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Hypokalaemia

Essentials

  • Hypokalaemia denotes a state where the concentration of potassium in the plasma and the entire extracellular space is lower than 3.3 mmol/l.
  • Hypokalaemia is detected in 20% of hospitalised patients. Hypokalaemia is only mild in most cases.
  • Severe hypokalaemia is present in 5% of hospitalised patients; plasma potassium concentration being below 2.5 mmol/l.
  • In primary health care, hypokalaemia is detected in 10-40% of patients using diuretics.
  • Identifying the cause of hypokalaemia is essential for selecting appropriate treatment.

Potassium homeostasis

  • The plasma potassium level is regulated by shifting potassium between extracellular and intracellular spaces and through maintaining a balance between potassium intake and renal excretion.
  • Insulin and catecholamines regulate the entry of potassium into the intracellular space through stimulating the Na+/K+-ATPase enzyme on the cell membrane. An infusion of insulin and a strong adrenergic stimulation will, therefore, lead to hypokalaemia.
  • Aldosterone and other mineralocorticoids affect the body's potassium stores through regulating the excretion of potassium in the urine by activating the epithelial sodium channels in the renal tubules.
  • An excessive amount of mineralocorticoids will lead to hypokalaemia and their deficiency to hyperkalaemia.
  • A feedback system operates between plasma potassium concentration and aldosterone secretion; hyperkalaemia stimulates the secretion of aldosterone whereas hypokalaemia prevents its secretion.
  • The effect of aldosterone on the distal renal tubule is regulated by the amount of sodium delivered to the distal tubule and the acid-base balance. Low sodium delivery will suppress the kaliuretic effect of aldosterone.
  • The most common cause of hypokalaemia is the loss of potassium through the digestive tract or the use of diuretics.
  • It is important to identify hypokalaemia associated with hypertension, and consequently to suspect secondary hypertension and inappropriate activation of mineralocorticoid receptors.

Causes of hypokalaemia

  • Insufficient intake of dietary potassium is rarely the cause of hypokalaemia and is only possible where the daily intake is less than 1 g.
    • Anorexia nervosa
    • Chronic malnourishment
  • Excessive sweating or extensive burns may lead to loss of potassium through skin.
  • Often the condition in is caused by a mixture of several mechanisms.

Gastrointestinal loss

  • Infectious diarrhoea (e.g. salmonellosis or cholera)
  • Tumours (colonic villous polyps, VIPoma, gastrinoma)
  • Bowel surgery
  • Fistulae
  • Laxatives
  • Congenital chloride diarrhoea
  • Chronic vomiting (surreptitious vomiting)

Loss in the urine resulting from mineralocorticoid activity or impaired renal tubular ion transport

Hypokalaemia without hypertension

  • Diuretics
  • Alkalosis (chloride deficiency resulting from vomiting)
  • Magnesium deficiency
  • Disturbances in sodium and chloride transport (Bartter and Gitelman syndromes, congenital or acquired distal renal tubula acidosis, repair phase of tubular necrosis)
  • Antimicrobials (penicillin and its synthetic derivatives, amphotericin B, foscarnet)
  • Several cytostatic drugs

Hypokalaemia with hypertension

  • Primary hyperaldosteronism
  • Secondary hyperaldosteronism (renovascular and malignant hypertension, reninoma)
  • Hypercortisolism (of adrenal or hypothalamic origin, ectopic ACTH syndrome or pharmacological glucocorticoid therapy)
  • Hyperaldosteronism sensitive to glucocorticoid
  • Apparent mineralocorticoid excess (consumption of liquorice, deficiency of 11β-hydroxysteroid dehydroxygenase, deoxycorticosterone-producing tumours)
  • Liddle's syndrome, pheochromocytoma

Shift of potassium into the intracellular space

  • Alkalosis
  • Beta-adrenergic agents
  • Theophylline
  • Caffeine
  • Insulin infusion
  • Hypokalaemic periodic paralysis
  • Rapid proliferation of leukaemia cells
  • Starting treatment for megaloblastic anaemia

Recognition

  • Hypokalaemia is diagnosed by determining the plasma potassium concentration
  • Hypokalaemia-induced ECG changes include T wave flattening and inversion, ST segment depression and the appearance of a U wave.

