Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis

Nature Clinical Practice Nephrology volume 4, pages 91–101 (2008)Cite this article

Abstract

Fluid, electrolyte and mineral perturbations are prevalent features of tropical disease. Hemodynamic alterations, fever, nitrogen wasting, and changes in membrane transport and acid–base balance contribute to these perturbations. Models of malaria and leptospirosis have been used to show that common hemodynamic changes in tropical disease include decreased systemic vascular resistance, increased cardiac output and increased renal vascular resistance. Blood volume is initially increased, but it decreases as disease progresses. Response to fluid loading is decreased. Diabetes insipidus is occasionally observed in malaria. Hyponatremia occurs frequently in tropical diseases, as a result of increased levels of antidiuretic hormone (vasopressin), entry of sodium into cells, sodium loss and resetting of osmoreceptors. Natriuresis and kaliuresis are observed in patients with leptospirosis. Large amounts of sodium and potassium are lost in stool as a result of diarrhea. Hypernatremia is uncommon, whereas hypokalemia caused by hyperventilation is often observed (more frequently in patients with leptospirosis and kaliuresis). During severe tropical infective episodes, hyperkalemia results from intravascular hemolysis or rhabdomyolysis, and occasionally from decreased activity of Na+,K+-ATPase. Hypocalcemia, hypomagnesemia and hypophosphatemia are common features of both malaria and leptospirosis. Loss of magnesium in the urine is uniquely associated with leptospiral nephropathy. Hypozincemia and hypocupremia can also develop during tropical infection, and might interfere with a patient's immune response. These electrolyte and mineral perturbations are transient and quickly resolve when the disease is controlled.

Key Points

  • A broad range of pathophysiological changes, comparable to those in patients with severe sepsis, are observed in people with severe tropical diseases

  • Malaria and leptospirosis are the best-studied tropical diseases

  • The pattern of renal hemodynamic changes induced by tropical disease depends on the severity of the condition and associated complications

  • Hemodynamic alterations generally include decreased systemic vascular resistance, renal blood flow and glomerular filtration rate, and increased cardiac output and renal vascular resistance

  • Changes in serum electrolyte and mineral levels associated with tropical disease include hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypophosphatemia, hyperphosphatemia and hypomagnesemia

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Hemodynamics in patients with tropical diseases (based on models of malaria and leptospirosis).
Figure 2: Hemodynamics in malaria.
Figure 3: Decreased response to water loading in patients with malaria and those with leptospirosis.

Similar content being viewed by others

References

  1. Sitprija V (1994) Tropical renal disease. In Textbook of Renal Disease, 201–211 (Eds Whitworth JA and Lawrence JR) London: Churchill Livingstone

    Google Scholar 

  2. Suvanapha R and Sitprija V (1992) Acute renal failure in the tropics. In Oxford Textbook of Clinical Nephrology, vol 2, 1124–1143 (Eds Cameron JS et al.) Oxford: Oxford University Press

    Google Scholar 

  3. Miller LH et al. (1967) Hyponatraemia in malaria. Ann Trop Med Parasitol 61: 265–279

    Article  CAS  PubMed  Google Scholar 

  4. Seguro AC et al. (1990) Acute renal failure in leptospirosis: nonoliguric and hypokalemic form. Nephron 55: 146–151

    Article  CAS  PubMed  Google Scholar 

  5. Davis TM et al. (1991) Calcium and phosphate metabolism in acute falciparum malaria. Clin Sci 81: 297–304

    Article  CAS  Google Scholar 

  6. Zaloga GP and Chernow B (1987) The multifactorial basis of hypocalcemia during sepsis: studies of the parathyroid hormone vitamin D axis. Ann Intern Med 107: 36–41

    Article  CAS  PubMed  Google Scholar 

  7. Sankaran RT et al. (1997) Laboratory abnormalities in patients with bacterial pneumonia. Chest 111: 595–600

    Article  CAS  PubMed  Google Scholar 

  8. Chesney PJ et al. (1981) Clinical manifestations of toxic shock syndrome. J Am Med Assoc 246: 741–748

    Article  CAS  Google Scholar 

  9. Torres AM et al. (2000) Central diabetes indispidus due to herpes simplex in a patient immunosuppressed by Cushing's syndrome. Endocr Pract 6: 26–28

    Article  CAS  PubMed  Google Scholar 

  10. Siriwanij T et al. (2005) Haemodynamics in leptospirosis: effects of plasmapheresis and continuous venovenous haemofiltration. Nephrology 10: 1–6

