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Hypokalemia

  • Author: Eleanor Lederer, MD, FASN; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Oct 07, 2015
 

Practice Essentials

Hypokalemia is generally defined as a serum potassium level of less than 3.5 mEq/L (3.5 mmol/L). Severe hypokalemia is a level of less than 2.5 mEq/L. Hypokalemia is a potentially life-threatening imbalance that may be iatrogenically induced.

Gitelman syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis and low blood pressure. See the image below.

A model of transport mechanisms in the distal conv A model of transport mechanisms in the distal convoluted tubule. Sodium-chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical membrane, and a putative Na/Mg exchanger in the basolateral membrane. These transport mechanisms play a role in familial hypokalemia-hypomagnesemia or Gitelman syndrome.

Signs and symptoms

Patients are often asymptomatic, particularly those with mild hypokalemia. Symptoms that are present are often from the underlying cause of the hypokalemia rather than the hypokalemia itself. The symptoms of hypokalemia are nonspecific and predominantly are related to muscular or cardiac function. Complaints may include the following:

  • Weakness and fatigue (most common)
  • Muscle cramps and pain (severe cases)
  • Worsening diabetes control or polyuria
  • Palpitations
  • Psychological symptoms (eg, psychosis, delirium, hallucinations, depression)

Physical findings are often within the reference range. Abnormal findings may reflect the underlying disorder. Severe hypokalemia may manifest as bradycardia with cardiovascular collapse. Cardiac arrhythmias and acute respiratory failure from muscle paralysis are life-threatening complications that require immediate diagnosis.

See Presentation for more detail.

Diagnosis

In most cases, the cause of hypokalemia is apparent from the history and physical examination. First-line studies include measurement of urine potassium, a serum magnesium assay, and an electrocardiogram (ECG).

If the urine potassium level is less than 20 mEq/L, consider the following:

  • Diarrhea and use of laxatives
  • Diet or total parenteral nutrition (TPN) contents
  • The use of insulin, excessive bicarbonate supplements, and episodic weakness

If the urine potassium level is higher than 40 mEq/L, consider diuretics. If diuretic use has been excluded, measure arterial blood gases (ABG) and determine the acid-base balance. Alkalosis suggests one of the following:

  • Vomiting
  • Bartter syndrome
  • Gitelman syndrome
  • Mineralocorticoid excess

Depending on history, physical examination findings, clinical impressions, and urine potassium results, the following tests may be appropriate, but they should not be first-line tests unless the clinical index of suspicion for the disorder is high:

  • Drug screen in urine and/or serum for diuretics, amphetamines, and other sympathomimetic stimulants
  • Serum renin, aldosterone, and cortisol
  • 24-hour urine aldosterone, cortisol, sodium, and potassium
  • Pituitary imaging to evaluate for Cushing syndrome
  • Adrenal imaging to evaluate for adenoma
  • Evaluation for renal artery stenosis
  • Enzyme assays for 17-beta hydroxylase deficiency
  • Thyroid function studies in patients with tachycardia, especially Asians [1]
  • Serum anion gap (eg, to detect toluene toxicity)

See Workup for more detail.

Management

The treatment of hypokalemia has 4 facets, as follows:

  • Reduction of potassium losses
  • Replenishment of potassium stores
  • Evaluation for potential toxicities
  • Determination of the cause to prevent future episodes, if possible

Decreasing potassium losses

  • Discontinue diuretics/laxatives
  • Use potassium-sparing diuretics if diuretic therapy is required (eg, severe heart failure)
  • Treat diarrhea or vomiting
  • Administer H2 blockers to patients receiving nasogastric suction
  • Control hyperglycemia if glycosuria is present

Replenishment

  • For every 1 mEq/L decrease in serum potassium, the potassium deficit is approximately 200-400 mEq; however, this calculation could either overestimate or underestimate the true potassium deficit
  • Patients with a potassium level of 2.5-3.5 mEq/L may need only oral potassium replacement
  • If the potassium level is less than 2.5 mEq/L, intravenous (IV) potassium should be given, with close followup, continuous ECG monitoring, and serial potassium levels
  • The serum potassium level is difficult to replenish if the serum magnesium level is also low

Surgical care

Surgical intervention is required only with certain etiologies, such as the following:

  • Renal artery stenosis
  • Adrenal adenoma
  • Intestinal obstruction producing massive vomiting
  • Villous adenoma

See Treatment and Medication for more detail.

