Hong Kong Journal of Nephrology
Volume 10, Issue 1 , Pages 14-26 , April 2008

A Practical and Pathophysiologic Approach to Hypokalemia

  • Shih-Hua Lin

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dr. Shih-Hua Lin, Division of Nephrology, Department of Medicine, Tri-Service General Hospital, No. 325, Section 2, Cheng-Kung Road, Taipei 114, Taiwan. Fax: (+886) 2-87927134;

References 

  1. Halfant RH . Hypokalemia and arrhythmias . Am J Med . 1986;80:13–22
  2. Coca SG , Perazella MA , Buller GK . The cardiovascular implications of hypokalemia . Am J Kidney Dis . 2005;45:233–247
  3. Lin YF , Lin SH , Tsai WS , Davis MR , Halperin ML . Severe hypokalemia in a Chinese male . QJM . 2002;95:695–704
  4. Schwartz WB , Relman AS . Effects of electrolyte disorders on renal structure and function . N Engl J Med . 1967;276:383–389
  5. Schwartz WB , Relman AS . Metabolic and renal studies in chronic potassium depletion resulting from overdose of laxatives . J Clin Invest . 1953;32:258–271
  6. Cremer W , Bock CW . Symptoms and course of chronic hypokalemic nephropathy in man . Clin Nephrol . 1977;17:654–657
  7. Brown RS . Potassium homeostasis and clinical implications . Am J Med . 1984;77:3–10
  8. Mandal AK . Hypokalemia and hyperkalemia . Med Clin North Am . 1997;81:611–639
  9. Weiner ID , Wingo CS . Hypokalemia—consequences, causes, and correction . J Am Soc Nephrol . 1997;8:1179–1188
  10. Halperin ML , Kamel KS . Potassium . Lancet . 1998;352:135–140
  11. Gennari FJ . Hypokalemia . N Engl J Med . 1998;339:451–458
  12. Lin SH , Halperin ML . Hypokalemia: a practical approach to diagnosis and its genetic basis . Curr Med Chem . 2007;14:1551–1565
  13. Sterns RH , Cox M , Feig PU , Singer I . Internal potassium balance and the control of the plasma potassium concentration . Medicine . 1981;60:339–354
  14. Giebisch G , Krapf R , Wagner C . Renal and extrarenal regulation of potassium . Kidney Int . 2007;72:397–410
  15. Clausen T . Clinical and therapeutic significance of the Na+, K+pump . Clin Sci . 1998;95:3–17
  16. Rosic NK , Standaert ML , Pollet RJ . The mechanism of insulin stimulation of (Na+,K+)-ATPase . J Biol Chem . 1985;260:6206–6212
  17. Klip A , Ramlal T , Cragoe EJ . Insulin-induced cytoplasmic alkalinization and glucose transport in muscle cells . Am J Physiol . 1986;250:C720–C728
  18. Shieh CC , Coghlan M , Sullivan JP , Gopalakrishnan M . Potassium channels: molecular defects, diseases, and therapeutic opportunities . Pharmacol Rev . 2000;52:557–594
  19. Hebert SC , Desir G , Giebisch G , Wang W . Molecular diversity and regulation of renal potassium channels . Physiol Rev . 2005;85:319–371
  20. Antes LM , Kujubu DA , Fernandez PC . Hypokalemia and the pathology of ion transport molecules . Semin Nephrol . 1998;18:31–45
  21. Giebisch G . Renal potassium transport: mechanisms and regulation . Am J Physiol . 1998;274:F817–F833
  22. Steele A , deVeber H , Quaggin SE , Scheich A , Ethier J , Halperin ML . What is responsible for the diurnal variation in potassium excretion? . Am J Physiol . 1994;267:R554–R560
  23. Fernandez-Repollet E , Maldonado MM , Opava-Stitzer S . The effects of antidiuretic hormone and state of potassium balance on the renin-angiotensin system in rats with diabetes insipidus . J Physiol . 1982;323:519–531
  24. Rutecki GW , Cox JW , Robertson GW , Francisco LL , Ferris TF . Urinary concentrating ability and antidiuretic hormone responsiveness in the potassium-depleted dog . J Lab Clin Med . 1982;100:53–60
  25. Lin SH , Cheema-Dhadli S , Gowrishankar M , Marliss EB , Kamel KS , Halperin ML . Control of excretion of potassium: lessons from studies during prolonged total fasting in human subjects . Am J Physiol . 1997;273:796–800
