Skip to main content
  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
  • Published:

Renal acification during chronic hypercapnia in the conscious dog

Abstract

Enhanced renal acidification during chronic hypercapnia (CH) results in transient augmentation in net acid excretion (NAE) (adaptation phase) and persistent acceleration in renal bicarbonate reclamation (adaptation and steady-state phases). The mechanisms responsible for the return of NAE to control values despite persistent acidemia during the steady state phase of CH remain undefined. In addition, it remains unsettled whether the enhancement of renal ammoniagenesis known to occur during the adaptation phase of CH persists during the steady-state phase. Furthermore it is uncertain if the alteration in whole-kidney acification observed in CH originates from augmentation in the acification of both proximal and distal nephronal segments.

To shed further light on these issues, observations on the profile of the urine acid-base moieties during the adaptive and steady-state phases of CH were carried out in dogs chronically exposed to hypercapnia (10% FiCO2) in an environmental chamber (13 days). Additionally, collecting duct hydrogen ion secretion (CDH+S) was evaluated by employing the U-BPCO2 in alkaline urine in intact unanesthetized dogs with either CH (10% FiCO2) or eucapnia. The balance studies demonstrated that NAE increased in early hypercapnia (4.84 meq/kg body weight, control 3.27 meq/kg body weight,p<0.05) and returned to baseline thereafter; by contrast, urine NH +4 which was augmented during the adaptation phase (3.71 meq/kg body weight, control 1.97 meq/kg body weight,p<0.05) remained elevated throughout (3.25 meq/kg body weight). Moreover, steady-state chronic hypercapnia was accompanied by a decrease in urine titratable acidity (1.07 meq/kg body weight, control 1.46 meq/kg body weight,p<0.05) and an increase in urine bicarbonate (0.51 meq/kg body weight, control 0.16 meq/kg body weight,p<0.05) and pH (6.44, control 6.06,p<0.05). Evaluation of the U-BPCO2 in alkaline urine in eucapnic and hypercapnic dogs revealed no significant differences between the two groups at comparable urine bicarbonate concentrations. Our data provide evidence that CH effects a persistent stimulation of renal ammoniagenesis but no augmentation in CDH+S. The return of NAE to baseline during the steady-state phase results from a decrease in titratable acidity and persistent bicarbonaturia that counterbalance the chronic enhancement in ammoniagenesis. The results suggest that the entire renal response to CH originates from proximal nephronal sites.

This is a preview of subscription content, access via your institution.

References

  • Adrogué HJ, Tasby J, Suki WN (1982) Intracellular pH in the control of the H+ pump: evidence from CO2 studies in the isolated turtle bladder. Trans Assoc Am Physicians 95:135–144

    Google Scholar 

  • Adrogué HJ, Stinebaugh BJ, Gougoux A, Lemieux G, Vinay P, Tam SC, Goldstein MB, Halperin ML (1983) Decreased distal acidification in acute hypercapnia in the dog. Am J Physiol 244:F19-F27

    Google Scholar 

  • Al-Awqati Q (1978) H+ transport in urinary epithelia. Am J Physiol 235:F77-F88

    Google Scholar 

  • Alexander EA, McNamara ER, Schwartz JH, Bengele HH (1984) Acute hypercapnia stimulates acidification along the inner medullary collecting duct (abstract). Kidney Int 25:270A

    Google Scholar 

  • Arruda JAL, Nascimento L, Kumar SK, Kurtzman NA (1977) Factors influencing the formation of urinary carbon dioxide tension. Kidney Int 11:307–317

    Google Scholar 

  • Batlle DC (1982) DeltaPCO2 rather than urine-bloodPCO2 as an index of distal acidification. Semin Nephrol 2:189–190

    Google Scholar 

  • Batlle D, Foley RJ, Itsarayoungyuen K, Downer M, Kurtzman NA (1982) The relationship and physiologic significance of urinaryPCO2 and bloodPCO2 during hypercapnia (abstract). Clin Res 30:441A

    Google Scholar 

  • Batlle DC, Downer M, Gutterman C, Kurtzman NA (1985) Relationship of urinary and blood carbon dioxide tension during hypercapnia in the rat. J Clin Invest 75:1517–1530

    Google Scholar 

  • Bengele HH, Graber ML, Alexander EA (1983) Effect of respiratory acidosis on acidification by the medullary collecting duct. Am J Physiol 244:F89-F94

    Google Scholar 

  • Berliner RW (1985) Carbon dioxide tension of alkaline urine. In: Seldin DW, Giebisch G (eds) The kidney: Physiology and pathophysiology. Raven Press, New York, pp 1527–1537

