HYPOKALEMIA

Major causes of hypokalemia are outlined in Table 1-3. Atrial and ventricular arrhythmias are the most serious health consequences of hypokalemia. Pts with concurrent Mg deficit and/or digoxin therapy are at a particularly increased risk of arrhythmias. Hypokalemia can directly prolong the QT interval and is a significant cofactor in arrhythmias due to other causes of a prolonged QT interval. Other clinical manifestations include muscle weakness, which may be profound at serum [K⁺] <2.5 mmol/L, and, if hypokalemia is sustained, hypertension, ileus, polyuria, renal cysts, and even renal failure.

TABLE 1-3: Causes of Hypokalemia
Decreased intake Starvation Clay ingestion Redistribution into cells Acid-base Metabolic alkalosis Hormonal Insulin Increased β₂-adrenergic sympathetic activity: post–myocardial infarction, head injury, theophylline β₂-Adrenergic agonists: bronchodilators, tocolytics α-Adrenergic antagonists Thyrotoxic periodic paralysis Downstream stimulation of Na⁺/K⁺-ATPase: theophylline, caffeine Anabolic state Vitamin B₁₂ or folic acid administration (red blood cell production) Granulocyte-macrophage colony-stimulating factor (white blood cell production) Total parenteral nutrition Other Pseudohypokalemia Hypothermia Familial hypokalemic periodic paralysis Barium toxicity: systemic inhibition of “leak” K⁺ channels Increased loss Nonrenal Gastrointestinal loss (diarrhea) Integumentary loss (sweat) Renal Increased distal flow and distal Na⁺ delivery: diuretics, osmotic diuresis, salt-wasting nephropathies Increased secretion of potassium Mineralocorticoid excess: primary hyperaldosteronism (APAs), PAH or UAH, IHA due to bilateral adrenal hyperplasia and adrenal carcinoma, familial hyperaldosteronism (FH-I, FH-II, congenital adrenal hyperplasias), secondary hyperaldosteronism (malignant hypertension, renin-secreting tumors, renal artery stenosis, hypovolemia), Cushing’s syndrome, Bartter’s syndrome, Gitelman’s syndrome Apparent mineralocorticoid excess: genetic deficiency of 11β-dehydrogenase-2 (syndrome of apparent mineralocorticoid excess), inhibition of 11β-dehydrogenase-2 (glycyrrhetinic/glycyrrhizinic acid and/or carbenoxolone; licorice, food products, drugs), Liddle’s syndrome (genetic activation of ENaC) Distal delivery of nonreabsorbed anions: vomiting, nasogastric suction, proximal renal tubular acidosis, diabetic ketoacidosis, glue sniffing (toluene abuse), penicillin derivatives (penicillin, nafcillin, dicloxacillin, ticarcillin, oxacillin, and carbenicillin) Magnesium deficiency, amphotericin B, Liddle’s syndrome

Abbreviations: APA, aldosterone-producing adenoma; ENaC, epithelial Na⁺ channels; IHA, idiopathic hyperaldosteronism; PAH, primary adrenal hyperplasia; UAH, unilateral adrenal hyperplasia.

The cause of hypokalemia is usually obvious from history, physical examination, and/or basic laboratory tests. However, persistent hypokalemia may require a more thorough, systematic evaluation (Fig. 1-2). Initial laboratory evaluation should include electrolytes, BUN, creatinine, serum osmolality, Mg²⁺, and Ca²⁺, a complete blood count, and urinary pH, osmolality, creatinine, and electrolytes. Serum and urine osmolality are required for calculation of the transtubular K⁺ gradient (TTKG), which should be <3 in the presence of hypokalemia (see also Hyperkalemia). Alternatively, a urinary K⁺-to-creatinine ratio of >13-mmol/g creatinine (>1.5-mmol/mmol creatinine) is compatible with excessive K⁺ excretion. Further tests such as urinary Mg²⁺ and Ca²⁺ and/or plasma renin and aldosterone levels may be necessary in specific cases.

FIGURE 1-2

The diagnostic approach to hypokalemia. See text for details. bp, blood pressure; DKA, diabetic ketoacidosis; FH-I, familial hyperaldosteronism type I; FHPP, familial hypokalemic periodic paralysis; HTN, hypertension; PA, primary aldosteronism; RAS, renal artery stenosis; RST, renin-secreting tumor; RTA, renal tubular acidosis; SAME, syndrome of apparent mineralocorticoid excess; TTKG, transtubular potassium gradient. (Reprinted with permission from Mount DB, Zandi-Nejad K: Disorders of potassium balance. In: Brenner and Rector’s The Kidney, 8th ed, Brenner BM [ed]. Philadelphia, Saunders, 2008.)

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