(See also Overview of Disorders of Potassium Concentration Overview of Disorders of Potassium Concentration Potassium is the most abundant intracellular cation, but only about 2% of total body potassium is extracellular. Because most intracellular potassium is contained within muscle cells, total... read more .)
Etiology of Hypokalemia
Hypokalemia can be caused by decreased intake of potassium but is usually caused by excessive losses of potassium in the urine or from the gastrointestinal (GI) tract.
Gastrointestinal tract losses
Abnormal GI potassium losses occur in all of the following:
Chronic diarrhea, including chronic laxative abuse and bowel diversion
Clay (bentonite) ingestion, which binds potassium and greatly decreases absorption
Rarely, villous adenoma of the colon, which causes massive potassium secretion
Protracted vomiting or gastric suction (which removes volume and hydrochloric acid) causes renal potassium losses due to metabolic alkalosis Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3−) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common causes... read more and stimulation of aldosterone due to volume depletion; aldosterone and metabolic alkalosis both cause the kidneys to excrete potassium.
The transcellular shift of potassium into cells may also cause hypokalemia. This shift can occur in any of the following:
After administration of insulin
Familial periodic paralysis
Glycogenesis during total parenteral nutrition or enteral hyperalimentation (stimulating insulin release)
Stimulation of the sympathetic nervous system, particularly with beta 2-agonists (eg, albuterol, terbutaline), which may increase cellular potassium uptake
Thyrotoxicosis (occasionally) due to excessive beta-sympathetic stimulation (hypokalemic thyrotoxic periodic paralysis)
Familial periodic paralysis Familial Periodic Paralysis Familial periodic paralysis is a rare autosomal dominant condition with considerable variation in penetrance characterized by episodes of flaccid paralysis with loss of deep tendon reflexes... read more is a rare autosomal dominant disorder characterized by transient episodes of profound hypokalemia thought to be due to sudden abnormal shifts of potassium into cells. Episodes frequently involve varying degrees of paralysis. They are typically precipitated by a large carbohydrate meal or strenuous exercise.
Renal potassium losses
Various disorders can increase renal potassium excretion.
Excess mineralocorticoid (ie, aldosterone) effect can directly increase potassium secretion by the distal nephrons and occurs in any of the following:
Adrenal steroid excess that is due to Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more , primary hyperaldosteronism Primary Aldosteronism Primary aldosteronism is aldosteronism caused by autonomous production of aldosterone by the adrenal cortex (due to hyperplasia, adenoma, or carcinoma). Symptoms and signs include episodic weakness... read more , rare renin-secreting tumors, glucocorticoid-remediable aldosteronism (a rare inherited disorder involving abnormal aldosterone metabolism), and congenital adrenal hyperplasia Overview of Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia is a group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. In the most common forms, accumulated hormone precursors... read more .
Bartter syndrome Bartter Syndrome and Gitelman Syndrome Bartter syndrome and Gitelman syndrome are autosomal recessive renal disorders characterized by fluid, electrolyte, urinary, and hormonal abnormalities, including renal potassium, sodium, chloride... read more , an uncommon genetic disorder that is characterized by renal potassium and sodium wasting, excessive production of renin and aldosterone, and normotension. Bartter syndrome is caused by mutations in a loop diuretic–sensitive ion transport mechanism in the loop of Henle.
Gitelman syndrome Bartter Syndrome and Gitelman Syndrome Bartter syndrome and Gitelman syndrome are autosomal recessive renal disorders characterized by fluid, electrolyte, urinary, and hormonal abnormalities, including renal potassium, sodium, chloride... read more is an uncommon genetic disorder characterized by renal potassium and sodium wasting, excessive production of renin and aldosterone, and normotension. Gitelman syndrome is caused by loss of function mutations in a thiazide-sensitive ion transport mechanism in the distal nephron.
Ingestion of substances such as glycyrrhizin (present in natural licorice and used in the manufacture of chewing tobacco), which inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11β-HSDH), preventing the conversion of cortisol, which has some mineralocorticoid activity, to cortisone, which does not, resulting in high circulating concentrations of cortisol and renal potassium wasting.
Liddle syndrome Liddle Syndrome Liddle syndrome is a rare hereditary disorder involving increased activity of the epithelial sodium channel (ENaC), which causes the kidneys to excrete potassium but retain too much sodium and... read more , a rare autosomal dominant disorder caused by unrestrained sodium reabsorption in the distal nephron due to one of several mutations found in genes encoding for epithelial sodium channel subunits. Inappropriately high reabsorption of sodium results in both severe hypertension and renal potassium wasting, resulting in hypokalemia.
Renal potassium wasting can also be caused by numerous congenital and acquired renal tubular diseases, such as the renal tubular acidoses Renal Tubular Acidosis Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired bicarbonate resorption (type 2), or abnormal aldosterone... read more and Fanconi syndrome Fanconi Syndrome Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting. It may be hereditary... read more , an unusual syndrome resulting in renal wasting of potassium, glucose, phosphate, uric acid, and amino acids.
