Mechanism of Concentration and Dilution of Urine

  • Esmail Koushanpour
  • Wilhelm Kriz


In Chapter 9, while discussing the sequential processing of the filtrate along Henle’s loop, we alluded to the role of this nephron segment in concentrating and diluting the urine. In this chapter we consider the principle of countercurrent multiplication and the evidence for its application to the kidney. We then examine the mechanism of concentration and dilution of urine, the measurement of the ability of the kidney to concentrate urine, and finally the action of some selective diuretics and their potential therapeutic effects. We begin with a comprehensive presentation of the structural organization of the renal medulla.


Renal Medulla Outer Medulla Collect Duct Tubular Fluid Outer Stripe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Agus ZS, Puschett JB, Senesky D, Goldberg M: Mode of action of parathyroid hormone nd cylcic adenosine 3’,5’monophosphate on renal tubular phosphate reab- 20. sorption in the dog. J Clin Invest 1971; 50: 617–626.PubMedCrossRefGoogle Scholar
  2. 2.
    Atherton JC, Hai MA, Thomas S: Effects of water diuresis and osmotic (mannitol) diuresis on urinary solute excretion by the conscious rat. J Physiol 1968; 21 197: 395–410.Google Scholar
  3. 3.
    Au WYW, Raisz LG: Studies on the renal concen¬trating mechanism. V. Effect of diuretic agents. J Clin 22. Invest 1960; 39: 1302–1311.CrossRefGoogle Scholar
  4. 4.
    Aukland K: Renal blood flow, in Thurau K (ed): Kid¬ney and Urinary Tract Physiology (International Re- 23. view of Physiology). Baltimore, University Park Press, 1976, vol 11, pp 23–79.Google Scholar
  5. 5.
    Baumgartl H, Leichtweiss HP, Lubbers DW, et al: 24. The oxygen supply of the dog kidney: Measurements of intrarenal PO2. Microvasc Res 1972; 4: 247–257.PubMedCrossRefGoogle Scholar
  6. 6.
    Bennett CM, Clapp JR, Berliner RW: Micropuncture 25. study of the proximal and distal tubule of the dog. Am J Physiol 1967; 213: 1254–1262.PubMedGoogle Scholar
  7. 7.
    Bennett CM, Brenner BM, Berliner RW: Micropunc¬ture study of nephron function in the Rhesus monkey. 26. J Clin Invest 1968; 47: 203–216.PubMedCrossRefGoogle Scholar
  8. 8.
    Berliner RW, Levinsky NG, Davidson DG, Eden M: Dilution and concentration of the urine and the action 27. of antidiuretic hormone. Am J Med 1958; 24: 730–743.PubMedCrossRefGoogle Scholar
  9. 9.
    Beyer KH: The mechanism of action of chlorothiazide. Ann NY Acad Sci 1958; 71: 363–379.PubMedCrossRefGoogle Scholar
  10. 10.
    Bohmann SO: The ultrastructure of the renal medulla 28. and the interstitial cells, in Mandal AK, Bohmann SO (eds): The Renal Papilla and Hypertension. New York, Plenum Medical Book Company, 1980, pp 7–33.CrossRefGoogle Scholar
  11. 11.
    Bonventre JV, Lechene C: Renal medullary concentrating process: an integrative hypothesis. Am JPhysiol 1980; 239: F578–588.Google Scholar
  12. 12.
    Bray GA, Preston AS: Effect of urea on urine concentration in the rat. J Clin Invest 1961; 40: 1952–1960.PubMedCrossRefGoogle Scholar
  13. 13.
    Brezis M, Rosen S, Silva P, Epstein FH: Renal ischemia: A new perspective. Kidney Int 1984; 26: 375–383.PubMedCrossRefGoogle Scholar
  14. 14.
    Clapp JR: Urea reabsorption by the proximal tubule of the dog. Proc Soc Exp Biol Med 1965; 120: 521–523.PubMedGoogle Scholar
  15. 15.
    Clapp JR, Robinson RR: Distal sites of action of diuretic drugs in the nephron. Am J Physiol 1968; 215: 225–235.Google Scholar
  16. 16.
    Cohen JJ, Kamm DE: Renal metabolism: Relation to renal function, in Brenner BM, Rector FC Jr (eds): The Kidney. Philadelphia, WB Saunders Co, 1981, pp 126–214.Google Scholar
  17. 17.
