The regulation of renal acid secretion: New observations from studies of distal nephron segments (original) (raw)

Abstract

Forty years ago, in a landmark paper, Pitts and Alexander [1] proposed that the renal excretion of acid is accomplished by 'a single fundamental process based primarily on the exchange of H ions for Na ions". Ten years later, Schwartz, Jenson and Relman [21 demonstrated that the acute infusion of sodium sulphate in humans ingesting a low sodium chloride diet was associated with a dramatic fall in urine pH, although systemic acid-base balance was not changed. The observation that hydrogen ion excretion can increase without a fall in blood pH has been relentlessly pursued by Schwartz and his colleagues [2]. Many meticulous chronic steady-state experiments have provided results which have been explained by a "non-homeostatic" hypothesis, elegantly presented by Schwartz and Cohen [3]. This view, to which we will hereafter refer as the cation exchange hypothesis, states that it is not blood pH but changes in sodium delivery, sodium avidity, and subsequent "Na-H exchange" of the distal nephron which determine the rate of renal hydrogen ion secretion. Chloride depletion or chloride substitution with less permeable anions are considered to also influence the rate of "Na-H exchange". Some of the situations studied by Schwartz and his colleagues include: alkalinization of systemic blood in chronic metabolic alkalosis, the different degrees of acidosis observed with chronic infusion of mineral acids of different anions, the normal bicarbonate concentration observed during vasopressin-induced volume expansion, and the induction of metabolic alkalosis by the administration of potassium and a non-reabsorbable anion to sodium and potassium depleted animals [4-8]. All have been explained on the basis of altered intrarenal sodium handling, subsequent stimulation of hydrogen ion secretion, and enhanced bicarbonate reabsorption. It is important to emphasize that this cation exchange hypothesis characterizes distal nephron H secretion as being uninfluenced by blood pH, but responsive primarily to Na handling and anion movements. Not surprisingly, such a comprehensive approach has strongly influenced current views on the renal regulation of acid-base balance. Recently, new studies have been completed which enable us to reconsider whether the regulation of hydrogen ion secretion "Na-H exchange" does not refer to any single mechanism but rather to some linkage (direct or indirect) between Na absorption and H secretion

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (75)

  1. PITTS RF, ALEXANDER RS: The nature of the renal tubular mech- anism for acidifying the urine. Am J Physiol 144:239-254, l945
  2. SCHWARTZ WB, JENSON RL, RELMAN AS: Acidification of the urine and increased ammonium excretion without change in acid-base equilibrium. Sodium reabsorption as a stimulus to the acidifying process. J C/in Invest 34:673-680, 1955
  3. SCHWARTZ WB, COHEN JJ: The nature of the renal response to chronic disorders of acid-base equilibrium. Am J Med 64:417-428, 1978
  4. GULYASSY PF, VAN YPERSELE DE STRIHOU C, SCHWARTZ WB: On the mechanism of nitrate-induced alkalosis. The possible role of selective chloride depletion in acid-base regulation. J C/in Invest 41:1850-1862, 1962
  5. NEEDLE MA, KALOYANIDES GJ, SCHWARTZ WB: The effects of selective depletion of hydrochloric acid on acid-base and electro- lyte equilibrium. iC/in Invest 43:1836-1846, 1964
  6. BLEICH HL, TANNEN RL, SCHWARTZ WB: The induction of metabolic alkalosis by correction of potassium deficiency. J C/in Invest 45:573-579, 1966
