Hypoventilation increases PaCO2 (hypercapnia) and initiates the acid-base disorder known as respiratory acidosis. Hyperventilation decreases PaCO2 (hypocapnia) and initiates the acid-base disorder known as respiratory alkalosis. The impact on acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma bicarbonate concentration that occur in two stages. Acutely, modest changes in plasma bicarbonate originate from titration of the body’s nonbicarbonate buffers. In chronic hypercapnia and hypocapnia, larger changes in plasma bicarbonate occur that reflect adjustments in renal acidification mechanisms. As a result, the amelioration of systemic acidity is more pronounced in the chronic forms of the respiratory acid-base disorders.

Brackett NC Jr, Cohen JJ, Schwartz WB: Carbon dioxide titration curve of normal man: effect of increasing degrees of acute hypercapnia on acid-base equilibrium. N Engl J Med 1965;272:6–12.
Madias NE, Adrogué HJ: Respiratory alkalosis and acidosis; in Seldin DW, Giebisch G (eds): The Kidney: Physiology and Pathophysiology, ed 3. Philadelphia, Lippincott/Williams & Wilkins, 2000, pp 2131–2166.
Schwartz WB, Brackett NC Jr, Cohen JJ: The response of extracellular hydrogen ion concentration to graded degrees of chronic hypercapnia: The physiologic limits of defense of pH. J Clin Invest 1965;44:291–301.
Adrogué HJ, Madias NE: Renal acidification during chronic hypercapnia in the conscious dog. Pflügers Arch 1986;406:520–528.
Cogan MG: Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat. J Clin Invest 1984;74:1942–1947.
Laski ME, Kurtzman NA: Collecting tubule adaptation to respiratory acidosis induced in vivo. Am J Physiol 1990;258:F15–F20.
Krapf R: Mechanisms of adaptation of chronic respiratory acidosis in the rabbit proximal tubule. J Clin Invest 1989;83:890–896.
Ruiz OS, Arruda JAL, Talor Z: Na-HCO3 cotransport and Na-H antiporter in chronic respiratory acidosis and alkalosis. Am J Physiol 1989:256:F414–F420.
Northrup TE, Garella S, Perticucci E, Cohen JJ: Acidemia alone does not stimulate rat renal Na+-H+ antiporter activity. Am J Physiol 1988;255:F237–F243.
Zeidel ML, Seifter JL: Regulation of Na/H exchange in renal microvillus vesicles in chronic hypercapnia. Kidney Int 1988;34:60–66.
Al-Awqati Q: The cellular renal response to respiratory acid-base disorders. Kidney Int 1985;28:845–855.
Bastani B, Gluck S, Hilden S, Johns C, Yang L, Madias NE: Adaptation if renal vascuolar H+-ATPase to acute or chronic respiratory acidosis in the rat (abstract). J Am Soc Nephrol 1993;4:831.
Madsen KM, Tischer CC: Cellular response to acute respiratory acidosis in rat medullary collecting duct. Am J Physiol 1983;245:F670–F679.
Verlander JW, Madsen KM, Tischer CC: Effect of acute respiratory acidosis on two populations of intercalated cells in rat cortical collecting duct. Am J Physiol 1987;253:F1142–F1156.
Eiam-Ong S, Laski ME, Kurtzman NA, Sabatini S: Effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes. Am J Physiol 1994;267:F390–F399.
Teixeira Da Silva JC Jr, Perrone RD, Johns CA, Madias NE: Rat kidney band 3 mRNA modulation in chronic respiratory acidosis. Am J Physiol 1991;260:F204–F209.
Madias NE, Wolf CJ, Cohen JJ: Regulation of acid-base equilibrium in chronic hypercapnia. Kidney Int 1985;27:538–543.
Brackett NC Jr, Wingo CF, Muren O, Solano JT: Acid-base response to chronic hypercapnia in man. N Engl J Med 1969;280:124–130.
Van Ypersele de Strihou C, Brasseur L, De Goninck J: The ‘carbon dioxide response curve’ for chronic hypercapnia in man. N Engl J Med 1966;275:117–122.
Adrogué HJ, Madias NE: Management of life-threatening acid-base disorders. N Engl J Med 1998;338:26–34, 107–111.
Arbus GS, Hebert LA, Levesque PR, Etsten BE, Schwartz WB: Characterization and clinical application of the ‘significance band’ for acute respiratory alkalosis. N Engl J Med 1969;280:117–123.
Gennari FJ, Kassirer JP: Respiratory alkalosis; in Cohen JJ, Kassirer JP (eds): Acid-Base. Boston, Little, Brown, 1982, pp 349–376.
Gledhill N, Beirne GJ, Dempsey JA: Renal response to short-term hypocapnia in man. Kidney Int 1975;8:376–386.
Gennari FJ, Goldstein MB, Schwartz WB: The nature of the renal adaptation to chronic hypocapnia. J Clin Invest 1972;51:I722–I730.
Jacobson HR: Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am J Physiol 1981;240:F54–F62.
Cogan M: Effects of acute alterations in PCO2 on proximal HCO3, Cl, and H2O reabsorption. Am J Physiol 1984;246:F21–F26.
Bengele HH, McNamara ER, Schwartz JH, Alexander EA: Acidification adaptation along the inner medullary collecting duct. Am J Physiol 1988;255:F1155–F1159.
Santella RN, Maddox DA, Gennari FJ: Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis. J Clin Invest 1991;87:631–638.
Hilden SA, Johns CA, Madias NE: Adaptation of rabbit renal cortical Na+-H+-exchange activity in chronic hypocapnia. Am J Physiol 1989;257:F615–F622.
Gougoux A, Kaehny WD, Cohen JJ: Renal adaptation to chronic hypocapnia: Dietary constraints in achieving H+ retention. Am J Physiol 1975;229:1330–1337.
Krapf R, Beeler I, Hertner D, Hulter HN: Chronic respiratory alkalosis: The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med 1991;324:1394–1401.
Cohen JJ, Madias NE, Wolf CJ, Schwartz WB: Regulation of acid-base equilibrium in chronic hypocapnia: Evidence that the response of the kidney is not geared to the defense of extracellular [H+]. J Clin Invest 1976;57:1483–1489.
Madias NE, Schwartz WB, Cohen JJ: The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog. J Clin Invest 1977;60:1393–1401.
Clark DD, Chang BS, Garella SG, Cohen JJ, Madias NE: Secondary hypocapnia fails to protect ‘whole body’ intracellular pH during chronic HCl-acidosis in the dog. Kidney Int 1983;23:336–341.
Gennari FJ, Kaehny WD, Levesque PR, Cohen JJ: Acid-base response to chronic hypocapnia in man (abstract). Clin Res 1980;28:533A.
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.