Klinische Wochenschrift

, Volume 60, Issue 19, pp 1212–1214 | Cite as

The role of chloride transport in the thick ascending limb in the pathogenesis of Bartter's syndrome

  • J. R. GillJr.


Fractional chloride reabsorption in the thick ascending limb of the loop of Henle, measured by clearance techniques, is subnormal in patients with Bartter's syndrome. This defect is a marker for the syndrome and, presumably, is the cause of the supranormal tubular secretion of potassium that characterizes the disorder. The potassium depletion that results from excessive potassium excretion is probably the stimulus for the increased synthesis of prostacyclin by blood vessels and prostaglandin E2 by kidneys that occurs in Bartter's syndrome. The overproduction of prostaglandins mediates hyperreninemia, supranormal plasma bradykinin, supranormal plasma norepinephrine and vascular resistance to the pressor effects of angiotensin II and norepinephrine; treatment with a prostaglandin synthetase inhibitor corrects these abnormalities. Increases in angiotensin II and in norepinephrine appear to be compensatory changes, occurring in response to vasodilatation induced by vascular prostaglandins to maintain blood pressure. The hyperreninemia also stimulates production of aldosterone with aggravation of potassium loss.

Key words

Bartter's syndrome Tubular chloride transport Potassium depletion Prostaglandins Renin Norepinephrine Bradykinin Blood vessels Aldosterone 

Renaler Chloridtransport beim Bartter Syndrom


Bei Patienten mit Bartter Syndrom ist die mittels Clearance-Technik gemessene fraktionelle Chloridresorption im dicken aufsteigenden Schenkel der Henleschen Schleife vermindert. Diese Störung ist kennzeichnend für das Syndrom und stellt wahrscheinlich die Ursache der erhöhten Kaliumsekretion bei dieser Erkrankung dar. Der Kaliummangel als Folge exzessiver Kaliumverluste dürfte der Stimulus für die beim Bartter Syndrom beobachtete Steigerung der vaskulären Prostacyclin- und renalen Prostaglandin E2-Synthese sein. Die gesteigerte Prostaglandin-Produktion führt zu Hyperreninämie, erhöhtem Plasma Bradykinin und Noradrenalin sowie zur Gefäßresistenz gegenüber der pressorischen Wirkung von Angiotensin II und Noradrenalin; diese Veränderungen werden durch Behandlung mit Prostaglandin-Synthesehemmern korrigiert. Die Zunahme von Angiotensin II und Noradrenalin erfolgt kompensatorisch zur Aufrechterhaltung des Blutdrucks als Antwort auf die durch vaskuläre Prostaglandine induzierte Gefäßerweiterung. Die Hyperreninämie stimuliert schließlich die Produktion von Aldosteron und führt damit zur Verschlimmerung des Kaliumverlusts.


