Introduction

Disorders of serum sodium concentration are commonly seen in critically ill patients and present a diagnostic and therapeutic challenge to the veterinarian. Clinical signs may be subtle and often masked by the primary disease process and there are significant risks associated with aggressive or inappropriate treatment. This presentation will focus on an approach to the diagnosis and treatment of patients with sodium disorders.

Physiology

The volume and tonicity of body fluids are normally maintained within a narrow range by regulation of sodium and water balance.¹ Abnormalities in extracellular fluid volume reflect changes in total body sodium content. Abnormalities in serum concentration are caused by changes in water balance. The maintenance of a normal serum sodium concentration is dependent on the balance between water intake and water excretion. An appreciation of the physiologic effects of changes in plasma osmolarity is important when dealing with hyponatremic or hypernatremic patients. Total body water is estimated to be 60% of lean body weight. The distribution of this water is 1/3 extracellular (intravascular and interstitial) and 2/3 intracellular. Each fluid compartment has one major solute restricted primarily to that compartment that acts to hold water within the compartment. The extracellular fluid compartment (ECF) volume is maintained by sodium salts while the intracellular fluid compartment (ICF) is maintained by potassium salts. Because the cell membrane is freely permeable to water, the ECF and ICF spaces are in osmotic equilibrium. If an osmotic gradient is established, water will flow from the compartment of low osmolarity to the compartment with high osmolarity until the osmotic pressures are equalized. An increase in osmolarity of the ECF results in cellular dehydration and conversely a decrease in ECF osmolarity results in cellular overhydration.

In contrast to regulation of ECF volume by changes in urinary sodium excretion, plasma osmolarity is maintained within narrow limits by balancing water intake (drinking, the water content of food and the water of oxidation) with water losses from urine, feces and insensible loss from the skin and respiratory tract. Small changes in plasma osmolarity are sensed by osmoreceptors in the hypothalamus which affect both thirst and water excretion via the secretion of ADH.²

Clinical Signs

The flow of water in and out of cells, particularly brain cells, is primarily responsible for the symptoms of both hyponatremia and hypernatremia. Symptoms of sodium disorders are nonspecific and may be difficult to separate from the underlying disease. Central nervous system signs are most common ranging from lethargy and weakness to ataxia, seizure, coma and death. The severity of neurologic dysfunction is related to the rapidity, as well as the degree of the change in serum sodium concentration.

Hyponatremia

Hyponatremia is defined as a serum sodium concentration <140 mEq/L in dogs, and <149 mEq/L cats.³ Clinically significant hyponatremia is associated with hypo-osmolarity. Normotonic and hypertonic hyponatremia are occasionally seen.⁴ Common causes of hyponatremia are listed in Table 1. In these conditions, therapy should be directed against the primary abnormality rather than the decreased serum sodium concentration. Figure 1 provides a diagnostic algorithm for hyponatremia.

Patients with hypertonic hyponatremia have normal body sodium and a dilutional drop in the measured serum sodium due to the presence of osmotically active molecules in the serum (glucose, mannitol, maltose) which cause a shift of water from the ICF compartment to the ECF compartment. Glucose produces a drop in serum sodium of 1.6mEq/L for each 100 mg/dl of serum glucose greater than 100 mg/dl. Because this relationship is nonlinear with greater reduction in sodium concentration over 400 mg/dl, some authors have suggested 2.4 mEq/L for each 100 mg/dl increase in glucose over 100mg/dl as a more accurate correction factor when glucose is grater than 400 mg/dl.⁵

Severe hyperlipidemia and paraproteinemia can lead to low measured serum sodium concentrations with normal serum osmolarity. Normally, the plasma water comprises 92-94% of plasma volume. The plasma water fraction falls with an increase in fats and proteins. The measured sodium concentration in the total plasma volume is reduced, although the plasma water sodium concentration and plasma osmolarity are unchanged. This artifactually low sodium is referred to as "pseudohyponatremia" and is secondary to measurement by flame photometry. It can be avoided by direct ion-selective electrode measurement.

Plasma osmolarity (and serum sodium concentration) is determined by the ratio of solute (primarily sodium and potassium) and water. Therefore hypotonic hyponatremia can result either from a loss of solute or retention of water. Clinically, solute loss (i.e., vomiting, diarrhea) most commonly occurs in a fluid that is isotonic or hypotonic to plasma. Isotonic fluid loss will not directly lower sodium concentration. However, hyponatremia may occur if isotonic fluid loss is replaced with water or hypotonic fluids. Hypotonic hyponatremia most often reflects the inability of the kidneys to handle the excretion of free water to match water intake. Common causes of hypotonic hyponatremia are listed in Table 1. Increased ADH levels resulting from physiologic stimulation (volume depletion) or secondary to an inappropriate secretion of ADH (SIADH) are responsible for increased water retention leading to hyponatremia in many cases.

The therapeutic approach to the hyponatremic patient should include identification and treatment of the underlying cause as well as treatment to increase the serum sodium level. Overly rapid correction of hyponatremia can be harmful. Central demyelination syndrome has been associated with the rapid correction of hyponatremia. Therapy should be instituted at a rate that balances the risk of hyponatremia with the risk of excessively rapid correction and should be guided primarily by the presence of neurologic symptoms and by the duration of the hyponatremia. Aggressive correction of hyponatremia is not indicated in an asymptomatic patient.

In general, therapy consists of sodium administration to patients that are volume depleted and water restriction in patients that are normovolemic or edematous. The amount of sodium required to raise the serum sodium concentration to a desired value can be estimated from the following formula:

Na⁺ deficit = 0.6 x lean body weight (kg) x (desired Na⁺ -patient's Na⁺)

In hypovolemic patients with secretion of ADH secondary to volume depletion, isotonic saline is the initial fluid of choice. Normal saline (154 mEq Na⁺/liter) will supply extra sodium. Additionally, ADH secretion will be suppressed following correction of the hypovolemia leading to production of dilute urine and excretion of the excess water. Hypertonic saline administration may be required in patients with very low sodium concentrations (<110 mEq/L) or in symptomatic patients. It is generally recommended serum sodium be raised at a rate of 0.5 mEq/l/hour until a level of 120 mEq/L is reached and the remainder of the calculated deficit be replaced over the next several days. The patient should be carefully monitored with frequent evaluation of serum sodium concentration.

In normovolemic or edematous patients, therapy must be aimed at water removal. In mild or asymptomatic patients water restriction is indicated. In more severe and symptomatic hypernatremia, the serum sodium concentration can be elevated more rapidly by the use of a loop diuretic and hypertonic saline. Water and sodium loss are induced by the diuretic and only the lost sodium is replaced. Demeclocycline induces ADH resistance and has been used to limit water retention.

Figure 1. Approach to hyponatremia.

Table 1. Causes of hypotonic hyponatremia.

References

1.  Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders. 4 ed. New York: McGraw-Hill, 1994;219.

2.  Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders. 4 ed. New York: McGraw-Hill, 1994:261.

3.  DiBartola SP. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice. 3 ed. St. Louis, MO: Saunders Elsivier, 2006:47.

4.  Adrogue HJ, et al. New Engl J Med 2000;342(21):1581.

5.  Hillier TA, et al. Am J Med 1999;106(4):399.