  7. LOWANCE DC, GARFINKEL HB, MATTERN WD, SCHWARTZ WB: The effect of chronic hypotonic volume expansion on the renal regulation of acid-base equilibrium. J C/in Invest 51:2928-2940, 1972
  8. DESOUSA RC, HARRINGTON iT, RICANATI ES, SHELKROT JW, SCHWARTZ WB: Renal regulation of acid-base equilibrium during chronic administration of mineral acid. J C/in Invest 53:465-476, 1974
  9. JACOBSON HR. SELDIN DW: On the generation, maintenance, and correction of metabolic alkalosis. Am J Physiol 245:F425-F432, 1983
  10. WOODHALL PB, TISHER CC: Response of the distal tubule and cortical collecting duct to vasopressin in the rat. J C/in Invest 52:3095-3108, 1973
  11. II. MALNIC G, DE MELLO-ARIES M, GIEBISCH G: Micropuncture study of renal tubular hydrogen ion transport in the rat. Am J Physio/ 222:147-158, 1972
  12. LUCCI MS. PUCACCO LR, DuBosE TD, JR, KOKKO JP, CARTER WW: Direct evaluation of acidification by rat proximal tubule: role of carbonic anhydrase. Am J Physio/ 238:F372-F379, 1980
  13. LOMBARD WE, K0KK0 JP, JACOBSON HR: Ion transport in super- ficial distal convoluted tubule perfused in vitro. (abstract) Proc 8th Int Cong Nephro/, 1981, p. 35
  14. LIJCCI MS, PUCACCO LR, CARTER NW, DuBosE TD, JR: Evalua- tion of bicarbonate transport in rat distal tubule: Effects of acid-base status. Am J Physio/ 243:F335-F34l, l982
  15. LEVINE DZ: An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats. J C/in invest 75:588-595, 1985
  16. WRIGHT FS: Increasing magnitude of electrical potential along the renal distal tubule. Am J Physio/ 220:624-633, l971
  17. HAYSLETT J, BOULPAEP E, KASHGARIAN M, GIEBISCH G: Electri- cal characteristics of the mammalian distal tubule. Comparison of Ling Gerard and microelectrodes. Kidney mt 12:324-33 I, 1977
  18. BARRATT U, RECTOR FC, KOKKOA JP, TI5HER CC, SELDIN DW: Transepithelial potential difference profile of the distal tubule of the rat kidney. Kidney mt 8:368-375, 1975
  19. VELASQUEZ H, WRIGHT FS, GOOD DW: Luminal influences on potassium secretion: chloride replacement with sulfate. Am J Physio/ 242:F46-F55, 1982
  20. STOKES JB, TISHER C, KOEKO JP: Structural-functional heteroge- neity along the rabbit collecting tubule. Kidney mt 14:585-593, l978
  21. KAI55LING B: Ultrastructural characterization of the connecting tubule and different segments of the collecting duct system in the rabbit kidney, in Biochemica/ Nephro/ogy, GUDER WG, SCHMIDT U, editors, Bern, Huber, 1978, pp. 435-445
  22. ROSEN 5: The turtle bladder: I. Morphological studies under varying conditions of fixation. Exp Mo! Patho! 12:286-296, 1970
  23. LE FURGEY A, TI5HER CC: Morphology of rabbit collecting duct. AmfAnat 155:111-124, 1979
  24. HIJSTED RF, MUELLER AL, KESSEL RG, STEINMETZ PR: Surface characteristics of carbonic anhydrase-rich cells in turtle urinary bladder. Kidney Int 19:491-502, 1981
  25. SCHWARTZ JH, BETHENCOURT D, ROSEN S: Specialized function of carbonic anhydrase-rich and granular cells of turtle bladder. Am JPhysio/ ll:F627-F633, 1982
  26. ROSEN 5, OLIVER JA, STEINMETZ PR: Urinary acidification and carbonic anhydrase distribution in bladders of Dominican and Colombian toads. J Memhr Bio/ 15:193-205, 1974
  27. FRAZIER LW: Cellular changes in toad urinary bladder in response to metabolic acidosis. J Membr Bio/ 40:165-177. 1978
  28. GLUCK 5, CANNON C, AL-AWQATI Q: Exocytosis regulates urinary acidification in turtle bladder by rapid insertion of H + pumps into the luminal membrane. Proc Nat! Acad Sci USA 79:4327-4331, 1982
  29. MADSEN KM, TISHER CC: Cellular response to acute respiratory acidosis in rat medullary collecting duct. Am J Physiol 245: F670-F679, 1983
  30. MADSEN KM, TISHER CC: Response of intercalated cells of rat outer medullary collecting duct to chronic metabolic acidosis. Lab Invest 51:268-276, 1984
  31. SCHWARTZ GJ, AL-AWQATI Q: Two functionally distinct types of mitochrondrial-rich cells in cortical collecting tubule as determined by changes in cells pH in individually identified cells. (abstract), Kidney mt 27:288, 1985
  32. VERLANDER JW, MADSEN KM, TISHER CC: Two populations of intercalated cells exist in the cortical collecting duct of the rat. (abstract) Clin Res 33:5OlA, 1985
  33. MCKINNEY TD, BURG MB: Bicarbonate transport by rabbit corti- cal collecting tubules. Effect of acid and alkali loads in vivo on transport in vitro. J Clin Invest 60:766-768, 1977
  34. MCKINNEY TD, BURG MB: Bicarbonate reabsorption by rabbit cortical collecting tubules in vitro. Am J Physiol, 234:Fl4l-Fl45, 1978
  35. MCKINNEY TD, BURG MB: Bicarbonate secretion by rabbit corti- cal collecting tubules in vitro. J Clin Invest 61:1421-1427, 1978
  36. LOMBARD EW, KOKKO JP, JACOBSON HR: Bicarbonate transport in cortical and outer medullary collecting tubules. Am J Physiol 244:F289-F296, 1983
  37. Lsu ME, WARNOCK DG, RECTOR FC, JR: Effects of chloride gradients on total CO2 flux in the rabbit cortical collecting tubule. Am J Physiol 244:F1l2-F12l, 1983
  38. KNEPPER MA, GooD DW, BURG MB: Mechanism of ammonia secretion by cortical collecting ducts of rabbits. Am J Physiol 247:F729-F738, 1984
  39. ATKINS JL, BURG MB: Secretion and absorption of bicarbonte by rat collecting ducts. (abstract) Clin Res 31:423A, 1983
  40. KOEPPEN BM, HELMAN SI: Acidification of luminal fluid by the rabbit cortical collecting tubule perfused in vitro. Am J Physiol 242:F52l-F531, 1982
  41. HANLEY MG, KOKKO JP, GROSS JB, JACOBSON HR: Electrophysi- ologic study of the cortical collecting tubule of the rabbit. Kidney mt 17:74-81, 1980
  42. STONER LC, BURG MB, ORLOFF J: Ion transport in cortical collecting tubule: effect of amilionde. Am J Physiol 227:453-459, 1974
  43. STARR, KNEPPER MA, BURG MB: Bicarbonate secretion by rabbit cortical collecting duct: role of chloride/bicarbonate exchange. (abstract) Kidney Int 27:289, 1985
  44. COHEN LH, MUELLER A, STEINMETZ PR: Inhibition of the bicar- bonate exit step in urinary acidification by a disulfonic stilbene. J Clin Invest 61:981-986, 1978
  45. FISCHER JL, HUSTED RF, STEINMETZ PR: Role of basolateral anion exchange in urinary acidification of the turtle bladder. (ab- stract) Clin Res 29:687A, 1982
  46. COHEN LH: HCO3-Cl exchange in the adaptive response to alkalosis by turtle bladder. Am J Physiol 239:F167-F170, 1980
  47. KOEPPEN BM, STEINMETZ PR: Basic mechanism of urinary acidi- fication. Med Clin N Amer 67:753-770, 1983
  48. STONE DK, SELDIN DW, KOKKO JP, JACOBsoN HR: Anion depen- dence of rabbit medullary collecting duct acidification. J Clin Invest 71:1505-1508, 1983
  49. BOYER J, BURG MB: Bicarbonate secretion by isolated perfused rabbit cortical collecting ducts. (abstract) Kidney mt 19:233, 1981
  50. GARCIA-AUSTT J, GOOD DW, BURG MB, KNEPPER MA: Deoxycorticosterone-stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading. Am J Physiol 249:F205-F2l2, 1985
  51. BREYER MD, K0RK0 JP, JACOBSON HR: Peritubular bicarbonate concentration but not pCO2 regulates acidification in the cortical collecting tubule. (abstract) Kidney mt 27:278, 1985
  52. LASKI ME, KURTZMAN NA: Characterization of acidification in the cortical and medullary collecting tubule of the rabbit. J Clin Invest 72:2050-2059, 1983
  53. STOKES JB: Sodium and potassium transport across the cortical and outer medullary collecting tubule of the rabbit: evidence for diffu- sion across the outer medullary portion. Am J Physiol 242: F514-F520, 1982
