Pseudohyponatremia

Patients with pseudohyponatremia have normal serum sodium concentrations, but the measured sodium level is falsely low. This artifact occurs when flame emission spectrometry is used to measure the serum sodium concentration in patients with severe hypertriglyceridemia or hyperparaproteinemia (e.g., multiple myeloma). Currently, most labs measure serum sodium with a sodium-selective electrode method, which does not cause this artifact. A normal osmolal gap excludes pseudohyponatremia (see “Approach to Finding the Cause of Hyponatremia” on p. 353).

Reduced Extracellular Volume

Hypovolemia of any cause (vomiting, diarrhea, diuretics, and excessive sweating) leads to sodium and water depletion. Appropriate compensatory activation of the renin–angiotensin–aldosterone system and antidiuretic hormone production leads to sodium and water reabsorption by the kidneys. Hyponatremia occurs when the sodium deficit exceeds the water deficit. Drinking hypotonic fluid, such as water or tea, can exacerbate the hyponatremia.

Normal or Near-Normal Extracellular Volume

Euvolemic hyponatremia can occur in patients with hypothyroidism, adrenal insufficiency, a reset osmostat, and SIADH.

SIADH has many causes, including medications, pain, excessive nausea and vomiting, tumors, and pulmonary or neurological disease (Box 19-1). These conditions either stimulate antidiuretic hormone release or increase the kidneys’ response to antidiuretic hormone. As a result, there is inappropriate retention of free water, dilution of normal extracellular amounts of sodium, and subsequent development of hyponatremia. SIADH does not typically cause clinically apparent volume overload because most of the retained free water moves into the intracellular compartment and does not remain in the bloodstream and interstitium.

The reset osmostat syndrome, a rare cause of hyponatremia, occurs when there is a lowering of the osmolality threshold that stimulates antidiuretic hormone release. These patients often have long-standing, disabling conditions, such as tuberculosis, quadriplegia, and psychosis, and tend to have chronically low but stable serum sodium concentrations. These patients can normally excrete a water load and achieve normal maximal urine dilution (these criteria are used to diagnose the syndrome). These patients are also able to concentrate the urine at serum osmolalities above the reset level.

Psychogenic polydipsia is an unusual cause of hyponatremia that is typically seen in patients with schizophrenia or other psychiatric diseases. Hyponatremia in this setting results from large ingestion of free water over a short time period. When renal function is normal, ingestion of more than 20 L/day is needed to cause hyponatremia by overcoming the kidneys’ ability to excrete the water.

Expanded Extracellular Volume

Hypervolemic hyponatremia is usually caused by heart failure, cirrhosis, and the nephrotic syndrome. Although these patients are volume overloaded, they typically have reduced effective circulating blood volume and poor renal perfusion. As a result, there is release of antidiuretic hormone from the posterior pituitary (which causes water retention by the kidneys) and activation of the renin–angiotensin–aldosterone system (which causes the kidneys to avidly retain sodium). Therefore, these patients have an increased amount of body sodium and water. Hyponatremia occurs if the increase in sodium is less than the increase in water.