Hypokalemia

Hypokalemia
An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval
Classification and external resources
Specialty	Critical care medicine
ICD-10	E87.6
ICD-9-CM	276.8
DiseasesDB	6445
MedlinePlus	000479
eMedicine	article/242008 emerg/273
Patient UK	Hypokalemia
MeSH	D007008

Hypokalemia (American English) or hypokalaemia (British English), also hypopotassemia or hypopotassaemia (ICD-9), refers to the condition in which the concentration of potassium (K⁺) in the blood is low. The Greek prefix hypo- means "under" (contrast with its opposite hyper-, meaning "over"); kal- refers to kalium, the Neo-Latin for potassium, and -emia means "condition of the blood" in Greek.

Normal plasma potassium levels are between 3.5 and 5.0 meq/l;^[1] about 98% of the body's potassium is found inside cells, with the remainder in the extracellular fluid including the blood. Alternately, the NIH denotes 3.7–5.2 meq/l as a normal range.^[2] This concentration gradient is maintained principally by the Na⁺/K⁺ pump.

Hyperkalemia refers to the opposite condition in which the concentration of the electrolyte potassium (K⁺) in the blood is elevated.

Signs and symptoms

Mild hypokalemia is often without symptoms, although it may cause elevation of blood pressure,^[3] and can provoke the development of an 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 many patients.

Some electrocardiographic (ECG) findings associated with hypokalemia include flattened or inverted T waves, a U wave, ST depression, and a wide PR interval. Due to prolonged repolarization of ventricular Purkinje fibers, a prominent U wave occurs, frequently superimposed upon the T wave and therefore produces the appearance of a prolonged QT interval.^[4]

Causes

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

Inadequate potassium intake

Perhaps the most obvious cause is insufficient consumption of potassium (that is, a low-potassium diet) or starvation. However, without excessive potassium loss from the body, this is a rare cause of hypokalemia. Usually only seen in anorexia nervosa patients and people 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 diarrhea, 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 postemetic bicarbonaturia force urinary potassium excretion (see Alkalosis below). Other GI 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 can cause temporary hypokalemia by two mechanisms. First, the alkalosis causes a shift of potassium from the plasma and interstitial fluids into cells in the kidney. Specifically, Type B intercalated cells in the collecting duct use H⁺-K⁺ATPase to reabsorb H⁺ into the interstitial fluid while secreting K⁺ into the lumen of the collecting duct.^[5] Second, an 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.^[6] Metabolic alkalosis is often present in states of volume depletion, so potassium is also lost via aldosterone-mediated mechanisms.
• Disease states that lead to abnormally high aldosterone levels can cause hypertension and excessive urinary losses of potassium. These include renal artery stenosis and tumors (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 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 ECF

• In addition to alkalosis, other factors can cause transient shifting of potassium into cells, presumably by stimulation of the Na⁺/K⁺ pump.^[7] These hormones and medications include insulin, epinephrine, and other beta agonists (e.g. salbutamol or salmeterol), and xanthines (e.g. theophylline).^[8]
• 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 catechols 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.^[9] The hypokalemia is thought to be from the combination of the diuretic effect of caffeine^[10] and copious fluid intake, although it may also be related to diarrhea caused by heavy fructose ingestion.^[11][12] A physiological response to hypercapnia, blood potassium (as well as calcium) helps offset acidosis, which is consistent with chronic, extreme consumption of carbonated beverages.

Pseudohypokalemia

• Pseudohypokalemia 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 artifact that may occur when blood samples remain in warm conditions for several hours before processing.^[13]

Pathophysiology

Potassium is essential for many body functions, including muscle and nerve activity. The electrochemical gradient of potassium between the intracellular and extracellular space is essential for nerve function; in particular, potassium is needed to repolarize the cell membrane to a resting state after an action potential has passed. Lower potassium levels in the extracellular space cause hyperpolarization of the resting membrane potential. This hyperpolarization is caused by the effect of the altered potassium gradient on resting membrane potential as defined by the Goldman equation. As a result, a greater than normal stimulus is required for depolarization of the membrane to initiate an action potential.

