K is the most abundant intracellular cation, but only about 2% of total body K is extracellular. Because most intracellular K is contained within muscle cells, total body K is roughly proportional to lean body mass. An average 70-kg adult has about 3500 mEq of K.
K is a major determinant of intracellular osmolality. The ratio between ICF and ECF K concentrations strongly influences cell membrane polarization, which in turn influences important cell processes, such as the conduction of nerve impulses and muscle (including myocardial) cell contraction. Thus, relatively small alterations in serum K concentration can have significant clinical manifestations.
In the absence of factors that shift K in or out of cells (see Electrolyte Disorders: Intracellular shift), the serum K concentration correlates closely with total body K content. Once intracellular and extracellular concentrations are stable, a decrease in serum K concentration of about 1 mEq/L indicates a total K deficit of about 200 to 400 mEq. Patients with K < 3 mEq/L typically have a significant K deficit.
Factors that shift K in or out of cells include the following:
Insulin moves K into cells; high concentrations of insulin thus lower serum K concentration. Low concentrations of insulin, as in diabetic ketoacidosis, cause K to move out of cells, thus raising serum K, sometimes even in the presence of total body K deficiency.
β-Adrenergic agonists, especially selective β2-agonists, move K into cells, whereas β-blockade and α-agonists promote movement of K out of cells.
Acute metabolic acidosis causes K to move out of cells, whereas acute metabolic alkalosis causes K to move into cells. However, changes in serum HCO3 concentration may be more important than changes in pH; acidosis caused by accumulation of mineral acids (nonanion gap, hyperchloremic acidosis) is more likely to elevate serum K. In contrast, metabolic acidosis due to accumulation of organic acids (increased anion gap acidosis) is not associated with hyperkalemia. Thus, the hyperkalemia common in diabetic ketoacidosis results more from insulin deficiency than from acidosis. Acute respiratory acidosis and alkalosis affect serum K concentration less than metabolic acidosis and alkalosis. Nonetheless, serum K concentration should always be interpreted in the context of the serum pH (and HCO3 concentration).
Dietary K intake normally varies between 40 and 150 mEq/day. In the steady state, fecal losses are usually close to 10% of intake. Urinary excretion contributes to K balance.
When K intake is > 150 mEq/day, about 50% of the excess K appears in the urine over the next several hours. Most of the remainder is transferred into the intracellular compartment, thus minimizing the rise in serum K. When elevated K intake continues, aldosterone secretion is stimulated and thus renal K excretion rises. In addition, K absorption from stool appears to be under some regulation and may fall by 50% in chronic K excess.
When K intake falls, intracellular K again serves to buffer wide swings in serum K concentration. Renal K conservation develops relatively slowly in response to decreases in dietary K and is far less efficient than the kidneys' ability to conserve Na. Thus, K depletion is a frequent clinical problem. Urinary K excretion of 10 mEq/day represents near-maximal renal K conservation and implies significant K depletion.
Acute acidosis impairs K excretion, whereas chronic acidosis and acute alkalosis can promote K excretion. Increased delivery of Na to the distal nephrons, as occurs with high Na intake or loop diuretic therapy, promotes K excretion.
False K concentrations
Pseudohypokalemia, or falsely low serum K, occasionally occurs in patients with chronic myelocytic leukemia with a WBC count > 105/μL when the specimen remains at room temperature before being processed because of uptake of serum K by abnormal leukocytes in the sample. It is prevented by prompt separation of plasma or serum in blood samples.
Pseudohyperkalemia, or falsely elevated serum K, is more common, typically occurring due to hemolysis and release of intracellular K. To prevent false results, phlebotomy personnel should not rapidly aspirate blood through a narrow-gauge needle or excessively agitate blood samples. Pseudohyperkalemia can also result from platelet count > 400,000/μL due to release of K from platelets during clotting. In cases of pseudohyperkalemia, the plasma K (unclotted blood), as opposed to serum K, is normal.
Hypokalemia is serum K concentration < 3.5 mEq/L caused by a deficit in total body K stores or abnormal movement of K into cells. The most common causes are excess losses from the kidneys or GI tract. Clinical features include muscle weakness and polyuria; cardiac hyperexcitability may occur with severe hypokalemia. Diagnosis is by serum measurement. Treatment is giving K and managing the cause.
