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Pathophysiology and management of hypokalemia: a clinical perspective

Nature Reviews Nephrology volume 7, pages 75–84 (2011)Cite this article

Abstract

Potassium (K+) ions are the predominant intracellular cations. K+ homeostasis depends on external balance (dietary intake [typically 100 mmol per day] versus excretion [95% via the kidney; 5% via the colon]) and internal balance (the distribution of K+ between intracellular and extracellular fluid compartments). The uneven distribution of K+ across cell membranes means that a mere 1% shift in its distribution can cause a 50% change in plasma K+ concentration. Hormonal mechanisms (involving insulin, β-adrenergic agonists and aldosterone) modulate K+ distribution by promoting rapid transfer of K+ across the plasma membrane. Extrarenal K+ losses from the body are usually small, but can be marked in individuals with chronic diarrhea, severe burns or prolonged sweating. Under normal circumstances, the kidney's distal nephron secretes K+ and determines final urinary excretion. In patients with hypokalemia (plasma K+ concentration <3.5 mmol/l), after the exclusion of extrarenal causes, alterations in sodium ion delivery to the distal nephron, mineralocorticoid status, or a specific inherited or acquired defect in distal nephron function (each of which affects distal nephron K+ secretion), should be considered. Clinical management of hypokalemia should establish the underlying cause and alleviate the primary disorder. This Review aims to inform clinicians about the pathophysiology and appropriate treatment for hypokalemia.

Key Points

  • Hypokalemia is common and generally limited; however, the condition can be life threatening

  • Understanding the basis of potassium (K+) distribution in the body is the first step in the diagnosis of hypokalemia

  • Levels of insulin, adrenergic activity, aldosterone, Na+,K+-ATPase activity, pH and osmolality can shift the internal distribution of K+ ions

  • Extrarenal losses, such as diarrhea or excess sweating, are generally (though not always) obvious

  • Renal losses of K+ ions are often an adverse effect of therapy

  • Successful treatment of hypokalemia requires the primary cause to be established and the underlying problem to be addressed

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Figure 1: Distribution of K+ in the body.
Figure 2: Cellular shifts in K+.
Figure 3: Renal K+ handling.
Figure 4: K+ secretion by principal cells.
Figure 5: A clinical algorithm for investigating hypokalemia.

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  1. Centre for Nephrology, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK

    Robert J. Unwin & David G. Shirley

  2. Experimental and Clinical Research Center and Max–Delbrück Center for Molecular Medicine, Robert-Rössle Strasse 10, Berlin, 13125, Germany

    Friedrich C. Luft

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R. J. Unwin, F. C. Luft and D. G. Shirley contributed equally to all aspects of this manuscript.

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Unwin, R., Luft, F. & Shirley, D. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol 7, 75–84 (2011). https://doi.org/10.1038/nrneph.2010.175

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