In the heart, hypokalemia causes hyperpolarization in the myocytes' resting membrane potential. The more negative membrane potentials in the atrium may cause arrhythmias because of more complete recovery from sodium-channel inactivation, making the triggering of an action potential less likely. In addition, the reduced extracellular potassium (paradoxically) inhibits the activity of the I_Kr potassium current^[14] and delays ventricular repolarization. This delayed repolarization may promote reentrant arrhythmias.

Treatment

The most important treatment in severe hypokalemia is addressing the cause, such as improving the diet, treating diarrhea, or stopping an offending medication. Patients without a significant source of potassium loss and who show no symptoms of hypokalemia may not require treatment.

Mild hypokalemia (>3.0 meq/l) may be treated with oral potassium chloride supplements (Klor-Con, Sando-K, Slow-K). As this is often part of a poor nutritional intake, potassium-containing foods may be recommended, such as leafy green vegetables, avocados, tomatoes, coconut water, citrus fruits, oranges, or bananas.^[15] Both dietary and pharmaceutical supplements are used for people taking diuretic medications.

Severe hypokalemia (<3.0 meq/l) may require intravenous supplementation. Typically, a saline solution is used, with 20–40 meq/l KCl per liter over 3–4 hours. Giving IV potassium at faster rates (20–25 meq/hr) may predispose to ventricular tachycardias and requires intensive monitoring. A generally safe rate is 10 meq/hr. Even in severe hypokalemia, oral supplementation is preferred given its safety profile. Sustained-release formulations should be avoided in acute settings.

Difficult or resistant cases of hypokalemia may be amenable to a potassium-sparing diuretic, such as amiloride, triamterene, spironolactone, or eplerenone. Concomittant hypomagnesemia will inhibit potassium replacement, as magnesium is a cofactor for potassium uptake.^[16]

When replacing potassium intravenously, infusion by a central line is encouraged to avoid the frequent occurrence of a burning sensation at the site of a peripheral infusion, or the rare occurrence of damage to the vein. When peripheral infusions are necessary, the burning can be reduced by diluting the potassium in larger amounts of fluid, or mixing 3 ml of 1% lidocaine to each 10 meq of KCl per 50 ml of fluid. The practice of adding lidocaine, however, raises the likelihood of serious medical errors.^[17]

See also

• Hyperkalemia
• Hypermagnesemia
• Hypernatremia
• Hypomagnesemia
• Hypokalemic acidosis
• Hyponatremia
• Potassium deficiency (plant disorder)
• Superior mesenteric artery syndrome

References

Further reading

• J, Firth (2010). "Chapter: Disorders of potassium homeostasis". In David A. Warrell, Timothy M. Cox, John D. Firth ; sub-editor, Graham S. Ogg. Oxford textbook of medicine (5th ed.). Oxford: Oxford University Press. doi:10.1093/med/9780199204854.003.210202_update_001. ISBN 0199204853. 
• Bia, MJ; DeFronzo, RA (Apr 1981). "Extrarenal potassium homeostasis.". The American journal of physiology 240 (4): F257–68. PMID 6111930. 
• Greenlee, M; Wingo, CS; McDonough, AA; Youn, JH; Kone, BC (May 5, 2009). "Narrative review: evolving concepts in potassium homeostasis and hypokalemia." (PDF). Annals of internal medicine 150 (9): 619–25. doi:10.7326/0003-4819-150-9-200905050-00008. PMID 19414841. 

External links

• MayoClinic.com: Low potassium (hypokalemia)
• MedicineNet.com: Low Potassium (Hypokalemia)
• eMedicineHealth.com: Low Potassium (Hypokalemia)
• Content of Selected Foods per Common Measure, sorted by nutrient content (Potassium)
• List of foods rich in potassium (U. Mass. Med.)
• National Organization for Rare Disorders: Hypokalemia