Etiology

Hypokalemia is common in children, with most cases related to gastroenteritis. Spurious hypokalemia occurs in patients with leukemia and elevated white blood cell counts if plasma for analysis is left at room temperature, permitting the white blood cells to take up potassium from the plasma. There are four basic mechanisms of hypokalemia (Table 36-1). Low intake, nonrenal losses, and renal losses all are associated with total body potassium depletion. With a transcellular shift, there is no change in total body potassium, although there may be concomitant potassium depletion secondary to other factors.

The transcellular shift of potassium after initiation of insulin therapy in children with diabetic ketoacidosis (see Chapter 171) can be dramatic. These patients have reduced total body potassium because of urinary losses, but they often have a normal serum potassium level before insulin therapy from a transcellular shift into the extracellular space secondary to insulin deficiency and metabolic acidosis. Children receiving aggressive doses of β-adrenergic agonists (albuterol) for asthma can have hypokalemia resulting from the intracellular movement of potassium. Poor intake is an unusual cause of hypokalemia, unless also associated with significant weight loss (anorexia nervosa).

Diarrhea has a high concentration of potassium, and the resulting hypokalemia usually is associated with a metabolic acidosis secondary to stool losses of bicarbonate. Urinary potassium wasting may be accompanied by a metabolic acidosis (proximal or distal renal tubular acidosis (see Chapter 37). With emesis or nasogastric suction, there is gastric loss of potassium, but this is fairly minimal given the low potassium content of gastric fluid (approximately 10 mEq/L). More important is the gastric loss of hydrochloride, leading to a metabolic alkalosis and a state of volume depletion. Metabolic alkalosis and volume depletion increase urinary losses of potassium.

Loop and thiazide diuretics lead to hypokalemia and a metabolic alkalosis. Bartter syndrome and Gitelman syndrome are autosomal recessive disorders resulting from defects in tubular transporters. Both disorders are associated with hypokalemia and a metabolic alkalosis. Bartter syndrome usually is associated with hypercalciuria, often with nephrocalcinosis, whereas children with Gitelman syndrome have low urinary calcium losses, but hypomagnesemia secondary to urinary losses.

In the presence of a high aldosterone level, there is urinary loss of potassium, hypokalemia, and a metabolic alkalosis. There also is renal retention of sodium, leading to hypertension. A variety of genetic and acquired disorders can cause high aldosterone levels. Liddle syndrome, an autosomal dominant disorder caused by constitutively active sodium channels, has the same clinical features as hyperaldosteronism, but the serum aldosterone level is low.

Clinical Manifestations

The heart and skeletal muscle are especially vulnerable to hypokalemia. Electrocardiographic (ECG) changes include a flattened T wave, a depressed ST segment, and the appearance of a U wave, which is located between the T wave (if still visible) and P wave. Ventricular fibrillation and torsades de pointes may occur, although usually only in the context of underlying heart disease. Hypokalemia makes the heart especially susceptible to digitalis-induced arrhythmias, such as supraventricular tachycardia, ventricular tachycardia, and heart block.

The clinical consequences in skeletal muscle include muscle weakness and cramps. Paralysis is a possible complication (generally only at potassium levels <2.5 mEq/L). Paralysis usually starts with the legs, followed by the arms. Respiratory paralysis may require mechanical ventilation. Some patients develop rhabdomyolysis; the risk increases with exercise. Hypokalemia slows gastrointestinal motility; potassium levels less than 2.5 mEq/L may cause an ileus. Hypokalemia impairs bladder function, potentially leading to urinary retention. Hypokalemia causes polyuria by producing secondary nephrogenic diabetes insipidus. Chronic hypokalemia may cause kidney damage, including interstitial nephritis and renal cysts. In children, chronic hypokalemia, as in Bartter syndrome, leads to poor linear growth.

Diagnosis

It is important to review the child’s diet, history of gastrointestinal losses, and medications. Emesis and diuretic use can be surreptitious. The presence of hypertension suggests excess mineralocorticoids. Concomitant electrolyte abnormalities are useful clues. The combination of hypokalemia and metabolic acidosis is characteristic of diarrhea, distal renal tubular acidosis, and proximal renal tubular acidosis. A concurrent metabolic alkalosis is characteristic of gastric losses, aldosterone excess, diuretics, and Bartter syndrome or Gitelman syndrome. Alkalosis also causes a transcellular shift of potassium and increased urinary losses of potassium.

Treatment

Factors that influence the therapy of hypokalemia include the potassium level, clinical symptoms, renal function, presence of transcellular shifts of potassium, ongoing losses, and the patient’s ability to tolerate oral potassium. Severe, symptomatic hypokalemia requires aggressive treatment. Supplementation is more cautious if renal function is decreased because of the kidney’s limited ability to excrete excessive potassium. The plasma potassium level does not always provide an accurate estimation of the total body potassium deficit because there may be shifts of potassium from the intracellular space to the plasma. Clinically, this shift occurs most commonly with metabolic acidosis and as a result of the insulin deficiency of diabetic ketoacidosis; the plasma potassium underestimates the degree of total body potassium depletion. When these problems are corrected, potassium moves into the intracellular space, and these patients require more potassium supplementation to correct the hypokalemia. Patients who have ongoing losses of potassium need correction of the deficit and replacement of the ongoing losses.

Because of the risk of hyperkalemia, intravenous (IV) potassium should be used cautiously. Oral potassium is safer, albeit not as rapid in urgent situations. The dose of IV potassium is 0.5 to 1 mEq/kg, usually given over 1 hour. The adult maximum dose is 40 mEq. Conservative dosing is generally preferred. For patients with excessive urinary losses, potassium-sparing diuretics are effective, but they need to be used cautiously in patients with renal insufficiency. When hypokalemia, metabolic alkalosis, and volume depletion are present, restoration of intravascular volume decreases urinary potassium losses. Disease-specific therapy is effective in many of the genetic tubular disorders.

