Hypokalemia Clinical Presentation

  • Author: Eleanor Lederer, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Aug 5, 2009
 

History

  • Symptoms are nonspecific and predominantly are related to muscular or cardiac function.
    • Weakness and fatigue are the most common complaints. The muscular weakness that occurs with hypokalemia can manifest in protean ways, ie, dyspnea, constipation or abdominal distention, or exercise intolerance. Rarely, muscle weakness progresses to frank paralysis.
    • Occasionally, a patient may complain of worsening diabetes control or polyuria due to a recent onset of hyperglycemia or nephrogenic diabetes insipidus.
    • The patient also may complain of palpitations.
    • With severe hypokalemia or total body potassium deficits, muscle cramps and pain can occur with rhabdomyolysis.
  • When the diagnosis of hypokalemia is discovered, investigate potential pathophysiologic mechanisms.
    • Poor intake may result from the following:
      • Eating disorders
      • Dental problems
      • Poverty
    • Increased excretion may be due to the following:
      • Medications, including diuretics, AIDS therapy, or antibiotics
      • Polyuria
      • Vomiting or diarrhea
    • Shift of potassium into the intracellular space may occur due to the following:
      • Recurrent episodes of paralysis
      • Use of high doses of insulin
      • High-dose beta agonist therapy (eg, for chronic obstructive pulmonary disease)
Next

Physical

  • Vital signs generally are normal, except for occasional tachycardia or tachypnea due to respiratory muscle weakness.
    • Hypertension may be a clue to primary hyperaldosteronism, renal artery stenosis, licorice ingestion, or the more unusual forms of genetically transmitted hypertensive syndromes such as congenital adrenal hyperplasia, glucocorticoid remediable hypertension, or Liddle syndrome.
    • Relative hypotension should suggest occult laxative use, diuretic use, bulimia, or one of the unusual tubular disorders such as Bartter syndrome or Gitelman syndrome (see Bartter Syndrome). Bear in mind that occult diuretic use is far more common than either congenital tubular disorder and is, in fact, also called "pseudo Bartter."
  • Muscle weakness and flaccid paralysis may be present.
  • Patients may have depressed or absent deep-tendon reflexes.
Previous
Next

Causes

Pathophysiologic mechanisms include poor intake, increased excretion, or a shift of potassium from the extracellular to the intracellular space. Mechanisms causing increased excretion are the most common. Singly, poor intake or an intracellular shift is a distinctly uncommon cause. Often, several disorders are present simultaneously.

