Definition and Epidemiology

The amount of potassium present in the average human body is approximately 50 mEq/kg. Of this, 90% is found in intracellular fluid, 8% in skin and bones, and 2% in extracellular fluid.^1–5 The maintenance of this relatively small amount of extracellular potassium is critical. Both hypokalemia and hyperkalemia are associated with an increased risk of complications, including cardiac arrhythmias and sudden death.

The definitions of hypokalemia and hyperkalemia are stated in terms of extracellular (or serum) potassium levels. Normal values for serum potassium levels depend on individual laboratories, but the usual range for normal values is approximately 3.5 to 5 mEq/L. Potassium imbalances can be defined as acute or chronic and can be further defined by the degree of severity.

Chronic hypokalemia and hyperkalemia develop in a minimum of weeks to months, and acute hypokalemia and hyperkalemia occur during hours to days. Mild hypokalemia occurs at serum levels of 3.5 to 4 mEq/L; moderate hypokalemia, 3 to 3.5 mEq/L; and severe hypokalemia, below 3 mEq/L. Mild to moderate hyperkalemia is defined as a serum level of 5.5 to 6.9 mEq/L, and severe hyperkalemia as a serum level of 7 mEq/L or higher.

Levels of potassium in the intracellular and extracellular fluids do not always correlate, as seen in diabetic ketoacidosis. Severe depletion of intracellular potassium (termed potassium deficiency) as a result of osmotic diuresis (which leads to increased renal loss of potassium), despite normal or even elevated extracellular (serum) levels of potassium, is caused by insulin deficiency.⁶ Once exogenous insulin has been administered, clinical hypokalemia can develop rapidly.⁶

In most cases, hypokalemia is drug induced; approximately 30% of all patients who are treated with non–potassium-sparing diuretics develop low serum potassium levels.⁵ Most cases of chronic hyperkalemia are caused by renal failure; however, the increased use of spironolactone after the publication of the Randomized Aldactone Evaluation Study has resulted in a marked increase in morbidity and mortality from hyperkalemia, with an estimated 50 excess hospital admissions per 1000 additional prescriptions for spironolactone.⁷

Specialist referral is indicated for serum potassium levels lower than 3 or higher than 6 mEq/L.

Pathophysiology

Potassium balance is affected by intake, excretion, and internal potassium regulation.^1–3 The minimum daily requirement for potassium intake in the normal adult is approximately 40 to 50 mEq.^1–3 Excretion occurs primarily in the kidneys and gastrointestinal tract, with a small amount excreted in perspiration. Internal potassium regulation depends on acid-base balance, plasma insulin levels, plasma catecholamine levels, and aldosterone activity.³

Because the kidneys are normally able to conserve potassium efficiently, hypokalemia is rarely a result of inadequate intake. The main causes of hypokalemia are increased renal loss from exogenous drug administration; primary or secondary hyperaldosteronism; and internal shifting of potassium from the extracellular to the intracellular space, which can occur with insulin administration or catecholamine excess (Box 209-1). Although vomiting may cause hypokalemia, it is not because of a loss of potassium from the gastrointestinal tract but rather because of secondary hyperaldosteronism related to volume depletion⁸ or, more rarely, metabolic alkalosis from loss of gastric secretions.⁵

The kidneys’ ability to maintain potassium homeostasis is preserved until the glomerular filtration rate (GFR) falls below 10 mL/min.⁸ Therefore, chronic hyperkalemia in patients with GFRs exceeding 20 mL/min is most likely caused by drug therapy, a defect in mineralocorticoid activity, or a lesion within the cortical collecting system.² Causes of hyperkalemia are listed in Box 209-2.

The prevention of clinically significant hypokalemia and hyperkalemia is essential. In the absence of early detection and treatment, hypokalemia can cause serious complications and even death. The major symptoms are associated with skeletal muscle.^2,4 Hypokalemia causes hyperpolarization, which decreases impulse conduction and muscle contraction.² Flaccid paralysis, beginning in the extremities and moving centrally, can eventually lead to respiratory paralysis. Possible cardiac complications include ventricular arrhythmias. Typical electrocardiographic findings include ST-segment depression, flattening and inversion of the T wave, and prominent U wave.^2,4 The appearance and severity of these electrocardiographic abnormalities do not correspond to the degree of hypokalemia, and they should not be used as a substitute for monitoring of serum levels.⁴

Clinical manifestations of hyperkalemia are chiefly cardiac, although neuromuscular complications can also occur.² Electrocardiographic changes associated with hyperkalemia include peaked T waves (often the first finding on electrocardiography [ECG]), ST-segment depression, widening of the QRS and PR intervals, and loss of the P wave.² A late sign on ECG is the appearance of a sine-wave pattern,^2,4 which usually indicates impending ventricular fibrillation and asystole.²

Although cardiac manifestations are obviously the most dangerous sequelae of hyperkalemia, neuromuscular complications, including paresthesias and fasciculations in the extremities, may be seen. Peripheral paralysis can occur, but paralysis of the respiratory muscles is rare.²

Physical Examination

A thorough history is the most important part of the physical examination. Any history of diuretic use, laxative use, vomit­ing, diarrhea, abnormal urinary output, diabetes mellitus, or hypertension, as well as a thorough diet and medication history, should be elicited. The physical examination should include a full assessment of vital signs (including orthostatic blood pressures); assessment of volume status⁵; and examination of the neuromuscular system, including assessment of muscle strength and reflexes.