Hypokalemia pathophysiology

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Hypokalemia Microchapters


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Aida Javanbakht, M.D.Assistant Editor(s)-In-Chief: Jack Khouri, Alieh Behjat, M.D.[3]



Hypokalemia can result from several conditions:

  • Trans-cellular shifts of potassium inside the cells (most common)
  • Renal loss of potassium
  • Gastrointestinal (GI) loss of potassium
  • Increased hematopoiesis (increased cellular use of potassium)
  • Decreased intake of potassium (least common)

Shown below is a table summarizing the different pathophysiological processes that can lead to hypokalemia. [1] [2] [3] [4]

Trans-cellular shifts Renal loss GI loss Increased hematopoiesis Decreased intake of potassium

Subject is normo or hypotensive
Associated with acidosis

Associated with alkalosis

Variable acid/base status

Subject is hypertensive
Primary hyperaldosteronism

  • Conn's syndrome

Secondary hyperaldosteronism

  • Renovascular disease
  • Renin secreting tumor

Non aldosterone increase in mineralcorticoid

Associated with metabolic acidosis

Associated with metabolic alkalosis

The Role of the Kidney


Factors Increasing Kidney Potassium Excretion

Some Factors Affecting Potassium Distribution Between the Cells and the Extracellular Fluid

The Physiologic Role of Potassium

  • Potassium is the most common intracellular cation. Approximately 98% of total potassium exists in the intracellular fluid (ICF), which has a normal range of 140–150 mEq/l. Merely 2% of this cation is placed in the extracellular fluids (ECF), where it ranges from 3.5 to 5 mEq/l.
  • Potassium is essential during numerous body functions, particularly for excitable cells such as muscle and nerve cells.
  • Diet, mostly fruits and vegetables, is the major source of potassium for the body.[7] [8]

The Cellular Effect of Hypokalemia

The normal ratio of intracellular to extracellular potassium in the body is vital for the generation of action potential and results in appropriate cardiac and neuromuscular cells performance. By decreasing the potassium concentration in extracellular space, the amount of the potassium gradient across the cell membrane is risen and results in hyperpolarization. This alteration moves the resting membrane potential from the threshold to a higher level; hence, a bigger than standard stimulus is necessary to generate an action potential. Consequently, reduced excitability in the neurons and muscle cells would appear and cause flaccid muscle paralysis, rhabdomyolysis (in severe hypokalemia), and paralytic ileus.[9]

Pathophysiology of Hypokalemic Heart Arrhythmias

  • Hypokalemia in neurons and muscle cells reduces the membrane responsiveness and causes hyperpolarization. But in cardiac cells, specifically in the conducting system, depolarization is observed. The main reason is the alteration of ion selectivity of TWIK-1 K+ channels, which in standard situation leak potassium. During pathological hypokalemia, these channels transport sodium inward the cells, leading to paradoxical depolarization and may result in cardiac arrhythmias.
  • Moreover, Hypokalemia can inhibit Na+-K+ ATPase activity, leading to intracellular Na+ And Ca2+ increase. The accumulation of intracellular ca2+ activates calmodulin kinase and, in turn, induces late Na+ and Ca2+ currents and causes a further reduction in repolarization reserve. This would result in early after-depolarization (EAD)–mediated arrhythmias.[10] [11]

Pathophysiology of Hypokalemic in GI system:


  1. Daly K, Farrington E (2013). "Hypokalemia and hyperkalemia in infants and children: pathophysiology and treatment". J Pediatr Health Care. 27 (6): 486–96, quiz 497–8. doi:10.1016/j.pedhc.2013.08.003. PMID 24139581.
  2. Unwin RJ, Luft FC, Shirley DG (February 2011). "Pathophysiology and management of hypokalemia: a clinical perspective". Nat Rev Nephrol. 7 (2): 75–84. doi:10.1038/nrneph.2010.175. PMID 21278718.
  3. Cheungpasitporn W, Suksaranjit P, Chanprasert S (February 2012). "Pathophysiology of vomiting-induced hypokalemia and diagnostic approach". Am J Emerg Med. 30 (2): 384. doi:10.1016/j.ajem.2011.10.005. PMID 22169581.
  4. Bisogni V, Rossi GP, Calò LA (June 2014). "Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology". Blood Press. 23 (3): 189–92. doi:10.3109/08037051.2013.832967. PMID 24053336.
  5. Hall, John (2016). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Elsevier. ISBN 978-1-4557-7005-2.
  6. Hall, John (2016). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Elsevier. ISBN 978-1-4557-7005-2.
  7. Weaver CM (2013). "Potassium and health". Adv Nutr. 4 (3): 368S–77S. doi:10.3945/an.112.003533. PMC 3650509. PMID 23674806.
  8. . doi:10.1159/000446268 Received: Check |doi= value (help). Missing or empty |title= (help)
  9. 9.0 9.1 Palmer, Biff F.; Clegg, Deborah J. (2016). "Physiology and pathophysiology of potassium homeostasis". Advances in Physiology Education. 40 (4): 480–490. doi:10.1152/advan.00121.2016. ISSN 1043-4046.
  10. Ma, L.; Zhang, X.; Chen, H. (2011). "TWIK-1 Two-Pore Domain Potassium Channels Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia". Science Signaling. 4 (176): ra37–ra37. doi:10.1126/scisignal.2001726. ISSN 1945-0877.
  11. Weiss, James N.; Qu, Zhilin; Shivkumar, Kalyanam (2017). "Electrophysiology of Hypokalemia and Hyperkalemia". Circulation: Arrhythmia and Electrophysiology. 10 (3). doi:10.1161/CIRCEP.116.004667. ISSN 1941-3149.
  12. Streeten, D. H. P.; Williams, E. M. Vaughan (1952). "Loss of cellular potassium as a cause of intestinal paralysis in dogs". The Journal of Physiology. 118 (2): 149–170. doi:10.1113/jphysiol.1952.sp004782. ISSN 0022-3751.

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