    Cohen HJ, Marsh DJ, Kyser B: Autoregulation in vasa recta of rat kidney. Am J Physiol 1983; 245: F32 - F40.PubMedGoogle Scholar
  18. 18.
    De Rouffignac C: Physiological role of the loop of Henle in urinary concentration. Kidney Int 1972; 2: 297–303.PubMedCrossRefGoogle Scholar
  19. 19.
    De Rouffignac C, Morel F: Micropuncture study of water, electrolyte and urea movements along the loops of Henle in Psammomys. J Clin Invest 1969; 48: 474–486.PubMedCrossRefGoogle Scholar
  20. 20.
    De Wardener HE, Mills IH, Clapham WF, Hayter CJ: Studies on the efferent mechanism of the sodium diuresis which follows the administration of intravenous saline in the dog. Clin Sci 1961; 21: 249–258.Google Scholar
  21. 21.
    Dirks JH, Cirksena WJ, Berliner RW: The effect of saline infusion on sodium reabsorption by the proximal tubule of the dog. J Clin Invest 1965; 44: 1160–1170.PubMedCrossRefGoogle Scholar
  22. 22.
    Dirks JH, Seely JF: Effect of saline infusion and furosemide on the dog distal nephron. Am J Physiol 1970; 219: 114–121.PubMedGoogle Scholar
  23. 23.
    Duarte CG, Chomety F, Giebisch G: Effect of amiloride, ouabain, and furosemide on distal tubular function in the rat. Am J Physiol 1971; 221: 632–639.PubMedGoogle Scholar
  24. 24.
    Earley LE, Kahn M, Orloff J: The effects of infusions of chlorothiazide on urinary dilution and concentration in the dog. J Clin Invest 1961; 40: 857–866.PubMedCrossRefGoogle Scholar
  25. 25.
    Ernst SA, Mills JE: Basolateral plasma membrane localization of oubain-sensitive sodium transport sites in the secretory epithelium of the avian salt gland. J Cell Biol 1977; 75: 74–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Ernst SA, Schreiber JH: Ultrastructural localization of Na’-K+-ATPase in rat and rabbit kidney medulla. J Cell Biol 1981; 91: 803–813.PubMedCrossRefGoogle Scholar
  27. 27.
    Forte LR: Effect of mineralocorticoid agonists and antagonists on binding of 3H-aldosterone to adernalectomized rat kidney plasma membrane. Life Sci 1972; 11: 461–473.CrossRefGoogle Scholar
  28. 28.
    Gamble JL, McKhann CF, Butler AM, Tuthill E: An economy of water in renal function referal to urea. Am J Physiol 1934; 109: 139–154.Google Scholar
  29. 29.
    Gatzy J: The effect of K sparing diuretics on ion transport across the excised toad bladder. J Pharmacol Exp Ther 1971; 176: 586–594.Google Scholar
  30. 30.
    Goldberg M: Real tubular sites of action of diuretics, in Fisher JW, Cafruny EJ (eds): Renal Pharmacology. New York, Appleton-Century-Crofts, 1971, pp 99–119.Google Scholar
  31. 31.
    Gottschalk CW: Micropuncture studies of tubular function in the mammalian kidney. Physiologist 1961; 4: 33–55.Google Scholar
  32. 32.
    Gottschalk CW, Mylle M: Micropuncture study of the mammalian urinary concentrating mechanism: Evidence for the countercurrent hypothesis. Am J Physiol 1959; 196: 927–936.PubMedGoogle Scholar
  33. 33.
    Hargitay B, Kuhn W: Das Multiplikations-prinzipals Grundlage der Harnkonzentrierung in der Niere. Z Elektrochem 1951; 55: 539–558.Google Scholar
  34. 34.
    Holliger CH, Lemley KV, Schmitt SL, et al: Direct determination of vasa recta blood flow in the rat renal papilla. Circ Res 1983; 53: 401–413.PubMedCrossRefGoogle Scholar
  35. 35.
    Imai K, Araki M: Internephron heterogeneity and interspecies differences in the function of the descending limbs of Henle’s loop (DLH). Abstract. Proc Int Union Physiol Sci. vol 15, Sydney, Australia, 1983.Google Scholar
  36. 36.
