Hypokalemia

For further information, see CMDT Part 21-04: Hypokalemia

Essentials of Diagnosis

• Serum K⁺ < 3.5 mEq/L (< 3.5 mmol/L)

• Severe hypokalemia may induce arrhythmias and rhabdomyolysis

• Transtubular potassium concentration gradient (TTKG) can distinguish renal from nonrenal loss of potassium

General Considerations

• Gastrointestinal loss due to infectious diarrhea is most common cause

• Potassium shift into the cell is transiently stimulated by insulin and glucose and facilitated by β-adrenergic stimulation

• α-Adrenergic stimulation blocks potassium shift into the cell

• Aldosterone is an important regulator of body potassium, increasing potassium secretion in the distal renal tubule

• Magnesium is an important cofactor for potassium uptake and for maintenance of intracellular potassium levels

• Magnesium depletion should be suspected in persistent hypokalemia refractory to potassium repletion

Etiology

• Potassium shift into cell (Table 21–4)

  • Insulin excess, eg, postprandial

  • Alkalosis

  • β-Adrenergic agonists

  • Trauma (via epinephrine release)

  • Hypokalemic periodic paralysis

  • Barium or cesium intoxication

• Renal potassium loss (urine K⁺ > 40 mEq/L)

  • Increased aldosterone (mineralocorticoid) effects

    • Primary hyperaldosteronism

    • Secondary hyperaldosteronism (dehydration, heart failure)

    • Renovascular or malignant hypertension

    • Cushing syndrome

    • European licorice (inhibits cortisol)

    • Renin-producing tumor

    • Congenital abnormality of steroid metabolism (eg, adrenogenital syndrome, 17α-hydroxylase defect)

  • Increased flow of distal nephron

    • Diuretics (furosemide, thiazides)

    • Salt-losing nephropathy

  • Hypomagnesemia

    • Unreabsorbable anion

    • Carbenicillin, penicillin

  • Renal tubular acidosis (type I or II)

    • Fanconi syndrome

    • Interstitial nephritis

    • Metabolic alkalosis (bicarbonaturia)

  • Genetic disorder of the nephron

    • Bartter syndrome

    • Liddle syndrome

• Extrarenal potassium loss (urine K⁺ < 20 mEq/L)

  • Vomiting, diarrhea, laxative abuse

  • Villous adenoma, Zollinger-Ellison syndrome

Symptoms and Signs

• Muscular weakness, fatigue, and muscle cramps are common in mild to moderate hypokalemia

• Constipation or ileus may result from smooth muscle involvement

• Flaccid paralysis, hyporeflexia, hypercapnia, tetany, and rhabdomyolysis may be seen in severe hypokalemia (serum K⁺ < 2.5 mEq/L)

• Hypertension may result from aldosterone or mineralocorticoid excess

• Renal manifestations include nephrogenic diabetes insipidus and interstitial nephritis

Laboratory Tests

• Serum K⁺ < 3.5 mEq/L (< 3.5 mmol/L)

• Urinary potassium concentration is low (< 20 mEq/L) as a result of extrarenal loss and inappropriately high (> 40 mEq/L) with renal loss

• Calculating TTKG is a rapid method to evaluate net potassium secretion

  

• Hypokalemia with TTKG > 4 suggests renal potassium loss with increased distal K⁺ secretion

  • In such cases, plasma renin and aldosterone levels are helpful in differential diagnosis

  • The presence of nonabsorbed anions, including bicarbonate, also increases the TTKG

Diagnostic Procedures

• ECG may show

  • Decreased amplitude and broadening of T waves

  • Prominent U waves

  • Premature ventricular contractions

  • Depressed ST segments

Medications

• Oral potassium is the safest way to treat mild to moderate deficiency

• Dietary potassium is almost entirely coupled to phosphate—rather than chloride—and does not correct potassium loss associated with chloride depletion, such as from diuretics or vomiting

• In the setting of abnormal kidney function and mild to moderate diuretic dosage

  • 20 mEq/day of oral potassium is generally sufficient to prevent hypokalemia

  • However, 40–100 mEq/day over a period of days to weeks is needed to treat hypokalemia and fully replete potassium stores

• Indications for intravenous potassium replacement

  • Severe hypokalemia

  • Inability to take oral supplementation

• For severe deficiency, potassium may be given through a peripheral intravenous line in a concentration that should not exceed 40 mEq/L at rates of up to 40 mEq/L/h

• Coexisting magnesium and potassium depletion can result in refractory hypokalemia despite potassium repletion if there is no magnesium repletion

Follow-Up

• Monitor ECG continuously when infusing intravenous potassium for severe hypokalemia

• Check serum potassium level every 3–6 hours

Complications

• Hypokalemia increases the likelihood of digitalis toxicity

• In patients with heart disease, hypokalemia induced by β₂-adrenergic agonists and diuretics may impose a substantial risk

Prognosis

• Most hypokalemia will correct with replacement after 24–72 h

When to Refer

• Patients with unexplained hypokalemia, refractory hyperkalemia, or clinical features suggesting alternative diagnoses (eg, aldosteronism or hypokalemic periodic paralysis) should be referred for endocrinology or nephrology consultation

When to Admit

• Patients with symptomatic or severe hypokalemia, especially with cardiac manifestations, require cardiac monitoring, frequent laboratory testing, and potassium supplementation