Metabolic Alkalosis: Biochemical Mechanisms, Pathophysiology, and Treatment

  • Sandra Sabatini
  • Neil A. Kurtzman


Metabolic alkalosis is a primary pathophysiologic event characterized by the gain of bicarbonate or the loss of nonvolatile acid from extracellular fluid such that arterial pH increases (normal pH = 7.40). More simply put, it is a primary increase in plasma bicarbonate concentration (normal plasma HCO3 = 24mEq/L). Like all acid-base disturbances, metabolic alkalosis commonly complicates the course of patients with preexisting disorders. An understanding of its pathophysiology makes the diagnosis and management of metabolic alkalosis a relatively simple process. Several series (1,2) have reported that metabolic alkalosis is the second most common acid-base disorder in hospitalized adults (Table 1). Most of these are patients with other underlying diseases predisposing them to one of the many complex acid-base disorders.


Proximal Tubule Metabolic Alkalosis Distal Nephron Distal Renal Tubular Acidosis Potassium Depletion 
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  1. 1.
    Mazzara JT, Ayres SM, Grace WJ: Extreme hypocapnia in the critically ill patient. Am J Med 56: 450, 1974.PubMedCrossRefGoogle Scholar
  2. 2.
    Hodgkin JE, Soeprono FF, Chan DM: Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med 8: 725, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Weinman EJ, Shenolikar S: Regulation of brush border Na+- H+ exchanger. Anna Rev Physiol 55: 289, 1993.CrossRefGoogle Scholar
  4. 4.
    Chan YL, Giebisch G: The relationship between sodium and bicarbonate ion transport in the rat proximal convoluted tubule. Am J Physiol 240: F222, 1981.PubMedGoogle Scholar
  5. 5.
    Akiba T, Rocco VK, Warnock DG: Parallel adaptation of rabbit renal cortical Na/H antiporter and Na/HC03 co-transporter in metabolic acidosis and alkalosis. J Clin Invest 80: 308, 1987.PubMedCrossRefGoogle Scholar
  6. 6.
    Sabatini S, Kurtzman NA: Overall renal regulation. In: DW Seldin, G Giebisch, eds, Regulation of Acid-Base Balance. Raven Press, New York, in press, 1988.Google Scholar
  7. 7.
    Hamm LL, Alpern RJ: Cellular mechanisms of renal tubular acidification. In: DW Seldin, G Giebisch, eds, The Kidney: Physiology and Pathophysiology, 2nd ed. Raven Press, New York, p 2581, 1992.Google Scholar
  8. 8.
    Kinne-Saffran E, Kinne R: Proton pump activity and Mg- ATPase activity in rat kidney cortex brush border membranes: effect of proton “ATPase” inhibitors. Pflugers Arch 407: 180, 1986.CrossRefGoogle Scholar
  9. 9.
    Sabolic I, Burchard R: Characteristics of the proton pump in rat renal cortical endocytic vesicles. Am J Physiol 250: F818, 1986.Google Scholar
  10. 10.
    Ait-Mohammed AK, Marsy S, Barlet C, Khadouri C, Doucet A: Characterization of N-ethylmaleimide-sensitive proton pump in rat kidney. J Biol Chem 261: 1 2526, 1986.Google Scholar
  11. 11.
    Brown D, Hirsch S, Gluck S: Localization of a proton pumping ATPase in rat kdiney. J Clin Inves 82: 2114, 1986.CrossRefGoogle Scholar
  12. 12.
    Kurtz I: Apical Na/H antiporter and glycolysis dependent H- ATPase regulate intracellular pH in rabbit S3 proximal tubule. J Clin Invest 80: 928, 1987.PubMedCrossRefGoogle Scholar
  13. 13.
    Sabatini S, Laski M, Kurtzman NA: NEM-sensitive ATPase activity in rat nephron: effect of metabolic acidosis and alkalosis. Am J Physiol 258: F297, 1990.PubMedGoogle Scholar
  14. 14.
    Lonnerholm G, Wistrand PJ: Carbonic anhydrase in human kidney: an histochemical and immunocytochemical study. Kidney Int 25: 886, 1984.PubMedCrossRefGoogle Scholar
  15. 15.
    Malnic G, de Mello-Aires M: Kinetics of bicarbonate reabsorption in proximal tubule of the rat. Am J Physiol 220: 1759, 1971.PubMedGoogle Scholar
  16. 16.