  • Poor intake
    • Eating disorders: Anorexia, bulimia, starvation, pica, and alcoholism
    • Dental problems: Inability to chew or swallow
    • Poverty: Lack of food, ie, "tea-and-toast" diet of elderly individuals
    • Hospitalization: Potassium-poor TPN
  • Increased excretion
    • Endogenous mineralocorticoid excess
      • Cushing disease
      • Primary hyperaldosteronism, most commonly due to adenoma or bilateral adrenal hyperplasia
      • Secondary hyperaldosteronism due to volume depletion, congestive heart failure, cirrhosis, or vomiting
      • Adrenocortical carcinoma
      • Tumor that is producing adrenocorticotropic hormone
      • Congenital disorders - Congenital adrenal hyperplasia (11-beta hydroxylase or 17-alpha hydroxylase deficiency) or glucocorticoid-remediable hypertension
    • Hyperreninism due to renal artery stenosis
    • Exogenous mineralocorticoid excess
      • Steroid therapy for immunosuppression
      • Glycyrrhizic acid - Inhibits 11-beta hydroxysteroid dehydrogenase; contained in licorice and Chinese herbal preparations
      • Renal tubular disorders - Type I and type II renal tubular acidosis
      • Hypomagnesemia
    • Congenital disorders
      • Bartter syndrome: This is a group of autosomal-recessive disorders characterized by hypokalemic metabolic alkalosis and hypotension. Mutations in 6 different renal tubular proteins in the loop of Henle have been discovered in individuals with clinical Bartter syndrome.[10, 11] They are the NaKCl (NKCC2) transporter; the ROMK1 potassium channel; the chloride channel CLCKa either alone or in combination with the chloride channel CLCKb; the calcium sensing receptor; and barttin, a protein required for the surface expression of the chloride channels. The most severe cases present antenatally or neonatally with profound volume depletion and hypokalemia. Less severe cases present in childhood or early adulthood with persistent hypokalemic metabolic alkalosis that is resistant to replacement therapy. Type IV, a variant to the classic Bartter syndrome, is associated with sensorineural hearing loss.
      • Gitelman syndrome: This is an autosomal-recessive disorder characterized by hypokalemic metabolic alkalosis and low blood pressure. It is caused by a defect in the thiazide-sensitive sodium chloride transporter in the distal tubule. Compared to Bartter syndrome, it generally is milder, presents later, and is complicated by hypomagnesemia. In contrast, patients with Bartter syndrome generally do not develop hypomagnesemia. Hypocalciuria is also frequently found in Gitelman syndrome, while the patients with Bartter syndrome are more likely to have increased urinary calcium excretion.
      • Liddle syndrome: This syndrome is an autosomal-recessive disorder characterized by a mutation in the epithelial sodium channel in the aldosterone-sensitive portion of the nephron, leading to unregulated sodium reabsorption, hypokalemic metabolic alkalosis, and severe hypertension.
    • Osmotic diuresis: Mannitol and hyperglycemia can cause osmotic diuresis.
    • Increased gastrointestinal losses: Losses can result from diarrhea or small intestine drainage. The problem can be particularly prominent in tropical illnesses, such as malaria or leptospirosis.[12] Severe hypokalemia has also been reported with villous adenoma or VIPomas.[13]
    • Drugs
      • Diuretics (carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics): Increased collecting duct permeability or increased gradient for potassium secretion can result in losses.
      • Some penicillins
      • Exogenous bicarbonate ingestion
      • Amphotericin B, azole class of antifungal agents, echinocandin class of antifungal agents[14]
      • Gentamicin
      • Cisplatin
      • Stacker 2[15]
      • Beta-agonist intoxication[16]
  • Shift of potassium from extracellular to intracellular space
    • Alkalosis, metabolic or respiratory
    • Insulin administration or glucose administration: This stimulates insulin release.
    • Intensive beta-adrenergic stimulation
    • Hypokalemic periodic paralysis is a rare disorder with recurrent periods of hypokalemic paralysis between periods of normal serum potassium levels. In most cases, it is due to an abnormality in the alpha 1 subunit of the dihydropyridine-sensitive calcium channel in the skeletal muscle. How a defect in a calcium channel produces hypokalemic paralysis is not well understood.
    • Thyrotoxic periodic paralysis is an acquired form of hypokalemic periodic paralysis and is most common in Asian males. The mechanism by which hyperthyroidism produces hypokalemic paralysis is not yet understood, but theories include increased Na-K-ATPase activity, which has been found in patients with both thyrotoxicosis and paralysis.
    • Refeeding: This is observed in prolonged starvation, eating disorders, and alcoholism.
Previous
Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Eleanor Lederer, MD  Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Rosemary Ouseph, MD  Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine

Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons

Disclosure: Nothing to disclose.

Leslie Ford, MD  Assistant Professor of Medicine, Kidney Disease Program, University of Louisville School of Medicine

Leslie Ford, MD is a member of the following medical societies: American Medical Association, American Society of Nephrology, and Kentucky Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

James W Lohr, MD  Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Christie P Thomas, MBBS, FRCP, FASN, FAHA  Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians

Disclosure: Genzyme Grant/research funds Other

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

References

  1. Harvey TC. Addison's disease and the regulation of potassium: the role of insulin and aldosterone. Med Hypotheses. 2007;69(5):1120-6. [Medline].

  2. Spat A. Glomerulosa cell--a unique sensor of extracellular K+ concentration. Mol Cell Endocrinol. Mar 31 2004;217(1-2):23-6. [Medline].

  3. Greenlee M, Wingo CS, McDonough AA, Youn JH, Kone BC. Narrative review: evolving concepts in potassium homeostasis and hypokalemia. Ann Intern Med. May 2009;150:619-625. [Medline].

  4. McDonough AA, Thompson CB, Youn JH. Skeletal muscle regulates extracellular potassium. Am J Physiol Renal Physiol. Jun 2002;282(6):F967-74. [Medline]. [Full Text].

  5. McDonough AA, Youn JH. Role of muscle in regulating extracellular [K+]. Seminars in Nephrology. 2005;25:335-342. [Medline].

  6. Greenfeld D, Mickley D, Quinlan DM, Roloff P. Hypokalemia in outpatients with eating disorders. Am J Psychiatry. 152(1):60-3. [Medline].

