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Hyponatremia 

Hyponatremia
Chapter:
Hyponatremia
Author(s):

Matthew McGuire

, and Subramaniam Pennathur

DOI:
10.1093/med/9780190862800.003.0043
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date: 18 September 2020

  1. A. Introduction

    1. a. Definition. Hyponatremia refers to a serum sodium concentration of less than 135 mEq/L.

      Hot Key

      Hyponatremia is the most common electrolyte disturbance in hospitalized patients.

    2. b. Action of antidiuretic hormone (ADH). Understanding the action of ADH is essential to understanding hyponatremia.

      1. i. The main action of ADH is to insert aquaporins into the apical membrane of the distal convoluted tubule. These aquaporins facilitate reabsorption of water out of the filtrate and back into the bloodstream, thus concentrating the filtrate.

      2. ii. Normally, the body regulates serum osmolality very closely by increasing or decreasing ADH secretion. When the effective circulating volume (ECV) decreases, the body senses that there is a lack of intravascular fluid and secretes ADH to help expand intravascular volume at the expense of serum osmolality.

      3. iii. Hyponatremia is thus caused by an:

        1. 1. Appropriate increase in ADH (as occurs with hypovolemic or some hypervolemic causes); or

        2. 2. Inappropriate increase in ADH (as seen in the syndrome of inappropriate secretion of ADH [SIADH])

    3. c. Clinical manifestations of hyponatremia depend on the cause, degree, and rapidity of hyponatremia. However, they are related to neuromuscular disturbance and include confusion, depressed reflexes, muscle cramps, nausea, and lethargy. In some cases, patients may develop cerebral edema that may present as seizures and coma. Most patients with a serum sodium >125 mEq/L have no symptoms.

  2. B. Approach to the Patient

    1. a. The initial step in evaluating patients with hyponatremia is to check the serum osmolality to determine whether the patient has hypertonic or isotonic hyponatremia.

      1. i. Hyperosmolar/hypertonic hyponatremia is caused by hyperglycemia or hypertonic infusions (e.g., mannitol, total parenteral nutrition [TPN]). These infusions shift free water from the intracellular compartment to the vasculature. For every 100 mg/dL of glucose above 100 mg/dL, serum sodium will decrease by about 1.6 mEq/L.

      2. ii. Isoosmolar/isotonic hyponatremia can also be caused by hyperglycemia and hypertonic infusions, but to a lesser degree than what would cause a hypertonic state. Hyperlipidemia or hyperproteinemia is often associated with hyponatremia due to laboratory error (pseudohyponatremia). However, newer laboratory techniques have largely eliminated this problem.

      3. iii. If the serum osmolality is low (<280 mOsm), the next step is to evaluate the patient’s volume status. With this information, it is possible to narrow the possible causes of the hypoosmolar hyponatremia.

  3. C. Hypoosmolar Hyponatremia

    1. a. Hypovolemic

      1. i. Physical examination will reveal signs of volume depletion (e.g., orthostasis, resting tachycardia, poor skin turgor, dry mucous membranes, low jugular venous pressure).

      2. ii. Causes are summarized in Table 43.1.

        Table 43.1 Causes of Hypoosmolar, Hypovolemic Hyponatremia

        Common Causes

        Urine Sodium (mEq/L)

        Serum Uric Acid (mg/dL)

        Skin loss

        <10

        >5

        Gastrointestinal loss

        <10

        >5

        Lung loss

        <10

        >5

        Third spacing of fluids

        <10

        >5

        Adrenal insufficiency

        >20

        >5

        Renal loss (diuretics, tubular damage)

        >20

        >5

      3. iii. Treatment entails intravascular volume expansion (with isotonic crystalloids) and treatment of the underlying cause. The initial goal of treatment for any cause of hyponatremia is to increase the sodium level to improve symptoms. After symptoms have resolved, sodium levels should not be raised by more than 8–10 mEq/L/day. Overly rapid correction increases the risk for osmotic demyelination, a syndrome in which the brain undergoes rapid shrinkage due to fluid shifts and is often associated with irreversible neurologic deficits, coma, or death.

    2. b. Hypervolemic

      1. i. Physical examination reveals signs of volume expansion (e.g., elevated jugular venous pressure, peripheral edema, ascites, pleural effusions, pulmonary edema).

      2. ii. Causes are summarized in Table 43.2.

        Table 43.2 Causes of Hypoosmolar Hypervolemic Hyponatremia

        Common Causes

        Urine Sodium (mEq/L)

        Serum Uric Acid (mg/dL)

        Nephrosis (i.e., nephrotic syndrome)

        <10 mEq/L

        >5

        Cirrhosis

        <10 mEq/L

        >5

        Congestive heart failure

        <10 mEq/L

        >5

      3. iii. Treatment usually involves a combination of fluid restriction and diuretics.

    3. c. Euvolemic

      1. i. Physical examination is notable for the lack of signs indicative of volume depletion or expansion.

      2. ii. Causes of euvolemic hypoosmolar hyponatremia are summarized in Table 43.3.

        Table 43.3 Causes of Hypoosmolar Euvolemic Hyponatremia

        Common Causes

        Urine Sodium (mEq/L)

        Serum Uric Acid

        SIADH

        >20

        <5 mg/dL

        Water intoxication (polydipsia)

        Variable

        <5 mg/dL

        Hypothyroidism, adrenal insufficiency

        Variable

        >5 mg/dL

        Renal dysfunction

        >10

        >5 mg/dL

        SIADH = syndrome of inappropriate secretion of antidiuretic hormone.

      3. iii. Treatment involves fluid restriction plus treatment of the underlying cause.

  4. D. Syndrome of Inappropriate Secretion of Antidiuretic Hormone. SIADH is a difficult but important diagnosis to make. Because the management of SIADH usually requires fluid restriction in a hospitalized patient (who may be nothing by mouth [NPO], febrile, or both), it is important to be fairly sure of the diagnosis to prevent dehydration. If a hyponatremic patient meets all (or at least most) of the following five criteria, you can feel confident about treating for SIADH:

    1. a. The patient has an underlying reason to have SIADH. The most common causes are malignancies, central nervous system (CNS) and pulmonary disease (e.g., meningitis or pneumonia), and certain drugs.

    2. b. The patient is clinically euvolemic to hypervolemic.

    3. c. The patient has normal renal, adrenal, and thyroid function.

    4. d. The patient’s urine osmolality is inappropriately increased and is usually greater than the serum osmolality.

    5. e. The patient may also have a low serum uric acid level. Of all the causes of hyponatremia, only two—SIADH and primary polydipsia—are characterized by hypouricemia. Also, in both disorders intravascular volume is expanded (even though the disorders are categorized as euvolemic). The kidney handles uric acid the same way it handles sodium; therefore, in states of intravascular expansion, sodium and uric acid elimination are enhanced. Thus, a patient with SIADH should have a urine sodium >20 mEq/L, suggestive of mild volume expansion.

Hot Key

Hypouricemia is an important diagnostic clue to the presence of SIADH.

Suggested Further Readings

Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342:1581–9. (Classic Article.)Find this resource:

Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med 2007;356:2064–72.Find this resource:

Kumar S, Berl T. Sodium. Lancet 1998;352:220–8. (Classic Article.)Find this resource:

Milionis HJ, Liamis GL, Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ 2002;166:1056–62. (Classic Article.)Find this resource:

Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014;29:i1–i39.Find this resource: