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- Potassium (K+) is the major intracellular cation and is important for all electrical activities in the body.
- Majority of K+ (98%) is located intracellularly and high intracellular K+ levels are required for normal metabolism and growth.
- Serum K+ levels are tightly regulated within a narrow range (generally 3.5 to 5 mEq/L in children and 4 to 5.5 mEq/L in infants depending on the lab), and even small changes in serum K+ levels can have significant effects on excitability of cells.
- Hypokalemia is defined as serum K+ <3.5 mEq/L and is graded according to level:
- Mild hypokalemia (3 to 3.5 mEq/L)
- Moderate hypokalemia (2.5 to 3 mEq/L)
- Severe hypokalemia (<2.5 mEq/L)
- Hypokalemia usually asymptomatic until serum K+ is <3 mEq/L, or unless there is a rapid fall in serum K+.
- Pseudohypokalemia can be seen due to uptake of K+ in cells when blood samples are inappropriately kept in warm conditions for several hours before processing. This issue is in particular important in primary care setting if samples are being shipped without processing.
Hypokalemia is common in the inpatient setting, and prevalence was reported to be as high as 40% in critically ill children.
- Malnutrition (more important in developing countries)
- Eating disorders (particularly anorexia nervosa, especially when in conjunction with laxative or diuretic abuse)
- Conditions associated with increased stool losses (diarrhea, vomiting, loss of gastrointestinal [GI] fluid via surgical or tube drainage) increase the risk of developing hypokalemia
There are a few causes of hypokalemia that are secondary to monogenic disorders including:
- Bartter syndrome
- Gitelman syndrome
- Liddle syndrome
- Syndrome of apparent mineralocorticoid excess
- Hypokalemic periodic paralysis
- Some types of congenital adrenal hyperplasia
- Congenital chloride diarrhea
- Cystic fibrosis
Prevention of malnutrition and checking serum K+ levels in high-risk patients (GI fluid losses, malnutrition, eating disorders) is the most important step in prevention of severe hypokalemia.
- There are three major mechanisms affecting serum K+ levels: intake, excretion, and transcellular shifts.
- Hypokalemia can develop due to the following reasons:
- Reduced intake
- Increased losses (GI, renal or skin)
- Transcellular shifts (β2-adrenergic receptor stimulation, insulin, alkalosis)
- The most common reason for hypokalemia in children is extrarenal causes including diarrhea, laxatives, vomiting, nasogastric suctioning, pyloric stenosis, ileostomy, congenital chloride diarrhea, excessive sweating.
- The conditions associated with reduced intake include malnutrition and anorexia nervosa.
- Hypokalemia due to renal losses is divided into two major groups according to the presence or absence of hypertension:
- Renal etiologies associated with normal blood pressure: renal tubular acidosis (RTA), diabetic ketoacidosis (due to osmotic diuresis), medications (diuretics, amphotericin B, aminoglycosides, cisplatin), Bartter syndrome, Gitelman syndrome, cystic fibrosis, hypomagnesemia, toluene intoxication
- Renal etiologies associated with high blood pressure: congenital adrenal hyperplasia (17-α hydroxylase or 11-β hydroxylase deficiency), primary hyperaldosteronism (tumors), syndrome of apparent mineralocorticoid excess (11-β hydroxysteroid dehydrogenase deficiency), Cushing syndrome, Liddle syndrome, renal artery stenosis, medications/herbs (mineralocorticoids, glucocorticoids, inhibition of 11-β hydroxysteroid dehydrogenase by licorice)
- Hypokalemia due to transcellular shifts: β2 agonists (albuterol), insulin, theophylline, alkalosis (metabolic or respiratory), hyperthyroidism, hypokalemic periodic paralysis, refeeding syndrome