    Google Scholar 

  • Breyer MD, Kokko JP, Jacobson HR (1984) Peritubular bicarbonate concentration but notPCO2 regulates acidification in the cortical collecting tubule (abstract). Proc Am Soc Nephrol 17:180A

    Google Scholar 

  • Buerkert J, Martin D, Trigg D (1984) Ammonium handling by deep nephrons and the collecting duct during acute respiratory acidosis (abstract). Kidney Int 25:272A

    Google Scholar 

  • Clarke E, Evans BE, MacIntyre I, Milne MD (1955) Acidosis in experimental electrolyte depletion. Clin Sci 14:421–440

    Google Scholar 

  • Cogan MG (1984) Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat. J Clin Invest 74:1942–1947

    Google Scholar 

  • Cogan MG, Rector FC, Seldin DW (1981) Acid-base disorders. In: Brenner BM, Rector FC (eds) The kidney. WB Saunders, Philadelphia, pp 841–907

    Google Scholar 

  • Downer M, Kurtzman NA, Batlle D (1984) Failure of the urine-bloodPCO2 gradient to characterize distal acidification: studies during hypocapnia (abstract). Kidney Int 25:274A

    Google Scholar 

  • DuBose TD (1982) Hydrogen ion secretion by the collecting duct as a determinant of the urine to bloodPCO2 gradient in alkaline urine. J Clin Invest 69:145–156

    Google Scholar 

  • Elkinton JR, Huth EJ, Webster GD, McCance RA (1960) The renal excretion of hydrogen ion in renal tubular acidosis. Am J Med 29:554–575

    Google Scholar 

  • Gamble JL, Ross GS, Tisdall FF (1923) The metabolism of fixed base during fasting. J Biol Chem 57:633–695

    Google Scholar 

  • Good DW, Burg MB (1984) Ammonia production by individual segments of the rat nephron. J Clin Invest 73:602–610

    Google Scholar 

  • Gougoux A, Vinay P, Lemieux G, Duran MA, Chen CB, Goldstein MB, Stinebaugh BJ, Tam SC, Halperin MH (1981) Studies on the mechanism whereby acidemia stimulates collecting duct hydrogen ion secretion in vivo. Kidney Int 20:643–648

    Google Scholar 

  • Gougoux A, Vinay P, Cardoso M, Duplain M, Lemieux G (1982) Immediate adaptation of the dog kidney to acute hypercapnia. Am J Physiol 243:F227-F234

    Google Scholar 

  • Gougoux A, Vinay P, Lemieux G, Goldstein M, Stinebaugh B, Halperin M (1983) Importance of medullary events in ammonium excretion: studies in acute respiratory acidosis and acute metabolic acidosis. Can J Physiol Pharmacol 61:35–42

    Google Scholar 

  • Graber ML, Bengele HH, Alexander EA (1982) Elevated urinaryPCO2 in the rat: an intrarenal event. Kidney Int 21:795–799

    Google Scholar 

  • Halperin ML, Goldstein MB, Haig A, Johnson MD, Stinebaugh BJ (1974) Studies on the pathogenesis of type I (distal) renal tubular acidosis as revealed by the urinaryPCO2 tensions. J Clin Invest 53:669–677

    Google Scholar 

  • Kurtzman NA, Arruda JAL (1978) Physiologic significance of urinary carbon dioxide tension. Miner Electrolyte Metab 1:241–246

    Google Scholar 

  • Lemann J, Litzow JR, Lennon EJ (1966) The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic acidosis. J Clin Invest 45:1608–1614

    Google Scholar 

  • Levine DZ (1971) Effect of acute hypercapnia on proximal tubular water and bicarbonate reabsorption. Am J Physiol 221:1164–1170

    Google Scholar 

  • Lombard WE, Jacobson HR, Kokko JP (1980) Effect of in vivo and in vitro acid-base manipulations on collecting duct bicarbonate transport (abstract). Clin Res 28:535A

    Google Scholar 

  • Lucci MS, Pucacco LR, Carter NW, DuBose TD (1982) Evaluation of bicarbonate transport in rat distal tubule: effects of acid-base status. Am J Physiol 243:F335-F341

    Google Scholar 

  • Madias NE, Cohen JJ (1982) Respiratory acidosis. In: Cohen JJ, Kassirer JP (eds) Acid-base. Little, Brown, Boston, pp 307–348

