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ETIOLOGY OF HYPONATREMIA

Disorders of serum Na+ concentration are caused by abnormalities in water homeostasis, leading to changes in the relative ratio of Na+ to body water. Water intake and circulating AVP constitute the two key effectors in the defense of serum osmolality; defects in one or both of these two defense mechanisms cause most cases of hyponatremia and hypernatremia. In contrast, abnormalities in sodium homeostasis per se lead to a deficit or surplus of whole-body Na+-Cl content, a key determinant of the ECFV and circulatory integrity. Notably, volume status also modulates the release of AVP by the posterior pituitary, such that hypovolemia is associated with higher circulating levels of the hormone at each level of serum osmolality. Similarly, in “hypervolemic” causes of arterial underfilling, e.g., heart failure and cirrhosis, the associated neurohumoral activation encompasses an increase in circulating AVP, leading to water retention and hyponatremia. Therefore, a key concept in sodium disorders is that the absolute plasma Na+ concentration tells one nothing about the volume status of a given patient, which furthermore must be taken into account in the diagnostic and therapeutic approach.

Hyponatremia, which is defined as a plasma Na+ concentration <135 mM, is a very common disorder, occurring in up to 22% of hospitalized patients. This disorder is almost always the result of an increase in circulating AVP and/or increased renal sensitivity to AVP, combined with an intake of free water; a notable exception is hyponatremia due to low solute intake (see below). The underlying pathophysiology for the exaggerated or “inappropriate” AVP response differs in patients with hyponatremia as a function of their ECFV. Hyponatremia is thus subdivided diagnostically into three groups, depending on clinical history and volume status, i.e., “hypovolemic,” “euvolemic,” and “hypervolemic” (Fig. 49-5).

FIGURE 49-5

The diagnostic approach to hyponatremia. (From S Kumar, T Berl: Diseases of water metabolism, in Atlas of Diseases of the Kidney, RW Schrier [ed]. Philadelphia, Current Medicine, Inc, 1999; with permission.)

Hypovolemic Hyponatremia

Hypovolemia causes a marked neurohumoral activation, increasing circulating levels of AVP. The increase in circulating AVP helps preserve blood pressure via vascular and baroreceptor V1A receptors and increases water reabsorption via renal V2 receptors; activation of V2 receptors can lead to hyponatremia in the setting of increased free water intake. Nonrenal causes of hypovolemic hyponatremia include GI loss (e.g., vomiting, diarrhea, tube drainage) and insensible loss (sweating, burns) of Na+-Cl and water, in the absence of adequate oral replacement; urine Na+ concentration is typically <20 mM. Notably, these patients may be clinically classified as euvolemic, with only the reduced urinary Na+ concentration to indicate the cause of their hyponatremia. Indeed, a urine Na+ concentration <20 mM, in the absence ...

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