Hypokalemia can be caused by decreased intake of K but is usually caused by excessive losses of K in the urine or from the GI tract.
GI tract losses
Abnormal GI K losses occur in all of the following:
GI K losses may be compounded by concomitant renal K losses due to metabolic alkalosis and stimulation of aldosterone due to volume depletion.
The transcellular shift of K into cells may also cause hypokalemia. This shift can occur in any of the following:
Various disorders can increase renal K excretion. Excess mineralocorticoid effect can directly increase K secretion by the distal nephrons and occurs in any of the following:
Liddle syndrome (see also Renal Transport Abnormalities: Liddle Syndrome) is a rare autosomal dominant disorder characterized by severe hypertension and hypokalemia. Liddle syndrome is caused by unrestrained Na reabsorption in the distal nephron due to one of several mutations found in genes encoding for epithelial Na channel subunits. Inappropriately high reabsorption of Na results in both hypertension and renal K wasting.
Renal K wasting can also be caused by numerous congenital and acquired renal tubular diseases, such as the renal tubular acidoses and Fanconi syndrome, an unusual syndrome resulting in renal wasting of K, glucose, phosphate, uric acid, and amino acids.
Hypomagnesemia is a common correlate of hypokalemia. Much of this is attributable to common underlying causes (ie, diuretics, diarrhea), but hypomagnesemia itself may also result in increased renal K losses.
Diuretics are by far the most commonly used drugs that cause hypokalemia. K-wasting diuretics that block Na reabsorption proximal to the distal nephron include
By inducing diarrhea, laxatives, especially when abused, can cause hypokalemia. Surreptitious diuretic or laxative abuse 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
Symptoms and Signs
Mild hypokalemia (serum K 3 to 3.5 mEq/L) rarely causes symptoms. Serum K < 3 mEq/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. Persistent hypokalemia can impair renal concentrating ability, causing polyuria with secondary polydipsia.
Hypokalemia (serum K < 3.5 mEq/L) may be found on 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 K concentrations are < 3 mEq/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 Fig. 1: Electrolyte Disorders: ECG patterns in hypokalemia and hyperkalemia.). Hypokalemia may cause premature ventricular and atrial contractions, ventricular and atrial tachyarrhythmias, and 2nd- or 3rd-degree atrioventricular block. 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 even from mild hypokalemia.
Diagnosis of cause
The cause is usually apparent by history (particularly the drug history); when it is not, further investigation is warranted. After acidosis and other causes of intracellular K shift (increased β-adrenergic effect, hyperinsulinemia) have been eliminated, 24-h urinary K and serum Mg concentrations are measured. In hypokalemia, K secretion is normally < 15 mEq/L. Extrarenal (GI) K loss or decreased K ingestion is suspected in chronic unexplained hypokalemia when renal K secretion is < 15 mEq/L. Secretion of > 15 mEq/L suggests a renal cause for K loss. Unexplained hypokalemia with increased renal K secretion and hypertension suggests an aldosterone-secreting tumor or Liddle syndrome. Unexplained hypokalemia with increased renal K loss and normal BP suggests Bartter or Gitelman's syndrome, but hypomagnesemia, surreptitious vomiting, and diuretic abuse are more common and should also be considered.
Many oral K supplements are available. Because high single doses can cause GI irritation and occasional bleeding, deficits are usually replaced in divided doses. Liquid KCl given orally elevates concentrations within 1 to 2 h but has a bitter taste and is tolerated particularly poorly in doses > 25 to 50 mEq. Wax-impregnated KCl preparations are safe and better tolerated. GI bleeding may be even less common with microencapsulated KCl preparations. Several of these preparations contain 8 or 10 mEq/capsule. Because a decrease in serum K of 1 mEq/L correlates with about a 200- to 400-mEq deficit in total body K stores, total deficit can be estimated and replaced over a number of days at 20 to 80 mEq/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 digitalis or who have significant heart disease or ongoing losses, K must be replaced IV. Because K solutions can irritate peripheral veins, the concentration should not exceed 40 mEq/L. The rate of correction of hypokalemia is limited because of the lag in K movement into cells. Routine infusion rates should not exceed 10 mEq/h. In hypokalemic-induced arrhythmia, IV KCl must be given more rapidly, usually through a central vein or using multiple peripheral veins simultaneously. Infusion of 40 mEq KCl/h can be undertaken but only with continuous cardiac monitoring and hourly serum K determinations. Glucose solutions are avoided because elevation in the serum insulin concentrations could result in transient worsening of hypokalemia.