    Jamison RL: Urinary concentration and dilution, in Brenner BM, Rector FC Jr (eds): The Kidney. Philadelphia, WB Saunders Co, 1976.Google Scholar
  37. 37.
    Jamison RL, Bennett CM, Berliner RW: Countercurrent multiplication by the thin loops of Henle. Am J Physiol 1967; 212: 357–366.PubMedGoogle Scholar
  38. 38.
    Jamison RL, Kriz W: Urinary Concentrating Mechanism. Structure and Function. New York, Oxford University Press, 1982.Google Scholar
  39. 39.
    Jamison RL, Lacy FB: Evidence for urinary dilution by the collecting tubule. Am J Physiol 1972; 223: 898–902.PubMedGoogle Scholar
  40. 40.
    Johnston CI, Davis JO, Howards SS, Wright FS: Cross-circulation experiments on the mechanism of the natriuresis during saline loading in the dog. Circ Res 1967; 20: 1–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Kawamura S, Kokko JP: Urea secretion by the straight segment of the proximal tubule. J Clin Invest 1976; 58: 604–612.PubMedCrossRefGoogle Scholar
  42. 42.
    Knepper MA: Urea transport in nephron segments from medullary ray of rabbits. Am J Physiol 1983; 244: F502 - F508.Google Scholar
  43. 43.
    Knepper MA, Burg M: Organization of nephron function. Am J Physiol 1983; 244: F579 - F589.PubMedGoogle Scholar
  44. 44.
    Kokko JP: Sodium chloride and water transport in the descending limb of Henle. J Clin Invest 1970; 49: 1838–1846.PubMedCrossRefGoogle Scholar
  45. 45.
    Kokko JP, Rector FC Jr: Countercurrent multiplication system without active transport in inner medulla. Kidney Int 1972; 2: 214–223.PubMedCrossRefGoogle Scholar
  46. 46.
    Koushanpour E, Tarica RR, Stevens WF: Mathematical simulation of normal nephron function in rat and man. J Theor Biol 1971; 31: 177–214.PubMedCrossRefGoogle Scholar
  47. 47.
    Kriz W: Structural organization of the renal medullary counterflow system. Fed Proc 1983; 42: 2379–2385.PubMedGoogle Scholar
  48. 48.
    Kriz W: Structural organization of the renal medulla: Comparative and functional aspects. Am J Physiol 1981; 241: R3 - R16.PubMedGoogle Scholar
  49. 49.
    Kriz W, Lever AF: Renal countercurrent mechanisms: Structure and function. Am HeartJ 1969; 78: 101–118.CrossRefGoogle Scholar
  50. 50.
    Kriz W, Schnermann J, Koepsell H: The position of short and long loops of Henle in the rat kidney. Z Anat Entwickl.-Gesch 1972; 138: 301–319.CrossRefGoogle Scholar
  51. 51.
    Kuhn W, Ramel A: Aktiver Salz-transport als moglicher (und wahr-scheinlicher) Einzeleffekt bei der Harn-konzentrierung in der Niere. Helv Chim Acta 1959; 42: 628–660.CrossRefGoogle Scholar
  52. 52.
    Kuhn W, Ryffel K: Herstellung konzentrierter Losunger aus verdunnten durch blosse Membranwirkung. (Ein Modellversuch zur Funktion der Niere) HoppeSeylers. Z Physiol Chem 1942; 276: 145–178.CrossRefGoogle Scholar
  53. 53.
    Kunau RT Jr, Weller DR, Webb HL: Clarification of the site of action of chlorothiazide in the rat nephron. J Clin Invest 1975; 56: 401–407.PubMedCrossRefGoogle Scholar
  54. 54.
    Landwehr DM, Klose RM, Giebisch G: Renal tubular sodium and water in the isotonic sodium chloride loaded rat. Am J Physiol 1967; 212: 1327–1333.PubMedGoogle Scholar
  55. 55.
    Lassiter WE, Gottschalk CW, Mylle M: Micropuncture study ofnet transtubular movement of water and urea in nondiuretic mammalian kidney. Am J Physiol 1961; 200: 1139–1147.PubMedGoogle Scholar
  56. 56.