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Background

Hypokalemia is generally defined as a serum potassium level of less than 3.5 mEq/L (3.5 mmol/L). Moderate hypokalemia is a serum level of 2.5-3 mEq/L, and severe hypokalemia is a level of less than 2.5 mEq/L. Hypokalemia is a potentially life-threatening imbalance that may be iatrogenically induced.

Potassium, the most abundant intracellular cation, is essential for the life of an organism. Potassium homeostasis is integral to normal cellular function, particularly of nerve and muscle cells, and is tightly regulated by specific ion-exchange pumps, primarily by cellular, membrane-bound, sodium-potassium adenosine triphosphatase (ATPase) pumps.

Potassium is obtained through the diet and excreted principally via the kidney. Potassium homeostasis is maintained predominantly through the regulation of renal excretion; the adrenal gland and pancreas also play significant roles (see Pathophysiology).

Hypokalemia may result from inadequate potassium intake, increased potassium excretion, or a shift of potassium from the extracellular to the intracellular space. Increased excretion is the most common mechanism. Poor intake or an intracellular shift by itself is a distinctly uncommon cause, but several causes often are present simultaneously. (See Etiology.)

The symptoms of hypokalemia are nonspecific and predominantly are related to muscular or cardiac function. Weakness and fatigue are the most common complaints. An electrocardiogram (ECG) may show atrial or ventricular tachyarrhythmias.

In most cases, the cause of hypokalemia is apparent from the history and physical examination (see Presentation). Measurement of urine potassium is of vital importance because it establishes the pathophysiologic mechanism and, thus, is used in formulating the differential diagnosis. This, in turn, will guide the choice of further tests (see Workup).

The treatment of hypokalemia has four facets, as follows (see Treatment):

  • Reduction of potassium losses
  • Replenishment of potassium stores
  • Evaluation for potential toxicities
  • Determination of the cause to prevent future episodes, if possible

Prognosis

The prognosis for patients with hypokalemia depends entirely on the condition’s underlying cause. For example, a patient with an acute episode of hypokalemia resulting from diarrhea has an excellent prognosis. Hypokalemia due to a congenital disorder such as Bartter syndrome has a poor to nonexistent potential for resolution.

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Pathophysiology

Gastrointestinal absorption of potassium is complete, resulting in daily excess intake of approximately 1 mEq/kg/day (60-100 mEq). Ninety percent of this excess is excreted through the kidneys, and 10% is excreted through the gut.

Potassium homeostasis is maintained predominantly through the regulation of renal excretion. The most important site of regulation is the collecting duct, where aldosterone receptors are present.

Potassium excretion is increased by the following factors:

  • Aldosterone
  • High sodium delivery to the collecting duct (eg, diuretics)
  • High urine flow (eg, osmotic diuresis)
  • High serum potassium levels
  • Delivery of negatively charged ions to the collecting duct (eg, bicarbonate)

Potassium excretion is decreased by the following factors:

  • Absolute aldosterone deficiency or resistance to aldosterone effects
  • Low sodium delivery to the collecting duct
  • Low urine flow
  • Low serum potassium levels
  • Renal failure

An acute increase in osmolality causes potassium to exit from cells. An acute cell/tissue breakdown releases potassium into extracellular space.

Renal factors in potassium homeostasis

Kidneys adapt to acute and chronic alterations in potassium intake. When potassium intake is chronically high, potassium excretion likewise is increased. In the absence of potassium intake, however, obligatory renal losses are 10-15 mEq/day. Thus, chronic losses occur in the absence of any ingested potassium.

The kidney maintains a central role in the maintenance of potassium homeostasis, even in the setting of chronic renal failure. Renal adaptive mechanisms allow the kidneys to maintain potassium homeostasis until the glomerular filtration rate drops to less than 15-20 mL/min.

Additionally, in the presence of renal failure, the proportion of potassium excreted through the gut increases. The colon is the major site of gut regulation of potassium excretion. Therefore, potassium levels can remain relatively normal under stable conditions, even with advanced renal insufficiency. However, as renal function worsens, the kidneys may not be capable of handling an acute potassium load.