    Costa-Silva VL, Campiglia SS, de Mello-Aires M, Giebisch G: Role of luminal buffers in renal tubular acidification. J Membr Biol 63: 13, 1981.PubMedCrossRefGoogle Scholar
  17. 17.
    Skou JC: Enzymatic basis for active transport of Na+ and K+ across cell membranes (an historial review). Physiol Rev 45: 596, 1965.PubMedGoogle Scholar
  18. 18.
    Glynn IM, Karlish SJD: The sodium pump. Annu Rev Physiol 37: 13, 1975.PubMedCrossRefGoogle Scholar
  19. 19.
    Kinne R, Schmitz JE, Kinne-Saffran E: The localization of the Na+-K+ ATPase in the cells of the rat kidney cortex. Pflugers Arch 329: 191, 1971.PubMedCrossRefGoogle Scholar
  20. 20.
    Eiam-Ong S, Spohn M, Sabatini S, Kurtzman NA: The biochemical mechanism of maleic acid-induced Fanconi syndrome. J Am Soc Nephrol 4: 812A, 1993.Google Scholar
  21. 21.
    Sabatini S, Kurtzman NA: The maintenance of metabolic alkalosis: factors which decrease bicarbonate excretion. Kidney Int 25: 357, 1984.PubMedCrossRefGoogle Scholar
  22. 22.
    Jacobson HR, Seidin DW: On the generation, maintenance and correction of metabolic alkalosis. Am J Physiol 245:F425Google Scholar
  23. 23.
    Kurtzman NA: Regulation of renal bicarbonate reabsorption by extracellular volume. J Clin Invest 49: 586, 1970.PubMedCrossRefGoogle Scholar
  24. 24.
    Pitts RF, Lotspeich WD: Bicarbonate and the renal regulation of acid-base balance. Am J Physiol 147: 138, 1946.PubMedGoogle Scholar
  25. 25.
    Pitts RF, Ayer JLK, Schiess WA: The renal regulation of acid-base balance in man. III. The reabsorption and excretion of bicarbonate. J Clin Invest 28: 35, 1949.CrossRefGoogle Scholar
  26. 26.
    Langberg H, Mathisen O, Holdaas H, Kiil F: Filtered bicarbonate reabsorption. Kidney Int 20: 780, 1981.PubMedCrossRefGoogle Scholar
  27. 27.
    Cogan MG, Maddox DAL, Lucci MS, Rector FC Jr: Control of proximal bicarbonate reabsorption in normal and acidotic rats. J Clin Invest 64: 1168, 1979.PubMedCrossRefGoogle Scholar
  28. 28.
    Berry CA, Cogan MA: Influence of peritubular protein on solute absorption in the rabbit proximal tubule. J Clin Invest 68: 506, 1981.PubMedCrossRefGoogle Scholar
  29. 29.
    Cohen JJ: Selective CI retention in repair of metabolic alkalosis without increasing filtered load. Am J Physiol 218: 165, 1970.PubMedGoogle Scholar
  30. 30.
    Kasirer JP, Schwartz WB: The response of normal man to selective depletion of hydrochloric acid. Factors in the genesis of persistent gastric alkalosis. Am J Med 40: 10, 1966.CrossRefGoogle Scholar
  31. 31.
    Schwartz WB, Van Ypersele de Striou C, Kassiere JP: Role of anions in metabolic alkalosis and potassium deficiency. N Engl J Med 279: 630, 1968.PubMedCrossRefGoogle Scholar
  32. 32.
    Galla JH, Bonduris DN, Luke RG: Effects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. J Clin Invest 80: 41, 1987.PubMedCrossRefGoogle Scholar
  33. 33.
    Galla JH, Bonduris DN, Sandres PW, Luke RG: Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. J Clin Invest 74:2002Google Scholar
  34. 34.
    Gifford JD, Sharkins K, Work J, Luke RG, Galla JH: Total C02 transport in rat cortical collecting dut in chloride-depletion alkalosis. Am J Physiol 258: F848, 1990.PubMedGoogle Scholar
  35. 35.
    Fuller GR, MacLeod MB, Pitts RF: Influence of administration of potassium salts on the renal tubular reabsorption of bicarbonate. Am J Physiol 182: 111, 1955.PubMedGoogle Scholar
  36. 36.
