Visual Abstract

Visual Abstract
Visual Abstract.
View largeDownload slide
Keywords:
Sodium, Electrolytes, Osmotic inactivation, Sodium space, Bicarbonate space

Background: We have previously investigated the fate of administered bicarbonate infused as a hypertonic solution in animals with each of the 4 chronic acid-base disorders. Those studies did not address the fate of sodium, the coadministered cation. Methods: We examined baseline total body water (TBW), Na+ space, HCO3– space, and urinary sodium and bicarbonate excretion after acute hypertonic NaHCO3 infusion (1-N solution, 5 mmol/kg body weight) in dogs with each of the 4 chronic acid-base disorders. Observations were made at 30, 60, and 90 min postinfusion. Retained sodium that remains osmotically active distributes in an apparent space that approximates TBW. Na+ space that exceeds TBW uncovers nonosmotic sodium storage. Results: Na+ space approximated TBW at all times in normal and hyperbicarbonatemic animals (metabolic alkalosis and respiratory acidosis), but exceeded TBW by ~30% in hypobicarbonatemic animals (metabolic acidosis and respiratory alkalosis). Such osmotic inactivation was detected at 30 min and remained stable. The pooled data revealed that Na+ space corrected for TBW was independent of the initial blood pH but correlated with initial extracellular bicarbonate concentration (y = –0.01x + 1.4, p= 0.002). The fate of administered sodium and bicarbonate (internal distribution and urinary excretion) was closely linked. Conclusions: This study demonstrates that hypobicarbonatemic animals have a Na+ space that exceeds TBW after an acute infusion of hypertonic NaHCO3 indicating osmotic inactivation of a fraction of retained sodium. In addition to an expanded Na+ space, these animals have a larger HCO3– space compared with hyperbicarbonatemic animals. Both phenomena appear to reflect the wider range of titration of nonbicarbonate buffers (Δ pH) occurring during NaHCO3– loading whenever initial [HCO3–]e is low. The data indicate that the fate of administered bicarbonate drives the internal distribution and the external disposal of sodium, the co-administered cation, and is responsible for the early, but non-progressive, osmotic inactivation of a fraction of the retained sodium.

