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. 1985 May;75(5):1517–1530. doi: 10.1172/JCI111856

Relationship of urinary and blood carbon dioxide tension during hypercapnia in the rat. Its significance in the evaluation of collecting duct hydrogen ion secretion.

D C Batlle, M Downer, C Gutterman, N A Kurtzman
PMCID: PMC425491  PMID: 2987305

Abstract

This study was designed to establish the relationship between urinary pCO2 and systemic blood pCO2 during acute hypercapnia and to investigate the significance of this relationship to collecting duct hydrogen ion (H+) secretion when the urine is acid and when it is highly alkaline. In rats excreting a highly alkaline urine, an acute increase in blood pCO2 (from 42 +/- 0.8 to 87 +/- 0.8 mmHg) resulted in a significant fall in urine minus blood (U-B) pCO2 (from 31 +/- 2.0 to 16 +/- 4.2 mmHg, P less than 0.005), a finding which could be interpreted to indicate inhibition of collecting duct H+ secretion by hypercapnia. The urinary pCO2 of rats with hypercapnia, unlike that of normocapnic controls, was significantly lower than that of blood when the urine was acid (58 +/- 6.3 and 86 +/- 1.7 mmHg, P less than 0.001) and when it was alkalinized in the face of accelerated carbonic acid dehydration by infusion of carbonic anhydrase (78 +/- 2.7 and 87 +/- 1.8 mmHg, P less than 0.02). The finding of a urinary pCO2 lower than systemic blood pCO2 during hypercapnia suggested that the urine pCO2 prevailing before bicarbonate loading should be known and the blood pCO2 kept constant to evaluate collecting duct H+ secretion using the urinary pCO2 technique. In experiments performed under these conditions, sodium bicarbonate infusion resulted in an increment in urinary pCO2 (i.e., a delta pCO2) which was comparable in hypercapnic and normocapnic rats (40 +/- 7.2 and 42 +/- 4.6 mmHg, respectively) that were alkalemic (blood pH 7.53 +/- 0.02 and 7.69 +/- 0.01, respectively). The U-B pCO2, however, was again lower in hypercapnic than in normocapnic rats (15 +/- 4.0 and 39 +/- 2.5 mmHg, respectively, P less than 0.001). In hypercapnic rats in which blood pH during bicarbonate infusion was not allowed to become alkalemic (7.38 +/- 0.01), the delta pCO2 was higher than that of normocapnic rats which were alkalemic (70 +/- 5.6 and 42 +/- 4.6 mmHg, respectively, P less than 0.005) while the U-B pCO2 was about the same (39 +/- 3.7 and 39 +/- 2.5 mmHg). We further examined urine pCO2 generation by measuring the difference between the urine pCO2 of a highly alkaline urine not containing carbonic anhydrase and that of an equally alkaline urine containing this enzyme. Carbonic anhydrase infusion to hypercapnic rats that were not alkalemic resulted in a fall in urine pCO(2) (from 122+/-5.7 to 77+/-2.2 mmHg) which was greater (P <0.02) than that seen in alkalemic normocapnic controls (from 73+/- 1.9 to 43+/-1.3 mmHg) with a comparable urine bicarbonate concentration and urine nonbicarbonate buffer capacity. CO(2) generation, therefore, from collecting dust H(+) secretion and titration of bicarbonate, was higher in hypercapnic rats that in normocapnic controls. We conclude that in rats with actue hypercapnia, the U-B p(CO(2)) achieved during bicarbonate loading greatly underestimates collecting duct H(+) secretion because it is artificially influenced by systemic blood pCO(2). the deltapCO(2) is a better qualitative index of collecting duct H+ secretion that the U-B pCO(2), because it is not artificially influenced by systemic blood pCO(2) and it takes into account the urine PCO(2) prevailing before bicarbonate loading.