    Kurtzman NA, White MG, Rogers PW: The effect of potassium and extracellular volume on renal bicarbonate reabsorption. Metabolism 22: 481, 1973.PubMedCrossRefGoogle Scholar
  37. 37.
    Kunau RT, Frick A, Rector FC, Seldin DW: Micropuncture study of the proximal tubular factors responsible for the maintenance of metabolic alkalosis during potassium deficiency in the rat. Clin Sei 34: 223, 1968.Google Scholar
  38. 38.
    Chan YL, Biagi B, Giebisch G: Control mechanisms of bicarbonate transport across rat proximal convoluted tubule. Am J Physiol 242: F532, 1982.PubMedGoogle Scholar
  39. 39.
    Adam WR, Koretsky AP, Weiner MW: 31P NMR in vivo measurement of renal intracellular pH: effects of acidosis and K+ depletion in rats. Am J Physiol 251: F904, 1986.PubMedGoogle Scholar
  40. 40.
    Spohn M, Hudson C, Muniyappa R, Sabatini S: Potassium depletion stimulates phospholipid and protein synthesis in rat kidney. J Am Soc Nephrol 4: 896, 1993.Google Scholar
  41. 41.
    Kurtzman N A: Relationship of extracellular volume and C02 tension to renal bicarbonate reabsorption. Am J Physiol 219: 1299, 1970.PubMedGoogle Scholar
  42. 42.
    Yang WC, Arruda JAL, Talor Z: Na+-H+ antiporter in the posthypercapnic state. Am J Physiol 253: F833, 1987.PubMedGoogle Scholar
  43. 43.
    Ruiz OS, Arruda JAL, Talor Z: Na-HCO, cotransport and Na-H antiporter in chronic respiratory acidosis and alkalosis. Am J Physiol 256: F414, 1989.PubMedGoogle Scholar
  44. 44.
    Zeidel ML, Seifter JL: Regulation of Na/H exchange in renal microvillus vesicles in chronic hypercapnia. Kidney Int 34: 60, 1988.PubMedCrossRefGoogle Scholar
  45. 45.
    Northrup TE, Garella S, Pertucucci E, Cohen JJ: Acidemia alone does not stimulate rat renal Na+-H+antiporter activity. Am J Physiol 255: F237, 1988.PubMedGoogle Scholar
  46. 46.
    Maren TH: Current status of membrane bound carbonic an-hydrase. Ann NY Acad Sci 341: 246, 1980.PubMedCrossRefGoogle Scholar
  47. 47.
    Cogan MG, Maddox DA, Warnock DG, Lin ET, Rector FC: Effect of acetazolamide on bicarbonate reabsorption in the proximal tubule of the rat. Am J Physiol 237: F447, 1979.PubMedGoogle Scholar
  48. 48.
    Lucci MS, Warnock DG, Rector FC Jr: Carbonic anhydrase-dependent bicarbonate reabsorption in the rat proximal tubule. Am J Physiol 236: F58, 1979.PubMedGoogle Scholar
  49. 49.
    Frommer JP, Laski ME, Wesson DE, Kurtzman NA: Internephron heterogeneity for carbonic anhydrase-independent bicarbonate reabsorption in the rat. J Clin Invest 73: 1034, 1984.PubMedCrossRefGoogle Scholar
  50. 50.
    Cruz-Soto M, Frommer JP, Itsarayoungyuen K, Batlle DC, Arruda JAL, Kurtzman NA: Carbonic anhydrase-independent bicarbonate reabsorption in rats with chronic papillary necrosis. Miner Electrolyte Metab 10: P319, 1984.CrossRefGoogle Scholar
  51. 51.
    Laski ME, Kurtzman NA: Characterization of acidification in the cortical and medullary collecting tubule of the rabbit. J Clin Invest 72: 2050, 1983.PubMedCrossRefGoogle Scholar
  52. 52.
    Schwartz JH, Rosen S, Steinmetz PR: Carbonic anhydrase function and the epithelial organization of H+ secretion in turtle urinary bladder. J Clin Invest 51: 2653, 1972.PubMedCrossRefGoogle Scholar
  53. 53.
    Sabatini S, Kurtzman NA: Evidence for voltage regulation of carbonic anhydrase independent acidification in the turtle bladder. Miner Electrolyte Metab 11: 277, 1985.PubMedGoogle Scholar
  54. 54.
    Rubinstein H, Batlle DC, Roseman MK, Sehy JT, Arruda JAL, Kurtzman NA: Urinary pœ2 during carbonic anhydrase inhibition. Miner Electrolyte Metab 11: 227, 1985.Google Scholar
  55. 55.
