Malattie del rene e delle vie urinarie - Hyponatriemia

Primary care review article: Hyponatremia

Hyponatremia is defined as a decrease in the serum sodium concentration to a level below 136 mmol per liter. Whereas hypernatremia always denotes hypertonicity, hyponatremia can be associated with low, normal, or high tonicity.^1,2

Effective osmolality or tonicity refers to the contribution to osmolality of solutes, such as sodium and glucose, that cannot move freely across cell membranes, thereby inducing transcellular shifts in water.³

Hypotonic (dilutional) hyponatremia represents an excess of water in relation to existing sodium stores, which can be decreased, essentially normal, or increased (Fig. 1). Retention of water most commonly reflects the presence of conditions that impair renal excretion of water;^1,7,8 in a minority of cases, it is caused by excessive water intake, with a normal or nearly normal excretory capacity (Table 1).⁷

Hypotonicity, in turn, can lead to cerebral edema, a potentially life-threatening complication.⁴ Hypotonic hyponatremia can be associated, however, with normal or even high serum osmolality if sufficient amounts of solutes that can permeate cell membranes (e.g., urea and ethanol) have been retained (Fig. 1C). Importantly, patients who have hypotonic hyponatremia but normal or high serum osmolality are as subject to the risks of hypotonicity as are patients with hypo-osmolar hyponatremia.

The nonhypotonic hyponatremias are hypertonic (or translocational) hyponatremia, isotonic hyponatremia, and pseudohyponatremia.^1,2 Translocational hyponatremia results from a shift of water from cells to the extracellular fluid that is driven by solutes confined in the extracellular compartment (as occurs with hyperglycemia or retention of hypertonic mannitol); serum osmolality is increased, as is tonicity, the latter causing dehydration of cells (Fig. 1D).

Retention in the extracellular space of large volumes of isotonic fluids that do not contain sodium (e.g., mannitol) generates iso-osmolar and isotonic hyponatremia but no transcellular shifts of water. Pseudohyponatremia is a spurious form of iso-osmolar and isotonic hyponatremia identified when severe hypertriglyceridemia or paraproteinemia increases substantially the solid phase of plasma and the sodium concentration is measured by means of flame photometry.^1,2

The increasing availability of direct measurement of serum sodium with the ion-specific electrode has all but eliminated this laboratory artifact.⁵

A common clinical problem, hyponatremia frequently develops in hospitalized patients. Although morbidity varies widely in severity, serious complications can arise from the disorder itself as well as from errors in management. In this article, we focus on the treatment of hyponatremia, emphasizing a quantitative approach to its correction.

Causes

Dilutional hyponatremia, by far the most common form of the disorder, is caused by water retention. If water intake exceeds the capacity of the kidneys to excrete water, dilution of body solutes results, causing hypo-osmolality and hypotonicity (Fig. 1B, 1E, 1F, and 1G).

Conditions of impaired renal excretion of water are categorized according to the characteristics of the extracellular-fluid volume, as determined by clinical assessment (Table 1).⁹ With the exception of renal failure, these conditions are characterized by high plasma concentrations of arginine vasopressin despite the presence of hypotonicity.^10,11

Depletion of potassium accompanies many of these disorders and contributes to hyponatremia, since the sodium concentration is determined by the ratio of the “exchangeable” (i.e., osmotically active) portions of the body’s sodium and potassium content to total body water (Fig. 1G).^12-14 Patients with hyponatremia induced by thiazides can present with variable hypovolemia or apparent euvolemia, depending on the magnitude of the sodium loss and water retention.^1,15-17

Excessive water intake can cause hyponatremia by overwhelming normal water excretory capacity (e.g., primary polydipsia) (Table 1). Frequently, however, psychiatric patients with excessive water intake have plasma arginine vasopressin concentrations that are not fully suppressed and urine that is not maximally dilute, thus contributing to water retention.^18,19

From the Department of Medicine, Baylor College of Medicine and Methodist Hospital, and the Renal Section, Department of Veterans Affairs Medical Center, Houston (H.J.A.); and the Department of Medicine, Tufts University School of Medicine, and the Division of Nephrology and Tufts-New England Medical Center, Boston (N.E.M.). Address reprint requests to Dr. Madias at the Division of Nephrology, New England Medical Center, Box 172, 750 Washington St., Boston, MA 02111, or at nmadias@infonet.tufts.edu.

