Hypokalemia is one of the most common water-electrolyte imbalances. It affects about 20% of people admitted to hospital.

An ECG in a person with a potassium level of 1.1 meq/l showing the classical changes of ST-segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval:

Signs and symptoms

Mild hypokalemia is often without symptoms, although it may cause elevation of blood pressure, and can provoke the development of abnormal heart rhythm. Severe hypokalemia, with serum potassium concentrations of 2.5–3 meq/l (Nl: 3.5–5.0 meq/l), may cause muscle weakness, myalgia, tremor, and muscle cramps (owing to disturbed function of skeletal muscle), and constipation (from disturbed function of smooth muscle). With more severe hypokalemia, flaccid paralysis and hyporeflexia may result. Reports exist of rhabdomyolysis occurring with profound hypokalemia with serum potassium levels less than 2 meq/l. Respiratory depression from severe impairment of skeletal muscle function is found in some people.

Causes

Hypokalemia can result from one or more of these medical conditions:

Inadequate potassium intake.

Not eating a diet with enough potassium-containing foods or fasting can cause a gradual onset of hypokalemia. This is a rare cause and may occur in those with anorexia nervosa or those on a ketogenic diet.

Gastrointestinal or skin loss.

A more common cause is excessive loss of potassium, often associated with heavy fluid losses that "flush" potassium out of the body. Typically, this is a consequence of diarrhoea, excessive perspiration, or losses associated with muscle-crush injury, or surgical procedures. Vomiting can also cause hypokalemia, although not much potassium is lost from the vomitus. Rather, heavy urinary losses of K+ in the setting of post-emetic bicarbonaturia force urinary potassium excretion (see Alkalosis below). Other gastrointestinal causes include pancreatic fistulae and the presence of adenoma.

Urinary loss.

Certain medications can cause excess potassium loss in the urine. Blood pressure medications such as loop diuretics (e.g. furosemide) and thiazide diuretics (e.g. hydrochlorothiazide) commonly cause hypokalemia. Other medications such as the antifungal, amphotericin B, or the cancer drug, cisplatin, can also cause long-term hypokalemia.

A special case of potassium loss occurs with diabetic ketoacidosis. Hypokalemia is observed with low total body potassium and a low intracellular concentration of potassium. In addition to urinary losses from polyuria and volume contraction, also an obligate loss of potassium from kidney tubules occurs as a cationic partner to the negatively charged ketone, β-hydroxybutyrate.

A low level of magnesium in the blood can also cause hypokalemia. Magnesium is required for adequate processing of potassium. This may become evident when hypokalemia persists despite potassium supplementation. Other electrolyte abnormalities may also be present.

An increase in the pH of the blood (alkalosis) can cause temporary hypokalemia by causing a shift of potassium out of the plasma and interstitial fluids into the urine via a number of interrelated mechanisms.

1) Type B intercalated cells in the collecting duct reabsorb H⁺ and secrete HCO₃, while in type A intercalated cells protons are secreted via both H⁺-K⁺ATPases and H⁺ ATP-ases on the apical/luminal surface of the cell. By definition, the H⁺-K⁺ATPase reabsorbs one potassium ion into the cell for every proton it secretes into the lumen of the collecting duct of a nephron. In addition, when H+ is expelled from the cell (by H⁺ATP-ase), cations—in this case, potassium—are taken up by the cell in order to maintain electroneutrality (but not through the direct exchange as with the H⁺-K⁺ATPase). In order to correct the pH during alkalosis, these cells will use these mechanisms to reabsorb great amounts of H⁺, which will concomitantly increase their intracellular concentrations of potassium. This concentration gradient drives potassium to be secreted across the apical surface of the cell into the tubular lumen through potassium channels (this facilitated diffusion occurs in both Type B intercalated cells and principal cells in the collecting duct).

2) Metabolic alkalosis is often present in states of volume depletion, such as vomiting, so potassium is also lost via aldosterone-mediated mechanisms.

3) During metabolic alkalosis, the acute rise of plasma HCO₃− concentration (caused by vomiting, for example) will exceed the capacity of the renal proximal tubule to reabsorb this anion, and potassium will be excreted as an obligate cation partner to the bicarbonate.

Disease states that lead to abnormally high aldosterone levels can cause hypertension and excessive urinary losses of potassium. These include renal artery stenosis and tumours (generally nonmalignant) of the adrenal glands, e.g., Conn's syndrome (primary hyperaldosteronism). Cushing's syndrome can also lead to hypokalemia due to excess cortisol binding the Na⁺/K⁺ pump and acting like aldosterone. Hypertension and hypokalemia can also be seen with a deficiency of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which allows cortisols to stimulate aldosterone receptors. This deficiency—known as apparent mineralocorticoid excess syndrome—can either be congenital or caused by consumption of glycyrrhizin, which is contained in the extract of licorice, sometimes found in herbal supplements, candies, and chewing tobacco.

Rare hereditary defects of renal salt transporters, such as Bartter syndrome or Gitelman syndrome, can cause hypokalemia, in a manner similar to that of diuretics. As opposed to disease states of primary excesses of aldosterone, blood pressure is either normal or low in Bartter's or Gitelman's.

Distribution away from the extracellular fluid.

In addition to alkalosis, other factors can cause transient shifting of potassium into cells, presumably by stimulation of the Na⁺/K⁺ pump. These hormones and medications include insulin, epinephrine, and other beta-agonists (e.g. salbutamol or salmeterol), and xanthines (e.g. theophylline).

Rare hereditary defects of muscular ion channels and transporters that cause hypokalemic periodic paralysis can precipitate occasional attacks of severe hypokalemia and muscle weakness. These defects cause a heightened sensitivity to the normal changes in potassium produced by catecholamines and/or insulin and/or thyroid hormone, which lead to movement of potassium from the extracellular fluid into the muscle cells.

Other.

A handful of published reports describe individuals with severe hypokalemia related to chronic extreme consumption (4–10 l/day) of colas. The hypokalemia is thought to be from the combination of the diuretic effect of caffeine and copious fluid intake, although it may also be related to diarrhoea caused by heavy fructose ingestion.

Pseudo hypokalemia.

Pseudo hypokalemia is a decrease in the amount of potassium that occurs due to excessive uptake of potassium by metabolically active cells in a blood sample after it has been drawn. It is a laboratory artefact that may occur when blood samples remain in warm conditions for several hours before processing.