    Arruda JAL, Subbarayudu K, Dytko G, Mola R, Kurtzman NA: Voltage dependent distal acidification defect induced by amiloride. J Lab Clin Med 95: 407, 1980.PubMedGoogle Scholar
  56. 56.
    Crumb CK, Martinez-Maldonado M, Eknoyan G, Suki WN: Effects of volume expansion, purified parathyroid extract and calcium on renal bicarbonate absorption in the dog. J Clin Invest 54: 1287, 1974.PubMedCrossRefGoogle Scholar
  57. 57.
    Karlinsky ML, Sager DS, Kurtzman NA, Pillay VKG: Effect of parathormone and cyclic adenosine monophosphate on renal bicarbonate reabsorption. Am J Physiol 227: 1226, 1974.PubMedGoogle Scholar
  58. 58.
    Bank N, Aynedjian HS: A micropuncture study of the effect of parathyroid hormone on renal bicarbonate reabsorption. J Clin Invest 58: 336, 1976.PubMedCrossRefGoogle Scholar
  59. 59.
    Puschett JB, Zurbach P: Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog. Kidney Int 9: 501, 1976.PubMedCrossRefGoogle Scholar
  60. 60.
    lino Y, Burg MB: Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro. Am J Physiol 236: F387, 1979.Google Scholar
  61. 61.
    McKinney TD, Myers P: Bicarbonate transport by proximal tubules: effect of parathryoid horone and dibutyryl cyclic AMP. Am J Physiol 238: F166, 1980.PubMedGoogle Scholar
  62. 62.
    McKinney TD, Myers P: PTH inhibition of bicarbonate transport by proximal convoluted tubules. Am J Physiol 239: F127, 1980.PubMedGoogle Scholar
  63. 63.
    Kahn AM, Dolson GM, Hise MK, Bennett SC, Weinman EJ: Parathyroid hormone and dibutyryl cAMP inhibit Na+/H+ exchange in renal brush border vesicles. Am J Physiol 248: F212, 1985.PubMedGoogle Scholar
  64. 64.
    Pollack AS, Warnock DG, Strewler GJ: Parathyroid hormone inhibition of Na+-H+ antiporter activity in a cultured renal cell line. Am J Physiol 250: F217, 1986.Google Scholar
  65. 65.
    Miller RT, Pollock AS: Modification of the internal pH sensitivity of the Na+/H+ antiporter by parathyroid hormone in a cultured renal cell line. J Biol Chem 262: 9115, 1987.PubMedGoogle Scholar
  66. 66.
    Cohn DE, Klahr S, Hammerman MR: Metabolic acidosis and parathyroidectomy increase Na+/H+ exchange in brush border vesicles. Am J Physiol 245: F217, 1983.PubMedGoogle Scholar
  67. 67.
    Weinman EJ, Dubinsky WP, Shenolikar S: Reconstitution of cAMP-dependnet protein kinase regulated renal Na+-H+ exchanger. J Membr Biol 101: 11, 1988.PubMedCrossRefGoogle Scholar
  68. 68.
    Weinman EJ, Shenolikar S, Khan AM: cAMP-associated inhibition of Na+-H+exchanger in rabbit kidney brush-border membranes. Am J Physiol 252: F19, 1987.PubMedGoogle Scholar
  69. 69.
    Hruska KA, Moskowitz D, Esbrit P, Civitelli R, Westbrook S, Huskey M: Stimulation of inositol triphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone. J Clin Invest 79: 230, 1987.PubMedCrossRefGoogle Scholar
  70. 70.
    Weinman EJ, Shenolikar S: Protein kinase C activates the renal apical membrane Na+/H+exchanger. J Membr Biol 93: 133, 1986.PubMedCrossRefGoogle Scholar
  71. 71.
    Mellas J, Hammerman MR: Phorbol ester-induced alkalin-ization of canine renal proximal tubular cells. Am J Physiol 250: F451, 1986.PubMedGoogle Scholar
  72. 72.
    Hulter HN, Peterson JC: Acid-base homeostasis during chronic PTH excess in humans. Kidney Int 28: 187, 1985.PubMedCrossRefGoogle Scholar
  73. 73.
