• Clinical science
  • Clinician

Hypokalemia

Summary

Hypokalemia (low serum potassium) is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or diuretic medication). Mild hypokalemia may be asymptomatic or cause mild nonspecific symptoms such as nausea, muscle weakness, and fatigue. Severe deficiency can cause cardiac arrhythmias and death. Treatment consists of oral or IV supplementation in conjunction with treatment of the underlying cause. In concurrent hypomagnesemia, which may lead to refractory hypokalemia, the simultaneous repletion of magnesium and potassium is necessary.

Definition

  • Serum potassium (K+) level < 3.5 mEq/L [1]
  • Severe hypokalemia: K+ level < 2.5 mEq/L

Etiology

Hypokalemia is most often caused by renal or gastrointestinal potassium loss. Other electrolyte imbalances (e.g., hypomagnesemia), alkalosis, and several medications can also have an impact on potassium homeostasis.

Etiology of hypokalemia [1][2]
Causes
Gastrointestinal loss
Renal loss
Intracellular shift
Insufficient intake

Pathophysiology

  • Potassium is an important factor in maintaining the resting membrane potential.
  • ↓ Extracellular K+ concentration → ↑ resting membrane potential (more negative than -90 mV) → ↓ excitability [3]
  • Alkalosis can impact potassium balance via intracellular shifts and vice versa.
    • Alkalosis ↓ extracellular H+ stimulation of the Na+/H+ antiporter (transfers H+ out of the cells in exchange for Na+) → ↑ intracellular Na+ ↑ sodium gradient stimulates the Na+/K+-ATPase (transfers K+ into the cells in exchange for Na+) → ↓ extracellular K+ concentration
    • Hypokalemia↓ extracellular K+ concentration → ↓ potassium gradient inhibits the Na+/K+-ATPase ↓ extracellular Na+↓ sodium gradient inhibits the Na+/H+ antiporter ↓ extracellular H+alkalosis
    • Exception: In renal tubular acidosis, findings include hypokalemia and metabolic acidosis!

K+ acts like H+: Hypokalemia leads to alkalosis and vice versa!

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

  • Hypomagnesemia can impact potassium balance via the following mechanisms of increased renal loss: [4]
    • Magnesium serves as a cofactor in Na+/K+-ATPases → hypomagnesemia disrupts the Na+/K+-ATPase in the basolateral membrane of the proximal convoluted loop of Henle ↓ Na+ reabsorption → ↑ luminal Na+ ↑ Na+ reabsorption and ↑ K+ secretion by the principal cells distally
    • Apical ROMK channels in principal cells are inhibited by intracellular magnesium. With low levels of magnesium available, the ROMK channels are not inhibited, resulting in increased K+ secretion.

Hypomagnesemia can lead to refractory hypokalemia!

Clinical features

Patients may be asymptomatic, particularly if the deficiency is mild. Symptoms usually occur if serum K+ levels are < 3.0 mEq/L and/or decrease rapidly. [2]

Hypokalemia (and hyperkalemia) can cause cardiac arrhythmia and may lead to ventricular fibrillation!

Diagnostics

All patients require an ECG and laboratory studies to confirm the diagnosis and rule out concurrent electrolyte abnormalities. Further diagnostic tests depend on the suspected underlying etiology.

Initial evaluation

Laboratory studies [1]

  • Electrolytes and kidney function
  • Blood gas (venous or arterial): : may show metabolic alkalosis
  • Urinary potassium: Consider measuring to narrow down underlying etiology [9][10][11]
    • Methods
      • Spot urine: rapid assessment, indicated in urgent cases , less reliable than 24-hour collections
      • 24-hour urine collection: less practical, indicated for chronic cases and uncertain diagnoses, more accurate than spot urine
    • Findings
      • Renal loss; : spot urine > 15–20 mEq/L (24 hour collection > 15 mEq/L) [10][1]
      • Extrarenal loss; : spot urine < 15–20 mEq/L (24 hour collection < 15 mEq/L) [11]

Consider confirming abnormal serum potassium levels with a repeat blood draw.

ECG [2][12]

To remember that low potassium may result in a flattened T wave, think of: "No pot, no tea (T)!"

Identification of underlying etiology

  • If the etiology is still unclear, further testing can help determine the underlying etiology.
  • Imaging is not routinely required but may be necessary if certain underlying etiologies are suspected. [1]
Evaluation of underlying etiology in hypokalemia [1][13]
Type of potassium loss Clinical features Recommended tests Findings and interpretation
Extrarenal losses
  • Symptoms of thyrotoxicosis
  • TSH
  • T3 and T4
  • TSH
  • ↑ T3 and T4
Renal loss
  • Hypotension or normotension
  • Serum bicarbonate (HCO3-)
  • OR blood gas

Treatment

Approach

Most patients require potassium chloride (KCl) repletion, management of concurrent electrolyte abnormalities (see electrolyte repletion), and treatment of the underlying cause. See potassium replacement for detailed repletion regimens for hypokalemia, treatment goals, warnings and adverse effects.