  7. Miller KK, Grinspoon SK, Ciampa J, et al. Medical findings in outpatients with anorexia nervosa. Arch Intern Med. Mar 14 2005;165(5):561-6. [Medline].

  8. Elisaf M, Liberopoulos E, Bairaktari E, Siamopoulos K. Hypokalaemia in alcoholic patients. Drug Alcohol Rev. 21(1):73-6. [Medline].

  9. Al-Momen A, El-Mogy I. Intragastric balloon for obesity: a retrospective evaluation of tolerance and efficacy. Obes Surg. Jan 2005;15(1):101-5. [Medline].

  10. Bichet DG, Fujiwara TM. Reabsorption of sodium chloride--lessons from the chloride channels. N Engl J Med. Mar 25 2004;350(13):1281-3. [Medline].

  11. Naesens M, Steels P, Verberckmoes R, et al. Bartter's and Gitelman's syndromes: from gene to clinic. Nephron Physiol. 2004;96(3):p65-78. [Medline].

  12. Sitprija V. Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis. Nat Clin Pract Nephrol. Feb 2008;4(2):91-101. [Medline].

  13. Kapoor R, Moseley RH, Kapoor JR, et al. Clinical problem-solving. Needle in a haystack. N Engl J Med. Feb 5 2009;360(6):616-21. [Medline].

  14. Lionakis MS, Samonis G, Kontoyiannis DP. Endocrine and Metabolic Manifestations of Invasive Fungal Infections and Systemic Antifungal Treatment. Mayo Clin Proc. 2008;83:1046-1060.

  15. de Wijkerslooth LR, Koch BC, Malingre MM, et al. Life-threatening hypokalaemia and lactate accumulation after autointoxication with Stacker 2, a 'powerful slimming agent'. Br J Clin Pharmacol. Nov 2008;66(5):728-31. [Medline].

  16. Matteucci MJ, Danen DA. A Levalbuterol Therapeutic Misadventure. Journal of Emergency Medicine. 2008;35:209-211.

  17. Weinstein AM. A mathematical model of rat cortical collecting duct: determinants of the transtubular potassium gradient. Am J Physiol Renal Physiol. Jun 2001;280(6):F1072-92. [Medline].

  18. West ML, Marsden PA, Richardson RM, et al. New clinical approach to evaluate disorders of potassium excretion. Miner Electrolyte Metab. 1986;12(4):234-8. [Medline].

  19. Karagiannis A, Tziomalos K, Papageorgiou A, Kakafika AI, Pagourelias ED, Anagnostis P, et al. Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism. Expert Opin Pharmacother. March 2008;9:509-515. [Medline].

  20. Pitt B, Bakris G, Ruilope LM, et al. Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation. Oct 14 2008;118(16):1643-50. [Medline].

  21. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Ann Intern Med. March 2009;150:387-395. [Medline].

  22. Born-Frontsberg E, Reincke M, Rump LC, et al. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry. J Clin Endocrinol Metab. Apr 2009;94(4):1125-30. [Medline].

  23. Toto A, Takahashi Y, Kishimoto M, Minowada S, Aibe H, Hasuo K, et al. Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia. Intern Med. 2009;48:219-223. [Medline].

  24. Shafi, T, Appel LJ, Miller III, ER, Klag MJ, et al. Changes in Serum Potassium Mediate Thiazide-Induced Diabetes. Hypertension. 2008;52:1022-1029.

  25. Amirlak I, Dawson KP. Bartter syndrome: an overview. QJM. Apr 2000;93(4):207-15. [Medline].

  26. Bloomfield RL, Wilson DJ, Buckalew VM Jr. The incidence of diuretic-induced hypokalemia in two distinct clinic settings. J Clin Hypertens. Dec 1986;2(4):331-8. [Medline].

  27. Carlisle EJ, Donnelly SM, Vasuvattakul S, et al. Glue-sniffing and distal renal tubular acidosis: sticking to the facts. J Am Soc Nephrol. 1(8):1019-27. [Medline].

  28. ChrisAnderson D, Heimburger DC, Morgan SL, et al. Metabolic complications of total parenteral nutrition: effects of a nutrition support service. JPEN J Parenter Enteral Nutr. May-Jun 1996;20(3):206-10. [Medline].

  29. Cohen JD, Neaton JD, Prineas RJ, Daniels KA. Diuretics, serum potassium and ventricular arrhythmias in the Multiple Risk Factor Intervention Trial. Am J Cardiol. 60(7):548-54. [Medline].