  26. Garty H . Regulation of the epithelial Na+ channel by aldosterone: open questions and emerging answers . Kidney Int . 2000;57:1270–1276
  27. West ML , Bendz O , Chen CB , Singer GG , Richardson RM , Sonnenberg H , et al.   Development of a test to evaluate the transtubular potassium concentration gradient in the cortical collecting duct in vivo . Miner Electrolyte Metab . 1986;12:226–233
  28. Kamel KS , Quaggin S , Scheich A , Halperin ML . Disorders of potassium homeostasis: an approach based on pathophysiology . Am J Kidney Dis . 1994;24:597–613
  29. Wang WH . Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects . Am J Physiol . 2006;290:F14–F19
  30. Pluznick JL , Sansom SC . BK channels in the kidney: role in K+secretion and localization of molecular components . Am J Physiol . 2006;291:F517–F529
  31. Finer G , Shalev H , Birk OS , Galron D , Jeck N , Sinai-Treiman L , et al.   Transient neonatal hyperkalemia in the antenatal (ROMK defective) Bartter syndrome . J Pediatr . 2003;142:318–323
  32. Bailey MA , Cantone A , Yan Q , MacGregor GG , Leng Q , Amorim JB , et al.   Maxi-K+ channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K+ diet . Kidney Int . 2006;70:51–59
  33. Narins RG , Jones ER , Stom MC , Rudnick MR , Bastl CP . Diagnostic strategies in disorders of fluid, electrolyte and acid-base homeostasis . Am J Med . 1982;72:496–520
  34. Kamel KS , Ethier JH , Richardson RM , Bear RA , Halperin ML . Urine electrolytes and osmolality: when and how to use them . Am J Nephrol . 1990;10:89–102
  35. Groeneveld JHM , Sijpkens YWJ , Lin SH , Davis MR , Halperin ML . Approach to the patients with a severe degree of hypokalemia: the potassium quiz . QJM . 2005;98:305–316
  36. Elisaf M , Siamopoulos KC . Fractional excretion of potassium in normal subjects and in patients with hypokalemia . Postgrad Med J . 1995;71:211–212
  37. Gagnnon RF , Halperin ML . Possible mechanisms to explain the absence of hyperkalemia in Addison's disease . Nephrol Dial Transplant . 2001;16:1280–1284
  38. Lin SH , Lin YF , Chen DT , Chu P , Hsu CW , Halperin ML . Laboratory tests to determine the causes for hypokalemia and paralysis . Arch Intern Med . 2004;164:1561–1566
  39. Groeneveld JH , Sijpkens YW , Lin SH , Davids MR , Halperin ML . An approach to the patient with severe hypokalemia . QJM . 2005;98:305–316
  40. Brown MJ , Brown DC , Murphy MB . Hypokalemia from beta2-receptor stimulation by circulating epinephrine . N Engl J Med . 1983;309:1414–1419
  41. Alazami M , Lin SH , Cheng CJ , Davids MR , Halperin ML . Unusual cases of hypokalemia and paralysis . QJM . 2006;99:181–192
  42. Wells JA , Wood KE . Acute barium poisoning treated with hemodialysis . Am J Emerg Med . 2001;19:175–177
  43. Clemessy JL , Favier C , Borron SW , Hantson PE , Vicaut E , Baud FJ . Hypokalemia related to acute chloroquine ingestion . Lancet . 1995;346:877–880
  44. Lin SH , Lin YF , Halperin ML . Hypokalemia and paralysis . QJM . 2001;94:133–139
  45. Lin SH . Thyrotoxic periodic paralysis . Mayo Clin Proc . 2005;80:99–105
  46. Kung AW . Thyrotoxic periodic paralysis: a diagnostic challenge . J Clin Endocrinol Metab . 2006;91:2490–2495
  47. Lin SH , Hsu YD , Cheng NL , Kao MC . Skeletal muscle dihydropyridine-sensitive calcium channel gene mutations in Chinese patients with hypokalemic periodic paralysis . Am J Med Sci . 2005;329:66–70
  48. Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ, et al  The primary periodic paralyses: diagnosis, pathogenesis and treatment . Brain . 2006;129:8–17
  49. Agarwal R , Afzalpurkar R , Fordtran JS . Pathophysiology of potassium absorption and secretion by the human intestine . Gastroenterology . 1994;107:548–571
  50. Kim HJ , Yoon YM , Park KN . The change in electrolytes and acid-base after artificially induced acute diarrhea by laxatives . J Korean Med Sci . 1994;9:388–393
  51. Lin SH , Chau T . A puzzling cause of hypokalemia . Lancet . 2002;360:224
  52. Lin SH , Chiu JS , Hsu CW , Chau T . A simple and rapid approach to hypokalemic paralysis . Am J Emerg Med . 2003;21:487–491
  53. Young WF . Primary aldosteronism: renaissance of a syndrome . Clin Endocrinol . 2007;66:607–618
  54. Cheng CJ , Chen YH , Chau T , Lin SH . A hidden cause of hypokalemic paralysis in a patient with prostate cancer . Support Care Cancer . 2004;12:810–812
  55. Tsai WS , Wu CP , Hsu YJ , Lin SH . Life-threatening hypokalemia in an asthmatic patient treated with high-dose hydrocortisone . Am J Med Sci . 2004;327:152–155
  56. Lin CS , Yao NS , Cheng MF , Lin SH . Ectopic ACTH syndrome associated with large cell neuroendocrine carcinoma of lung . Am J Med Sci . 2007;334:487–489
  57. New MI . Diagnosis and management of congenital adrenal hyperplasia . Ann Rev Med . 1998;49:311–328
  58. Palmer BF , Alpern RJ . Liddle's syndrome . Am J Med . 1998;104:301–309
  59. Mune T , Rogerson FM , Nikkilä H , Agarwal AK , White PC . Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase . Nat Genet . 1995;10:394–399
  60. Lin SH , Yang SS , Chau T , Halperin ML . An unusual cause of hypokalemic paralysis: chronic licorice ingestion . Am J Med Sci . 2003;325:153–156
  61. Saruta T , Fujimaki M , Senba S , Saito I , Konishi K . Aldosterone and other mineralocorticoids in Bartter's syndrome . J Lab Clin Med . 1984;103:848–853
  62. Simpson DP . Control of hydrogen ion homeostasis and renal acidosis . Medicine . 1971;50:503–541
  63. Kamel KS , Briceno LF , Sanchez MI , Brenes L , Yorgin P , Kooh SW , et al.   A new classification for renal defects in net acid excretion . Am J Kidney Dis . 1997;29:136–146
  64. Carlisle EJ , Donnelly SM , Vasuvattakul S , Kamel KS , Tobe S , Halperin ML . Glue-sniffing and distal renal tubular acidosis: sticking to the facts . J Am Soc Nephrol . 1991;1:1019–1027
  65. Cheng CJ , Chu P , Huang GS , Lin SH . Diffuse bone pain in a young women . Lancet . 2004;364:1910
  66. Orman RA , Lewia JB . Flaccid quadriparesis with Yersinia enterocolitis-induced hypokalemia . Arch Intern Med . 1989;149:1193–1194
  67. Murakami K , Tomita M , Kawamura N , Hasegawa M , Nabeshima K , Hiki Y , et al.   Severe metabolic acidosis and hypokalemia in a patient with enterovesical fistula . Clin Exp Nephrol . 2007;11:225–229
  68. Bates CM , Baum M , Quigley R . Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent . J Am Soc Nephrol . 1997;8:352–355
  69. Kamel KS , Ethier J , Levin A , Halperin ML . Hypokalemia in the “beautiful people” . Am J Med . 1990;88:534–536
  70. Peters M , Jeck N , Reinalter SS , Leonhardt A , Tonshoff B , Klaus GG , et al.   Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies . Am J Med . 2002;112:183–190
  71. Lin SH , Shiang JC , Huang CC , Yang SS , Hsu YJ , Cheng CJ . Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome . J Clin Endocrinol Metab . 2005;90:2500–2507
  72. Chou CL , Chen YH , Chau T , Lin SH . Acquired Bartter-like syndrome associated with gentamicin administration . Am J Med Sci . 2005;329:144–149
  73. Lin SH , Cheng NL , Hsu YJ , Halperin ML . Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter . Am J Kidney Dis . 2004;443:304–312
  74. Bettinelli A , Bianchetti MG , Girardin E , Caringella A , Cecconi M , Appiani AC , et al.   Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes . J Pediatr . 1992;120:38–43
  75. Lin SH . Gitelman's syndrome: from clinic to gene . Acta Nephrologica . 2003;17:113–120
  76. Luthy C , Bettinelli A , Iselin S , Metta MG , Basilico E , Oetliker OH , et al.   Normal prostaglandinuria E2 in Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome . Am J Kidney Dis . 1995;25:824–828