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Selected References

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  1. Adrogué H. J., Stinebaugh B. J., Gougoux A., Lemieux G., Vinay P., Tam S. C., Goldstein M. B., Halperin M. L. Decreased distal acidification in acute hypercapnia in the dog. Am J Physiol. 1983 Jan;244(1):F19–F27. doi: 10.1152/ajprenal.1983.244.1.F19. [DOI] [PubMed] [Google Scholar]
  2. Arruda J. A., Nascimento L., Kumar S. K., Kurtzman N. A. Factors influencing the formation of urinary carbon dioxide tension. Kidney Int. 1977 May;11(5):307–317. doi: 10.1038/ki.1977.48. [DOI] [PubMed] [Google Scholar]
  3. Arruda J. A., Nascimento L., Mehta P. K., Rademacher D. R., Sehy J. T., Westenfelder C., Kurtzman N. A. The critical importance of urinary concentrating ability in the generation of urinary carbon dioxide tension. J Clin Invest. 1977 Oct;60(4):922–935. doi: 10.1172/JCI108847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BARKER E. S., SINGER R. B., ELKINTON J. R., CLARK J. K. The renal response in man to acute experimental respiratory alkalosis and acidosis. J Clin Invest. 1957 Apr;36(4):515–529. doi: 10.1172/JCI103449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BRAZEAU P., GILMAN A. Effect of plasma CO2 tension on renal tubular reabsorption of bicarbonate. Am J Physiol. 1953 Oct;175(1):33–38. doi: 10.1152/ajplegacy.1953.175.1.33. [DOI] [PubMed] [Google Scholar]
  6. BRODSKY W. A., MILEY J. F., KAIM J. T., SHAH N. P. Characteristics of acidic urine after loading with weak organic acids in dogs; current concepts on renal mechanisms of acidification in relation to data on CO2 tension. Am J Physiol. 1958 Apr;193(1):108–122. doi: 10.1152/ajplegacy.1958.193.1.108. [DOI] [PubMed] [Google Scholar]
  7. Batlle D. C., Itsarayoungyuen K., Downer M., Foley R., Arruda J. A., Kurtzman N. A. Suppression of distal urinary acidification after recovery from chronic hypocapnia. Am J Physiol. 1983 Oct;245(4):F433–F442. doi: 10.1152/ajprenal.1983.245.4.F433. [DOI] [PubMed] [Google Scholar]
  8. Batlle D., Gaviria M., Grupp M., Arruda J. A., Wynn J., Kurtzman N. A. Distal nephron function in patients receiving chronic lithium therapy. Kidney Int. 1982 Mar;21(3):477–485. doi: 10.1038/ki.1982.49. [DOI] [PubMed] [Google Scholar]
  9. Batlle D., Grupp M., Gaviria M., Kurtzman N. A. Distal renal tubular acidosis with intact capacity to lower urinary pH. Am J Med. 1982 May;72(5):751–758. doi: 10.1016/0002-9343(82)90540-x. [DOI] [PubMed] [Google Scholar]
  10. Bengele H. H., Graber M. L., Alexander E. A. Effect of respiratory acidosis on acidification by the medullary collecting duct. Am J Physiol. 1983 Jan;244(1):F89–F94. doi: 10.1152/ajprenal.1983.244.1.F89. [DOI] [PubMed] [Google Scholar]
  11. Buerkert J., Martin D., Trigg D. Segmental analysis of the renal tubule in buffer production and net acid formation. Am J Physiol. 1983 Apr;244(4):F442–F454. doi: 10.1152/ajprenal.1983.244.4.F442. [DOI] [PubMed] [Google Scholar]
  12. Cohen L. H., Steinmetz P. R. Control of active proton transport in turtle urinary bladder by cell pH. J Gen Physiol. 1980 Sep;76(3):381–393. doi: 10.1085/jgp.76.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cruz-Soto M., Batlle D., Sabatini S., Arruda J. A., Kurtzman N. A. Distal acidification in the rabbit: role of diet and blood pH. Am J Physiol. 1982 Oct;243(4):F364–F371. doi: 10.1152/ajprenal.1982.243.4.F364. [DOI] [PubMed] [Google Scholar]
  14. Cunarro J. A., Weiner M. W. A comparison of methods for measuring urinary ammonium. Kidney Int. 1974 Apr;5(4):303–305. doi: 10.1038/ki.1974.41. [DOI] [PubMed] [Google Scholar]
  15. DORMAN P. J., SULLIVAN W. J., PITTS R. F. Factors determining carbon dioxide tension in urine. Am J Physiol. 1954 Oct;179(1):181–187. doi: 10.1152/ajplegacy.1954.179.1.181. [DOI] [PubMed] [Google Scholar]