    Article  PubMed  Google Scholar 

  11. Quezado ZM and Natanson C (1992) Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. Am J Kidney Dis 20: 214–222

    Article  CAS  PubMed  Google Scholar 

  12. Sitprija V et al. (1996) Renal and systemic hemodynamics, in falciparum malaria. Am J Nephrol 16: 513–519

    Article  CAS  PubMed  Google Scholar 

  13. Barsoum R and Sitprija V (2007) Tropical nephrology. In Diseases of the Kidney and Urinary Tract, 2013–2055 (Ed Schrier RW) Philadelphia, PA: Lippincott, Williams & Wilkins

    Google Scholar 

  14. Choovichian P et al. (1988) Renal function in acute febrile disease. Intern Med J Thai 4: 105–107

    Google Scholar 

  15. Sitprija V et al. (2003) Leptospiral nephropathy. Semin Nephrol 23: 42–48

    Article  PubMed  Google Scholar 

  16. Schrier RW and Wang W (2004) Acute renal failure in sepsis. N Engl J Med 351: 159–169

    Article  CAS  PubMed  Google Scholar 

  17. Soule HC et al. (1928) Blood volume in fever. J Clin Invest 5: 229–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sitprija V et al. (1997) Renal failure in malaria: a pathophysiologic study. Nephron 18: 277–287

    Article  Google Scholar 

  19. Feldman HA and Murphy FD (1945) The effect of alteration in blood volume on the anemia and hypoproteinemia of human malaria. J Clin Invest 24: 780–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miller LH et al. (1968) Comparative studies on the pathology and host physiology of malarias. V: hypovolaemia of Plasmodium coatneyi malaria. Ann Trop Med Parasitol 62: 218–232

    Article  CAS  PubMed  Google Scholar 

  21. Chongsuphajaisiddhi T et al. (1971) Changes in blood volume in falciparum malaria. Southeast Asian J Trop Med Public Health 2: 344–350

    CAS  PubMed  Google Scholar 

  22. Overman RR et al. (1949) Physiological studies in the human malarial host. I: blood, plasma, “extracellular” fluid volumes and ionic balance in therapeutic P. vivax and P. falciparum infections. J Natl Malar Soc 8: 14–31

    CAS  PubMed  Google Scholar 

  23. Sitprija V et al. (1967) Renal failure in malaria. Lancet 1: 185–188

    Article  CAS  PubMed  Google Scholar 

  24. Malloy JP et al. (1967) Pathophysiology of acute falciparum malaria. I: fluid compartmentalization. Am J Med 43: 745–750

    Article  CAS  PubMed  Google Scholar 

  25. Sitprija V et al. (1996) The kidney in malaria: renal and systemic haemodynamics. Nephrology 2 (Suppl 1): S94–S97

    Article  Google Scholar 

  26. Tuchinda P (1973) Hemorrhagic fever in Thailand: physiologic derangement. J Med Assoc Thai 56: 1–5

    CAS  PubMed  Google Scholar 

  27. Pongpanich B and Kumponpant S (1973) Studies of dengue hemorrhagic fever. V: hemodynamic studies of clinical shock associated with dengue hemorrhagic fever. J Pediatr 83: 1073–1077

    Article  CAS  PubMed  Google Scholar 

  28. Pamba A and Maitland K (2004) Fluid management of severe falciparum malaria in African children. Trop Doct 34: 67–70

    Article  PubMed  Google Scholar 

  29. Sitprija V (2003) Overview of tropical nephrology. Semin Nephrol 23: 3–11

    Article  PubMed  Google Scholar 

  30. Losuwanrak K and Sitprija V (2003) Fluid administration in leptospirosis: the potential use of dopamine. Intern Med J Thai 19: 180–184

    Google Scholar 

  31. Coelho M et al. (2004) Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia. Clin Neurol Neurosurg 106: 129–131

    Article  PubMed  Google Scholar 

  32. Hill AR et al. (1990) Altered water metabolism in tuberculosis: role of vasopressin. Am J Med 88: 357–364

    Article  CAS  PubMed  Google Scholar 

  33. Sabria M and Campins M (2003) Legionnaires' disease: update on epidemiology and management options. Am J Respir Med 2: 235–243

    Article  PubMed  Google Scholar 

  34. Agarwal A et al. (1989) Hyponatremia in patients with the acquired immune deficiency syndrome. Nephron 53: 317–321

    Article  CAS  PubMed  Google Scholar 

  35. Sowunmi A et al. (2000) Arginine vasopressin secretion in Kenyan children with severe malaria. J Trop Pediatr 46: 195–199

