Water balance made easy: Hyponatremia is the most commonly seen sodium disturbance in small animals. It can result either from an excess of free water (e.g., water drinking, antidiuretic hormone (ADH) secretion) or from loss of sodium (in excess to water), which is rare in living organisms as sodium is usually followed by water, although examples exist (e.g., salt-losing nephropathy). If hyponatremia means that water is present in excess that sodium, an easy thing to remember that "hyponatremia means too much water". Conversely, "hypernatremia means not enough water," either by removing free water (mostly by evaporation from skin or respiratory system) or by adding sodium (e.g., following intravenous fluid therapy).

Osmoregulation and volume regulation: Overall, there is no predictable relationship between Na and extracellular fluid volume (ECF). However, plasma sodium concentration and plasma osmolality vary in parallel. Plasma osmolality is regulated by osmoreceptors that trigger ADH release and thirst behavior. The ADH secretion in response to changes in osmolality is very sensitive (1–2 mmol/L changes in Na). This sensitivity also explains that a small change in Na can be abnormal for "that patient," despite being within the reference range. ADH secretion increases water retention in the collecting tubules of the kidneys. ADH secretion is also triggered by hypovolemia. Thirst is triggered by a variety of causes, including hypovolemia and increase osmolality. Thirst is mainly regulated centrally, and the sensation of thirst is so powerful that normal subjects cannot become hypernatremic as long as they have access to enough water. This is true even in patients with diabetes insipidus, which explains why those patients are usually presented with normal sodium unless they lack access to water. It should be noticed that hypovolemia triggers both isotonic (through aldosterone) and hypotonic (through ADH) fluid reabsorption. The hypotonic fluid reabsorption would in return create an hypo-osmolar state which would turn off the ADH release. However, release due to changes in hypovolemia is very powerful, and changes will happen at the expense of osmoregulation.

Hyponatremia: Causes of hyponatremia can be divided into three categories: hypo-osmolar (itself divided into hypovolemic, normovolemic, and hypervolemic), normo-osmolar, and hyper-osmolar. The vast majority of hyponatremic patients fall in the hypovolemic, hypo-osmolar category. Hypovolemia causes reduction of effective circulating volume, triggering ADH secretion and free water retention. It is almost impossible to predict serum concentration with history and physical examination. An actual serum concentration is needed as well as some other clinicopathological data to rule out pseudo-hyponatremia. If acute (i.e., a few hours) plasma hyponatremia happens, an osmotic gradient will follow and water will rush into the brain, increasing brain cell volume and creating severe acute brain edema. If a similar hyponatremia happens over several days, the brain cells will excrete electrolytes as well as idiogenic osmoles (i.e., osmolytes). Those idiogenic osmoles create an osmotic pull that shifts free water back out of brain cells and slowly allows those to re-equilibrate their volume, although it does not correct brain hyperosmolality. This explains why chronic hyponatremia causes minimal clinical signs. This concept is more important for the correction of hyponatremia. The major in-hospital deleterious consequence of chronic hyponatremia is mismanagement of the problem. If too rapid, the rise of plasma sodium provokes osmotic water movement out of the cells and brain cell shrinkage. Brain shrinkage can cause vascular rupture leading to cerebral bleeding, responsible for acute neurological signs such as seizures, decreased mental state, and even death. In addition to the immediate changes, rapid correction of hyponatremia may cause a delayed syndrome called osmotic demyelination syndrome (ODS) or central pontine demyelination (CPD). This syndrome is characterized by irreversible neurological damage including ataxia, paresis, dysphagia, or coma.

The goal of correction of chronic severe hyponatremia or hypernatremia is to minimize changes to 0.5 mEq/L per hour, or a maximum of 10–12 mEq/L per day. Acute hyponatremia can be corrected relatively quickly (1–2 mEq/L per hour or quicker), if the clinician is absolutely sure the change is acute. Furthermore, severe symptoms (e.g., seizures) due to severe hyponatremia (i.e., 115–120 mEq/L) can also be corrected rapidly, with the goal of increasing serum sodium by 3–7 mEq/L and stopping clinical manifestations such as seizures, before resuming a slower pace of sodium correction. Rapid correction of hyponatremia should stop as soon as severe clinical signs are resolved. When presented with a hyponatremic patient, it is very important for the clinician to review the causes of hyponatremia, as treating the cause of hyponatremia is the most important part of correcting hyponatremia. The indiscriminate use of 0.9% NaCl or 3% NaCl is not warranted in all cases of hyponatremia. The majority of patients with hyponatremia have a depletion of extracellular-fluid volume, in other words, a loss of "total body sodium," or hypovolemia. Those patients require volume replacement with any isotonic fluids (e.g., LRS or 0.9% NaCl).

Several equations to calculate the Na deficit are available, including: sodium deficit = body weight (in kg) × 0.6 × (normal Na − patient Na) (Eq. 1). That sodium deficit (in mEq) should be replace over "x" hours at an average rate of 0.5 mEq/L/h. Sodium replacement can be accomplished using 0.9% NaCl ([Na] = 154 mEq/L), 3% NaCl ([Na] = 513 mEq/L), 7.5% NaCl ([Na] = 1,300 mEq/L) or 23.4% NaCl ([Na] = 4,000 mEq/L). Some clinicians use the following equation (Eq. 2), which provides a rate of infusion in mL/h: Rate of infusion (mL/h) = (0.6 × body weight [kg] × [desired Na − Na measured] × 1,000) / ([Na content of the fluid] × hours) (Eq. 2). Some clinicians calculate the change in Na with the infusion of a liter of a given fluid. This equation can also be used for hypernatremia (see below): change in serum Na = (Na + K in 1 L of solute − patient Na) / (0.6 × body weight [kg] + 1) (Eq. 3). For patients that are asymptomatic, complications from the correction of the hyponatremia can happen, usually due to overzealous correction of hyponatremia and brain shrinkage. Careful calculation and monitoring of serum sodium (sometimes every hour) is warranted to avoid such complications. In case those complications arise, administration of hypotonic fluids is indicated.

Hypernatremia: Hypernatremia can be divided based on volume status: hypovolemia (e.g., renal loss), normovolemia (diabetes insipidus with decreased water intake, and hypervolemia (e.g., salt intoxication). Hypernatremia is mainly associated with more water loss than sodium (the most common) or a salt gain (occasionally). For example, although diarrheal loss is isosmotic (same osmolality), it has a Na+K content less than plasma (usually around 40–100 mEq/L). In that case, more free water is lost and the patient becomes hypernatremic. The same applies to renal losses. Loss of free water through osmotic diuresis or lack of ADH secretion/action is also common. The clinical symptoms of hypernatremia are usually vague, and neurological in nature, such as lethargy, confusion, decreased mental state. Acute hypernatremia (e.g., large amount of salted water intake or hypertonic saline administration) can lead to seizures and death due to acute brain shrinkage. Similar (although in opposite direction) to what happens in chronic hyponatremia, chronic hypernatremia induces increased production of osmolytes, leading to normalization of brain cell volume. This explains why only acute hypernatremia leads to clinical signs. Clinical signs may arise in cases of acute normalization of chronic hypernatremia, when the rapid lowering of sodium may cause brain edema. Understanding and addressing the underlying cause is important, although usually easily identified. Correction of hypernatremia (i.e., free water loss) is achieved by free water replacement. The rate for correction of hypernatremia is identical to the correction of hyponatremia, with a maximum of 12 mEq/L a day and goal of 0.5–1 mEq/L per hour.

Water deficit calculations: More than half of a dozen of equations exist but the classic water deficit equation is: water deficit = 0.6 × body weight (kg) × (plasma Na/normal Na − 1) (Eq. 4). As mentioned before, equation #3, which calculates the change in Na with the infusion of a liter of a given fluid, can also be used. The water deficit formula has been challenged for several and may underestimate true water deficit by as much as 50%. The important clinical implication is that serial monitoring (q 4–6 h) is necessary to track sodium and osmolality changes and adjust fluid rate as needed, which is invariably needed. Ongoing losses of hypotonic fluid can also persist and make the calculation unpredictable.

References

References are available upon request.