Even when K deficits are severe, it is rarely necessary to give > 100 to 120 mEq of K in a 24-h period unless K loss continues. In K deficit with high serum K concentration, as in diabetic ketoacidosis, IV K is deferred until the serum K starts to fall. When hypokalemia occurs with hypomagnesemia, both the K and Mg deficiencies must be corrected to stop ongoing renal K wasting (see Electrolyte Disorders: Hypomagnesemia).
Routine K replacement is not necessary in most patients receiving diuretics. However, serum K should be monitored during diuretic use when risk of hyperkalemia or of its complications is high. Risk is high in
Triamterene 100 mg po once/day or spironolactone 25 mg po qid does not increase K excretion and may be useful in patients who become hypokalemic but must use diuretics. When hypokalemia develops, K supplementation, usually with oral KCl, is indicated.
Hyperkalemia is serum K concentration > 5.5 mEq/L resulting from excess total body K stores or abnormal movement of K out of cells. There are usually several simultaneous contributing factors, including increased K intake, drugs that impair renal K excretion, and acute or chronic kidney disease. It can also occur in metabolic acidosis as in diabetic ketoacidosis. Clinical manifestations are generally neuromuscular, resulting in muscle weakness and cardiac toxicity that, when severe, can degenerate to ventricular fibrillation or asystole. Diagnosis is by measuring serum K. Treatment may involve decreasing K intake, adjusting drugs, giving a cation exchange resin and, in emergencies, Ca gluconate, insulin, and dialysis.
The most common cause of increased serum K concentration is probably pseudohyperkalemia caused by hemolysis of RBCs in the blood sample. Normal kidneys eventually excrete K loads, so sustained, nonartifactual hyperkalemia usually implies diminished renal K excretion. However, other factors usually contribute. They can include increased K intake, increased K release from cells, or both (see Table 6: Electrolyte Disorders: Factors Contributing to Hyperkalemia). When sufficient KCl is ingested or given parenterally, severe hyperkalemia may result even with normal renal function but is usually temporary.
Hyperkalemia due to total body K excess is particularly common in oliguric states (especially acute renal failure) and with rhabdomyolysis, burns, bleeding into soft tissue or the GI tract, and adrenal insufficiency. In chronic renal failure, hyperkalemia is uncommon until the GFR falls to < 10 to 15 mL/min unless dietary or IV K intake is excessive.
Symptoms and Signs
Although flaccid paralysis occasionally occurs, hyperkalemia is usually asymptomatic until cardiac toxicity develops
In the rare disorder hyperkalemic familial periodic paralysis, weakness frequently develops during attacks and can progress to frank paralysis.
Hyperkalemia (serum K > 5.5 mEq/L) may be found on routine serum electrolyte measurement. It should be suspected in patients with typical changes on an ECG or patients at high risk, such as those with renal failure, advanced heart failure treated with ACE inhibitors and K-sparing diuretics, or urinary obstruction.
ECG should be done on patients with hyperkalemia. ECG changes (see Fig. 1: Electrolyte Disorders: ECG patterns in hypokalemia and hyperkalemia.) are frequently visible when serum K is > 5.5 mEq/L. Slowing of conduction characterized by an increased PR interval and shortening of the QT interval as well as tall, symmetric, peaked T waves are visible initially. K > 6.5 mEq/L causes further slowing of conduction with widening of the QRS interval, disappearance of the P wave, and nodal and escape ventricular arrhythmias. Finally, the QRS complex degenerates into a sine wave pattern, and ventricular fibrillation or asystole ensues.
Diagnosis of the cause
Pseudohyperkalemia should be considered in patients without risk factors or ECG abnormalities. Hemolysis may be reported by the laboratory. When pseudohyperkalemia is suspected, K concentration should be repeated, taking measures to avoid hemolysis of the sample.
