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Disorders of potassium homeostasis 

Disorders of potassium homeostasis

Disorders of potassium homeostasis

J Firth



Hypokalaemia—enhanced discussion of (1) association with hypomagnesaemia and treatment in this circumstance; (2) investigative approach, with use of the urinary potassium to creatinine ratio or calculation of the transtubular potassium concentration gradient (TTKG) to differentiate renal and non-renal causes; (3) channelopathies as the basis for at least some cases of thyrotoxic periodic paralysis.

Hyperkalaemia—only minor changes to this section of the chapter required and made.

Updated on 25 May 2011. The previous version of this content can be found here.
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date: 24 April 2017

The normal range of potassium concentration in serum is 3.5 to 5.0 mmol/litre and within cells it is 150 to 160 mmol/litre, the ratio of intracellular to extracellular potassium concentration being a critical determinant of cellular resting membrane potential and thereby of the function of excitable tissues.


Hypokalaemia is defined as serum potassium concentration lower than 3.5 mmol/litre, which is the most common electrolyte abnormality seen in clinical practice, found in about 20% of hospital inpatients.

Clinical features and investigation—mild hypokalaemia is asymptomatic, but a variety of nonspecific symptoms develop with more severe disturbance, and serious neuromuscular problems sometimes arise at serum potassium concentration lower than 2.5 mmol/litre. Extensive testing of patients with mild hypokalaemia is almost certainly inappropriate and likely to be fruitless if pursued.

Emergency management—this is rarely required, but intravenous infusion of potassium (maximum 1 mmol/min by volumetric pump, with close monitoring) should be given in the rare circumstances of life-threatening cardiac arrhythmia or muscular paralysis.

Aetiology—there are a very large number of possible causes of hypokalaemia, but in most instances the diagnosis is immediately apparent, the most common causes being: (1) diuretics—particularly thiazides; (2) vomiting—where the renal response to metabolic alkalosis leads to hypokalaemia due to renal loss of potassium; and (3) diarrhoea—with direct loss of potassium in stool. Patients with unexplained severe hypokalaemia are a considerable challenge for both diagnosis and management, with the differential diagnosis usually comprising: (1) various abnormalities of tubular potassium transport; (2) concealed vomiting and/or usage of purgatives—which are strongly supported by the finding of a low plasma chloride concentration with the virtual absence of chloride from the urine; and (3) concealed ingestion of diuretics—which should be tested for if urinary chloride is greater than 20 mmol/litre.

Renal tubular causes of hypokalaemia—the most common genetic cause is Gitelman’s syndrome, an autosomal recessive condition caused by mutations in the Na–Cl cotransporter (NCCT) in the distal convoluted tubule. It may be asymptomatic, but can cause nonspecific symptoms, and is associated with hypotension, alkalosis, hypomagnesaemia, hypocalciuria, and hypermagnesuria. Management is with potassium and magnesium supplements. Other causes of tubular wasting of potassium include: (1) Bartter’s syndrome—four types are recognized, due to mutations in different tubular cotransporters, channels, or associated proteins (NKCC2, ROMK, CLCNKA, CLCNKB, and barttin); and (2) mineralocorticoid excess—real or apparent, each of various types.

Altered internal balance causing hypokalaemia—there are several rare conditions in which hypokalaemia is associated with episodes of extreme weakness/paralysis, including: (1) thyrotoxic periodic paralysis—mainly affects Asian men; attacks are treated with β‎-blocker (propranolol) and prevented by treatment of hyperthyroidism; and (2) familial hypokalaemic periodic paralysis—caused by mutations in one of three genes (CACNL1A3, SCN4A, and KCNE3); attacks are treated with intravenous potassium and prevented by carbonic anhydrase inhibitor (dichlorphenamide).


Hyperkalaemia, defined as serum potassium concentration of greater than 5.0 mmol/litre, is asymptomatic, and severe hyperkalaemia (>7 mmol/litre) is the most serious of all electrolyte disorders because it can cause cardiac arrest.

Clinical assessment—the electrocardiogram (ECG) is the best guide to the significance of hyperkalaemia in any particular individual—as the serum potassium rises the following changes are seen: (1) tenting of the T wave; (2) P-wave flattening, prolongation of the P–R interval, and widening of the QRS complex; and (3) a ‘sine wave’ pattern as a prelude to ventricular fibrillation and death.

Emergency management—patients with ECG manifestations more severe than tenting of the T waves should be given intravenous calcium gluconate (10 ml of 10%) followed by intravenous insulin and glucose, or nebulized salbutamol (see Chapter 21.5 for further discussion).

Aetiology—there are many causes of hyperkalaemia, but by far the most common are: (1) renal failure—acute kidney injury or chronic kidney disease; and/or (2) drugs—in particular potassium supplements, potassium-sparing diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers.

Other causes of hyperkalaemia—these include: (1) hyporeninaemic hypoaldosteronism—patients with tubulointerstitial renal disease or diabetes often have a high serum potassium despite a glomerular filtration rate (GFR) that should be sufficient to maintain normokalaemia; the reason for this is not known, and diagnostic criteria are not well defined; treatment is with dietary potassium restriction and avoidance of drugs that can cause hyperkalaemia; (2) other drugs—nonsteroidal anti-inflammatory agents, heparin, calcineurin inhibitors, and trimethoprim–sulfamethoxazole; and (3) renal transport abnormalities—type IV renal tubular acidosis and pseudohypoaldosteronism types 1 and 2 (Gordon’s syndrome).

Altered internal balance causing hyperkalaemia: (1) exhaustive exercise; (2) acidosis; (3) drugs—including digoxin and depolarizing muscle relaxants; and (4) hyperkalaemic periodic paralysis (very rare).

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