  16. DORMAN P. J., SULLIVAN W. J., PITTS R. F. The renal response to acute respiratory acidosis. J Clin Invest. 1954 Jan;33(1):82–90. doi: 10.1172/JCI102874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. DuBose T. D., Jr Application of the disequilibrium pH method to investigate the mechanism of urinary acidification. Am J Physiol. 1983 Nov;245(5 Pt 1):F535–F544. doi: 10.1152/ajprenal.1983.245.5.F535. [DOI] [PubMed] [Google Scholar]
  18. DuBose T. D., Jr Hydrogen ion secretion by the collecting duct as a determinant of the urine to blood PCO2 gradient in alkaline urine. J Clin Invest. 1982 Jan;69(1):145–156. doi: 10.1172/JCI110425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. GIEBISCH G., BERGER L., PITTS R. F. The extrarenal response to acute acid-base disturbances of respiratory origin. J Clin Invest. 1955 Feb;34(2):231–245. doi: 10.1172/JCI103076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gennari F. J., Caflisch C. R., Johns C., Maddox D. A., Cohen J. J. PCO2 measurements in surface proximal tubules and peritubular capillaries of the rat kidney. Am J Physiol. 1982 Jan;242(1):F78–F85. doi: 10.1152/ajprenal.1982.242.1.F78. [DOI] [PubMed] [Google Scholar]
  21. Giammarco R. A., Goldstein M. B., Halperin M. L., Stinebaugh B. J. The effect of hyperventilation on distal nephron hydrogen ion secretion. J Clin Invest. 1976 Jul;58(1):77–82. doi: 10.1172/JCI108462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gougoux A., Vinay P., Cardoso M., Duplain M., Lemieux G. Immediate adaptation of the dog kidney to acute hypercapnia. Am J Physiol. 1982 Sep;243(3):F227–F234. doi: 10.1152/ajprenal.1982.243.3.F227. [DOI] [PubMed] [Google Scholar]
  23. Gougoux A., Vinay P., Lemieux G., Goldstein M., Stinebaugh B., Halperin M. Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis. Can J Physiol Pharmacol. 1983 Jan;61(1):35–42. doi: 10.1139/y83-004. [DOI] [PubMed] [Google Scholar]
  24. Gougoux A., Vinay P., Lemieux G., Richardson R. M., Tam S., Goldstein M. B., Stinebaugh B. J., Halperin M. L. Effect of blood pH on distal nephron hydrogen ion secretion. Kidney Int. 1980 May;17(5):615–621. doi: 10.1038/ki.1980.72. [DOI] [PubMed] [Google Scholar]
  25. Graber M. L., Bengele H. H., Alexander E. A. Elevated urinary PCO2 in the rat: an intrarenal event. Kidney Int. 1982 Jun;21(6):795–799. doi: 10.1038/ki.1982.101. [DOI] [PubMed] [Google Scholar]
  26. Graber M. L., Bengele H. H., Schwartz J. H., Alexander E. A. pH and PCO2 profiles of the rat inner medullary collecting duct. Am J Physiol. 1981 Dec;241(6):F659–F668. doi: 10.1152/ajprenal.1981.241.6.F659. [DOI] [PubMed] [Google Scholar]
  27. Halperin M. L., Goldstein M. B., Haig A., Johnson M. D., Stinebaugh B. J. Studies on the pathogenesis of type I (distal) renal tubular acidosis as revealed by the urinary PCO2 tensions. J Clin Invest. 1974 Mar;53(3):669–677. doi: 10.1172/JCI107604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hulter H. N., Ilnicki L. P., Licht J. H., Sebastian A. On the mechanism of diminished urinary carbon dioxide tension caused by amiloride. Kidney Int. 1982 Jan;21(1):8–13. doi: 10.1038/ki.1982.2. [DOI] [PubMed] [Google Scholar]
  29. KENNEDY T. J., Jr, ORLOFF J., BERLINER R. W. Significance of carbon dioxide tension in urine. Am J Physiol. 1952 Jun;169(3):596–608. doi: 10.1152/ajplegacy.1952.169.3.596. [DOI] [PubMed] [Google Scholar]
  30. Kurtzman N. A. Relationship of extracellular volume and CO2 tension to renal bicarbonate reabsorption. Am J Physiol. 1970 Nov;219(5):1299–1304. doi: 10.1152/ajplegacy.1970.219.5.1299. [DOI] [PubMed] [Google Scholar]
  31. Levine D. Z. Effect of acute hypercapnia on proximal tubular water and bicarbonate reabsorption. Am J Physiol. 1971 Oct;221(4):1164–1170. doi: 10.1152/ajplegacy.1971.221.4.1164. [DOI] [PubMed] [Google Scholar]
  32. Lucci M. S., Pucacco L. R., Carter N. W., DuBose T. D., Jr Evaluation of bicarbonate transport in rat distal tubule: effects of acid-base status. Am J Physiol. 1982 Oct;243(4):F335–F341. doi: 10.1152/ajprenal.1982.243.4.F335. [DOI] [PubMed] [Google Scholar]