Etiology

Three basic mechanisms cause hyperkalemia (Table 36-2). In the individual patient, the etiology is sometimes multifactorial. Fictitious hyperkalemia is common in children because of the difficulties in obtaining blood specimens. This hyperkalemia is usually due to hemolysis during phlebotomy, but it can be the result of prolonged tourniquet application or fist clenching, which causes local potassium release from muscle. Falsely elevated serum potassium levels can occur when serum levels are measured in patients with markedly elevated white blood cell counts; a promptly analyzed plasma sample usually provides an accurate result.

Because of the kidney’s ability to excrete potassium, it is unusual for excessive intake, by itself, to cause hyperkalemia. This mechanism can occur in a patient who is receiving large quantities of IV or oral potassium for excessive losses that are no longer present. Frequent or rapid blood transfusions can increase the potassium level acutely secondary to the high potassium content of blood. Increased intake may precipitate hyperkalemia if there is an underlying defect in potassium excretion.

The intracellular space has a high potassium concentration, so a shift of potassium from the intracellular space to the extracellular space can have a significant impact on the plasma potassium. This shift occurs with acidosis, cell destruction (rhabdomyolysis or tumor lysis syndrome), insulin deficiency, medications (succinylcholine, β-blockers), malignant hyperthermia, and hyperkalemic periodic paralysis.

Hyperkalemia secondary to decreased excretion occurs with renal insufficiency. Aldosterone deficiency or unresponsiveness to aldosterone causes hyperkalemia, often with associated metabolic acidosis (see Chapter 37) and hyponatremia. A form of congenital adrenal hyperplasia, 21-hydroxylase deficiency, is the most frequent cause of aldosterone deficiency in children. Male infants typically present with hyperkalemia, metabolic acidosis, hyponatremia, and volume depletion. Female infants with this disorder usually are diagnosed as newborns because of ambiguous genitalia; treatment prevents the development of electrolyte problems.

Renin, via angiotensin II, stimulates aldosterone production. A deficiency in renin, resulting from kidney damage, can lead to decreased aldosterone production. These patients typically have hyperkalemia and a metabolic acidosis, without hyponatremia. Some patients have impaired renal function, partially accounting for the hyperkalemia, but the impairment in potassium excretion is more extreme than expected for the degree of renal insufficiency.

Children with pseudohypoaldosteronism type 1 have hyperkalemia, metabolic acidosis, and salt wasting, leading to hyponatremia and volume depletion; aldosterone levels are elevated. In the autosomal recessive variant, there is a defect in the renal sodium channel that is normally activated by aldosterone. In the autosomal dominant form, patients have a defect in the aldosterone receptor, and the disease is milder, often remitting in adulthood. Pseudohypoaldosteronism type 2, also called Gordon syndrome, is an autosomal dominant disorder characterized by hypertension secondary to salt retention and impaired excretion of potassium and acid leading to hyperkalemia and metabolic acidosis. The risk of hyperkalemia secondary to medications that decrease renal potassium excretion is greatest in patients with underlying renal insufficiency.

Clinical Manifestations

The most import effects of hyperkalemia are due to the role of potassium in membrane polarization. The cardiac conduction system is usually the dominant concern. ECG changes begin with peaking of the T waves. As the potassium level increases, an increased P-R interval, flattening of the P wave, and widening of the QRS complex occur; this eventually can progress to ventricular fibrillation. Asystole also may occur. Some patients have paresthesias, weakness, and tingling, but cardiac toxicity usually precedes these clinical symptoms.

Diagnosis

The etiology of hyperkalemia is often readily apparent. Spurious hyperkalemia is common in children, so a repeat potassium level is often appropriate. If there is a significant elevation of the white blood cells, the repeat sample should be from plasma that is evaluated promptly. The history initially should focus on potassium intake, risk factors for transcellular shifts of potassium, medications that cause hyperkalemia, and the presence of signs of renal insufficiency, such as oliguria or an abnormal urinalysis. Initial laboratory evaluation should include serum creatinine and assessment of acid-base status. Many causes of hyperkalemia, such as renal insufficiency and aldosterone insufficiency or resistance, cause a metabolic acidosis, worsening hyperkalemia by the transcellular shift of potassium out of cells. Cell destruction, as seen in rhabdomyolysis or tumor lysis syndrome, can cause concomitant hyperphosphatemia, hyperuricemia, and an elevated serum lactate dehydrogenase.

Treatment

The plasma potassium level, the ECG, and the risk of the problem worsening determine the aggressiveness of the therapeutic approach. A high serum potassium level with ECG changes requires more vigorous treatment. An additional source of concern is a patient with increasing plasma potassium despite minimal intake. This situation can occur if there is cellular release of potassium (tumor lysis syndrome), especially in the setting of diminished excretion (renal failure).

The first action in a child with a concerning elevation of plasma potassium is to stop all sources of additional potassium (oral and IV). If the potassium level is greater than 6 to 6.5 mEq/L, an ECG should be obtained to help assess the urgency of the situation. Therapy of hyperkalemia has two basic goals:

Treatments that acutely prevent arrhythmias all work quickly (within minutes), but do not remove potassium from the body. Measures that remove potassium from the body do not act quickly but should be started as soon as possible.

Long-term management of hyperkalemia includes reducing intake via dietary changes and eliminating or reducing medications that cause hyperkalemia. Some patients require medications, such as sodium polystyrene sulfonate and loop or thiazide diuretics, to increase potassium losses. The disorders due to a deficiency in aldosterone respond to replacement therapy with fludrocortisone, a mineralocorticoid.