Hypomagnesemia Hypomagnesemia Hypomagnesemia is serum magnesium concentration 1.8 mg/dL ( 0.70 mmol/L). Causes include inadequate magnesium intake and absorption or increased excretion due to hypercalcemia or drugs such... read more is a common correlate of hypokalemia. Much of this correlation is attributable to common causes (ie, diuretics, diarrhea), but hypomagnesemia itself may also result in increased renal potassium losses.
Diuretics are by far the most commonly used drugs that cause hypokalemia. Potassium-wasting diuretics that block sodium reabsorption proximal to the distal nephron include
By inducing diarrhea, laxatives, especially when abused, can cause hypokalemia. Surreptitious diuretic or laxative use or both is a frequent cause of persistent hypokalemia, particularly among patients preoccupied with weight loss and among health care practitioners with access to prescription drugs.
Other drugs that can cause hypokalemia include
Antipseudomonal penicillins (eg, carbenicillin)
Penicillin in high doses
Theophylline (both acute and chronic intoxication)
Symptoms and Signs of Hypokalemia
Mild hypokalemia (serum potassium 3 to 3.5 mEq/L [3 to 3.5 mmol/L]) rarely causes symptoms. Serum potassium < 3 mEq/L (< 3 mmol/L) generally causes muscle weakness and may lead to paralysis and respiratory failure. Other muscular dysfunction includes cramping, fasciculations, paralytic ileus, hypoventilation, hypotension, tetany, and rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more . Persistent hypokalemia can impair renal concentrating ability, causing polyuria with secondary polydipsia.
Diagnosis of Hypokalemia
Serum potassium measurement
When the mechanism not evident clinically, 24-hour urinary potassium excretion and serum magnesium concentration
Hypokalemia (serum potassium < 3.5 mEq/L [< 3.5 mmol/L]) may be found during routine serum electrolyte measurement. It should be suspected in patients with typical changes on an ECG or who have muscular symptoms and risk factors and confirmed by blood testing.
ECG should be done on patients with hypokalemia. Cardiac effects of hypokalemia are usually minimal until serum potassium concentrations are < 3 mEq/L (< 3 mmol/L). Hypokalemia causes sagging of the ST segment, depression of the T wave, and elevation of the U wave. With marked hypokalemia, the T wave becomes progressively smaller and the U wave becomes increasingly larger. Sometimes, a flat or positive T wave merges with a positive U wave, which may be confused with QT prolongation (see figure ECG patterns in hypokalemia ECG patterns in hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more ). Hypokalemia may cause premature ventricular beats Ventricular Premature Beats (VPB) Ventricular premature beats (VPB) are single ventricular impulses caused by reentry within the ventricle or abnormal automaticity of ventricular cells. They are extremely common in both healthy... read more and premature atrial contractions Atrial premature beats Various rhythms result from supraventricular foci (usually in the atria). Diagnosis is by electrocardiography. Many are asymptomatic and require no treatment. (See also Overview of Arrhythmias... read more , ventricular Ventricular Tachycardia (VT) Ventricular tachycardia is ≥ 3 consecutive ventricular beats at a rate ≥ 120 beats/minute. Symptoms depend on duration and vary from none to palpitations to hemodynamic collapse and death. Diagnosis... read more and supraventricular tachyarrhythmias Reentrant Supraventricular Tachycardias (SVT) including Wolff-Parkinson-White Syndrome Reentrant supraventricular tachycardias (SVT) involve reentrant pathways with a component above the bifurcation of the His bundle. Patients have sudden episodes of palpitations that begin and... read more , and 2nd- or 3rd-degree atrioventricular block Atrioventricular Block Atrioventricular (AV) block is partial or complete interruption of impulse transmission from the atria to the ventricles. The most common cause is idiopathic fibrosis and sclerosis of the conduction... read more . Such arrhythmias become more severe with increasingly severe hypokalemia; eventually, ventricular fibrillation may occur. Patients with significant preexisting heart disease and patients receiving digoxin are at risk of cardiac conduction abnormalities as a result of even mild hypokalemia.
ECG patterns in hypokalemia
Serum potassium is in mEq/L and mmol/L.
Diagnosis of cause
The cause of hypokalemia is usually apparent by history (particularly the drug history); when it is not, further investigation is warranted.