  54. JACOBSON HR: Medullary collecting duct acidification effects of potassium, HCO3 concentration and pCO2. J Clin Invest 74:2107-2114, 1984
  55. STONE DK, SELDIN DW, KOKKO JP, JACOBSON HR: Mineralocor- ticoid modulation of rabbit medullary collecting duct acidification: a sodium-independent effect. J Clin Invest 72:77-83, 1983
  56. GLUCK 5, AL-AWQATI Q: An electrogenic proton-translocating adenosine triphosphatase from bovine kidney medulla. J Clin Invest 73:1704-1710, 1984
  57. HAYSLETr JP, BACKMAN KA, SCHON DA: Electrical properties of the medullary collecting duct in the rat. Am J Physiol 239: F258-F264, 1980
  58. RAVE WS, FROMTER E: Electrical properties of the medullary collecting ducts of the golden hamster kidney. I. The transepithelial potential difference. Pfluegers Arch 351:99-111, 1974
  59. ROCHA AS, KUDO LH: Water, urea, sodium, chloride and potas- sium transport in the in vitro perfused papillary collecting duct. Kidney mt 22:485-491, 1982
  60. RICHARDSON RMA, KUNAU RT: Bicarbonate reabsorption in the papillary collecting duct: Effect of acetazolamide. Am J Physiol 243:F74-F80, 1982
  61. DUBOSE TD: Hydrogen ion secretion by the collecting duct as a determinant of the urine to blood pCO2 gradiant in alkaline urine. J Clin Invest 69: 145-156, 1982
  62. WESSON DE, FROMMER JP: Carbonic-anhydrase-independent HCO3 reabsorption in the rat: Effect of ethoxzolamide. (abstract) Kidney Int 27:290, 1985
  63. GRABER ML, BENGELE HH, SCHWARTZ JH, ALEXANDER EA: pH and PCO2 of the rat inner medullary collecting duct. Am J Physiol 241:F659-F668, 1981
  64. ULLRICH KJ, PAPAVSSILIOU F: Bicarbonate reabsorption in the papillary collecting duct of rats. Pflugers Arch 389:271-275, 1981
  65. HAMID B, TANNEN RL: Adaptive changes in renal acidification in response to chronic respiratory acidosis (CRA). (abstract) Clin Res 32:533A, 1984
  66. GIAMMARCO RA, GOLDSTEIN MB, HALPERIN ML, STINEBAUGH BJ: The effect of hyperventilation on distal nephron hydrogen ion secretion. J Clin Invest 58:77-82, 1976
  67. GOUGOUX A, VINAY P, LEMIEUX G, RICHARDSON RMA, TAM SIU-CHEUNG, GOLDSTEIN MB, STEINBAUGH BJ, HALPERIN ML: Effect of blood pH on distal nephron hydrogen ion secretion. Kid mt 17:615-621, 1980
  68. HALPERIN ML, GOLDSTEIN MB, GOUGOUX A, CHEN CHING-BUN, PICHETTE C, STINEBAUGH BJ, TAM SIU-CHEUNG: Regulation of distal acidification. Proceedings 8th mt Congr Nephrol Athens, pp. 206-217, 1981
  69. KASSIRER JP, SCHWARTZ WB: Correction of metabolic alkalosis in man without repair of potassium deficiency. A re-evaluation of the role of potassium. (abstract) Am J Med 40:19, 1966
  70. GENNARI FJ, PONTE ML, CORTELL 5: Distal tubule chloride delivery and reabsorption after hydrochloric acid administration in the rat. Mineral Electrolyte Metab 3:217-222, 1980
  71. WILCOX CS, CEMERIKIC DA, GIEBISCH G: Differential effects of acute mineralo-and glucortico-steroid administration on renal acid elimination. Kid mt 2 1:546-556, 1982
  72. DUBROVSKY AHE, NAIR RC, BYERS MK, LEVINE DZ: Renal net acid excretion in the adrenalectomized rat. Kidney Int 19:516-528, 1981
  73. DITELLA P, SODHI B, MCCREARY J, ARRUDA J, KURTZMAN NA: Mechanism of the metabolic acidosis of selective mineralocorticoid deficiency. Kidney Int 14:466-477, 1978
  74. KASSIRER JP, APPLETON FM, CHAZAN JA, SCHWARTZ WB: Aldos- terone in metabolic alkalosis. J Clin Invest 46:1558-1571, 1967
  75. COHEN JJ, HULTER HN, SMITHLINE N, MELBY JC, SCHWARTZ WB: The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. Evi- dence that chronic hyponatremia is a potent stimulus to aldosterone secretion. J Clin Invest 58:1201-1208, 1976