  30. 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. 160(16):2429-36. [Medline].

  31. Dargie HJ, Cleland JG, Leckie BJ, et al. Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure. Circulation. May 1987;75(5 Pt 2):IV98-107. [Medline].

  32. Freis ED. The efficacy and safety of diuretics in treating hypertension. Ann Intern Med. Feb 1 1995;122(3):223-6. [Medline].

  33. Gennari FJ. Hypokalemia. N Engl J Med. Aug 13 1998;339(7):451-8. [Medline].

  34. Gordon RD, Stowasser M, Klemm SA, Tunny TJ. Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes. Steroids. Jan 1995;60(1):35-41. [Medline].

  35. Konrad M, Vollmer M, Lemmink HH, et al. Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol. 11(8):1449-59. [Medline].

  36. Krishna GG. Effect of potassium intake on blood pressure. J Am Soc Nephrol. Jul 1990;1(1):43-52.

  37. Kurtz I. Molecular pathogenesis of Bartter''s and Gitelman''s syndromes. Kidney Int. Oct 1998;54(4):1396-410. [Medline].

  38. Materson BJ. Diuretics, potassium, and ventricular ectopy. Am J Hypertens. May 1997;10(5 Pt 2):68S-72S. [Medline].

  39. Moser M. Current hypertension management: separating fact from fiction. Cleve Clin J Med. Jan-Feb 1993;60(1):27-37. [Medline].

  40. Moser M. Diuretics and cardiovascular risk factors. Eur Heart J. Dec 1992;13 Suppl G:72-80. [Medline].

  41. Nadler JL, Rude RK. Disorders of magnesium metabolism. Endocrinol Metab Clin North Am. Sep 1995;24(3):623-41. [Medline].

  42. Packer M. Pathophysiological mechanisms underlying the effects of beta-adrenergic agonists and antagonists on functional capacity and survival in chronic heart failure. Circulation. Aug 1990;82(2 Suppl):I77-88. [Medline].

  43. Paice BJ, Paterson KR, Onyanga-Omara F, et al. Record linkage study of hypokalaemia in hospitalized patients. Postgrad Med J. Mar 1986;62(725):187-91. [Medline].

  44. Papademetriou V. Diuretics in hypertension: clinical experiences. Eur Heart J. Dec 1992;13 Suppl G:92-5. [Medline].

  45. Perazella MA, Brown E. Electrolyte and acid-base disorders associated with AIDS: an etiologic review. J Gen Intern Med. Apr 1994;9(4):232-6. [Medline].

  46. Rude RK. Magnesium deficiency: a cause of heterogeneous disease in humans. J Bone Miner Res. Apr 1998;13(4):749-58. [Medline].

  47. Schurman SJ, Shoemaker LR. Bartter and Gitelman syndromes. Adv Pediatr. 2000;47:223-48. [Medline].

  48. Simon DB, Lifton RP. Ion transporter mutations in Gitelman''s and Bartter''s syndromes. Curr Opin Nephrol Hypertens. Jan 1998;7(1):43-7. [Medline].

  49. Stewart PM. Mineralocorticoid hypertension. Lancet. Apr 17 1999;353(9161):1341-7. [Medline].

  50. van Gilst WH, Tijssen JG, van Es GA, Lubsen J. Serum potassium values in relation to the use of diuretics in patients with unstable angina pectoris. Eur Heart J. 9(7):795-9. [Medline].

  51. Victor N. Uebeler, Cindy E. Nuss, John J. Renger and Thomas M. Connolly. Role of voltage-gated calcium channels in potassium-stimulated aldosterone secretion from rat adrenal zona glomerulosa cells. The Journal of Steroid Biochemistry and Molecular Biology. October 2004;92:209-218. [Medline].

  52. Wahr JA, Parks R, Boisvert D, et al. Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter Study of Perioperative Ischemia Research Group. JAMA. Jun 16 1999;281(23):2203-10. [Medline].

  53. Warnock DG. Liddle syndrome: an autosomal dominant form of human hypertension. Kidney Int. Jan 1998;53(1):18-24. [Medline].

  54. Weiner ID, Wingo CS. Hypokalemia--consequences, causes, and correction. J Am Soc Nephrol. Jul 1997;8(7):1179-88. [Medline].

  55. Young JH, Massy S, Ahmad S. Hypertension with hypokalemia. Nephrology Rounds. 1998;2:1-7.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.