Diagnosis of the cause of hyperkalemia requires a detailed history, including a review of drugs, a physical examination with emphasis on volume status, and measurement of electrolytes, BUN, and creatinine. In cases in which renal failure is present, additional tests, including renal ultrasonography to exclude obstruction, are needed (see Renal Failure: Diagnosis).
Patients with serum K < 6 mEq/L and no ECG abnormalities may respond to diminished K intake or stopping K-elevating drugs. The addition of a loop diuretic enhances renal K excretion as long as volume depletion is not present.
Na polystyrene sulfonate in sorbitol can be given (15 to 30 g in 30 to 70 mL of 70% sorbitol po q 4 to 6 h). It acts as a cation exchange resin and removes K through the GI mucosa. Sorbitol is administered with the resin to ensure passage through the GI tract. Patients unable to take drugs orally because of nausea or other reasons may be given similar doses by enema. Enemas are not as effective at lowering K in patients with ileus. Enemas should not be used if acute abdomen is suspected. About 1 mEq of K is removed per gram of resin given. Resin therapy is slow and often fails to lower serum K significantly in hypercatabolic states. Because Na is exchanged for K when Na polystyrene sulfonate is used, Na overload may occur, particularly in oliguric patients with preexisting volume overload.
Moderate to severe hyperkalemia
Serum K between 6 and 6.5 mEq/L needs prompt attention, but the actual treatment depends on the clinical situation. If no ECG changes are present and renal function is intact, maneuvers described previously are usually effective. Follow-up serum K levels are needed to ensure that the hyperkalemia has been successfully treated. If serum K is >6.5 mEq/L, more aggressive therapy is required. Administration of regular insulin 5 to 10 units IV is followed immediately by or administered simultaneously with rapid infusion of 50 mL 50% glucose. Infusion of 10% D/W should follow at 50 mL/h to prevent hypoglycemia. The effect on serum K peaks in 1 h and lasts for several hours.
If ECG changes include the loss of P-wave or widening of the QRS complex, treatment with IV Ca as well as insulin and glucose is indicated; 10 to 20 mL 10% Ca gluconate (or 5 to 10 mL 22% Ca gluceptate) is given IV over 5 to 10 min. Ca antagonizes the effect of hyperkalemia on cardiac muscle. Ca should be given with caution to patients taking digoxin because of the risk of precipitating hypokalemia-related arrhythmias. If the ECG shows a sine wave pattern or asystole, Ca gluconate may be given more rapidly (5 to 10 mL IV over 2 min). CaCl can also be used but can be irritating to peripheral veins and cause tissue necrosis if extravasated. CaCl should be given only through a correctly positioned central venous catheter. The benefits of Ca occur within minutes but last only 20 to 30 min. Ca infusion is a temporizing measure while awaiting the effects of other treatments or initiation of hemodialysis and may need to be repeated.
A high-dose β2-agonist, such as albuterol 10 to 20 mg inhaled over 10 min (5 mg/mL concentration), can lower serum K by 0.5 to 1.5 mEq/L and may be a helpful adjunct. The peak effect occurs in 90 min. However, β2-agonists are contraindicated in patients with unstable angina and acute MI.
Administration of IV NaHCO3 is controversial. It may lower serum K over several hours. Reduction may result from alkalinization or the hypertonicity due to the concentrated Na in the preparation. The hypertonic Na that it contains may be harmful for dialysis patients who also may have volume overload. When given, the usual dose is 45 mEq (1 ampule of 7.5% NaHCO3) infused over 5 min and repeated in 30 min. HCO3 therapy has little effect when used by itself in patients with severe renal insufficiency unless acidemia is also present.
In addition to strategies for lowering K by shifting it into cells, maneuvers to remove K from the body should also be done early in the treatment of severe or symptomatic hyperkalemia. K can be removed via the GI tract by administration of Na polystyrene sulfonate (see Electrolyte Disorders: Mild hyperkalemia) or by hemodialysis. Hemodialysis should be instituted promptly after emergency measures in patients with renal failure or when emergency treatment is ineffective. Dialysis should be considered early in patients with end-stage renal disease and hyperkalemia because they are at increased risk of progression to more severe hyperkalemia and serious cardiac arrhythmias. Peritoneal dialysis is relatively inefficient at removing K.
Last full review/revision May 2009 by James L. Lewis, III, MD