Potassium distribution

Potassium is predominantly an intracellular cation; therefore, serum potassium levels can be a very poor indicator of total body stores. Because potassium moves easily across cell membranes, serum potassium levels reflect movement of potassium between intracellular and extracellular fluid compartments, as well as total body potassium homeostasis.

Several factors regulate the distribution of potassium between the intracellular and extracellular space, as follows:

  • Glycoregulatory hormones: (1) Insulin enhances potassium entry into cells, and (2) glucagon impairs potassium entry into cells
  • Adrenergic stimuli: (1) Beta-adrenergic stimuli enhance potassium entry into cells, and (2) alpha-adrenergic stimuli impair potassium entry into cells
  • pH: (1) Alkalosis enhances potassium entry into cells, and (2) acidosis impairs potassium entry into cells

Physiologic mechanisms for sensing extracellular potassium concentration are not well understood. Adrenal glomerulosa cells and pancreatic beta cells may play a role in potassium sensing, resulting in alterations in aldosterone and insulin secretion.[2, 3] As the adrenal and pancreatic hormonal systems play important roles in potassium homeostasis, this would not be surprising; however, the molecular mechanisms by which these potassium channels signal changes in hormone secretion and activity have still not been determined.

Muscle contains the bulk of body potassium, and the notion that muscle could play a prominent role in the regulation of serum potassium concentration through alterations in sodium pump activity has been promoted for a number of years. Potassium ingestion stimulates the secretion of insulin, which increases the activity of the sodium pump in muscle cells, resulting in an increased uptake of potassium.

Studies in a model of potassium deprivation demonstrate that acutely, skeletal muscle develops resistance to insulin-stimulated potassium uptake even in the absence of changes in muscle cell sodium pump expression. However, prolonged potassium deprivation leads to a decrease in muscle cell sodium-pump expression, resulting in decreased muscle uptake of potassium.[4, 5, 6]

Thus, there appears to be a well-developed system for sensing potassium by the pancreas and adrenal glands. High potassium states stimulate cellular uptake via insulin-mediated stimulation of sodium-pump activity in muscle and stimulate potassium secretion by the kidney via aldosterone-mediated enhancement of distal renal expression of secretory potassium channels (ROMK).

Low potassium states result in insulin resistance, impairing potassium uptake into muscle cells, and cause decreased aldosterone release, lessening renal potassium excretion. This system results in rapid adjustments in immediate potassium disposal and helps to provide long-term potassium homeostasis.

Pathogenic mechanisms

Hypokalemia can occur via the following pathogenetic mechanisms:

  • Deficient intake
  • Increased excretion
  • A shift from the extracellular to the intracellular space

Although poor intake or an intracellular shift by itself is a distinctly uncommon cause, several causes often are present simultaneously.

Increased excretion

The most common mechanisms leading to increased renal potassium losses include the following:

  • Enhanced sodium delivery to the collecting duct, as with diuretics
  • Mineralocorticoid excess, as with primary or secondary hyperaldosteronism
  • Increased urine flow, as with an osmotic diuresis

Gastrointestinal losses, from diarrhea, vomiting, or nasogastric suctioning, also are common causes of hypokalemia. Vomiting leads to hypokalemia via a complex pathogenesis. Gastric fluid itself contains little potassium, approximately 10 mEq/L. However, vomiting produces volume depletion and metabolic alkalosis, which are accompanied by increased renal potassium excretion.

Volume depletion leads to secondary hyperaldosteronism, which in turn leads to enhanced cortical collecting tubule secretion of potassium in response to enhanced sodium reabsorption. Metabolic alkalosis also increases collecting tubule potassium secretion due to the decreased availability of hydrogen ions for secretion in response to sodium reabsorption.

Extracellular/intracellular shift

Hypokalemia caused by a shift from extracellular to intracellular space often accompanies increased excretion, leading to a potentiation of the hypokalemic effect of excessive loss. Intracellular shifts of potassium often are episodic and frequently are self-limited, as, for example, with acute insulin therapy for hyperglycemia.

Additional considerations

Regardless of the cause, hypokalemia produces similar signs and symptoms. Because potassium is overwhelmingly an intracellular cation and a variety of factors can regulate the actual serum potassium concentration, an individual can incur very substantial potassium losses without exhibiting frank hypokalemia. For example, diabetic ketoacidosis results in a significant potassium deficit; however, serum potassium in a patient presenting with diabetic ketoacidosis is rarely low and frequently is frankly elevated.