    Article  CAS  PubMed  Google Scholar 

  36. Holst FG et al. (1994) Inappropriate secretion of antidiuretic hormone and hyponatremia in severe falciparum malaria. Am J Trop Med Hyg 50: 602–607

    Article  CAS  PubMed  Google Scholar 

  37. English MC et al. (1996) Hyponatremia and dehydration in severe malaria. Arch Dis Child 74: 201–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Grimwade K et al. (2004) Polyuria in association with Plasmodium falciparum malaria in a region of unstable transmission. Trans R Soc Trop Med Hyg 98: 255–260

    Article  CAS  PubMed  Google Scholar 

  39. Schubert S et al. (2006) Central diabetes insipidus in a patient with malaria tropica. J Endocrinol Invest 29: 265–266

    Article  CAS  PubMed  Google Scholar 

  40. Greger R (1996) Cellular transduction processes. In Comprehensive Human Physiology, vol I, 95–113 (Eds Greger R and Windhorst U) Berlin: Springer

    Chapter  Google Scholar 

  41. Watten RH et al. (1959) Water and electrolyte studies in cholera. J Clin Invest 38: 1879–1889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shiau YF et al. (1985) Stool electrolyte and osmolality measurements in the evaluation of diarrheal disorders. Ann Intern Med 102: 773–775

    Article  CAS  PubMed  Google Scholar 

  43. Canani RB et al. (2005) Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes. J Infect Dis 191: 1072–1077

    Article  CAS  PubMed  Google Scholar 

  44. Andrade L et al. (2007) Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung. Am J Physiol Renal Physiol 292: F586–F592

    Article  CAS  PubMed  Google Scholar 

  45. Niwattayakul K et al. (2002) Hypotension, renal failure, and pulmonary complications in leptospirosis. Ren Fail 24: 297–305

    Article  PubMed  Google Scholar 

  46. Rabb H et al. (2003) Acute renal failure leads to dysregulation of lung salt and water channels. Kidney Int 63: 600–606

    Article  CAS  PubMed  Google Scholar 

  47. Towne JE et al. (2000) Decreased expression of aquaporin (AQP) 1 and AQP5 in mouse lung after acute viral infection. Am J Respir Cell Mol Biol 22: 34–44

    Article  CAS  PubMed  Google Scholar 

  48. Jain L et al. (1998) Nitric oxide inhibits sodium transport through a cGMP-mediated inhibition of epithelial cation channels. Am J Physiol 274: L475–L484

    CAS  PubMed  Google Scholar 

  49. Malaton S and O'Brodovich H (1999) Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance. Annu Rev Physiol 61: 627–661

    Article  Google Scholar 

  50. Campos SB et al. (2001) Effects of sodium artesunate, a new antimalarial drug, on renal function. Kidney Int 59: 1044–1051

    Article  CAS  PubMed  Google Scholar 

  51. Matthay MA et al. (1996) Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol 270: L487–L503

    CAS  PubMed  Google Scholar 

  52. Sitprija V (2006) Renal dysfunction in leptospirosis: a view from the tropics. Nat Clin Pract Nephrol 2: 658–659

    Article  PubMed  Google Scholar 

  53. Sahr Y et al. (2006) Does dopamine administration in shock influence outcome? Results of the sepsis occurrence in acutely ill patients (SOAP) study. Crit Care Med 34: 589–597

    Article  CAS  Google Scholar 

  54. Karthik S and Lisbon A (2006) Low-dose dopamine in the intensive care unit. Semin Dial 19: 465–471

    Article  PubMed  Google Scholar 

  55. Jeha LE et al. (2003) West Nile virus infection: a new acute paralytic illness. Neurology 61: 55–59

    Article  CAS  PubMed  Google Scholar 

  56. Cosentini R et al. (2001) Community-acquired pneumonia: role of atypical organisms. Monaldi Arch Chest Dis 56: 527–534

    CAS  PubMed  Google Scholar 

  57. Kabra SK et al. (1999) Dengue hemorrhagic fever: clinical manifestations and management. Indian J Pediatr 66: 93–101

    Article  CAS  PubMed  Google Scholar 

  58. Uysal G et al. (2000) Clinical risk factors for fatal diarrhea in hospitalized children. Indian J Pediatr 67: 329–333