  • Severe hypokalemia (< 2.5 mEq/L) and/or high risk of recurrent severe hypokalemia
    • KCl: High-dose IV repletion
    • Consider admission to ICU, continuous cardiac monitoring, and central line placement.
  • Moderate hypokalemia (2.5–2.9 mEq/L)
    • KCl: Oral or IV repletion may be used.
    • Disposition usually determined by treatment of underlying disorder
  • Mild hypokalemia with easily reversible cause (3.0–3.5 mEq/L)
    • Prioritize treatment of the underlying condition (e.g., GI fluid losses).
    • Consider oral supplementation.
    • Consider increasing dietary potassium intake. [14]
    • Patients can usually be discharged after stabilization.

IV potassium may cause local irritation and lead to cardiac arrhythmias. Therefore, it should always be administered slowly (max. rate of 10 mEq/hour via a peripheral line or 40 mEq/hour via a central line)

Treatment of underlying condition

Potassium supplementation will be ineffective if concurrent hypomagnesemia is left untreated (see magnesium repletion).

  • 1. Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G, Vryonidou A. Hypokalemia: a clinical update. Endocrine Connections. 2018; 7(4): pp. R135–R146. doi: 10.1530/ec-18-0109.
  • 2. Domino FJ. The 5-Minute Clinical Consult 2011. Lippincott Williams & Wilkins; 2010.
  • 3. Porth C. Essentials of Pathophysiology. Lippincott Williams & Wilkins; 2011.
  • 4. Unwin RJ, Luft FC, Shirley DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nature Reviews Nephrology. 2011; 7(2): pp. 75–84. doi: 10.1038/nrneph.2010.175.
  • 5. Mehta M, Mathews A. The Hospitalist Manual. PMPH-USA; 2010.
  • 6. Liamis G. Diabetes mellitus and electrolyte disorders. World J Clin Cases. 2014; 2(10): p. 488. doi: 10.12998/wjcc.v2.i10.488.
  • 7. Lote CJ. Principles of Renal Physiology. Springer Science & Business Media; 2000.
  • 8. Bryson PD. Comprehensive Reviews in Toxicology. CRC Press; 1996.
  • 9. Marini JJ, Wheeler AP. Critical Care Medicine. Lippincott Williams & Wilkins; 2010.
  • 10. Ronco C, Bellomo R, Kellum JA. Critical Care Nephrology. Elsevier Health Sciences; 2009.
  • 11. Greenberg A. Primer on Kidney Diseases E-Book. Elsevier Health Sciences; 2009.
  • 12. Levis JT. ECG diagnosis: hypokalemia. Perm J. 2012; 16(2): p. 57. doi: 10.7812/tpp/12-015.
  • 13. Gleadle J, Li J, Yong T. Clinical Investigations at a Glance. John Wiley & Sons; 2017.
  • 14. Magee CC, Tucker JK, Singh AK. Core Concepts in Dialysis and Continuous Therapies. Springer; 2016.
  • Agabegi SS, Agabegi ED. Step-Up To Medicine. Baltimore, MD, USA: Lippincott Williams & Wilkins; 2013.
  • Lederer E. Hypokalemia. In: Batuman V. Hypokalemia. New York, NY: WebMD. http://emedicine.medscape.com/article/242008-overview. Updated December 29, 2016. Accessed February 9, 2017.
  • Viera AJ, Wouk N. Potassium disorders: Hypokalemia and hyperkalemia. Am Fam Physician. 2015; 92(6): pp. 487–495. url: http://www.aafp.org/afp/2015/0915/p487.html.
  • Mount DB. Clinical manifestations and treatment of hypokalemia in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-treatment-of-hypokalemia-in-adults?source=search_result&search=hypokalemia&selectedTitle=1~150#H3819731. Last updated January 7, 2016. Accessed February 9, 2017.
  • Yuval Grober, Hagit Grober, Max Wintermark, John A. Jane, Edward H. Oldfield. Comparison of MRI techniques for detecting microadenomas in Cushing's disease. J Neurosurg. 2018; 128(4): pp. 1051–1057. doi: 10.3171/2017.3.jns163122.
last updated 10/20/2020
{{uncollapseSections(['Xj19_g0', '2j1T-g0', 'cj1azg0', 'Vj1Gzg0', 'dj1ozg0', '1j12zg0', 'Wj1Pzg0'])}}