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[1,2,3,4,5]. The maintenance of this relatively small amount of extracellular potassium is critical; small changes can cause serious clinical consequences.

Chronic hypokalemia and hyperkalemia develop in a minimum of weeks to months, and acute hypokalemia and hyperkalemia occur over hours to days. Mild hypokalemia occurs at serum levels of less than 3.5 mEq/L, but greater than 3 mEq/L; moderate hypokalemia at 2.5–3 mEq/L; and levels less than 2.5 mEq/L are considered severe [7,8]. Mild-to-moderate hyperkalemia is defined as a serum level of 5.5–6.9 mEq/L, and severe hyperkalemia is a serum level of 7 mEq/L or greater [9]. Physician consultation is indicated for serum potassium levels less than 3 mEq/L or greater than 6 mEq/L.

In the vast majority of cases, hypokalemia is drug induced; approximately 20% to 50% of all patients who are treated with non-potassium-sparing diuretics develop low serum potassium levels [7,9]. Other populations with a high incidence of hypokalemia include individuals who have undergone bariatric surgery and those with eating disorders, acquired immune deficiency syndrome (AIDS), and/or alcohol use disorder [10]. The incidence of hyperkalemia in the pediatric population is unknown, though it can exceed 50% in extremely low birth weight premature infants [9]. 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 1,000 additional prescriptions for spironolactone [11,12]. Careful surveillance of potassium and creatinine may improve survival in patients with severe heart failure being treated with spironolactone [13,14].

As noted, hyperkalemia is caused by excessive intake, impaired elimination, or increased shift of potassium from intracellular to extracellular space (Table 2). Excessive intake of potassium causing hyperkalemia is rarely seen in patients with normal renal function. Nonetheless, patients taking large doses of over-the-counter potassium supplements (often labeled "for heart health") may indeed present with clinically significant hyperkalemia. Usually, ingestion of potassium only causes significant elevation in patients with low glomerular filtration rates (GFRs).

Occasionally, hypokalemia is not due to increased renal loss; these patients will have low urinary potassium (<20 mEq/L) [5]. The differential diagnosis is fairly limited and generally involves some sort of gastrointestinal loss, through laxative abuse, villous adenoma, or severe diarrhea [5]. Patients previously treated with non-potassium-sparing diuretics who are potassium depleted will also have low urinary potassium [5]. Catecholamine excess, whether endogenous (as seen in acute myocardial infarction) or exogenous (as in beta-adrenergic agonist administration), may also cause transient hypokalemia because of an increased cellular uptake of potassium [5].

Treatment of hyperkalemia involves the following principles and practice, many of which occur parallel to each other. First, the patient should have an ECG to evaluate for toxicity and should be placed on a monitor, if warranted [9]. If the patient does have ECG changes, consider hospitalization if still in the outpatient setting. Next, identify sources of potassium intake and eliminate if possible. Consider whether to initiate a plan to shift potassium from the extracellular to the intracellular. Lastly, increase potassium excretion if needed for either short-term or long-term management [17].

Treatment of acute hyperkalemia with life-threatening symptoms (generally seen with potassium levels ≥7 mEq/L) is accomplished by the administration of IV calcium [2,3,4]. The usual recommended dose is 10 mL of a 10% calcium solution, such as calcium chloride [9,18]. The ECG should be monitored while calcium is administered, and calcium should be administered only when ECG changes, such as a widening QRS, have occurred [3,4]. Calcium does not correct the underlying hyperkalemia; it only counters the adverse neuromuscular effects [4]. Calcium infusion should always be followed by specific therapy aimed at lowering the plasma potassium level (e.g., insulin and glucose infusion) [9].

Type 1 RTA is caused by a failure of the distal tubule to secrete acid into the urine, leading to acidosis and hypokalemia. Diagnostic workup will reveal alkalotic urine and possibly metabolic acidosis. (Renal excretion of uric acid and bicarbonate is the primary homeostatic mechanism of the body for maintaining normal pH within a very limited pH range.) Renal and bladder calculi may be seen due to high urine pH, and osteopenia or osteoporosis may develop due to urinary loss of calcium.