    Article  CAS  PubMed  Google Scholar 

  59. Beisel WR et al. (1967) Metabolic effects of intracellular infections in man. Ann Intern Med 67: 744–779

    Article  CAS  PubMed  Google Scholar 

  60. Beisel WR et al. (1967) Adrenocortical response during tularemia in humans. J Clin Endocr 27: 61–69

    Article  CAS  PubMed  Google Scholar 

  61. Cook DJ et al. (1992) Serum cortisol: a predictor of mortality in sepsis? J Intensive Care Med 6: 84–89

    Article  Google Scholar 

  62. Sibbald WH et al. (1977) Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections. Ann Surg 186: 29–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Younes-Ibrahim M et al. (1995) Inhibition of Na,K-ATPase by an endotoxin extracted from Leptospira interrogans: a possible mechanism for the physiopathology of leptospirosis. CR Acad Sci III 318: 619–625

    CAS  Google Scholar 

  64. Dunn MJ (1969) Alterations of red blood cell sodium transport during malarial infection. J Clin Invest 48: 674–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sarikabhuti B and Niyomkha P (1982) Adenosine triphosphate levels in mouse erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium berghei. Ann Trop Med Parasitol 76: 657–659

    Article  CAS  PubMed  Google Scholar 

  66. Ustianowski A et al. (2002) Case report: severe acute symptomatic hyponatraemia in falciparum malaria. Trans R Soc Trop Med Hyg 96: 647–648

    Article  PubMed  Google Scholar 

  67. Raman GV et al. (1988) Rabies presenting with myocarditis and encephalitis. J Infect 17: 155–158

    Article  CAS  PubMed  Google Scholar 

  68. Lisic M et al. (1991) The clinical picture of rabies in a child. Neurol Croat 40: 307–318

    CAS  PubMed  Google Scholar 

  69. Moses AM et al. (2003) Central diabetes insipidus due to cytomegalovirus infection of the hypothalamus in a patient with acquired immunodeficiency syndrome: a clinical, pathological, and immunohistochemical case study. J Clin Endocrinol Metab 88: 51–54

    Article  CAS  PubMed  Google Scholar 

  70. Price TG and Kallenborn JC (2000) Infant hypernatremia: a case report. J Emerg Med 19: 153–157

    Article  CAS  PubMed  Google Scholar 

  71. Keuneke C et al. (1999) Adipsic hypernatremia in two patients with AIDS and cytomegalovirus encephalitis. Am J Kidney Dis 33: 379–382

    Article  CAS  PubMed  Google Scholar 

  72. Maitland K et al. (2004) Hypokalemia in children with severe falciparum malaria. Pediatr Crit Care Med 5: 81–85

    Article  PubMed  Google Scholar 

  73. Benyajati C et al. (1960) Acute renal failure in Asiatic cholera: clinicopathologic correlations with acute tubular necrosis and hypokalemic nephropathy. Ann Intern Med 52: 960–975

    Article  CAS  PubMed  Google Scholar 

  74. Lin CL et al. (1999) Leptospirosis associated with hypokalemia and thick ascending limb dysfunction. Nephrol Dial Transplant 14: 193–195

    Article  CAS  PubMed  Google Scholar 

  75. Wu MS et al. (2004) Reduced renal Na+-K+-Cl−-co-transporter activity and inhibited NKCC2 mRNA expression by Leptospira shermani: from bed-side to bench. Nephrol Dial Transplant 19: 2472–2479

    Article  CAS  PubMed  Google Scholar 

  76. Tosukhowong P et al. (1999) Environmental distal renal tubular acidosis in Thailand: an enigma. Am J Kidney Dis 33: 1180–1186

    Article  CAS  PubMed  Google Scholar 

  77. Maitland K et al. (2005) Perturbations in electrolyte levels in Kenyan children with severe malaria complicated by acidosis. Clin Infect Dis 40: 9–16

    Article  PubMed  Google Scholar 

  78. Boyce BF et al. (1989) Bolus injections of recombinant human interleukin-1 cause transient hypocalcemia in normal mice. Endocrinology 125: 2780–2783

    Article  CAS  PubMed  Google Scholar 

  79. Barak V et al. (1998) Prevalence of hypophosphatemia in sepsis and infection: the role of cytokines. Am J Med 104: 40–47

    Article  CAS  PubMed  Google Scholar 

  80. Van Landenberg P and Shoenfeld Y (2001) New approaches in the diagnosis of sepsis. Isr Med Assoc J 3: 439–442

    Google Scholar 

  81. Prabha MR et al. (1998) Clinical implications of hypocalcemia in malaria. Indian J Med Res 108: 62–65

    CAS  PubMed  Google Scholar 

  82. Soni CL et al. (2000) Prognostic implication of hypocalcemia and QTc interval in malaria. Indian J Malariol 37: 61–67