    Hulter HN: Effects and interrelationships of PTH, Ca, vitamin D, and Pi in acid-base homeostasis. Am J Physiol 248: F739, 1985.PubMedGoogle Scholar
  74. 74.
    Adelsberg V, Al-Awqati Q: Regulation of cell pH by Ca-mediated insertion of H+-ATPase. J Cell Biol 102: 1638, 1986.PubMedCrossRefGoogle Scholar
  75. 75.
    Siegfried D, Kumar R, Arruda JAL, Kurtzman NA: Influence of vitamin D on bicarbonate reabsorption. In: SG Massry, E Ritz, eds, Phosphate Metabolism. Plenum Press, New York, p 395, 1978.Google Scholar
  76. 76.
    Gold LS, Massry SG, Arieff AI, Coburn JW: Renal bicarbonate wasting during phosphate depletion. J Clin Invest 52: 2556, 1973.PubMedCrossRefGoogle Scholar
  77. 77.
    Sabatini S: Pathophysiology of phosphate depletion: new insights into mechanism. In: F Consolo, G Gellinghieri, V Savica, eds, 2nd Taormina Course of Nephrology, Editoriale Bios, Consenza, Italy, p 183, 1992.Google Scholar
  78. 78.
    Knochel JP: The clinical and physiological implications of phosphorus deficiency. In: DW Seldin, G Giebisch, eds, The Kidney: Physiology and Pathophysiology, 2nd ed. Raven Press, New York, p 2533, 1992.Google Scholar
  79. 79.
    Spohn M, Sabatini S: Phosphate depletion markedly enhances lipid and protein metabolism in rat renal cortex. Clin Res 41: 254A, 1993.Google Scholar
  80. 80.
    Steinbaugh B, Schloeder FX: Glucose-induced alkalosis in fasting subjects. I Clin Invest 51: 1326, 1972.CrossRefGoogle Scholar
  81. Suki WN, Herbert CS, Steinbaugh B, Martinez-Maldonado M, Eknoyan G: Effects of glucose on bicarbonate reabsorption in the dog kidney. J Clin Invest 54: 1, 1974.PubMedCrossRefGoogle Scholar
  82. 82.
    Garrett ES, Nahmias C: The effect of glucose on the urinary excretion of sodium and hydrogen ion in man. Clin Sei Mol Biol 47: 589, 1974.Google Scholar
  83. 83.
    Lentner C, ed, Geigy Scientific Tables, 8th ed, vol. 1. Ciba- Geigy, Switzerland, 1981.Google Scholar
  84. 84.
    Knepper MA, Packer R, Good DW: Ammonium transport in teh kidney. Am Physiol Soc 69: 179, 1989.Google Scholar
  85. 85.
    Halperin ML, Kamel KS, Ethier JH, Stinebaugh BJ, Jungas RL. Biochemistry and physiology of ammonium excretion. In: DW Seldin, G Giebisch, eds, The Kidney: Physiology and Pathophysiology, 2nd ed. Raven Press, New York, p 2645, 1992.Google Scholar
  86. 86.
    Good DW, Knepper MA, Burg MB: Ammonia absorption by the thick ascending limb off Henle’s loop. Contrib Nephrol 47: 110, 1985.PubMedGoogle Scholar
  87. 87.
    Good DW, DuBose TD Jr: Ammonia transport by early and late proximal convoluted tubule of the rat. J Clin Invest 79: 684, 1987.PubMedCrossRefGoogle Scholar
  88. 88.
    Schoolwerth A, Gesek F, Culpepper R: Proton compart-mentation in rat renal cortex tubules. Am J Physiol 256: F986, 1989.PubMedGoogle Scholar
  89. 89.
    Kurtzman NA: Ammonia secretion and urinary acidification. Semin Nephrol 2: 1, 1982.Google Scholar
  90. 90.
    Arruda JAL, Dytko G, Withers L: Ammonia transport by the turtle urinary bladder. Am J Physiol 246: F569, 1984.Google Scholar
  91. 91.
    Tannen RL: The effect of uncomplicated potassium depletion on urine acidification./Clin Invest 49: 813, 1970.Google Scholar
  92. 92.
    Sastrasinh S, Tannen RL: Effect of potassium on renal NH3 production. Am J Physiol 244: F383, 1983.PubMedGoogle Scholar
  93. 93.
    Kornandakieti C, Tannen RL: Hydrogen ion secretion by the distal nephron in the rat: effect of potassium. J Lab Clin Med 104: 293, 1984.PubMedGoogle Scholar
  94. 94.