After acidosis and other causes of intracellular potassium shift (increased beta-adrenergic effect, hyperinsulinemia) have been eliminated, 24-hour urinary potassium and serum magnesium concentrations are measured. In hypokalemia, potassium secretion is normally < 15 mEq/L (< 15 mmol/L). Extrarenal (GI) potassium loss or decreased potassium ingestion is suspected in chronic unexplained hypokalemia when renal potassium secretion is < 15 mEq/L (< 15 mmol/L). Secretion of > 15 mEq/L (< 15 mmol/L). suggests a renal cause for potassium loss. Unexplained hypokalemia with increased renal potassium secretion and hypertension suggests an aldosterone-secreting tumor or Liddle syndrome. Unexplained hypokalemia with increased renal potassium loss and normal blood pressure suggests Bartter syndrome or Gitelman syndrome, but hypomagnesemia, surreptitious vomiting, and diuretic abuse are more common and should also be considered.
Treatment of Hypokalemia
Oral potassium supplements
IV potassium supplements for severe hypokalemia or ongoing potassium losses
Many oral potassium supplements are available. Because high single doses can cause GI irritation and occasional bleeding, deficits are usually replaced in divided doses. Liquid potassium chloride given orally elevates concentrations within 1 to 2 hours but has a bitter taste and is tolerated particularly poorly in doses > 25 to 50 mEq. (> 25 to 50 mmol). Wax-impregnated potassium chloride preparations are safe and better tolerated. GI bleeding may be even less common with microencapsulated potassium chloride preparations. Several of these preparations contain 8 or 10 mEq/capsule. Because a decrease in serum potassium of 1 mEq/L (1 mmol/L) correlates with about a 200- to 400-mEq (200 to 400 mmol) deficit in total body potassium stores, total deficit can be estimated and replaced over a number of days at 20 to 80 mEq (20 to 80 mmol)/day.
When hypokalemia is severe (eg, with ECG changes or severe symptoms), is unresponsive to oral therapy, or occurs in hospitalized patients who are taking digoxin or who have significant heart disease or ongoing losses, potassium must be replaced IV. Because potassium solutions can irritate peripheral veins, the concentration should not exceed 40 mEq/L (40 mmol/L). The rate of correction of hypokalemia is limited because of the lag in potassium movement from the extracellular space into cells. Routine infusion rates should not exceed 10 mEq (10 mmol)/hour.
In hypokalemia-induced arrhythmia, IV potassium chloride must be given more rapidly, usually through a central vein or using multiple peripheral veins simultaneously. Infusion of 40 mEq (40 mmol) potassium chloride/hour can be undertaken but only with continuous cardiac monitoring and hourly serum potassium determinations. Glucose solutions are avoided because elevation in the serum insulin concentrations could result in transient worsening of hypokalemia.
Even when potassium deficits are severe, it is rarely necessary to give > 100 to 120 mEq (> 100 to 120 mmol) of potassium in a 24-hour period unless potassium loss is ongoing. In potassium deficit with high serum potassium concentration, as in diabetic ketoacidosis, IV potassium is deferred until the serum potassium starts to fall. When hypokalemia occurs with hypomagnesemia Treatment Hypomagnesemia is serum magnesium concentration 1.8 mg/dL ( 0.70 mmol/L). Causes include inadequate magnesium intake and absorption or increased excretion due to hypercalcemia or drugs such... read more , both the potassium and magnesium deficiencies must be corrected to stop ongoing renal potassium wasting.
Prevention of Hypokalemia
Routine potassium replacement is not necessary in most patients receiving diuretics. However, serum potassium should be monitored during diuretic use when risk of hypokalemia or of its complications is high. Risk is high in
Patients with decreased left ventricular function
Patients taking digoxin
Patients with diabetes (in whom insulin concentrations can fluctuate)
Patients with asthma who are taking beta 2-agonists
Triamterene 100 mg orally once a day or spironolactone 25 mg orally 4 times a day does not increase potassium excretion and may be useful in patients who become hypokalemic but must use diuretics. When hypokalemia develops, potassium supplementation, usually with oral potassium chloride, is indicated.
Hypokalemia can be caused by decreased intake of potassium or shift of extracellular potassium into cells, but it is usually caused by excessive losses of potassium in the urine or from the gastrointestinal tract.
Clinical signs include muscle weakness, cramping, fasciculations, paralytic ileus, and when hypokalemia is severe, hypoventilation, and hypotension.
ECG changes typically occur when serum potassium is < 3 mEq/L (< 3 mmol/L), and include ST segment sagging, T wave depression, and U wave elevation. With marked hypokalemia, the T wave becomes progressively smaller and the U wave becomes increasingly larger.
Hypokalemia may cause premature ventricular and atrial contractions, ventricular and atrial tachyarrhythmias, and 2nd- or 3rd-degree atrioventricular block; eventually, ventricular fibrillation may occur.
Replace potassium orally, giving 20 to 80 mEq (20 to 80 mmol)/day unless patients have ECG changes or severe symptoms.
For hypokalemic arrhythmia, give IV potassium chloride through a central vein at a maximum of 40 mEq (40 mmol)/hour and only with continuous cardiac monitoring; routine IV infusion should be no more than 10 mEq (10 mmol)/hour.