    Lassiter WE, Mylle M, Gottschalk CW: Micropuncture study of urea transport in rat renal medulla. Am J Physiol 1966; 210: 965–970.PubMedGoogle Scholar
  57. 57.
    Lemley KV, Schmitt SL, Holliger CH, et al: Prostaglandin synthesis inhibitors and vasa recta erythrocyte velocities inthe rat. Am J Physiol 1984; 247: F562 - F567.PubMedGoogle Scholar
  58. 58.
    Liddle GW: Specific and non-specific inhibition of mineralocorticoid activity. Metabolism 1961; 10: 1021–1030.Google Scholar
  59. 59.
    Macey RI: Transport of water and urea in red blood cells. Am J Physiol 1984; 246: C195 - C203.PubMedGoogle Scholar
  60. 60.
    Maren TH: Carbonic anhydrase: chemistry, physiology and inhibition. Physiol Rev 1967; 47: 597–781.Google Scholar
  61. 61.
    Miwa T, Imai M: Flow-dependent water permeability of the rabbit descending limb of Henle’s loop. Am J Physiol 1983; 245: F743 - F754.PubMedGoogle Scholar
  62. 62.
    Mollendorff Wv: Der Exkretionsapparat, in: Handbuch der mikroskopischen Anatomie des Menschen, vol 7. Berlin, Springer-Verlag, 1930, pp 1–327.Google Scholar
  63. 63.
    Moore LC, Marsh DJ: How descending limb of Henle’s loop permeability affects hypertonic urine formation. Am J Physiol 1980; 239: F57 - F71.PubMedGoogle Scholar
  64. 64.
    Morgan T, Berliner RW: Permeability of loop of Henle, vasa recta and collecting duct to water, urea and sodium. Am J Physiol 1968; 215: 108–115.PubMedGoogle Scholar
  65. 65.
    Morgan T, Tadokoro M, Martin D, Berliner RW: Effect of furosemide on Na’ and K transport studied by microperfusion of the rat nephron. Am J Physiol 1970; 218: 292–297.PubMedGoogle Scholar
  66. 66.
    Muller-Suur R, Ulfendahl HR, Persson AEG: Evidence for tubuloglomerular feedback in juxtamedul. Ann Rev Biophys Bioeng 1978; 7: 315–339.CrossRefGoogle Scholar
  67. 67.
    Pennell JP, Lacy FB, Jamison RL: An in vivo study Henle’s loop. Kidney Int 1974; 5: 337–347.PubMedCrossRefGoogle Scholar
  68. 68.
    Rocha AS, Kokko JP. Permeability of medullary ne phron segments to urea and water: Effect of vaso pressin. Kidney Int 1974; 6: 379–387.PubMedCrossRefGoogle Scholar
  69. 69.
    Roch-Ramel F, Peters G: Renal transport of urea, in Gregor R, Lang F, Silbernagl S (eds): Renal transport of organic substances. Berlin, Springer Verlag, 1981, pp 134–153.CrossRefGoogle Scholar
  70. 70.
    Sanjana V, Johnston PA, Troy JL, et al: Hydraulic and oncotic pressure measurements in the inner medul la of the mammalian kidney. Am J Physiol 1975; 228: 1921–1926.PubMedGoogle Scholar
  71. 71.
    Sanjana VM, Johnston PA, Robertson CR, Jamison in the renal inner medulla. Am J Physiol 1976; 231: 313–318.PubMedGoogle Scholar
  72. 72.
    Sardet C, Pisam M, Maetz J: The surface epithelium of teleostean fish gills. Cellular and junctional adap tations of the chloride cell in relation to salt adaptation. J Cell Biol 1979; 80: 96–117.PubMedCrossRefGoogle Scholar
  73. 73.
    Scholander PF: The wonderful net. Sci Am 1957; 196: 96–108.CrossRefGoogle Scholar
  74. 74.
    Schmidt-Nielsen B: Urea excretion in mammals. Phys iol Rev 1958; 38: 139–168.Google Scholar
  75. 75.
    Schmidt-Nielsen B, O’Dell R: Structure and concen trating mechanism in the mammalian kidney. Am J Physiol 1961; 200: 1119–1124.Google Scholar
  76. 76.
    Seely JF, Dirks JH: Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney. J Clin Invest 1969; 48: 2330–2339.PubMedCrossRefGoogle Scholar
  77. 77.
