Hypokalemia
| Hypokalemia | |
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| Potassium | |
| ICD-10 | E87.6 |
| ICD-9 | 276.8 |
| DiseasesDB | 6445 |
| MedlinePlus | 000479 |
| MeSH | D007008 |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Assistant Editor(s)-In-Chief: Jack Khouri
Overview
Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. It is defined as a serum potassium level below 3.5 mEq/L. The condition is also known as potassium deficiency. The prefix hypo- means low (contrast with hyper-, meaning high). The middle kal refers to kalium, which is Neo-Latin for potassium. The end portion of the word, -emia, means "in the blood" (note, however, that hypokalemia is usually indicative of a systemic potassium deficit).
Potassium Homeostasis
The role of the kidney
Normally, total potassium excretion in stool is low and most ingested K is absorbed. The kidney is the main regulator of Potassium balance through excretion (the kidney excretes 90-95% of dietary potassium). At the glomerulus, potassium is freely filtered and then largely reabsorbed in the proximal tubule and thick ascending loop of Henle (>60 % of filtered potassium). The cortical collecting duct receives 10–15%of filtered potassium and constitutes the kidney’s major site of potassium excretion. Potassium excretion at the cortical collecting duct depends on the amount of Sodium delivered there and the activity of aldosterone. The absorption of sodium by the principal cells of the cortical collecting ducts is mediated by the apical epithelial sodium channels (ENaC); when the amount of sodium delivered to the cortical collecting duct is very high, the absorption of sodium increases without concomitant absorption of the accompanying anions (eg, bicarbonates and chloride ions) which are not easy to absorb. This physiologic process causes the formation of a negative charge within the cortical collecting duct lumen causing potassium and proton secretion. Aldosterone increases sodium absorption at the cortical collecting duct by means of enhancing the activity of Na-K-ATPase pumps, and augmenting the number of the ENaC channels.
Factors increasing kidney potassium excretion
- Aldosterone
- High urine flow rate
- High distal sodium delivery
- Metabolic alkalosis
Some factors affecting potassium distribution between the cells and the extracellular fluid
- Na/K ATPase
- Insulin
- Catecholamines
- plasma potassium concentration
- Extracellular pH
- Hyperosmolarity
Pathophysiology
The physiologic role of potassium
Potassium is essential for many body functions, especially excitable cells such as muscle and nerve cells. Diet, mostly meats and fruits, is the major source of potassium for the body. Potassium is the principal intracellular cation, with a concentration of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in extracellular fluid, including blood. More than 98% of the body's potassium is intracellular; measuring it from a blood sample is relatively insensitive, with small fluctuations in the blood corresponding to very large changes in the total bodily reservoir of potassium.
The cellular effect of Hypokalemia
The electrochemical gradient of potassium between 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. Decreased potassium levels in the extracellular space will cause hyperpolarization of the resting membrane potential ie, it becomes more negative. 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, the cell becomes less sensitive to excitation and a greater than normal stimulus is required for depolarization of the membrane in order to initiate an action potential. Clinically, this membrane hyperpolarization results in muscle flaccid paralysis, rhabdomyolysis (in severe hypokalemia) and paralytic ileus. At the Renal level, hypokalemia can cause metabolic alkalosis due to potassium/proton exchange across the cells and nephrogenic diabetes insipidus.
Pathophysiology of Hypokalemic Heart Arrythmias
Potassium is essential to the normal muscular function, in both voluntary (i.e skeletal muscle, e.g. the arms and hands) and involuntary muscle (i.e. smooth muscle in the intestines or cardiac muscle in the heart). Severe abnormalities in potassium levels can seriously disrupt cardiac function, even to the point of causing cardiac arrest and death. As explained above, hypokalemia makes the resting potential of potassium [E(K)] more negative. In certain conditions, this will make cells less excitable. However, in the heart, it causes myocytes to become hyperexcitable. This is due to two independent effects that may lead to aberrant cardiac conduction and subsequent arrhythmia:
- There are more inactivated sodium (Na) channels available to fire, and
- The overall potassium permeability of the ventricle is reduced (perhaps by the loss of a direct effect of extracellular potassium on some of the potassium channels), which can delay ventricular repolarization.
Causes
Hypokalemia can be the consequence of decreased ingestion, increased losses or transcellular shift from the extracellular to the intracellular compartment.