    Batlle DC, Sehy JT, Roseman MK, Arruda JAL, Kurtzman NA: Clinical and pathophysiological spectrum of acquired distal renal tubular acidosis. Kidney Int 20: 389, 1981.PubMedCrossRefGoogle Scholar
  95. 95.
    Kurtzman NA: Disorders of distal acidification. Kidney Int 38: 720, 1990.PubMedCrossRefGoogle Scholar
  96. 96.
    Batlle DC, Kurtzman NA: Acid-base physiology and pathophysiology. Contemp Nephrol 3: 191, 1985.Google Scholar
  97. 97.
    Batlle DC, Arruda JAL, Kurtzman NA: Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy. N Engl J Med 304: 373, 1981.PubMedCrossRefGoogle Scholar
  98. 98.
    Batlle DC, Itsarayoungyuen K, Arruda JAL, Kurtzman NA: Hyperkalemic hyperchloremic metabolic acidosis in sickle cell hemoglobinopathies. Am J Med 72: 188, 1982.PubMedCrossRefGoogle Scholar
  99. 99.
    Batlle DC, Kurtzman NA: Distal renal tubular acidosis: pathogenesis and classification. Am J Kidney Dis 1: 328, 1982.PubMedGoogle Scholar
  100. 100.
    Schambelan M, Sebastian A, Rector FC Jr: Mineralocorti-coid-resistance renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): role of increased renal chloride reabsorption. Kidney Int 19: 716, 1981.PubMedCrossRefGoogle Scholar
  101. 101.
    Giammarco RA, Goldstein MB, Halperin ML, Stinebaugh BJ: The effect of hyperventilation of distal nephron hydrogen ion secretion. J Clin Invest 58: 77, 1976.PubMedCrossRefGoogle Scholar
  102. 102.
    Batlle DC, Schlueter W, Gutterman C, Kurtzman NA: Assessment of collecting tubule hydrogen ion secretion in acute respiratory alkalosis using the urinary pœ2. Pflugers Arch 411: 692, 1988.PubMedCrossRefGoogle Scholar
  103. 103.
    Eiam-Ong S, Laski ME, Kurtzman NA, Sabatini S: The effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes. Am J Physiol 267: F390, 1994.PubMedGoogle Scholar
  104. 104.
    Marver: Corticosteroids and the kidney. Semin Nephrol 10: 310, 1990.Google Scholar
  105. 105.
    Stone DK, Crider BP, Xie X-S: Aldosterone and urinary acidification. Semin Nephrol 10: 375, 1990.PubMedGoogle Scholar
  106. 106.
    Eiam-Ong S, Kurtzman NA, Sabatini S: Regulation of collecting tubule ATPases by aldosterone and potassium. J Clin Invest 91: 2385, 1993.PubMedCrossRefGoogle Scholar
  107. 107.
    Mujais SK: Effects of aldosterone on rat collecting tubule N- ethylmaleimide-sensitive adenosine triphosphatase. J Lab Clin Med 109: 34, 1987.PubMedGoogle Scholar
  108. 108.
    Al-Awqati Q, Norby LH, Mueller A, Steinmetz PR: Characteristics of stimulation of H transport by aldosterone in turtle urinary bladder. J Clin Invest 58: 351, 1976.PubMedCrossRefGoogle Scholar
  109. 109.
    Stone DK, Seldin DW, Kokko JP, Jacobson HR: Mineralo-corticoid modulation of rabbit medullary collecting duct acidification. J Clin Invest 72: 77, 1983.PubMedCrossRefGoogle Scholar
  110. 110.
    Seldin DW, Welt LG, Cort JH: The role of sodium salts and adrenal steroids in the production of hypokalemic alkalosis. Yale J Biol Med 29:229, 1956.Google Scholar
  111. 111.
    DiTella PJ, Sodhi B, McCreary J, Arruda JAL, Kurtzman NA: Mechanism of the metabolic acidosis of selective miner-alocorticoid deficiency. Kidney Int 14: 466, 1978.PubMedCrossRefGoogle Scholar
  112. 112.
    Sebastian A, Sutton JM, Hulter HN: Effect of mineralocorti-coid replacement therapy on renal acid-base homeostasis in adrenalectomized patients. Kidney Int 18: 762, 1981.CrossRefGoogle Scholar
  113. 113.