  33. MAREN T. H. A simplified micromethod for the determination of carbonic anhydrase and its inhibitors. J Pharmacol Exp Ther. 1960 Sep;130:26–29. [PubMed] [Google Scholar]
  34. Maren T. H. Carbon dioxide equilibria in the kidney: the problems of elevated carbon dioxide tension, delayed dehydration, and disequilibrium pH. Kidney Int. 1978 Nov;14(5):395–405. doi: 10.1038/ki.1978.144. [DOI] [PubMed] [Google Scholar]
  35. OCHWADT B. K., PITTS R. F. Effects of intravenous infusion of carbonic anhydrase on carbon dioxide tension of alkaline urine. Am J Physiol. 1956 May;185(2):426–429. doi: 10.1152/ajplegacy.1956.185.2.426. [DOI] [PubMed] [Google Scholar]
  36. PORTWOOD R. M., SELDIN D. W., RECTOR F. C., Jr, CADE R. The relation of urinary CO2 tension to bicarbonate excretion. J Clin Invest. 1959 May;38(5):770–776. doi: 10.1172/JCI103858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. POY R. K., WRONG O. The urinary pCO2 in renal disease. Clin Sci. 1960 Nov;19:631–639. [PubMed] [Google Scholar]
  38. Pucacco L. R., Carter N. W. An improved pCO2 microelectrode. Anal Biochem. 1978 Oct 1;90(1):427–434. doi: 10.1016/0003-2697(78)90047-7. [DOI] [PubMed] [Google Scholar]
  39. RECTOR F. C., Jr, PORTWOOD R. M., SELDIN D. W. Examination of the mixing hypothesis as an explanation for elevated urinary carbon dioxide tensions. Am J Physiol. 1959 Oct;197:861–864. doi: 10.1152/ajplegacy.1959.197.4.861. [DOI] [PubMed] [Google Scholar]
  40. RECTOR F. C., Jr, SELDIN D. W., ROBERTS A. D., Jr, SMITH J. S. The role of plasma CO2 tension and carbonic anhydrase activity in the renal reabsorption of bicarbonate. J Clin Invest. 1960 Nov;39:1706–1721. doi: 10.1172/JCI104193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. REID E. L., HILLS A. G. DIFFUSION OF CARBON DIOXIDE OUT OF THE DISTAL NEPHRON IN MAN DURING ANTIDIURESIS. Clin Sci. 1965 Feb;28:15–28. [PubMed] [Google Scholar]
  42. RELMAN A. S., ETSTEN B., SCHWARTZ W. B. The regulation of renal bicarbonate reabsorption by plasma carbon dioxide tension. J Clin Invest. 1953 Oct;32(10):972–978. doi: 10.1172/JCI102823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. RYBERG C. Some investigations on the carbon dioxide tension of the urine in man. Acta Physiol Scand. 1948 Apr 20;15(2):123–139. doi: 10.1111/j.1748-1716.1948.tb00490.x. [DOI] [PubMed] [Google Scholar]
  44. Sajo I. M., Goldstein M. B., Sonnenberg H., Stinebaugh B. J., Wilson D. R., Halperin M. L. Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis. Kidney Int. 1981 Sep;20(3):353–358. doi: 10.1038/ki.1981.146. [DOI] [PubMed] [Google Scholar]
  45. Sehy J. T., Roseman M. K., Arruda J. A., Kurtzman N. A. Characterization of distal hydrogen ion secretion in acute respiratory alkalosis. Am J Physiol. 1978 Sep;235(3):F203–F208. doi: 10.1152/ajprenal.1978.235.3.F203. [DOI] [PubMed] [Google Scholar]
  46. Steinmetz P. R., Andersen O. S. Electrogenic proton transport in epithelial membranes. J Membr Biol. 1982;65(3):155–174. doi: 10.1007/BF01869960. [DOI] [PubMed] [Google Scholar]
  47. Stinebaugh B. J., Esquenazi R., Schloeder F. X., Suki W. N., Goldstein M. B., Halperin M. L. Control of the urine-blood PCO2 gradient in alkaline urine. Kidney Int. 1980 Jan;17(1):31–39. doi: 10.1038/ki.1980.4. [DOI] [PubMed] [Google Scholar]
  48. Tam S. C., Goldstein M. B., Stinebaugh B. J., Chen C. B., Gougoux A., Halperin M. L. Studies on the regulation of hydrogen ion secretion in the collecting duct in vivo: evaluation of factors that influence the urine minus blood PCO2 difference. Kidney Int. 1981 Nov;20(5):636–642. doi: 10.1038/ki.1981.187. [DOI] [PubMed] [Google Scholar]
  49. Uhlich E., Baldamus C. A., Ullrich K. J. Verhalten von CO2-Druck und Bicarbonat im Gegenstromysystem des Nierenmarks. Pflugers Arch. 1968;303(1):31–48. doi: 10.1007/BF00586825. [DOI] [PubMed] [Google Scholar]

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