HYPOKALEMIA

HYPOKALEMIA is a topic covered in the Harrison's Manual of Medicine.

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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
  1. Decreased intake
    1. Starvation
    2. Clay ingestion
  2. Redistribution into cells
    1. Acid-base
      1. Metabolic alkalosis
    2. Hormonal
      1. Insulin
      2. Increased β2-adrenergic sympathetic activity: post–myocardial infarction, head injury, theophylline
      3. β2-Adrenergic agonists: bronchodilators, tocolytics
      4. α-Adrenergic antagonists
      5. Thyrotoxic periodic paralysis
      6. Downstream stimulation of Na+/K+-ATPase: theophylline, caffeine
    3. Anabolic state
      1. Vitamin B12 or folic acid administration (red blood cell production)
      2. Granulocyte-macrophage colony-stimulating factor (white blood cell production)
      3. Total parenteral nutrition
    4. Other
      1. Pseudohypokalemia
      2. Hypothermia
      3. Familial hypokalemic periodic paralysis
      4. Barium toxicity: systemic inhibition of “leak” K+ channels
    5. Increased loss
      1. Nonrenal
        1. Gastrointestinal loss (diarrhea)
        2. Integumentary loss (sweat)
      2. Renal
        1. Increased distal flow and distal Na+ delivery: diuretics, osmotic diuresis, salt-wasting nephropathies
        2. Increased secretion of potassium
          1. 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
          2. 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)
          3. 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)
        3. 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
hmom20_ch1_f002a.png
hmom20_ch1_f002b.png

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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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
  1. Decreased intake
    1. Starvation
    2. Clay ingestion
  2. Redistribution into cells
    1. Acid-base
      1. Metabolic alkalosis
    2. Hormonal
      1. Insulin
      2. Increased β2-adrenergic sympathetic activity: post–myocardial infarction, head injury, theophylline
      3. β2-Adrenergic agonists: bronchodilators, tocolytics
      4. α-Adrenergic antagonists
      5. Thyrotoxic periodic paralysis
      6. Downstream stimulation of Na+/K+-ATPase: theophylline, caffeine
    3. Anabolic state
      1. Vitamin B12 or folic acid administration (red blood cell production)
      2. Granulocyte-macrophage colony-stimulating factor (white blood cell production)
      3. Total parenteral nutrition
    4. Other
      1. Pseudohypokalemia
      2. Hypothermia
      3. Familial hypokalemic periodic paralysis
      4. Barium toxicity: systemic inhibition of “leak” K+ channels
    5. Increased loss
      1. Nonrenal
        1. Gastrointestinal loss (diarrhea)
        2. Integumentary loss (sweat)
      2. Renal
        1. Increased distal flow and distal Na+ delivery: diuretics, osmotic diuresis, salt-wasting nephropathies
        2. Increased secretion of potassium
          1. 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
          2. 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)
          3. 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)
        3. 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
hmom20_ch1_f002a.png
hmom20_ch1_f002b.png

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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