Symptoms

  • Hypokalaemia causes muscle weakness, asthenia, constipation, polyuria and loss of appetite
  • Muscular symptoms appear when plasma potassium concentration falls to below 2.5 mmol/l
  • Hypokalaemia of an abrupt onset may cause frank paralysis
  • Hypokalaemia increases the risk of cardiac arrhythmias (extrasystoles, conduction defects, tachyarrhythmias), especially in coronary heart disease, heart failure and in patients using digoxin.
  • Glucose control is impaired, since insulin excretion from beta cells is reduced and insulin resistance increases.

Diagnosis

  • Ask the patient about
    • use of diuretics, glucocorticoids, laxatives and other drugs that cause hypokalaemia
    • liquorice consumption
    • gastrointestinal symptoms (diarrhoea, vomiting).
  • Physical examination
    • Blood pressure
    • Appearance
    • Nutritional state
    • Tooth erosion
  • First line investigations: acid-base balance, plasma potassium, sodium, chloride, ionised calcium, magnesium, creatinine
  • ECG
  • For differential diagnosis it is essential to establish whether the patient is hypertensive or normotensive.
    • The differential diagnosis of hypokalaemia in a normotensive patient must include the evaluation of renal chloride excretion.
    • The differential diagnosis in hypertensive patients concentrates on the results of renin and aldosterone assays.
  • If the cause of hypokalaemia cannot be ascertained, further investigations are indicated:
    • 24 hour urine sodium, potassium, chloride and magnesium
    • plasma renin activity and serum aldosterone
    • 1 mg overnight dexamethasone suppression test, salivary cortisol test or 24 hour urine cortisol, if Cushing syndrome is suspected
    • urine pH.
  • A urine drug screen may be appropriate in order to diagnose surreptitious diuretic use.
  • Alkalosis as such will maintain kaliuresis despite existing hypokalaemia.

Treatment

  • The mainstay of treatment is discontinuation of drugs that reduce blood potassium concentration and the correction of potassium deficiency and possible magnesium deficiency.
  • The extent of potassium deficiency cannot be accurately assessed from the plasma potassium concentration. As a rule of thumb it may be considered that when potassium stores diminish by 100 mmol the plasma potassium concentration falls 0.3 mmol/l. If plasma potassium is 2.5 mmol/l, the body's potassium deficiency is at least 300 mmol.
  • Potassium deficiency is primarily corrected by administering 2-6 g potassium chloride by mouth. The daily dose is 25-80 mmol (1 g = 13 mmol).
  • The maximum hourly dose of intravenous potassium is 20 mmol, which would increase plasma potassium concentration by 1 mmol/l in the absence of ongoing potassium loss. In alkalosis some of the potassium administered is excreted in the urine, and the actual effect is, therefore, smaller.
  • Potassium is infused in a peripheral vein as a glucose solution (≤ 40 mmol/l); the solution infused in a central vein may be stronger.
  • The rapid correction of severe hypokalaemia requires continuous ECG monitoring, measurements of plasma potassium concentrations every 2-4 hours, and it is carried out in a unit with appropriate monitoring capacity.
  • Fluids containing glucose or administration of insulin may initially worsen the hypokalaemia as potassium is shifted into the intracellular space.
  • For the same reason, correction of metabolic acidosis by bicarbonate or treatment with a beta2-agonist is safest to start only when the potassium concentration is ≥ 3 mmol/l.
  • Hypomagnesaemia is corrected by administering magnesium sulphate 40-60 mmol/day by infusion or as an oral preparation containing magnesium 0.5-1.5 mmol/kg/day.
  • Drug therapies tailored according to the underlying disease in hypokalaemia are for example

References

  • Medford-Davis L, Rafique Z. Derangements of potassium. Emerg Med Clin North Am 2014;32(2):329-47. [PubMed]