- Perhaps the most obvious cause is insufficient consumption of potassium (that is, a low-potassium diet). However, without excessive potassium loss from the body, this is a rare cause of hypokalemia. Alcoholism, anorexia nervosa, dental problems and dysphagia can all impair food intake and cause hypokalemia. In the hospital setting, hypokalemia can present in patients on total parenteral nutrition or potassium-free IV fluids.
- Excessive loss of potassium, often associated with excess water loss, which "flushes" potassium out of the body. Typically, this is a consequence of GI losses (vomiting and diarrhea), or excessive perspiration.
- Increased urinary losses:
- Certain medications can accelerate the removal of potassium from the body; including thiazide diuretics, such as hydrochlorothiazide; loop diuretics, such as furosemide; as well as various laxatives. The antifungal amphotericin B has also been associated with hypokalemia.
- A special case of potassium loss occurs with diabetic ketoacidosis. In addition to urinary losses from polyuria and volume contraction, there is also obligate loss of potassium from kidney tubules as a cationic partner to the negatively charged ketone, β-hydroxybutyrate.
- Hypomagnesemia can 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.
- 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 non-malignant) of the adrenal glands. Hypertension and hypokalemia can also be seen with a deficiency of the 11β-hydroxylase enzyme which allows cortisol to stimulate aldosterone receptors. This deficiency 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.
- Transcellular potassium shift to the intracellular space:
- Increased extracellular pH (each 0.11 unit increase in pH corresponds to a 0.4 meq/l decrease in potassium level)
- Elevated insulin
- Elevated beta-adrenergic activity (stress, beta-agonist intake, etc)
- 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 catechols and/or insulin and/or thyroid hormone that lead to sudden influx of potassium from the extracellular fluid into the muscle cells.
- Hypothermia
- Thyrotoxicosis
- Theophylline
- Rapid expansion of cell mass (eg, during refeeding after prolonged starvation, when patients with pernicious anemia are treated with vitamin B12 and with tumors having rapid cell turnover)
Differential Diagnosis
Differential Diagnosis[1][2]
- Acute hyperventilation
- Acute pancreatitis
- Adrenogenital Syndrome
- Alcoholism with reduced intestinal absorption of potassium
- Alkalosis
- Anabolic states or conditions of rapid cell multiplication
- Anorexia Nervosa
- Barium or toluene ingestion
- Bartter's Syndrome
- Bilateral Adrenal Hyperplasia
- Bulimia
- Carbenoxolon
- Chewing tobacco
- Chloroquine overdose
- Chronic glomerulonephritis
- Chronic inflammatory bowel disease
- Chronic laxative abuse
- Clay ingestion
- Cushing's Syndrome
- Diabetes Insipidus
- Diabetes with glucosuria
- Diabetic Ketoacidosis
- Diarrhea
- Digibind therapy
- Drugs
- Excessive sweating
- "Fad" diets
- Gastroenteritis
- Gastrointestinal (GI) fistula
- Geophagia
- Heart failure
- Heriditary pseudohyperaldosteronism
- Hyperaldosteronism
- Hypokalemic periodic paralysis
- Hypomagnesemia
- Hypothermia
- Hypovolemia
- Ileus
- Leukemia
- Licorice excess
- Liddle's Syndrome
- Malabsorption syndrome
- Malignant hypertension
- Metabolic acidosis
- Mineralacorticoid excess
- Nasogastric suction
- Polyuric phase after acute renal failure
- Postoperative
- Pseudohypokalemia
- Pyloric Stenosis
- Renal Artery Stenosis
- Renal Tubular Acidosis
- Renin-secreting tumor
- Starvation
- Steroid therapy
- Stress
- Total parenteral nutrition
- Ureterosigmoidostomy
- Villous adenoma of the rectum
- Vomiting
Diagnosis
Symptoms and signs
- Fatigue
- Weakness
- Vomiting
- Constipation
- Muscle cramps and paralysis (the lower extremity muscles are most commonly involved) which may involve the intestine and cause ileus
- Respiratory muscle weakness leading to respiratory failure
Cardiac
- Hypertension
- Arrhythmias including premature atrial and ventricular complexes, paroxysmal atrial or junctional tachycardia and even ventricular tachycardia or fibrillation
- Heart block
- Digoxin therapy, CAD and left ventricular hypertrophy potentiate hypokalemia effects on the heart
Renal
- Nephrogenic diabetes insipidus due to decreased concentrating ability. As a consequence, the patient presents with polyuria and polydipsia
- Increased bicarbonate reabsorption
- Increased ammonia formation which may precipitate hepatic encephalopathy in cirrhotic patients
- Decreased sodium reabsorption resulting in hyponatremia
Other
- Rhabdomyolysis
- Hyperglycemia
History
A detailed history can help depict the cause of hypokalemia.