Conversely, hypokalemia does not always reflect a true deficit in total body potassium stores. Acute insulin administration can drive potassium into cells transiently, producing short-lived hypokalemia but not signifying potassium depletion.

Complications

Cardiovascular complications

Hypokalemia has widespread actions in many organ systems that, over time, may result in cardiovascular disease. Cardiovascular complications are clinically the most important harbingers of significant morbidity or mortality from hypokalemia.

Although hypokalemia has been implicated in the development of atrial and ventricular arrhythmias, ventricular arrhythmias have received the most attention. Even moderate hypokalemia may inhibit the sodium-potassium pump in myocardial cells, promoting spontaneous early afterdepolarizations that lead to ventricular tachycardia/fibrillation.[7]

Increased susceptibility to cardiac arrhythmias is observed with hypokalemia in the following settings:

  • Congestive heart failure
  • Underlying ischemic heart disease/acute myocardial ischemia
  • Aggressive therapy for hyperglycemia, such as with diabetic ketoacidosis
  • Digitalis therapy
  • Treatment with class III antiarrhythmic drugs (eg, dofetilide) [7]
  • Methadone therapy [8]
  • Conn syndrome [9]

Low potassium intake has been implicated as a risk factor for the development of hypertension and/or hypertensive end-organ damage. Hypokalemia leads to altered vascular reactivity, likely from the effects of potassium depletion on the expression of adrenergic receptors, angiotensin receptors, and mediators of vascular relaxation. The result is enhanced vasoconstriction and impaired relaxation, which may play a role in the development of diverse clinical sequelae, such as ischemic central nervous system events or rhabdomyolysis.

Treatment of hypertension with diuretics without due attention to potassium homeostasis exacerbates the development of end-organ damage by fueling the metabolic abnormalities. These patients are then at higher risk for lethal hypokalemia under stress conditions such as myocardial infarction, septic shock, or diabetic ketoacidosis.

Muscular complications

Muscle weakness, depression of the deep-tendon reflexes, and even flaccid paralysis can complicate hypokalemia. Rhabdomyolysis can be provoked, especially with vigorous exercise. However, rhabdomyolysis has also been seen as a complication of severe hypokalemia, complicating primary hyperaldosteronism in the absence of exercise.[10]

Renal complications

Abnormalities of renal function often accompany acute or chronic hypokalemia. These may include nephrogenic diabetes insipidus. They also may include metabolic alkalosis from impaired bicarbonate excretion and enhanced ammoniagenesis, as well as cystic degeneration and interstitial scarring.

Gastrointestinal complications

Hypokalemia decreases gut motility, which can lead to or exacerbate an ileus. Hypokalemia also is a contributory factor in the development of hepatic encephalopathy in the setting of cirrhosis.

Metabolic complications

Hypokalemia has a dual effect on glucose regulation by decreasing insulin release and peripheral insulin sensitivity. Clinical evidence suggests that the hypokalemic effect of thiazide is the causative factor in thiazide-associated diabetes mellitus.[11]

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Etiology

As mentioned, hypokalemia can result from inadequate potassium intake, increased potassium excretion, or a shift of potassium from the extracellular to the intracellular space. Increased excretion is the most common mechanism. Poor intake or an intracellular shift by itself is a distinctly uncommon cause, but several causes often are present simultaneously.

Inadequate potassium intake

Inadequate potassium intake may result from any of the following:

  • Eating disorders [12] : Anorexia, bulimia, starvation, pica, and alcoholism
  • Dental problems: Impaired ability to chew or swallow
  • Poverty: Inadequate quantity or quality of food (eg, "tea-and-toast" diet of elderly individuals)
  • Hospitalization: Potassium-poor TPN

Increased potassium excretion

Increased excretion of potassium, especially coupled with poor intake, is the most common cause of hypokalemia. Increased potassium excretion may result from any of the following:

  • Mineralocorticoid excess (endogenous or exogenous)
  • Hyperreninism from renal artery stenosis
  • Osmotic diuresis: Mannitol and hyperglycemia can cause osmotic diuresis
  • Increased gastrointestinal losses
  • Drugs
  • Genetic disorders