  77. Reinalter SC , Jeck N , Brochhausen C , Watzer B , Nusing RM , Seyberth HW , et al.   Role of c yclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome . Kidney Int . 2002;62:253–260
  78. Cohn JN , Kowey PR , Whelton PK , Prisant LM . New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice . Arch Intern Med . 2000;160:2429–2436
  79. Kunin AS , Surawicz B , Sims EAH . Decrease in serum potassium concentration and appearance of cardiac arrhythmia during infusion of potassium with glucose in potassium depleted patients . N Engl J Med . 1962;266:288–296
  80. Casteels K , Mathieu C . Diabetic ketoacidosis . Rev Endocr Metab Disord . 2003;4:159–166
  81. Wang WH . Regulation of renal K+ transport by dietary K intake . Annu Rev Physiol . 2004;66:547–569
  82. Perazella MA , Mahnensmith RL . Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis . J Gen Intern Med . 1997;12:646–656
  83. Crop MJ , Hoorn EJ , Lindemans J , Zietse R . Hypokalemia and subsequent hyperkalemia in hospitalized patients . Nephrol Dial Transplant . 2007;22:3471–3477
  84. Lu KC , Hsu YJ , Chiu JS , Hsu YD , Lin SH . Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis . Am J Emerg Med . 2004;22:544–547
  85. Manoukain MA , Foote JA , Crapo LM . Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes . Arch Intern Med . 1999;159:601–606
  86. Lin SH , Lin YF . Propranolol rapidly terminates the hypokalemia, hypophosphatemia and paralysis in thyrotoxic periodic paralysis . Am J Kidney Dis . 2001;37:620–623
  87. Shayne P , Hart A . Thyrotoxic periodic paralysis terminated with intravenous propranolol . Ann Emerg Med . 1994;24:736–740
  88. Conway MJ , Seibel JA , Eaton RP . Thyrotoxicosis and periodic paralysis: improvement with beta blockade . Ann Intern Med . 1974;81:332–336
  89. Lin SH , Chau T , Wu CC , Yang SS . Osmotic demyelination syndrome following correction of chronic hyponatremia with normal saline . Am J Med Sci . 2002;323:259–262
  90. Lohr JW . Osmotic demyelination syndrome following correction of hyponatremia: association with hypokalemia . Am J Med . 1994;96:408–413
  91. Lin SH , Hsu YJ , Chiu JS , Chau T , Hsu CW , Davids MR , et al.   Osmotic demyelination syndrome: a potentially avoidable disaster . QJM . 2003;96:935–947
  92. Knochel JP . Diuretic-induced hypokalemia . Am J Med . 1984;77:18–27
  93. Whang R , Flink EB , Dyckner T , Wester PO , Alkawa JK , Rayn MP . Magnesium depletion as a cause of refractory potassium repletion . Arch Intern Med . 1985;149:186–189
  94. Francisco LL , Sawin LL , DiBona GF . Mechanism of negative potassium balance in the magnesium-deficient rat . Proc Soc Exp Biol Med . 1981;168:382–388
  95. Lu Z , MacKinnon R . Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel . Science . 1994;371:243–245
  96. Huang CL , Kuo E . Mechanism of hypokalemia in magnesium deficiency . J Am Soc Nephrol . 2007;18:2649–2652
  97. Ruml LA , Pak CY . Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss . Am J Kidney Dis . 1999;34:107–113
  98. Magner PO , Robinson L , Halperin RM , Zettle R , Halperin ML . The plasma potassium concentration in metabolic acidosis; a re-evaluation . Am J Kidney Dis . 1988;11:220–224
  99. Palmer L , Frindt G . Regulation of the apical K+ channels in the rat cortical collecting tubule during changes in K+ intake . Am J Physiol . 1999;277:F805–F812
  100. Cheema-Dhadli S , Lin SH , Chee KC , Kamel KS , Halperin ML . Requirement for a high rate of potassium excretion in rats consuming a low electrolyte diet . J Physiol . 2006;572:493–501

PII: S1561-5413(08)60014-9

doi: 10.1016/S1561-5413(08)60014-9

Hong Kong Journal of Nephrology
Volume 10, Issue 1 , Pages 14-26 , April 2008

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