Although Ms. H.L. isn't distressed, she is disoriented about the time and place of her location. Her blood pressure is 140/80 mm Hg while supine and 135/85 mm Hg when seated, with a pulse rate of 68. She is afebrile and there is no neck vein distension. A cardiac assessment reveals a regular rhythm with grade 1/6 systolic ejection murmur. A chest exam shows a barrel-shaped chest with increased expiration, but no crackles or wheezes. The abdomen is unremarkable. There's no peripheral edema and her peripheral pulses are normal. A neurologic test is non-focal.
Initial laboratory data reveal:
Further investigations show: normal serum thyroid-stimulating hormone of 3.2 mIU/L, normal morning serum cortisol, low serum uric acid of 136 µmol/L, normal serum albumin of 38 g/L, low serum osmolality of 255 mOsm/kg H2O. A urinalysis reveals specific gravity of 1.030, but negative for blood and protein, random urine sodium of 60 mmol/L and urine osmolality of 200 mOsm/kg H2O.
Making the case
Hyponatremia is defined as abnormally low concentration of sodium ions in the blood (< 135 mmol/L), and occurs in up to 4% of hospitalized patients. Hyponatremia often results from the body's inability to appropriately excrete dilute urine, except in rare circumstances where water intake exceeds the water-excreting capability of the kidneys (i.e. as in patients with psychogenic polydipsia).
Hyponatremia can be associated with high, normal or low plasma osmolality. With high or normal plasma osmolality, hyponatremia occurs in patients with either hyperglycemia, or in those receiving infusions of mannitol. Here, water moves from the cellular to extracellular space because of the osmotic effect of glucose or mannitol, which stimulates antidiuretic hormone (ADH) and thirst.
In most patients, however, hyponatremia is associated with low plasma osmolality (hypo-osmolar hyponatremia), meaning excessive amounts of water in the body in relation to sodium. This occurs secondary to non-osmotic stimulation of ADH, which may arise on a volume or non-volume basis.
What to look for
The first step in evaluating patients with hypo-osmolar hyponatremia is to assess the extracellular fluid (ECF) status through clinical exam, checking for orthostatic changes in blood pressure and skin turgor. Based on the volume status, hyponatremia is further classified into the following three sub-groups: hypovolemic (decrease in body water and sodium), euvolemic and hypervolemic (increase in sodium and an even greater increase in body water).
In patients with hypovolemia, to restore volume, ADH stimulation leads to reabsorption of water, resulting in excretion of concentrated urine. BUN and serum uric acid levels will also be elevated as a result of volume depletion. The urine sodium is typically < 10 mmol/L because the kidneys are trying to conserve sodium and water to maintain volume status. On the other hand, if the cause of the volume depletion is renal (resulting in renal salt wasting), urine sodium would be elevated. The key to managing these patients is to replenish the volume status through IV fluids, thereby removing the stimulus for ADH release.
Patients with congestive heart failure, cirrhosis, or nephrotic syndrome have low effective circulatory volume despite expanded ECF volume. The low effective circulatory volume, in such circumstances, stimulates ADH release, causing sodium and water retention, and thereby low urine sodium of < 10 mmol/L. Treatment of these patients includes effective management of the underlying condition, in addition to restriction of salt and water intake (the latter particularly when serum sodium is < 125 mmol/L). Loop diuretics are useful as these agents favour excretion of more water than sodium.
Cortisol and thyroid deficiencies may also cause increased ADH release, causing hyponatremia. Stimulation of ADH occurs in all patients with true hyponatremia, and this stimulation may be osmotic or volume based. When there is no obvious cause of ADH stimulation, then the ADH secretion is "inappropriate," which is referred to as syndrome of inappropriate antidiuretic hormone (SIADH) secretion.
SIADH is the continued secretion of ADH despite low serum osmolality and increased extracellular volume. It occurs in up to a third of hospitalized patients with hyponatremia. Common causes include:
Because of the inappropriate secretion of ADH, the urine is inappropriately concentrated (urine osmolality > 100 mOsm/kg water), with levels of urine sodium going higher than 20 mmol/L. However, the levels of BUN and serum uric acid are often low. Low levels of BUN (< 4.0 mmol/L) and serum uric acid (< 240 µmol/L) in a patient with euvolemic hyponatremia suggests SIADH.
Coma and death may result if serum sodium drops below 110 mmol/L. Treatment usually requires infusion of hypertonic saline, with or without furosemide. For symptomatic hyponatremia, the rate of correction is guided by the rate of its development. In acute cases, the rate of correction shouldn't exceed 8-12 mmol/L in the first 24 hours. Because rapid correction of serum sodium may lead to severe neurologic injury (i.e. central pontine myelinolysis), the rate of correction should be aimed at a rate of < 0.5 mmol/hour to a concentration of 120 mmol/L. In chronic asymptomatic hyponatremia, correction is best accomplished by water restriction. Vasopressin V2 receptor antagonists have been used effectively to treat hyponatremia in patients with cirrhosis and SIADH and may be considered.
Malvinder S. Parmar, MD, FRCPC, FACP is Associate Professor, Northern Ontario School of Medicine. He is also a consultant physician and Director of Dialysis at the Timmins and District Hospital in Timmins, Ontario.