    Vinay P, Allignet E, Pichette C, Watford M, Lemieux G, Gougoux A: Changes in renal metabolite profile and ammoniagenesis during acute and chronic metabolic acidosis in dog and rat. Kidney Int 17: 312, 1980.PubMedCrossRefGoogle Scholar
  114. 114.
    Wingo CS, Cain BD: The renal H-K-ATPase: physiological significance and role in potassium homeostasis. Annu Rev Physiol 55: 323, 1993.PubMedCrossRefGoogle Scholar
  115. 115.
    Arruda JAL, Julka NK, Rubenstein H, Sabatini S, Kurtzman NA: Distal acidification defect induced by phosphate deprivation. Metabolism 29: 826, 1980.PubMedCrossRefGoogle Scholar
  116. 116.
    Arruda JAL, Alia V, Rubinstein H, Cruz-Soto M, Sabatini S, Batlle D, Kurtzman NA: Metabolic and hormonal factors influencing extrarenal buffering of an acute acid load. Miner Electrolyte Metab 8: 36, 1982.PubMedGoogle Scholar
  117. 117.
    Arruda JAL, Julka NK, Rubinstein H, Cruz-Soto M, Sabatini S, Batlle DC, Kurtzman NA: Parathyroid hormone and extrarenal acid-base buffering. Am J Physiol 239: 533, 1980.Google Scholar
  118. 118.
    Sabatini S: The effect of parathyroid hormone and other metabolic factors on extrarenal acid buffering. Miner Electrolyte Metab 20: 53, 1994.PubMedGoogle Scholar
  119. 119.
    Hulter HN, Ilnicki L, Harbottle J, Sebastian A: Impaired renal H secretion and ammonia production in mineralocorti-coid-deficient glucocorticoid-replete dogs. Am J Physiol 232: F136, 1977.PubMedGoogle Scholar
  120. 120.
    Batlle DC: Hyperkalemic hyperchloremic metabolic acidosis associated with selective aldosterone deficiency and distal renal tubular acidosis. Semin Nephrol 1: 260, 1981.Google Scholar
  121. 121.
    Good DW: Ammonium transport by the thick ascending limb of Henle’s loop. Annu Rev Physiol 56: 623, 1994.PubMedCrossRefGoogle Scholar
  122. 122.
    Knepper MA, Packer R, Good DW: Ammonium transport in the kidney. Physiol Rev 69: 179, 1989.PubMedGoogle Scholar
  123. 123.
    Breyer MD, Ando Y: Hormonal signaling and regulation of salt and water transport in the collecting duct. Annu Rev Physiol 56: 711, 1994.PubMedCrossRefGoogle Scholar
  124. 124.
    Fraley DS, Adler S: An extrarenal role for parathyroid hormone in the disposal of acute acid loads in rats and dogs. J Clin Invest 63: 985, 1979.PubMedCrossRefGoogle Scholar
  125. 125.
    Seldin DW, Rector FC: The generation and maintenance of metabolic alkalosis. Kidney Int 1: 306, 1972.PubMedCrossRefGoogle Scholar
  126. 126.
    Kurtzman NA, White MG, Rogers PW: Aldosterone deficiency and renal bicarbonate reabsorption. J Lab Clin Med 77: 931, 1971.PubMedGoogle Scholar
  127. 127.
    Cogan MG: Atrial natriuretic factor ameliorates chronic metabolic alkalosis by increasing glomerular filtration. Science 229: 1405, 1985.PubMedCrossRefGoogle Scholar
  128. 128.
    Maack T: Receptors of atrial natriuretic factor. Annu Rev Physiol 54: 11, 1992.PubMedCrossRefGoogle Scholar
  129. 129.
    Linas SL, Dickman D: Mechanism of the decreased renal blood flow in the potassium-depleted conscious rat. Kidney Int 21: 757, 1982.PubMedCrossRefGoogle Scholar
  130. 130.
    Cogan MG, Liu FY: Metabolic alkalosis in the rat: Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state. J Clin Invest 7: 1141, 1983.CrossRefGoogle Scholar
  131. 131.
    Abboud HE, Luke RG, Galla JH, Kotchen TA: Stimulation of renin by acute selective chloride depletion. Circ Res 44: 815, 1979.PubMedCrossRefGoogle Scholar
  132. 132.
