Hypokalaemia is a disorder of potassium homeostasis characterised by low levels of potassium (<3.5 mmol/L). It's a relatively uncommon electrolyte abnormality. It's most frequently caused by loop diuretics, gastrointestinal loss, or hyperaldosteronism. Most common symptoms include muscle weakness and constipation, as well as ECG changes. Management involves treating the underlying cause and p.i. or i.v. supplementation. Hypokalaemia can be lethal due to rhabdomyolysis or ventricular arrhythmia. Hypokalaemia is less common than hyperkalaemia.

Hypokalaemia
DefinitionSerum potassium level < 3.5
SymptomsMuscle weakness, constipation/ileus
ComplicationsVentricular arrhythmia, rhabdomyolysis
CausesLoop diuretics, gastrointestinal loss, hyperaldosteronism
TreatmentP.o. or i.v. supplementation

Grading of severity

Potassium level Severity
3.5 - 3.0 Mild
2.9 - 2.5 Moderate
< 2.5 Severe

Etiology

Hypokalaemia can occur due to increased potassium loss, redistribution of potassium into cells, or (rarely) insufficient potassium intake. Because the kidneys can reduce potassium excretion to a minimum, and the daily potassium requirement is really low, insufficient intake of potassium rarely causes hypokalaemia by itself, but it may contribute to hypokalaemia due to other causes

Most common causes of hypokalaemia
Increased potassium loss Redistribution of potassium into cells
Loop diuretics Excessive insulin (treatment of diabetic ketoacidosis or hyperglycaemic hypoerosmolar syndrom, refeeding syndrome)
Vomiting or other gastrointestinal loss Excessive beta-adrenergic activity (severe stress (like myocardial infarction, traumatic head injury, alcohol withdrawal), administration of beta-adrenergic agonists)
Hyperaldosteronism, e.g. due to hormone-producing adrenal adenoma Alkalosis

Upper gastrointestinal fluids don't contain much potassium, so loss of the fluid itself does not cause severe hypokalaemia. However, the resulting hypovolaemia can cause hyperaldosteronism, which can cause hypokalaemia. Lower gastrointestinal fluids, however, contain much potassium, and so loss of these fluids (usually due to diarrhoea) can cause hypokalaemia.

Pathomechanism

Hypokalaemia causes the resting membrane potential of muscle cells to be lower than normal (that is, more negative, also called hyperpolarised). This makes the membranes harder to excite, which causes weakness.

Hypokalaemia has many effects on the heart:

  • Hypokalaemia decreases Na-K-ATPase activity, leading to increased intracellular sodium, which inhibits Na-Ca exchanger activity, leading to increased intracellular calcium, which stimulates Ca2+/calmodulin-dependent protein kinase II, which eventually leads to ventricular arrhythmia
  • In the conducting system of the heart, hypokalaemia paradoxically causes depolarisation by triggering sodium influx into cells. This increases membrane excitability in the conducting system, predisposing to arrhythmia.
  • In ventricular cells, hypokalaemia delays ventricular repolarisation

Clinical features

Symptoms are more severe if the drop in serum potassium is rapid than if it is chronic. Mild hypokalaemia is usually asymptomatic. Moderate hypokalaemia can cause muscle weakness, constipation, ileus, and restless legs. Severe hypokalaemia can cause arrhythmia, rhabdomyolysis, and paresis. Hyporeflexia is a possible sign.

Severe hypokalaemia can cause ECG changes:

  • Low or inverted T-waves
  • Presence of U-waves
  • ST depression
  • Supraventricular or ventricular tachyarrhythmia
  • Prolonged QT interval

Diagnosis and evaluation

The serum potassium level may be up to 0,5 units higher than the true level of potassium in the blood, due to release of potassium from thrombocytes. To get the most accurate potassium value, an arterial blood gas should be taken.

The cause of hypokalaemia is usually evident from the list of medications, the anamnesis, or from clinical features of the underlying cause.

A urine potassium of > 20 mmol/L in the setting of hypokalaemia is indicative of renal loss of potassium.

Management

Mild hypokalaemia does not usually require hospitalisation, but moderate, severe, or symptomatic hypokalaemia requires hospitalisation. Severe hypokalaemia requires intensive care. Severe cases should be continously monitored with ECG. The underlying cause should be adressed if possible. Any concomitant hypomagnesaemia must also be treated, as hypomagnesaemia maintains hypokalaemia.

Potassium can be supplemented p.o. or i.v. P.o is the first choice, while i.v. is used in severe hypokalaemia, if there is a high risk of arrhythmia, or if p.o. supplementation is insufficient.

Complications

Arrhythmia

Arrhythmia in case of hypokalaemia can be fatal and is the most dangerous complication. Hypokalaemia can cause a variety of arrhythmias, from relatively benign ones like premature atrial beats, sinus bradycardia, atrial tachycardia, to rapidly life-threatening ones like ventricular tachycardia or fibrillation. Elderly, as well as people with heart disease, previous ventricular arrhythmia, or digitalis treatment are at extra high risk for arrhythmia.

Rhabdomyolysis

Main article: Rhabdomyolysis

Rhabdomyolysis occurs due to the skeletal muscle membrane becoming unexcitable, which causes necrosis. Hypokalaemia also reduces muscle blood flow (as potassium is usually a vasodilator in skeletal muscle), which causes ischaemic necrosis.