Bartter Syndrom tubulärer Chloridtransport Kaliummangel Prostaglandine Renin Noradrenalin Bradykinin Blutgefäße Aldosteron 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baehler RW, Work J, Kotchen TA, McMorrow G, Guthrie G (1980) Studies on the pathogenesis of Bartter's syndrome. Am J Med 69:933Google Scholar
  2. 2.
    Bartter FC, Delea CS, Kawasaki T, Gill JR jr (1974) The adrenal cortex and the kidney. Kidney Int 6:272Google Scholar
  3. 3.
    Bartter FC, Pronove P, Gill JR jr, MacCardle RC (1962) Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Am J Med 33:811Google Scholar
  4. 4.
    Bryan GT, MacCardle RC, Bartter FC (1966) Hyperaldosteronism, hyperplasia of the juxtaglomerular complex, normal blood pressure and dwarfism: Report of a case. Pediatrics 37:43Google Scholar
  5. 5.
    Burg MB, Bourdeau JE (1978) Function of the thick ascending limb of Henle's loop. In: Vogel HG, Ullrich KJ (eds) Newer Aspects of Renal Function. Excerpta Medica, Amsterdam Oxford, pp 91–102Google Scholar
  6. 6.
    Chaimovitz C, Levi J, Better OS, Oslander L, Benderli A (1973) Studies on the site of renal salt loss in a patient with Bartter's syndrome. Pediatr Res 7:89Google Scholar
  7. 7.
    Chan JCM, Malekzedeh MH, Anand SK (1975) Defect in renal tubular sodium reabsorption in a patient with Bartter's syndrome. Clin. Proc. Child. Hosp. Natl Med Cent 31:67Google Scholar
  8. 8.
    Danovitch GM, Bricker NS (1976) Influence of volume expansion on NaCl reabsorption in the diluting segments of the nephron. A study using clearance methods. Kidney Int 10:229Google Scholar
  9. 9.
    Eknoyan G, Suki WN, Rector FC jr, Seldin DW (1967) Functional characteristics of the diluting segment of the dog nephron and the effect of extracellular volume expansion on its reabsorptive capacity. J Clin Invest 46:1178Google Scholar
  10. 10.
    Fujita T, Sakuguchi H, Shibagaki M, Fukui T, Nomura M, Sekiguchi S (1977) The pathogenesis of Bartter's syndrome. Am J Med 63:467Google Scholar
  11. 11.
    Galvez OG, Bay WH, Roberts BW, Ferris TF (1977) The hemodynamic effects of potassium deficiency in the dog. Circ Res 40:Suppl I:I-11Google Scholar
  12. 12.
    Gill JR jr (1980) Bartter's syndrome. Ann Rev Med 31:405Google Scholar
  13. 13.
    Gill JR jr (1981) Prostaglandins in Bartter's syndrome and in potassium-deficient disorders that mimic it. Mineral Electrolyte Metab 6:76Google Scholar
  14. 14.
    Gill JR jr, Bartter FC (1978) 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 65:766Google Scholar
  15. 15.
    Gill JR jr, Frölich JC, Bowden RE, Taylor AA, Keiser, HR, Seyberth HW, Oates JA, Bartter FC (1976) Bartter's syndrome: A disorder characterized by high urinary prostaglandins and a dependence of hyperreninemia on prostaglandin synthesis. Am J Med 61:43Google Scholar
  16. 16.
    Güllner H-G, Bartter FC, Cerletti C, Smith JB, Gill JR jr (1979) Prostacyclin overproduction in Bartter's syndrome. Lancet II:767Google Scholar
  17. 17.
    Güllner H-G, Gill JR jr, Bartter FC, Chan JCM, Dickman PS (1979) A familial disorder with hypokalemic alkalosis, hyperreninemia, aldosteronism, high urinary prostaglandins and normal blood pressure that is not Bartter's syndrome. Trans Assoc Am Phys 92:175Google Scholar
  18. 18.
    Güllner, H-G, Gill JR jr, Bartter FC, Lake RL, Lakatua DJ (1980) Correction of increased sympathoadrenal activity in Bartter's syndrome by inhibition of prostaglandin synthesis. J Clin Endocr Metab 50:857Google Scholar
  19. 19.
    Gunther S, Gimbrone MA jr, Alexander RW (1980) Regulation by angiotensin II of its receptors in resistance blood vessels. Nature 287:230Google Scholar
  20. 20.
    Kono T, Oseko F, Shimbo S, Nanno M, Ikeda F, Endo J (1976) Blood pressure fall by angiotensin II antagonist in patients with Bartter's syndrome. J Clin Endocrinol 43:692Google Scholar
  21. 21.
    Nielsen I, Hesse B, Christensen P (1979) On the pathogenetic role of prostaglandins in Bartter's syndrome. Acta Med Scan 625:Suppl 135Google Scholar
  22. 22.
    Radfar N, Gill JR jr, Bartter FC, Bravo E, Taylor AA, Bowden RE (1978) Hypokalemia, in Bartter's syndrome and other disorders, produces resistance to vasopressors via prostaglandin overproduction. Proc Soc Exp Biol Med 158:502Google Scholar
  23. 23.
    Ramos E, Hall-Craggs M, Demers LM (1980) Surreptitious, habitual vomiting simulating Bartter's syndrome. J Am Med Assoc 43:1070Google Scholar
  24. 24.
    Sasaki H, Okumura M, Asano T, Arakawa K, Kawasaki T (1977) Responses to angiotensin II antagonist before and after treatment with indomethacin in Bartter's syndrome. Br Med J 2:975Google Scholar
  25. 25.
    Stokes JB (1979) Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle. J Clin Invest 64:495Google Scholar
  26. 26.
    Stokes JB, Kokko JP (1977) Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule. J Clin Invest 59:1099Google Scholar
  27. 27.
    Veldhuis JD, Bardin CW, Demers LM (1979) Metabolic mimicry of Bartter's syndrome by covert vomiting. Am J Med 66:361Google Scholar
  28. 28.
    Vinci JM, Gill JR jr, Bowden RE, Pisano JJ, Izzo JL jr, Radfar N, Taylor AA, Zusman RM, Bartter FC, Keiser HR (1978) The kallikrein-kinin system in Bartter's syndrome and its response to prostaglandin synthetase inhibition. J Clin Invest 61:1671Google Scholar
  29. 29.
    White MG (1972) Bartter's syndrome. A manifestation of renal tubular defects. Arch Intern Med 129:41Google Scholar
  30. 30.
    Wong PY, Talamo RC, Williams GH, Coleman RW (1975) Response of kallikrein-kinin and renin-angiotensin systems to saline infusion and upright posture. J Clin Invest 55:691Google Scholar
  31. 31.
    Wright FC, Giebisch G (1978) Renal potassium transport: contributions of individual nephron segments and populations. Am J Physiol 235:F515Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • J. R. GillJr.
    • 1
    • 2
  1. 1.Hypertension-Endocrine BranchNational HeartLung
  2. 2.Blood InstituteNational Institutes of HealthBethesdaUSA

Personalised recommendations