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Hyponatremia: pathophysiology, classification, manifestations and management

  • Nephrology - Review
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Abstract

Hyponatremia has complex pathophysiology, is frequent and has potentially severe clinical manifestations, and its treatment is associated with high risks. Hyponatremia can be hypertonic, isotonic or hypotonic. Hypotonic hyponatremia has multiple etiologies, but only two general mechanisms of development, defective water excretion, usually because of elevated serum vasopressin levels, or excessive fluid intake. The acute treatment of symptomatic hypotonic hyponatremia requires understanding of its targets and risks and requires continuous monitoring of the patient’s clinical status and relevant serum biochemical values. The principles of fluid restriction, which is the mainstay of management of all types of hypotonic hyponatremia, should be clearly understood and followed. Treatment methods specific to various categories of hyponatremia are available. The indications and risks of these treatments should also be well understood. Rapid correction of chronic hypotonic hyponatremia may lead to osmotic demyelination syndrome, which has severe clinical manifestations, and may lead to permanent neurological disability or death. Prevention of this syndrome should be a prime concern of the treatment of hypotonic hyponatremia.

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References

  1. Upadhyay A, Jaber BL, Madias NE (2006) Incidence and prevalence of hyponatremia. Am J Med 119(7 Suppl. 1):S30–S35

    Article  PubMed  CAS  Google Scholar 

  2. Liamis G, Rodenburg EM, Hofman A et al (2013) Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med 126(3):256–263

    Article  PubMed  CAS  Google Scholar 

  3. Verbalis JG, Goldsmith SR, Greenberg A et al (2013) Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 126(10 Suppl 1):S1–S42

    Article  PubMed  Google Scholar 

  4. Spasovski G, Vamholder R, Allolio B et al (2014) Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 170(3):G1–G47

    Article  PubMed  CAS  Google Scholar 

  5. Arieff AI, Carroll HJ (1972) Nonketotic hyperosmolar come with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine (Baltimore) 51(2):73–94

    Article  CAS  Google Scholar 

  6. Tomkins AM, Dormandy TL (1971) Osmolality pattern during recovery from diabetic coma. Lancet 2(7731):952–955

    Article  PubMed  CAS  Google Scholar 

  7. Tzamaloukas AH, Sun Y, Konstantinov NK et al (2013) Principles of quantitative fluid and cation replacement in extreme hyperglycemia. Cureus 5(3):3110. doi:10.17759/cureus.110

    Google Scholar 

  8. Katz MA (1973) Hyperglycemia-induced hyponatremia: calculation of the expected serum sodium depression. N Engl J Med 289(16):843–844

    Article  PubMed  CAS  Google Scholar 

  9. Al-Kudzi RR, Daugirdas JT, Ing TS et al (1982) Extreme hyperglycemia in dialysis patients. Clin Nephrol 17(5):228–231

    Google Scholar 

  10. Liamis G, Liberopoulos E, Barkas F, Elisaf M (2013) Spurious electrolyte disorders: a diagnostic challenge for clinicians. Am J Nephrol 38(1):50–57

    Article  PubMed  Google Scholar 

  11. Agarwal R, Emmett M (1994) The post-transurethral resection of prostate syndrome: therapeutic proposals. Am J Kidney Dis 24(1):108–111

    Article  PubMed  CAS  Google Scholar 

  12. Ayus JC, Achinger SG, Arieff A (2008) Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am J Physiol Renal Physiol 295(3):F619–F624

    Article  PubMed  CAS  Google Scholar 

  13. Edelman IS, Leibman J, O’Meara MP, Birkenfeld LW (1958) Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest 37(9):1236–1256

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Rose BD (1986) New approach to disturbances in plasma sodium concentration. Am J Med 81(6):1033–1040

    Article  PubMed  CAS  Google Scholar 

  15. Ayus JC, Moritz ML (2010) Bone disease as a new complication of hyponatremia: moving beyond brain injury. Clin J Am Soc Nephrol 5(2):167–168

    Article  PubMed  CAS  Google Scholar 

  16. Pham PC, Pham PM, Pham PT (2006) Vasopressin excess and hyponatremia. Am J Kidney Dis 47(5):727–737

    Article  PubMed  CAS  Google Scholar 

  17. Thaler SM, Teitelbaum I, Berl T (1998) “Beer potomania” in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis 31(6):1028–1031

    Article  PubMed  CAS  Google Scholar 

  18. Subramanian D, Ayus JC (1992) Severe symptomatic hyponatremia associated with lisinopril therapy. Am J Med Sci 303(3):177–179

    Article  PubMed  CAS  Google Scholar 

  19. Olesen ET, Fenton RA (2013) Is there a role for PGE2 in urinary concentration? J Am Soc Nephrol 24(2):169–178

    Article  PubMed  CAS  Google Scholar 

  20. Leaf A, Bartter FC, Santos RF, Wrong O (1953) Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J Clin Invest 32(9):868–878

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Warms PC, Michelis MF, Brafdon RW et al (1974) Micropuncture study of tubule sodium reabsorption in dilutional hyponatremia. Metabolism 23:203–208

    Article  PubMed  CAS  Google Scholar 

  22. Verbalis JG (2006) Whole-body volume regulation and escape from antidiuresis. Am J Med 119(7 Suppl 1):S21–S29

    Article  PubMed  Google Scholar 

  23. Bourque CW (2008) Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci 9(7):519–531

    Article  PubMed  CAS  Google Scholar 

  24. Verbalis JG (2010) Brain volume regulation in response to changes in osmolality. Neuroscience 168(4):862–870

    Article  PubMed  CAS  Google Scholar 

  25. Ayus JC, Arieff AI (1995) Pulmonary complications of hyponatremic encephalopathy: noncardiogenic pulmonary edema and hypercapnic respiratory failure. Chest 107(2):517–521

