, which reflected net ketoacid production, paralleled acid production, decreasing from 213 +/- 24 mmol/day in the NaHCO3 fasts to 67 +/- 18 mmol/day in the NH4Cl fasts. Thus, during starvation, alterations in hydrogen ion intake and the associated changes in acid-base balance modify the net production of endogenous acid by influencing the synthesis or utilization of ketoacids. Although the specific site of this metabolic regulation is undefined, these results indicate that systemic acid-base status can exert feedback control over hydrogen ion production.

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Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood

AJP Renal Physiology ◽

10.1152/ajprenal.00144.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. F1228-F1235

Author(s):

Danika Krupp ◽

Timm H. Westhoff ◽

Jonas Esche ◽

Thomas Remer

Keyword(s):

Blood Pressure ◽

Young Adulthood ◽

Acid Excretion ◽

Acid Base Balance ◽

Acid Base ◽

Adult Body Mass ◽

Base Balance ◽

Central Organ ◽

Multivariable Adjustment ◽

Net Acid Excretion

Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of nonvolatile acids, and renal citrate excretion has been shown to be a sensitive, noninvasive marker of changes in systemic acid balance. We thus analyzed the prospective relation of 24-h citrate excretion, as well as net acid excretion capacity (NAEC; a noninvasive indicator of the renal ability to excrete protons), during adolescence (boys: 10–15 yr; girls: 9–14 yr) with BP levels in young adulthood (18–30 yr) in 374 healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In linear-regression analyses adjusted for age, sex, 24-h urinary excretions of sodium and potassium, as well as further relevant confounders, a 1-mmol/1.73 m2/day higher adolescent citrate excretion was related to 1.2 mmHg lower systolic BP ( P = 0.02) but not to diastolic BP ( P = 0.6). A 10-mEq higher NAEC during adolescence was related to 1.7 mmHg lower systolic BP in young men, but this association was statistically nonsignificant ( P = 0.07) after multivariable adjustment. Additional adjustment for adult body mass index did not alter these findings. To conclude, subtle changes in systemic acid-base balance during adolescence are already indicative for later BP. Potential sex differences in these associations should be investigated in further studies.

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Whole body acid-base modeling revisited

AJP Renal Physiology ◽

10.1152/ajprenal.00560.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. F647-F653 ◽

Cited By ~ 8

Author(s):

Troels Ring ◽

Søren Nielsen

Keyword(s):

Acid Production ◽

Negative Charge ◽

Whole Body ◽

Acid Excretion ◽

Acid Base Balance ◽

Acid Base ◽

Conventional Model ◽

Renal Net Acid Excretion ◽

Base Balance ◽

Alkali Absorption

The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis.

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Ca2+-driven intestinal HCO3− secretion and CaCO3 precipitation in the European flounder in vivo: influences on acid-base regulation and blood gas transport

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00513.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. R870-R876 ◽

Cited By ~ 12

Author(s):

Christopher A. Cooper ◽

Jonathan M. Whittamore ◽

Rod W. Wilson

Keyword(s):

Teleost Fish ◽

Gas Transport ◽

Driving Forces ◽

Marine Teleost ◽

Acid Excretion ◽

Acid Base ◽

Marine Teleost Fish ◽

Net Acid Excretion

Marine teleost fish continuously ingest seawater to prevent dehydration and their intestines absorb fluid by mechanisms linked to three separate driving forces: 1) cotransport of NaCl from the gut fluid; 2) bicarbonate (HCO3−) secretion and Cl− absorption via Cl−/HCO3− exchange fueled by metabolic CO2; and 3) alkaline precipitation of Ca2+ as insoluble CaCO3, which aids H2O absorption). The latter two processes involve high rates of epithelial HCO3− secretion stimulated by intestinal Ca2+ and can drive a major portion of water absorption. At higher salinities and ambient Ca2+ concentrations the osmoregulatory role of intestinal HCO3− secretion is amplified, but this has repercussions for other physiological processes, in particular, respiratory gas transport (as it is fueled by metabolic CO2) and acid-base regulation (as intestinal cells must export H+ into the blood to balance apical HCO3− secretion). The flounder intestine was perfused in vivo with salines containing 10, 40, or 90 mM Ca2+. Increasing the luminal Ca2+ concentration caused a large elevation in intestinal HCO3− production and excretion. Additionally, blood pH decreased (−0.13 pH units) and plasma partial pressure of CO2 (Pco2) levels were elevated (+1.16 mmHg) at the highest Ca perfusate level after 3 days of perfusion. Increasing the perfusate [Ca2+] also produced proportional increases in net acid excretion via the gills. When the net intestinal flux of all ions across the intestine was calculated, there was a greater absorption of anions than cations. This missing cation flux was assumed to be protons, which vary with an almost 1:1 relationship with net acid excretion via the gill. This study illustrates the intimate link between intestinal HCO3− production and osmoregulation with acid-base balance and respiratory gas exchange and the specific controlling role of ingested Ca2+ independent of any other ion or overall osmolality in marine teleost fish.

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