Endogenous sources of excess mineralocorticoid include the following:

  • Primary hyperaldosteronism, most commonly from an adrenal adenoma or bilateral adrenal hyperplasia
  • Secondary hyperaldosteronism from volume depletion, congestive heart failure, cirrhosis, or vomiting
  • Tumor that is producing adrenocorticotropic hormone
  • Genetic disorders

Exogenous causes of mineralocorticoid excess include the following:

  • Steroid therapy for immunosuppression
  • Glycyrrhizic acid - Inhibits 11-beta hydroxysteroid dehydrogenase; contained in licorice and Chinese herbal preparations
  • Renal tubular disorders - Type I and type II renal tubular acidosis
  • Hypomagnesemia

Gastrointestinal loss of potassium can result from vomiting, diarrhea, or small intestine drainage. The problem can be particularly prominent in tropical illnesses, such as malaria and leptospirosis.[13] Severe hypokalemia has also been reported with villous adenomas and VIPomas.[14]

Drugs that can cause hypokalemia include the following:

  • Diuretics (carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics): Increased collecting duct permeability or increased gradient for potassium secretion can result in losses
  • Methylxanthines (theophylline, aminophylline, caffeine)
  • Verapamil (with overdose)
  • Quetiapine (particularly in overdose)
  • Ampicillin, carbenicillin, high-dose penicillins
  • Bicarbonate
  • Antifungal agents (amphotericin B, azoles, echinocandins) [15, 16]
  • Gentamicin
  • Cisplatin
  • Ephedrine (from Ephedra; banned in the United States, but available over the Internet) [17]
  • Beta-agonist intoxication [18]

Genetic disorders

The following genetic disorders may result in hypokalemia:

  • Congenital adrenal hyperplasia (11-beta hydroxylase or 17-alpha hydroxylase deficiency)
  • Glucocorticoid-remediable hypertension
  • Bartter syndrome
  • Gitelman syndrome
  • Liddle syndrome
  • Gullner syndrome
  • Glucocorticoid receptor deficiency
  • Hypokalemic period paralysis
  • Thyrotoxic periodic paralysis (TTPP)
  • Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome)

Bartter syndrome

Bartter syndrome is a group of autosomal recessive disorders characterized by hypokalemic metabolic alkalosis and hypotension.[19] Sensorineural hearing loss is also a feature of this syndrome. Mutations in 6 different renal tubular proteins in the loop of Henle have been discovered in individuals with clinical Bartter syndrome.[20, 21]

Antenatal Bartter syndrome types 1, 2, 3, and 4A are inherited in an autosomal recessive manner. They result from the following mutations:

  • Type 1 is caused by mutation in the Na-K-2Cl cotransporter NKCC2 gene
  • Type 2 is caused by a mutation in the adenosine triphosphate (ATP)–sensitive potassium channel ROMK gene
  • Type 3 is caused by mutations in the kidney chloride channel B CLCNKB gene [22]
  • Type 4A is caused by mutation in the BSND gene; it can also be associated with hearing loss

Bartter syndrome 4B is caused by mutations in both the CLCNKA and the CLCNKB gene, giving it a unique digenic mode of inheritance.

Autosomal dominant hypocalcemia (ADH) is caused by mutations in the calcium-sensing receptor gene CASR. ADH is characterized by hypocalcemia and hypoparathyroidism; when accompanied by hypokalemia and metabolic alkalosis, it is classified as type 5 Bartter syndrome.[23] Four activating CASR mutations have been identified in Bartter syndrome type 5.[24]

The most severe cases of Bartter syndrome manifest antenatally or neonatally as profound volume depletion and hypokalemia. Patients with less severe cases present in childhood or early adulthood with persistent hypokalemic metabolic alkalosis that is resistant to replacement therapy. In general, however, onset of true Bartter syndrome occurs by age 5 years.

Gitelman syndrome

Gitelman syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis and low blood pressure. It is caused by a defect in the thiazide-sensitive sodium chloride transporter in the distal tubule, which is encoded by the SLC12A3 gene (see the image below).

A model of transport mechanisms in the distal conv A model of transport mechanisms in the distal convoluted tubule. Sodium-chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical membrane, and a putative Na/Mg exchanger in the basolateral membrane. These transport mechanisms play a role in familial hypokalemia-hypomagnesemia or Gitelman syndrome.

