Hyponatremia: Causes, Consequences & Treatment
ACVIM 2008
David Polzin, DVM, PhD, DACVIM
St. Paul, MN, USA


Hyponatremia is defined as serum [Na+] < 140 mmol/L in dogs and < 149 mmol/L in cats. Serum sodium is the ratio of sodium to water. It is unique in that the value tells more about the denominator than the numerator. Hyponatremia most often reflect water loss or retention. Sodium concentration also reflects the tonicity of body fluids and thus intracellular fluid (ICF) volume. Since there is little change in number of particles in ICF of most cells, hyponatremia implies swollen cells.

Sodium and Water are Regulated Independently

Sodium balance is regulated by the kidneys in response to changes in "effective" circulating fluid volume (tonicity). Water balance is regulated by a combination of thirst and the renal actions of ADH. Because Na+ are restricted to the extracellular fluid, total body Na+ content determines extracellular fluid (ECF) volume. Since water moves to osmotic equilibrium, total body sodium determines ECF volume. For diagnosis and therapy, consider Na+ and water separately. Fluid changes can be described in terms of 2 compartments: 1) an isotonic component, and 2) an electrolyte-free water component.


Two components are needed to develop hyponatremia: 1) A source of electrolyte-free water (EFW) and 2) Antidiuretic hormone (ADH) to prevent water excretion. The most important defense that guards against hyponatremia is renal excretion of EFW. The factor limiting electrolyte free water excretion is almost always an increase in ADH. Factors that may increase ADH include:

Physiologic Stimuli

 Low "effective" circulating volume





Absence of a Physiologic Stimulus

 Drugs that stimulate or augment ADH release:

 Nicotine and morphine (increase central ADH release)

 Some chemotherapeutic drugs (by causing nausea)

 Drugs that promote actions of ADH:

 Oral hypoglycemics (e.g., chlorpropamide)


 NSAIDS, aspirin

 Drugs that simulate ADH:



 Endocrine causes:


 Adrenal insufficiency

 Vasopressin producing neoplasms

 Vasopressin producing granulomas

 CNS or lung lesions (reset osmostat)

 Certain metabolic lesions (porphyria)

Clinical Approach

To develop hyponatremia, there must be both a source of electrolyte free water and a means to decrease the rate of excretion.

The single most important decision in addressing a patient with hyponatremia is determining whether the hyponatremia is acute or chronic. Acute hyponatremia means less than 48 hours. To be considered acute, duration must be documentable. The diagnostic issue in acute hyponatremia is to identify the source of EFW, as the cause for excess ADH is usually obvious. However, treatment of the hyponatremia should take precedence over the diagnostic evaluation in patients with acute hyponatremia because their condition may rapidly deteriorate. The main risk in acute hyponatremia is brain swelling. Acute hyponatremia should be corrected quickly before the onset of brain injury.

Chronic hyponatremia is defined as lasting greater than 48 hours. The diagnostic issue here is to identify why ADH is present, and the main risk is overly aggressive therapy causing the brain to swell. Brain volume is actively regulated with chronic changes in plasma sodium concentrations. Beyond 48 hours of hyponatremia, the brain reduces intracellular osmoles which can cause the brain to contract as the serum sodium is therapeutically increased. Chronic hyponatremia should be corrected slowly so as to avoid inducing brain injury.

From a diagnostic standpoint, the amount of water taken in relative to the rate of excretion of EFW is a critical factor in development of hyponatremia. It can be assessed by performing a tonicity balance: [Water In] > [EFW Out] = Hyponatremia. It is important to recognize that production of "concentrated" urine does not necessarily mean that sodium is being excreted. It is necessary to measure urine sodium to determine whether it is being retained or excreted. Low urine sodium is usually a good clinical marker for reduced effective circulating volume. The composition of urine must be compared to fluid/sodium intake to ascertain tonicity balance!

Possible sources for water in acute hyponatremia include: administration of D5W or hypotonic saline (almost always an error in surgical patients), ingested water, and desalination of administered isotonic or hypotonic saline. Desalination occurs when there is an excess of ADH while there is a stimulus for sodium excretion. For example, a post-surgical patient fluid overloaded with intravenous isotonic saline, but that has ADH release due to pain or drug stimulus.

It is always important to examine body fluid volume in patients with hyponatremia. Hyponatremia may develop in volume depleted, normal or over hydrated patients. Clues suggesting volume contraction include physical findings, elevated PCV & TPP, reduced potassium levels (consistent with release of aldosterone), reduced plasma bicarbonate levels (consistent with release of aldosterone), and elevated BUN & BUN:Creatinine ratio.

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

 Hyponatremia with true hypoosmolality

 Inappropriately high urine osmolality

 Normal renal and adrenal function

 Natriuresis despite hyponatremia

 No evidence of hypovolemia

 Hyponatremia corrects with water restriction

Treatment of Hyponatremia

If possible, always strive to correct the underlying condition. In asymptomatic patients, reducing/eliminating EFW intake alone may be all that is necessary. In addition, eliminate causes for ADH release if possible. Patients with documented acute hyponatremia and severe CNS signs require prompt elevation of tonicity to reduce brain cell swelling. Generally isotonic solutions are recommended and monitor serum [Na+] serially during therapy. Be certain that hyponatremia is acute--remember--the main risk is brain swelling. Indications for aggressive therapy are acute onset of hyponatremia and severity of clinical signs (coma, seizures). Reduce brain cell volume by administering hypertonic saline to symptomatic patients with plasma [Na+] less than 125 mmol/L. Increase [Na+] 3 to 5 mmol/L over about 1 hour. Dose calculation: TBW x 3 mmol/L = mmol of Na (Use (0.6 x BW) as TBW). Remember: Acute Discovery of a Chronic Condition Does Not Make It An Acute Condition!

With chronic hyponatremia, the key to therapy is to be certain that therapy does not cause plasma [Na+] to rise more rapidly than about 8 mmol/day. Brain cell have reduced their intracellular osmoles & volumes, so it is important to increase plasma [Na+] slowly by up to 8 mmol/L per 24 hours to allow restoration of normal intracellular osmolality. Temporary, more aggressive therapy is used only when patient is having a seizure or is comatose. Use isotonic saline to correct ECF volume deficit and serially monitor plasma [Na+] to detect deviations from expected correction. The major risk is development of Osmotic Demyelination Syndrome (Pontine Myelinosis) which occurs when chronic hyponatremia is corrected too quickly (> 8 meq/L/day). The lesions occur primarily in the pontine region in humans, but are thalamic in dogs. Clinical signs typically develop 3 to 4 days after therapy. In dogs signs may include lethargy, weakness, ataxia, progressing to hypermetria & quadriparesis. There is an increased risk for ODS with malnutrition & hypokalemia.


1.  Halperin ML, Bohn D. Clinical approach to disorders of salt and water balance. Emphasis on integrative physiology. Crit Care Clinics 18:249-272, 2002.

Speaker Information
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David Polzin, DVM, PhD, DACVIM
University of Minnesota
St. Paul, MN

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