Dysnatremias

1. What are dysnatremias?

The term dysnatremia applies when an aberration in plasma sodium concentration is present. Changes in plasma sodium concentration can result in fluid shifts between the intra- and extracellular compartments of the body. In the healthy state, the body’s osmoregulatory system maintains the plasma sodium concentration between 135 and 145 mEq/L. Failure of this system begets an imbalance of free water intake and excretion. When free water intake exceeds excretion, the plasma sodium concentration decreases below 135 mEq/L, a condition known as hyponatremia. In contrast, hypernatremia, defined as a serum sodium concentration >145 mEq/L, occurs when electrolyte-free water excretion exceeds intake. Less commonly, pure loss or addition of sodium without a primary disturbance in water balance may also lead to hypo- or hypernatremia.

2. How is plasma osmolality determined?

Plasma osmolality can be calculated with the following equation:

As the equation implies, serum sodium concentration is by far the main determinant of plasma osmolality. Plasma osmolality can be directly measured with an osmometer. An osmolar gap exists if there is greater than a 10 mOsm/kg H ₂ O discrepancy between the calculated and measured osmolality, indicative of the presence of a solute not routinely measured in plasma.

3. Can osmolality be normal despite an abnormal serum sodium concentration?

Yes! Serum sodium concentration is usually measured using indirect ion-selective electrodes with specimen dilution and depends on the assumption that water comprises approximately 93% of plasma. The presence of high concentrations of plasma lipid or protein, however, will reduce the aqueous contribution to plasma volume. As a result, the measured serum sodium concentration will be falsely low. This condition is known as pseudohyponatremia. Ultracentrifugation and separation of the lipid layer can correct for lab artifact due to hyperlipidemia. Direct ion-selective electrodes are not confounded by hyperlipidemia or hyperproteinemia, but only about a third of chemical analyzers use this technique. Blood gas laboratories use ion-selective electrodes and thus are not susceptible to this artifact.

4. Is plasma osmolality the same as plasma tonicity?

No! While plasma hypertonicity implies hyperosmolality, hyperosmolar plasma is not necessarily hypertonic. The effective osmolality, often termed plasma tonicity, denotes the concentration of osmoles in plasma that do not move freely across the cell membrane. Such osmoles can generate concentration gradients across cell membranes and in turn drive shifts in water between the extra- and intracellular compartments. While sodium and glucose as effective osmoles contribute to tonicity, urea and ethanol are ineffective osmoles as they freely cross cell membranes. High concentrations of these latter molecules confer hyperosmolality without affecting tonicity. In the absence of ethanol or other unexpected solutes, the effective osmolality is simply the measured osmolality minus blood urea nitrogen (BUN) (mg/dL)/2.8.

5. In what states of tonicity and osmolality can dysnatremias occur?

Because sodium is an effective osmole, hypernatremia by definition indicates both a hyperosmolar and hypertonic state. Hyponatremia, however, can arise in various states of osmolality and tonicity.

6. In what hyponatremic states can a patient be hyperosmolar or hypertonic?

The two most clinically relevant occurrences of hyperosmolar hyponatremia are azotemia and hyperglycemia. Buildup of nitrogenous waste, that is, urea, in the setting of impaired kidney function increases plasma osmolality. If present alone, kidney dysfunction does not lead to a change in serum sodium concentration. However, if a simultaneous disorder in water balance leading to hyponatremia is present, hyponatremia with normal or elevated serum osmolality may result. Such patients are truly hypotonic , because the decreased sodium, an effective osmole, leads to a decrease in tonicity while urea, an ineffective osmole, does not increase tonicity.

In hyperglycemia, increased serum glucose increases both the total and effective plasma osmolality, leading to a hypertonic state. The hypertonic plasma draws water from the cells into the extracellular compartment, lowering the serum sodium concentration. For every 100 mg/dL increase in glucose above normal, the serum sodium falls by approximately 1.6 mEq/L even as tonicity rises due to the hyperglycemia. In cases of more severe hyperglycemia (i.e., serum glucose >400 mg/dL), the ratio approximates a 2.4 mEq/L drop in serum sodium for every 100 mg/dL rise in serum glucose. A similar process occurs with administration of mannitol. Any such correction factor is an approximation, and osmolality should be measured directly when clinically relevant.

7. What causes hypotonic hyponatremia?

While there are many discrete etiologies of hypotonic hyponatremia, there are three general processes:

• 1.

  Inadequate solute intake

• 2.

  Excess electrolyte-free water intake

• 3.

  Retention of electrolyte-free water

Not infrequently, the latter two are present simultaneously.

8. What are the clinical manifestations of hyponatremia?

Not all patients with hyponatremia will be symptomatic. While neurons are especially sensitive to osmotic stress, astrocyte-mediated expulsion of electrolytes into the extracellular fluid (ECF) over several hours followed by organic osmolytes (e.g., taurine and glutamate) over the ensuing 24 to 48 hours prevents intracellular swelling. Thus, patients who develop a serum sodium concentration between 125 and 135 mEq/L over greater than 48 hours will often have minimal or no symptoms. Observational studies, however, have demonstrated an association between even mild hyponatremia (serum sodium concentration 130 to 134 mEq/L) and increased in-hospital mortality, falls, and reduced bone density. Other studies have noted impaired motor function and gait even with modest reductions in serum sodium concentration. The combination of cognitive impairment, unsteady gait, increased falls, and osteoporosis constitute a “perfect storm” for development of bone fractures. An increase in fracture risk has indeed been documented. Rapid decreases in plasma sodium concentration (from >134 to <125 mEq/L within 48 hours) are faster than compensatory loss of intracellular solute, so the relatively hypertonic intracellular compartment osmotically absorbs water. This cellular swelling particularly affects the brain given the limit to expansion within a tightly encasing cranium. Thus, the manifestations of hyponatremia are predominantly neurologic and include nausea, vomiting, malaise, headache, lethargy, confusion, and muscle cramps. In severe cases, seizures, coma, tentorial herniation, and neurogenic pulmonary edema can occur.