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Key Features

Essentials of Diagnosis

  • Serum Na+ < 135 mEq/L (< 135 mmol/L)

  • Hyponatremia usually reflects excess water retention relative to sodium, rather than sodium deficiency

  • Sodium concentration is not a measure of total body sodium

  • Volume status and serum osmolality are essential to determine etiology

  • Hypotonic fluids commonly cause hyponatremia in hospitalized patients

General Considerations

  • Most cases reflect water imbalance and abnormal water handling, not sodium imbalance

  • Antidiuretic hormone (ADH) plays primary role in the pathophysiology of hyponatremia

  • A diagnostic algorithm using serum osmolality and volume status separates the causes of hyponatremia into therapeutically useful categories (Figure 21–1)

Figure 21–1.

Evaluation of hyponatremia using serum osmolality and extracellular fluid volume status. ACE, angiotensin-converting enzyme; SIADH, syndrome of inappropriate antidiuretic hormone. (Adapted, with permission, from Narins RG et al. Diagnostic strategies in disorders of fluid, electrolyte and acid-base homeostasis. Am J Med. 1982 Mar;72(3):496–520. Copyright © Elsevier.)


  • Isotonic hyponatremia or pseudohyponatremia (Figure 21–1)

    • Pseudohyponatremia does not occur with hyperproteinemia or lipemia if the serum sodium is measured with an ion-specific electrode in a direct assay of an undiluted serum specimen

    • Consultation with the clinical laboratory may be necessary to determine whether lipemia (including chylomicrons, triglycerides, and cholesterol) or hyperproteinemia (> 10 g/dL [100 g/L], eg, paraproteinemias and intravenous immunoglobulin therapy) are causing pseudohyponatremia as an assay artifact

  • Hypotonic hyponatremia

    • Hypovolemic

      • Occurs with renal or extrarenal volume loss and hypotonic fluid replacement

      • Total body sodium and total body water are decreased

      • Cerebral salt wasting seen in patients with intracranial disease; clinical features include refractory hypovolemia and hypotension

    • Euvolemic

      • Syndrome of inappropriate antidiuretic hormone (SIADH) (see Table 21–2)

      • Postoperative hyponatremia

      • Hypothyroidism

      • Adrenal insufficiency

      • Psychogenic polydipsia

      • Beer potomania

      • Idiosyncratic drug reaction (thiazides, ACE inhibitors)

      • Endurance exercise

      • Reset osmostat

    • Hypervolemic (edematous states)

      • Heart failure

      • Cirrhosis

      • Nephrotic syndrome

      • Advanced kidney disease

  • Hypertonic hyponatremia

    • Occurs in cases of hyperglycemia and with mannitol administration for increased intracranial pressure

    • Glucose and mannitol osmotically pull intracellular water into the extracellular space

Table 21–2.Causes of syndrome of inappropriate ADH secretion (SIADH).

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