    Article  PubMed  CAS  Google Scholar 

  26. Decaux G (2006) Is asymptomatic hyponatremia really asymptomatic? Am J Med 119(7 Suppl. 1):S79–S82

    Article  PubMed  Google Scholar 

  27. Lee DS, Austin PC, Rouleau JL et al (2003) Predicting mortality among patients hospitalized for heart failure: derivation of and validation of a clinical model. JAMA 290(19):2581–2587

    Article  PubMed  CAS  Google Scholar 

  28. Ayus JC, Negri AL, Kalantar-Zadeh K, Moritz ML (2012) Is chronic hyponatremia a novel risk factor for hip fracture in the elderly? Nephrol Dial Transplant 27(10):3725–3731

    Article  PubMed  Google Scholar 

  29. Verbalis JG, Barsony J, Sugimura Y et al (2010) Hyponatremia-induced osteoporosis. J Bone Miner Res 25(3):554–563

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Adrogué HJ, Madias NE (2000) Hyponatremia. N Engl J Med 341(21):1581–1589

    Article  Google Scholar 

  31. Lien YH, Shapiro JI (2007) Hyponatremia: clinical diagnosis and management. Am J Med 120(8):653–658

    Article  PubMed  CAS  Google Scholar 

  32. Tzamaloukas AH, Malhotra D, Rosen BH et al (2013) Principles of management of severe hyponatremia. J Am Heart Assoc 2:3005199. doi:10.1161/JAHA.112.005199

    Article  Google Scholar 

  33. Mellits ED, Cheek DB (1970) The assessment of body water and fatness from infancy to adulthood. Monogr Soc Res Child Dev 45(7):12–16

    Article  Google Scholar 

  34. Watson PE, Watson ID, Batt RD (1980) Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr 33(1):27–39

    PubMed  CAS  Google Scholar 

  35. Chumlea WC, Guo SS, Zeller CM et al (2002) Total body water reference values and prediction equations for adults. Kidney Int 59(6):2250–2258

    Article  Google Scholar 

  36. Ellison DH, Berl T (2007) The syndrome of inappropriate antidiuresis. N Engl J Med 356(20):2064–2072

    Article  PubMed  CAS  Google Scholar 

  37. Furst H, Hallows KR, Post J et al (2000) The urine/plasma electrolyte ratio: a predictive guide to water restriction. Am J Med Sci 319(4):240–244

    Article  PubMed  CAS  Google Scholar 

  38. Gennari FJ, Weise WJ (2008) Acid–base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol 3(6):1861–1868

    Article  PubMed  CAS  Google Scholar 

  39. Oster JR, Singer I, Thatte L et al (1997) The polyuria of solute diuresis. Arch Intern Med 157(7):721–729

    Article  PubMed  CAS  Google Scholar 

  40. Berl T (2008) Impact of solute intake on urine flow and water excretion. J Am Soc Nephrol 19(6):1076–1078

    Article  PubMed  CAS  Google Scholar 

  41. Soupart A, Silver S, Schroeder B et al (2002) Rapid (2-hour) reaccumulation of brain organic osmolytes (particularly myo-inositol) in azotemic rats after correction of chronic hyponatremia. J Am Soc Nephrol 13(6):1433–1441

    Article  PubMed  CAS  Google Scholar 

  42. Jovanovich AJ, Berl T (2013) Where vaptans do and do not fit in the treatment of hyponatremia. Kidney Int 83(4):563–567

    Article  PubMed  CAS  Google Scholar 

  43. Sood L, Sterns RH, Hix JK et al (2013) Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis 61(4):571–578

    Article  PubMed  CAS  Google Scholar 

  44. Tzamaloukas AH, Shapiro JI, Raj DS et al. Management of severe hyponatremia: infusion of hypertonic saline and desmopressin or infusion of vasopressin inhibitors. Am J Med Sci (in press)

  45. Sterns RH, Hix JK, Silver S (2010) Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis 56(4):774–779

    Article  PubMed  CAS  Google Scholar 

  46. Norenberg MD (2010) Central pontine myelinolysis: historical and mechanistic considerations. Metab Brain Dis 25(1):97–106

    Article  PubMed  Google Scholar 

  47. King JD, Rosner MH (2010) Osmotic demyelination syndrome. Am J Med Sci 339(6):561–567

    PubMed  Google Scholar 

  48. Gangam Kengne F, Nicaise C, Soupart A et al (2011) Astrocytes are an early target in osmotic demyelination syndrome. J Am Soc Nephrol 22(10):1834–1845

    Article  Google Scholar 

  49. Berl T, Rastegar A (2010) A patient with severe hyponatremia and hypokalemia: osmotic demyelination following potassium repletion. Am J Kidney Dis 55(4):742–748

    Article  PubMed  Google Scholar 

  50. Soupart A, Penninckx R, Crenier L et al (1994) Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering. Kidney Int 45(1):193–200

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, A915 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Helbert Rondon-Berrios

  2. Division of Nephrology, Department of Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria

    Emmanuel I. Agaba

  3. Medicine Service, Section of Nephrology, Raymond G. Murphy Veterans Affairs Medical Center, University of New Mexico School of Medicine, Albuquerque, NM, USA

    Antonios H. Tzamaloukas

Authors
  1. Helbert Rondon-Berrios
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  2. Emmanuel I. Agaba
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  3. Antonios H. Tzamaloukas
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Correspondence to Helbert Rondon-Berrios.

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Rondon-Berrios, H., Agaba, E.I. & Tzamaloukas, A.H. Hyponatremia: pathophysiology, classification, manifestations and management. Int Urol Nephrol 46, 2153–2165 (2014). https://doi.org/10.1007/s11255-014-0839-2

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