    Google Scholar 

  • Mello-Aires M, Malnic G (1975) Peritubular pH andPCO2 in renal tubular acidification. Am J Physiol 228:1766–1774

    Google Scholar 

  • Pitts RF, Lotspeich WD (1946) Bicarbonate and the renal regulation of acid-base balance. Am J Physiol 147:138–154

    Google Scholar 

  • Polak A, Haynie GD, Hays RM, Schwartz, WB (1961) Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. I. Adaptation. J Clin Invest 40:1223–1237

    Google Scholar 

  • Rector FC Jr (1973) Acidification of the urine. In: Orloff J, Berliner RW (eds) Handbook of physiology. Renal physiology American Physiological Society, Washington DC, pp 431–453

    Google Scholar 

  • Reid EL, Hills AG (1965) Diffusion of carbon dioxide out of the distal nephron in man during antidiuresis. Clin Sci 28:15–28

    Google Scholar 

  • Rodriguez-Nichols F, Tannen RL (1983) Absence of adaptation in renal NH3 production to chronic respiratory acidosis (abstract). Clin Res 31:518A

    Google Scholar 

  • Rosenthal TB (1948) The effect of temperature on the pH of blood and plasma in vitro. J Biol Chem 173:25–30

    Google Scholar 

  • Sartorius OW, Roemmelt JC, Pitts RF (1949) The renal regulation of acid-base balance in man. IV. The nature of the renal compensations in ammonium acidosis. J Clin Invest 28:423–439

    Google Scholar 

  • Schloeder FX, Stinebaugh BJ (1966) Defect of urinary acification during fasting. Metabolism 15:17–25

    Google Scholar 

  • Schloeder FX, Stinebaugh BJ (1977) Urinary ammonia content as a determinant of urinary pH during chronic metabolic acidosis. Metabolism 26:1321–1331

    Google Scholar 

  • Schwartz JH (1976) H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder. Am J Physiol 231:565–572

    Google Scholar 

  • Schwartz WB, Silverman L (1965) A large environmental chamber for the study of hypercapnia and hypoxia. J Appl Physiol 20:767–774

    Google Scholar 

  • Schwartz WB, Brackett NC, Cohen JJ (1965) The response of extracellular hydrogen ion concentration to graded degrees of chronic hypercapnia: the physiologic limits of the defense of pH. J Clin Invest 44:291–301

    Google Scholar 

  • Severinghaus JW, Stupfel M, Bradley AF (1956a) Accuracy of blood pH andPCO2 determinations. J Appl Physiol 9:189–196

    Google Scholar 

  • Severinghaus JW, Stupfel M, Bradley AF (1956b) Variations of serum carbonic acid pK′ with pH and temperature. J Appl Physiol 9:197–200

    Google Scholar 

  • Stinebaugh BJ, Esquenazi R, Schloeder FX, Suki WN, Goldstein MB, Halperin ML (1980) Control of the urine-bloodPCO2 gradient in alkaline urine. Kidney Int 17:31–39

    Google Scholar 

  • Tam SC, Goldstein MB, Stinebaugh BJ, Chen CB, Gougoux A, Halperin ML (1981) Studies on the regulation of hydrogen ion secretion in the collecting duct in vivo: evaluation of factors that influence the urine minus bloodPCO2 difference. Kidney Int 20:636–642

    Google Scholar 

  • Tannen RL (1980) Control of acid excretion by the kidney. Ann Rev Med 31:35–49

    Google Scholar 

  • Tannen RL, Sastrasinh S (1984) Response of ammonia metabolism to acute acidosis. Kidney Int 25:1–10

    Google Scholar 

  • Tannen RL, Bleich HL, Schwartz WB (1966) The renal response of acid loads in metabolic alkalosis: an assessment of the mechanisms regulating acid excretion. J Clin Invest 45:562–572

    Google Scholar 

  • Trivedi B, Cole L, Tannen RL (1984) Effect of chronic respiratory acidosis (CRA) on the intracellular pH of the proximal tubule as reflected by changes in pH sensitive metabolites (abstract). Proc Am Soc Nephrol 17:192A

    Google Scholar 

  • Wood FJY (1955) Ammonium chloride acidosis. Clin Sci 14:81–89

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Adrogué, H.J., Madias, N.E. Renal acification during chronic hypercapnia in the conscious dog. Pflugers Arch. 406, 520–528 (1986). https://doi.org/10.1007/BF00583376

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00583376

Key words

  • Acid-base equilibrium
  • Bicarbonate reabsorption
  • Respiratory acidosis
  • Renal ammoniagenesis
  • Net acid excretion