Compared with Bartter syndrome, Gitelman syndrome generally is milder and presents later; in addition, Gitelman syndrome is complicated by hypomagnesemia, which generally does not occur in Bartter syndrome. Hypocalciuria is also frequently found in Gitelman syndrome, while patients with Bartter syndrome are more likely to have increased urine calcium excretion.

Liddle syndrome

Liddle syndrome is an autosomal recessive disorder characterized by a mutation affecting either the beta or gamma subunit of the epithelial sodium channel in the aldosterone-sensitive portion of the nephron. These subunits are encoded by the SCNN1G and SCNN1B genes and are inherited in an autosomal dominant fashion.

Mutations to these genes lead to unregulated sodium reabsorption, hypokalemic metabolic alkalosis, and severe hypertension. It has been shown that amiloride and triamterene are effective treatments for Liddle syndrome, but spironolactone is not.[25]

Gullner syndrome

Gullner syndrome, first described in the 1970s, after being diagnosed in 2 brothers, was reported to be a “new” form of familial hypokalemia.[26] Three additional siblings were also found to have elevated renin and decreased potassium levels. The 2 brothers had fatigue and muscle cramps. One responded to a low sodium diet, and the other required use of a potassium-sparing diuretic. Additional patients were described in 1980 and 1983.[27, 28]

This syndrome was described as being like Bartter syndrome, except that renal histology showed normal juxtaglomerular apparatus and changes to the proximal tubules. Although the locus for the gene associated with Gullner syndrome showed linkage to the HLA-A and HLA-B genes, its identity is still unknown.

Glucocorticoid receptor deficiencysyndrome

Glucocorticoid receptor deficiency syndrome is caused by mutations to the NR3C1 gene and has different clinical manifestations in patients who are homozygous than it does in those who are heterozygous. Homozygotes for this condition display mineralocorticoid excess, hypertension, hypokalemia, and metabolic alkalosis.

Heterozygotes may have increased plasma cortisol levels and generally do not have hypokalemia or metabolic alkalosis. However, several reports in the literature have described likely heterozygotes for this condition who have symptoms of either partial adrenal insufficiency or mild virilization in females.[29, 30]

Hypokalemic periodic paralysis

Hypokalemic periodic paralysis types 1 and 2 are caused by mutations in the CACNL1A3 and SCN4A genes, respectively, and are both inherited in an autosomal dominant fashion. Patients with this disorder experience episodes of flaccid, generalized weakness, usually without myotonia. Patients will have hypokalemia during the flaccid attacks. The disorder is treated by administration of potassium and can be precipitated by a large glucose or insulin load, as both forms tend to drive potassium from the extracellular to the intracellular space.

Thyrotoxic periodic paralysis (TTPP)

TTPP is a form of hypokalemic periodic paralysis in which episodes of weakness associated with hypokalemia are seen in individuals with hyperthyroidism. TTPP is most common in Asian males.

The mechanism by which hyperthyroidism produces hypokalemic paralysis is not yet understood, but theories include increased Na-K-ATPase activity, which has been found in patients with both thyrotoxicosis and paralysis. Three single-nucleotide polymorphisms in 3 different regions of the CACNA1S gene have been associated with increased rates of TTPP, compared with normal controls or patients with Graves disease.[31]

SeSAME syndrome

In addition to seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance, some patients with SeSAME syndrome will have short stature, salt craving with polydipsia, renal potassium and sodium wasting, and polyuria. Hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis are seen.

This syndrome is caused by mutations in the KCNJ10 gene, which encodes an inwardly rectifying potassium channel. It is inherited in an autosomal recessive fashion.[32]

Shift of potassium from extracellular to intracellular space

A shift of potassium to the intracellular space may result from any of the following:

  • Alkalosis (metabolic or respiratory)
  • Insulin administration or glucose administration (the latter stimulates insulin release)
  • Intensive beta-adrenergic stimulation
  • Hypokalemic periodic paralysis
  • Thyrotoxic periodic paralysis
  • Refeeding: This is observed in prolonged starvation, eating disorders, and alcoholism
  • Hypothermia
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Epidemiology

The frequency of hypokalemia in the general population is difficult to estimate; however, probably fewer than 1% of people who are not taking medication have a serum potassium level lower than 3.5 mEq/L. Potassium intake varies according to age, sex, ethnic background, and socioeconomic status. Whether these differences in intake produce different degrees of hypokalemia or different sensitivities to hypokalemic insults is not known.