Dietary history
Malnutrition: lack of meat and fruit intake
Medication history
- Diuretics (loop and thiazides)
- Beta agonists
- Chloroquine
- Theophylline
- Insulin
- Corticosteroids
- Licorice
- Nephrotoxic drugs (platinum-based chemotherapy, aminoglycosides)
- Laxatives
Past medical history
- Uncontrolled diabetes
- Hyperthyroidism
- Pernicious anemia
- COPD (treated with Beta agonists and theophylline)
- Cushing’s disease
- Periodic paralysis
- Ileostomy/short bowel
- Primary hyperaldosteronism
- Liddle syndrome
- Bartter and Gitelman syndrome
- Prolonged starvation
- Cancer
- Renal tubular acidosis type I and type II
Laboratory Findings
- Complete blood count (CBC)
- Blood urea nitrogen (BUN)/creatinine
- Calcium
- Magnesium
- Glucose
- Arterial blood gases
- Aldosterone level
- Renin levels
- Urinary sodium
- Urine potassium
- Levels <25 meq/day (or <15 meq/L on urine spot) rule out a renal cause of hypokalemia and suggest extrarenal potassium loss or transcellular shift
- Higher potassium excretion suggest renal losses.
- Transtubular potassium gradient (TTKG)
- TTKG= (Urine K x Plasma osmolarity)/(Plasma K x Urine osmolarity)
- A TTKG less than 2-3 indicates renal potassium conservation in a hypokalemic patient
- A urine osmolality less than plasma osmolality or urine sodium <20 mEq/L, the formula is not applicable
- Urine chloride
- <25 meq/L: vomiting or remote diuretic use
- >40 meq/L: diuretics, Bartter's, Gitelman's and mineralocorticoid excess
Electrocardiography
Overview
- Caused mainly by delayed ventricular repolarization
- Seen at potassium levels <3 meq/L (90% of patients with potassium levels <2.7 meq/L have abnormal ECG findings)
- Rapidly reversible with potassium depletion
ECG changes
- ST segment depression, decreased T wave amplitude, prominent U waves
- seen in 78% of patients with a K < 2.7 meq
- seen in 35% of patients with a K > 2.7 and < 3.0
- seen in 10% of patients with a K > 3.0 and < 3.5
- U waves are also prominent in bradycardia and LVH
- Prolongation of the QRS duration
- uncommon except in severe hyperkalemia
- Increase in the amplitude and duration of the P-wave
- Cardiac arrhythmias and AV block
- Contrary to popular belief there is not prolongation of the QTc, this is artifactually prolonged due to the U wave. In some cases there is fusion of the T and the U wave making interpretation impossible.
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Long QT interval, ST segment depression, low T waves amplitude and TU wave fusion in a hypokalemic patient.
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Consecutive ECGs of a patient with hypokalemia. ECG1
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Consecutive ECGs of a patient with hypokalemia. ECG2
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Consecutive ECGs of a patient with hypokalemia. After correction of potassium levels.
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Hypokalemia with LVH. Image courtesy of Dr Jose Ganseman
Treatment
The most important step in severe hypokalemia is removing the cause, such as treating diarrhea or stopping offending medication.
Mild hypokalemia (>3.0 mEq/L) may be treated with oral potassium chloride supplements (Sando-K®, Slow-K®). As this is often part of a poor nutritional intake, potassium-containing foods may be recommended, such as tomatoes, orange oranges or bananas. Both dietary and pharmaceutical supplements are used for people taking diuretic medications (see Causes, above).
Severe hypokalemia (<3.0 mEq/L) may require intravenous supplementation. Typically, saline is used, with 20-40 mEq KCl per liter over 3-4 hours. Giving intravenous potassium at faster rates may predispose to ventricular tachycardias and requires intensive monitoring.
Difficult or resistant cases of hypokalemia may be amenable to amiloride, a potassium-sparing diuretic, or spironolactone.
When replacing potassium intravenously, infusion via central line is encouraged to avoid the frequent occurrence of a burning sensation at the site of a peripheral iv, 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 IV fluid, or mixing 3 ml of 1% lidocaine to each 10 meq of kcl per 50 ml of IV fluid. The practice of adding lidocaine, however, raises the likelihood of serious medical errors [3].