©2000, Massachusetts Medical Society.

Extracellular fluid and intracellular fluid

Normal conditions

A. Normal conditions

B. Hypotonic hyponatremia due to water retention in the presence of essentially normal sodium stores (e.g., from the syndrome of inappropriate secretion of antidiuretic hormone)

C. Hypotonic hyponatremia without anticipated hypo-osmolality (e.g., from renal failure)

D. Hypertonic hyponatremia due to gain of impermeable solutes other than sodium (e.g., from hyperglycemia)

E. Hypotonic hyponatremia due to water retention in association with sodium depletion (e.g., from diarrhea)

F. Hypotonic hyponatremia due to water retention in association with sodium gain (e.g., from the nephrotic syndrome)

G. Hypotonic hyponatremia due to water retention in association with sodium gain and potassium loss (e.g., from congestive heart failure treated with diuretics)

Figure 1. Extracellular-Fluid and Intracellular-Fluid Compartments under Normal Conditions and during States of Hyponatremia. Normally, the extracellular-fluid and intracellular-fluid compartments make up 40 percent and 60 percent of total body water, respectively (Panel A). With the syndrome of inappropriate secretion of antidiuretic hormone, the volumes of extracellular fluid and intracellular fluid expand (although a small element of sodium and potassium loss, not shown, occurs during inception of the syndrome) (Panel B). Water retention can lead to hypotonic hyponatremia without the anticipated hypo-osmolality in patients who have accumulated ineffective osmoles, such as urea (Panel C). A shift of water from the intracellular-fluid compartment to the extracellular-fluid compartment, driven by solutes confined in the extracellular fluid, results in hypertonic (translocational) hyponatremia (Panel D). Sodium depletion (and secondary water retention) usually contracts the volume of extracellular fluid but expands the intracellular-fluid compartment. At times, water retention can be sufficient to restore the volume of extracellular fluid to normal or even above-normal levels (Panel E). Hypotonic hyponatremia in sodium-retentive states involves expansion of both compartments, but predominantly the extracellular-fluid compartment (Panel F). Gain of sodium and loss of potassium in association with a defect of water excretion, as they occur in congestive heart failure treated with diuretics, lead to expansion of the extracellular-fluid compartment but contraction of the intracellular-fluid compartment (Panel G). In each panel, open circles denote sodium, solid circles potassium, large squares impermeable solutes other than sodium, and small squares permeable solutes; the broken line between the two compartments represents the cell membrane, and the shading indicates the intravascular volume.

Table 1. Causes of hypotonic hyponatremia

Impaired capacity of renal water excretion

Excessive water intake

• Primary polydipsia†
• Dilute infant formula
• Sodium-free irrigant solutions (used in hysteroscopy, laparoscopy, or transurethral resection of the prostate)‡
• Accidental intake of large amounts of water (e.g., during swimming lessons)
• Multiple tap-water enemas

*Sodium depletion, potassium depletion, stimulation of thirst, and impaired urinary dilution are implicated.

†Often a mild reduction in the capacity for water excretion is also present.

‡Hyponatremia is not always hypotonic.

Hyperglycemia is the most common cause of translocational hyponatremia (Fig. 1D). An increase of 100 mg per deciliter (5.6 mmol per liter) in the serum glucose concentration decreases serum sodium by approximately 1.7 mmol per liter, with the end result a rise in serum osmolality of approximately 2.0 mOsm per kilogram of water. Retention of hypertonic mannitol, which occurs in patients with renal insufficiency, has the same effect. In both conditions, the resultant hypertonicity can be aggravated by osmotic diuresis; moderation of hyponatremia or frank hypernatremia can develop, since the total of the sodium and potassium concentrations in the urine falls short of that in serum.²⁰

Massive absorption of irrigant solutions that do not contain sodium (e.g., those used during transurethral prostatectomy) can cause severe and