    Seldin DW, Eknoyan G, Suki WW, Rector FC Jr: Localization of diuretic action from the pattern of water and electrolyte excretion. Ann NY Acad Sci 1966; 139: 328–343.PubMedCrossRefGoogle Scholar
  78. 78.
    Sonnenberg H: Medullary collecting duct function in antidiuretic and in salt-or water-diuretic rats. Am J Physiol 1974; 226: 501–506.Google Scholar
  79. 79.
    Stein JH, Mauk RC, Boonjaren S, Ferris TF: Differences in the effect of furosemide and chlorothiazide on the distribution of renal cortical blood flow in the dog. J Lab Clin Med 1972; 79: 995–1003.PubMedGoogle Scholar
  80. 80.
    Stephenson JL: The renal concentrating mechanism: Fundamental theoretical concepts. Fed Proc 1983; 42: 2386–2391.PubMedGoogle Scholar
  81. 81.
    Stephenson JL: Countercurrent transport in the kidney. lary nephrons. Am J Physiol 1983; 244: F425 - F431.Google Scholar
  82. 82.
    Stephenson JL: Central core model of the renal counterflow system. Kidney Int 1972; 2: 85–94.PubMedCrossRefGoogle Scholar
  83. 83.
    Stephenson JL, Tewarson RP, Mejia R: Quantitative analysis of mass and energy balance in non-ideal models of the renal counterflow system. Proc Nall Acad Sci USA 1974; 71: 1618–1622.CrossRefGoogle Scholar
  84. 84.
    Stokes JB: Integrated actions of renal medullary Prostaglandins in the control of water excretion. Am J Physiol 1981; 240: F471 - F480.PubMedGoogle Scholar
  85. 85.
    Tabei K, Imai M: Ion selectivity in the upper portion of descending limb of long-loop nephron (LDLu) of the hamster Abstract. Proc Int Union Physiol Sci. Los Angeles, 1984.Google Scholar
  86. 86.
    Thurau K: Renal hemodynamics. Am J Med 1964; 36: 698–719.PubMedCrossRefGoogle Scholar
  87. 87.
    Ullrich KJ, Jarausch KH: Untersuchungen zum Prob- RL: An examination of the transcapillary water flux lem der Harnkonzentrierung und Harnverdunnung: uber die Verteilung der Elektrolyte. Harnstoff, Aminosauren und exogenem Kreatinin in Rinde und Mark der Hundeniere bei verschiedenen Diuresezustanden. Arch Ges Physiol 1956; 262: 537–550.CrossRefGoogle Scholar
  88. 88.
    Ullrich KJ, Schmidt-Nielsen B, O’Dell R, et al: Micropuncture study of composition of the proximal and distal tubular fluid in rat kidney. Am J Physiol 1963; 204: 527–531.PubMedGoogle Scholar
  89. 89.
    Wesson LG Jr: Physiology of the Human Kidney. New York, Grune and Stratton, 1969.Google Scholar
  90. 90.
    Wirz H, Hargitay B, Kuhn W: Lokalisation des Konzentrierungsprozesses in der Niere durch direkte Kryoskopie. Heiv Physiol Pharmacol Acta 1951; 9: 196–207.Google Scholar
  91. 91.
    Wirz H, Dirix R: Urinary concentration and dilution, in Orloff J, Berliner RW (eds): Handbook of Physi ology, Section 8, Renal Physiology. Washington DC, American Physiological Society, 1973, pp 415–430.Google Scholar
  92. 92.
    Wright FS, Schnermann J: Interference with feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide. J Clin Invest 1974; 53: 1695–1708.PubMedCrossRefGoogle Scholar
  93. 93.
    Zimmerhackl B, Robertson CR, Jamison RL: Effect of arginine vasopressin (AVP) on vasa recta blood flow. Proc Am Soc Nephrol. 204A, 1984.Google Scholar
  94. 94.
    Zimmerhackl B, Robertson CR, Jamison RL: The microcirculation of the renal medulla. Circ Res 1985; 57: 657–667.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Esmail Koushanpour
    • 1
  • Wilhelm Kriz
    • 2
  1. 1.Northwestern University Medical SchoolChicagoUSA
  2. 2.University of HeidelbergHeidelbergFederal Republic of Germany

Personalised recommendations