    Kotchen TC, Guthrie GP, Boucher LD, Lorenz JN, Oh CE: Disassociation between plasma renin and plasma aldosterone induced by dietary glycine hydrochloride. Am J Physiol 254: E187, 1988.PubMedGoogle Scholar
  133. 133.
    Galla JL, Bonduris DN, Dumbald SL, Luke RG: Segmental chloride and fluid handling during corrections of chloride-depletion alkalosis in the rat. J Clin Invest 73: 96, 1984.PubMedCrossRefGoogle Scholar
  134. 134.
    Galla JH, Luke RG: Effect of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat: A reassessment of the classical hypothesis of the maintenance of metabolic alkalosis. J Clin Invest 80: 41, 1987.PubMedCrossRefGoogle Scholar
  135. 135.
    Craig DM, Galla JH, Bonduris DN, Luke RG: Importance of the kidney in the correction of chloride-depletion alkalosis in the rat. Am J Physiol 250: F54, 1986.PubMedGoogle Scholar
  136. 136.
    Alpern R, Cogan M, Rector FC: Effect of luminal bicarbonate concentration on proximal acidification in the rat. Am J Physiol 243: F53, 1982.PubMedGoogle Scholar
  137. 137.
    Cogan MG, Liu FY: Metabolic alkalosis in the rat. J Clin Invest 71: 1124, 1983.CrossRefGoogle Scholar
  138. 138.
    Stokes JB, Ingram MJ, Williams AD, Ingram D: Heterogeneity of the rabbit collecting tubule: localization of mineralo-corticoid hormone action to the cortical portion. Kidney Int 20: 340, 1981.PubMedCrossRefGoogle Scholar
  139. 139.
    Liddle GW: The adrenals. In: JD Wilson, DW Foster, eds, Textbook of Endocrinology, 8th ed. WB Saunders, Philadelphia, p 249, 1992.Google Scholar
  140. 140.
    Liddle GW, Bledsoe T, Coppage WS: A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Phys 76: 188, 1963.Google Scholar
  141. 141.
    Eiam-Ong S, Kurtzman NA, Sabatini S: Effect of furosemide-induced hypokalemic metabolic alkalosis on renal transport enzymes. Kidney Int 43: 1015, 1993.PubMedCrossRefGoogle Scholar
  142. 142.
    Kurtzman NA, Gutierrez LF: The pathophysiology of Bartter’s syndrome. JAMA 234: 758, 1975.PubMedCrossRefGoogle Scholar
  143. 143.
    Gill JR, Bartter FC: Evidence for a prostaglandin independent defect in chloride reabsorption in the loop of Henle as a proximal cause of Bartter’s syndrome. Am J Med 65: 766, 1978.PubMedCrossRefGoogle Scholar
  144. 144.
    Westenfelder C, Kurtzman NA: Bartter’s syndrome: a disorder of active sodium and/or passive chloride transport in the thick ascending limb of Henle’s loop. Miner Electrolyte Metab 5: 135, 1981.Google Scholar
  145. 145.
    Carrow DC: Congenital alkalosis with diarrhea. J Pediatr 26: 519, 1945.CrossRefGoogle Scholar
  146. 146.
    Evansen TM, Stanbury SW: Congenital chloridorrhea or so-called congenital alkalosis with diarrhea. Gut 6: 29, 1965.CrossRefGoogle Scholar
  147. 147.
    Homberg C, Perheentupa J, Lauiala K, et al.: Congenital chloride diarrhea: clinical analysis of 21 Finnish patients. Arch Dis Child 52: 255, 1977.CrossRefGoogle Scholar
  148. 148.
    Hulter H, Sebastian A, Toto RD, Bonner EL, Ilnicki LP: Renal and systmeic acid-base effects on chronic hypercalcemia-producing agents: calcitriol, PTH and intravenous calcium. Kidney Int 21: 445, 1982.PubMedCrossRefGoogle Scholar
  149. 149.
    Carrel JE, Landry AS, Elliot ME, Goodfriend D: Effect of pH on adrenal angiotensin receptors and responses. J Lab Clin Med 108: 23, 1986.Google Scholar
  150. 150.
    Sabatini S, Barboriak JJ, Hardman HF: Utilization of glucose in the anaerobically perfused turtle heart. J Pharmacol Exp Therap 155: 395, 1967.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Sandra Sabatini
    • 1
  • Neil A. Kurtzman
    • 2
  1. 1.Department of PhysiologyTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of MedicineTexas Tech University Health Sciences CenterLubbockUSA

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