Keywords:
Sodium, Electrolytes, Osmotic inactivation, Sodium space, Bicarbonate space
1.
Adrogué HJ, Brensilver J, Cohen JJ, Madias NE. Influence of steady-state alterations in acid-base equilibrium on the fate of administered bicarbonate in the dog.
J Clin Invest
. 1983 Apr;71(4):867–83.
2.
Adrogué HJ, Mandayam S, Tighiouart H, Madias NE. Osmotic and nonosmotic sodium storage during acute hypertonic sodium loading. Am J Nephrol. 2019;50(1):11–8.
3.
Schwartz WB, Silverman L. A large environmental chamber for the study of hypercapnia and hypoxia.
J Appl Physiol
. 1965 Jul;20(4):767–74.
4.
Schwartz WB, Brackett NC Jr, Cohen JJ. The response of extracellular hydrogen ion concentration to graded degrees of chronic hypercapnia: the physiologic limits of the defense of pH.
J Clin Invest
. 1965 Feb;44(2):291–301.
5.
Adrogué HJ, Madias NE. Renal acidification during chronic hypercapnia in the conscious dog. Pflugers Arch. 1986 May;406(5):520–8.
6.
Gennari FJ, Goldstein MB, Schwartz WB. The nature of the renal adaptation to chronic hypocapnia.
J Clin Invest
. 1972 Jul;51(7):1722–30.
7.
De Sousa RC, Harrington JT, Ricanati ES, Shelkrot JW, Schwartz WB. Renal regulation of acid-base equilibrium during chronic administration of mineral acid.
J Clin Invest
. 1974 Feb;53(2):465–76.
8.
Madias NE, Adrogué HJ, Cohen JJ. Maladaptive renal response to secondary hypercapnia in chronic metabolic alkalosis.
Am J Physiol
. 1980 Apr;238(4):F283–9.
9.
Walser M, Seldin DW, Grollman A. An evaluation of radiosulfate for the determination of the volume of extracellular fluid in man and dogs. J Clin Invest. 1953 Apr;32(4):299–311.
10.
Rubini ME, Wolf AV. Refractometric determination of total solids and water of serum and urine.
J Biol Chem
. 1957 Apr;225(2):869–76.
11.
Elkinton JR, Danowsky TS.
The Body Fluids
. Baltimore (MD): The Williams & Wilkins Company; 1955. p. 85.
12.
Oh MS, Carroll HJ. Regulation of intracellular and extracellular volume. In: Arieff AI, DeFronzo RA, editors.
Fluid, Electrolyte, and Acid-Base Disorders
. 2nd ed. New York (NY): Churchill Livingstone; 1995. pp. 1–28.
13.
Edelman IS, Leibman J. Anatomy of body water and electrolytes.
Am J Med
. 1959 Aug;27(2):256–77.
14.
Woodbury DM. Physiology of body fluids. In: Ruch TC, Patton HD, editors.
Physiology and Biophysics
. 20th ed. Philadelphia (PA): Saunders; 1974.
15.
Hays RM. Dynamics of body water and electrolytes. In: Maxwell MH, Kleeman CR, editors.
Clinical Disorders of Fluid and Electrolyte Metabolism
. 3rd ed. New York (NY): McGraw-Hill; 1980. pp. 1–36.
16.
Rose BD.
Clinical Physiology of Acid-Base and Electrolyte Disorders
. 4th ed. New York (NY): McGraw-Hill; 1994. pp. 219–34.
17.
Swan RC, Axelrod DR, Seip M, Pitts RF, Madisso H. Distribution of sodium bicarbonate infused into nephrectomized dogs.
J Clin Invest
. 1955 Dec;34(12):1795–801.
18.
Farber SJ. Mucopolysaccharides and sodium metabolism.
Circulation
. 1960 May;21(5):941–7.
19.
Farber SJ, Schubert M, Schuster N. The binding of cations by chondroitin sulfate.
J Clin Invest
. 1957 Dec;36(12):1715–22.
20.
Titze J, Machnik A. Sodium sensing in the interstitium and relationship to hypertension.
Curr Opin Nephrol Hypertens
. 2010 Jul;19(4):385–92.
21.
Titze J. Sodium balance is not just a renal affair.
Curr Opin Nephrol Hypertens
. 2014 Mar;23(2):101–5.
22.
Titze J, Lang R, Ilies C, Schwind KH, Kirsch KA, Dietsch P, et al. Osmotically inactive skin Na+ storage in rats.
Am J Physiol Renal Physiol
. 2003;285: F1108–17.
23.
Heer M, Baisch F, Kropp J, Gerzer R, Drummer C. High dietary sodium chloride consumption may not induce body fluid retention in humans.
Am J Physiol Renal Physiol
. 2000 Apr;278(4):F585–95.
24.
Titze J, Maillet A, Lang R, Gunga HC, Johannes B, Gauquelin-Koch G, et al. Long-term sodium balance in humans in a terrestrial space station simulation study.
Am J Kidney Dis
. 2002 Sep;40(3):508–16.
25.
Titze J, Shakibaei M, Schafflhuber M, Schulze-Tanzil G, Porst M, Schwind KH, et al. Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin.
Am J Physiol Heart Circ Physiol
. 2004 Jul;287(1):H203–8.
26.
Gennari FJ. Intracellular acid-base homeostasis. In: Gennari FJ, Adrogué HJ, Galla JH, Madias NE, editors. Acid-Base Disorders and their Treatment. Boca Raton: Taylor & Francis; 2005. pp. 25–46.
27.
Frelin C, Vigne P, Lazdunski M. The role of the Na+/H+ exchange system in cardiac cells in relation to the control of the internal Na+ concentration. A molecular basis for the antagonistic effect of ouabain and amiloride on the heart. J Biol Chem. 1984 Jul;259(14):8880–5.
28.
Wieth JO. Effects of bicarbonate and thiocyanate on fluxes of Na and K, and on glucose metabolism of actively transporting human red cells.
Acta Physiol Scand
. 1969 Mar;75(3):313–29.
29.
Villamil MF, Deland EC, Henney RP, Maloney JV Jr. Anion effects on cation movements during correction of potassium depletion.
Am J Physiol
. 1975 Jul;229(1):161–6.
30.
Madias NE, Adrogué HJ. Cross-talk between two organs: how the kidney responds to disruption of acid-base balance by the lung.
Nephron, Physiol
. 2003;93(3):61–6.
31.
González SB, Menga G, Raimondi GA, Tighiouart H, Adrogué HJ, Madias NE. Secondary response to chronic respiratory acidosis in humans: A prospective study.
Kidney Int Rep
. 2018 Jun;3(5):1163–70.
© 2020 S. Karger AG, Basel
2020
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.