Up to 21% of hospitalized patients have serum potassium levels lower than 3.5 mEq/L, with 5% of patients exhibiting potassium levels lower than 3 mEq/L. Among elderly patients, 5% demonstrate potassium levels lower than 3 mEq/L.

Of patients taking non–potassium-sparing diuretics, 20-50% develop hypokalemia. African Americans and women are more susceptible. The higher frequency of hypokalemia in the former group may be from lower intake of potassium in African-American men (approximately 25 mEq/day) than in their white counterparts (70-100 mEq/day). Risk of hypokalemia in patients taking diuretics is enhanced by concomitant illness, such as heart failure or nephrotic syndrome.

Other factors associated with a high incidence of hypokalemia include the following:

  • Eating disorders (incidence of 4.6-19.7% in an outpatient setting [33, 34] )
  • AIDS (23.1% of hospitalized patients) [35]
  • Alcoholism (incidence reportedly as high as 12.6% [36] in the inpatient setting), likely from a hypomagnesemia-induced decrease in tubular reabsorption of potassium
  • Bariatric surgery [37]

The frequency of hypokalemia increases with age because of increased use of diuretics and potassium-poor diets. However, infants and younger children are more susceptible to viral GI infections; emesis or diarrhea from such infections places them at increased risk for hypokalemia because the depletion of fluid volume and electrolytes from GI loss is relatively higher than that in older children and adults.

Hypokalemia generally is associated with higher morbidity and mortality, especially from cardiac arrhythmias or sudden cardiac death. However, an independent contribution of hypokalemia to increased morbidity/mortality has not been conclusively established. Patients who develop hypokalemia often have multiple medical problems, making the separation and quantitation of the contribution by hypokalemia, per se, difficult.

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Patient Education

Instruct patients on the symptoms of hypokalemia or hyperkalemia, as follows:

  • Palpitations or notable cardiac arrhythmias
  • Muscle weakness
  • Increasing difficulty with diabetes control
  • Polyuria

Instruct patients on the effects of medications; specifically, which of their drugs will produce serum potassium abnormalities in either direction. For example, tell patients to discontinue diuretics if nausea and vomiting or diarrhea occurs and to call the physician if such gastrointestinal losses persist. Depending on patients' underlying disease or diseases, sudden fluid losses can result in either hypokalemia or hyperkalemia if diuretics, potassium supplements, or antihypertensives are continued.

Diet modification is recommended for those patients who are predisposed to hypokalemia. High sodium intake tends to enhance renal potassium losses. Therefore, instruct patients about the establishment of a low-sodium, high-potassium diet. Bananas, tomatoes, oranges, and peaches are high in potassium.

For patient education information, see Low Potassium (Hypokalemia).

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Contributor Information and Disclosures
Author

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Coauthor(s)

Vibha Nayak, MD Assistant Professor of Nephrology, Director of Home Dialysis, Kidney Disease Program, University of Louisville School of Medicine

Vibha Nayak, MD is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Zygimantas C Alsauskas, MD Assistant Professor of Medicine, Division of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

Zygimantas C Alsauskas, MD is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Lina Mackelaite, MD Assistant Professor of Medicine, University of Louisville School of Medicine

Lina Mackelaite, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Transplantation, National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

Leslie Ford, MD Assistant Professor of Medicine, Kidney Disease Program, University of Louisville School of Medicine

Leslie Ford, MD is a member of the following medical societies: American Medical Association, American Society of Nephrology, and Kentucky Medical Association

Disclosure: Nothing to disclose.

James W Lohr, MD Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Nothing to disclose.

Rosemary Ouseph, MD Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine

Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians

Disclosure: Genzyme Grant/research funds Other

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A model of transport mechanisms in the distal convoluted tubule. Sodium-chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical membrane, and a putative Na/Mg exchanger in the basolateral membrane. These transport mechanisms play a role in familial hypokalemia-hypomagnesemia or Gitelman syndrome.
 
 
 
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