    CAS  PubMed  Google Scholar 

  83. Buranakarl C and Chaiyabutr N (1990) The role of calcium in the response of renal function during Russell's viper venom administration in dogs. Thai J Vet Med 20: 375–391

    Google Scholar 

  84. Krishna S and Ng LL (1989) Cation metabolism in malaria-infected red cells. Exp Parasitol 69: 402–406

    Article  CAS  PubMed  Google Scholar 

  85. Dockrell DH and Poland GA (1997) Hypercalcemia in a patient with hypoparathyroidism and Nocardia asteroides infection: a novel observation. Mayo Clin Proc 72: 757–760

    Article  CAS  PubMed  Google Scholar 

  86. Gknonos PJ et al. (1984) Hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in a patient with end-stage renal disease and active tuberculosis. N Engl J Med 311: 1683–1685

    Article  Google Scholar 

  87. Hoffman VH and Korgeniowski OM (1986) Leprosy, hypercalcemia and elevated serum calcitriol levels. Ann Intern Med 105: 890–891

    Article  CAS  PubMed  Google Scholar 

  88. Ahmed B and Jaspan JB (1993) Case report: hypercalcemia in a patient with AIDS and Pneumocystis carinii pneumonia. Am J Med Sci 306: 313–316

    Article  CAS  PubMed  Google Scholar 

  89. Zaloga GP et al. (1985) Hypercalcemia and disseminated cytomegalovirus infection in the acquired immunodeficiency syndrome. Ann Intern Med 102: 331–333

    Article  CAS  PubMed  Google Scholar 

  90. Liu JW et al. (1999) Acute disseminated histoplasmosis complicated with hypercalcaemia. J Infect 39: 88–90

    Article  CAS  PubMed  Google Scholar 

  91. Kantarjian HM et al. (1983) Hypercalcemia in disseminated candidiasis. Am J Med 74: 721–724

    Article  CAS  PubMed  Google Scholar 

  92. da Cunha DF et al. (1998) Hypophosphatemia in acute-phase response syndrome patients: preliminary data. Miner Electrolyte Metab 24: 337–340

    Article  CAS  PubMed  Google Scholar 

  93. Liberopoulos E et al. (2002) Reversible proximal tubular dysfunction in a patient with acute febrile illness, marked hyperbilirubinemia and normal renal function: evidence of leptospirosis. Nephron 91: 532–533

    Article  PubMed  Google Scholar 

  94. Khositseth S et al. (2007) Renal magnesium wasting and tubular dysfunction in leptospirosis. Nephrol Dial Transplant [doi: 10.1093/ndt/gfm698]

  95. de Araujo M et al. (2005) Magnesium supplementation combined with N-acetylcysteine protects against postischemic acute renal failure. J Am Soc Nephrol 16: 3339–3349

    Article  CAS  PubMed  Google Scholar 

  96. Garba IH and Ubom G (2006) Potential role of serum magnesium measurement as a biomarker of acute falciparum malaria infection in adult patients. Biol Trace Elem Res 114: 115–120

    Article  CAS  PubMed  Google Scholar 

  97. Middleton JR et al. (2004) Short communication: influence of Staphylococcus aureus intramammary infection on serum copper, zinc, and iron concentrations. J Dairy Sci 87: 976–979

    Article  CAS  PubMed  Google Scholar 

  98. Garba IH et al. (2006) Serum copper concentration in adults with acute uncomplicated falciparum malaria infection. Biol Trace Elem Res 113: 125–130

    Article  CAS  PubMed  Google Scholar 

  99. Cue vas LE and Koyanagi A (2005) Zinc and infection: a review. Ann Trop Paediatr 25: 149–160

    Article  Google Scholar 

  100. Fischer Walker C and Black RE (2004) Zinc and the risk for infectious disease. Annu Rev Nutr 24: 255–275

    Article  PubMed  CAS  Google Scholar 

  101. Toribio RE et al. (2005) Alterations in serum parathyroid hormone and electrolyte concentrations and urinary excretion of electrolytes in horses with induced endotoxemia. J Vet Intern Med 19: 223–231

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Queen Saovabha Memorial Institute, 1871 Rama 4 Road, Bangkok 10330, Thailand visithstprj@yahoo.com

Authors and Affiliations

  1. V Sitprija is Emeritus Professor of Medicine at Chulalongkorn University Medical School and Director of the Queen Saovabha Memorial Institute, Bangkok, Thailand.,

    Visith Sitprija

Authors
  1. Visith Sitprija
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sitprija, V. Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis. Nat Rev Nephrol 4, 91–101 (2008). https://doi.org/10.1038/ncpneph0695

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneph0695

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing