A Q u i c k R e f e ren c e o n

H y p e r n a t rem i a
a, b
Julien Guillaumin, Doct Vet *, Stephen P. DiBartola, DVM

KEYWORDS
 Hypernatremia  Sodium distribution  Hypertonicity

KEY POINTS
 Hypernatremia most commonly is associated with water loss in excess of sodium (Na) or
salt gain (typically associated with restriction of access to water).
 Most of the signs of hypernatremia arise from the central nervous system; the more rapid
the development of hypernatremia, the more severe the neurologic signs are likely to be.
 Anorexia, lethargy, vomiting, muscular weakness, behavioral changes, disorientation,
ataxia, seizures, coma, and death have been identified in dogs and cats with hypernatre-
mia and hypertonicity.

SUMMARY OF SODIUM DISTRIBUTION AND HYPERNATREMIA

 Most Na is located in the extracellular water.1 Low intracellular Na concentration is
maintained by the activity of cell membrane sodium (Na)-potassium (K)-ATPase.
 Intracellular Na in muscle is approximately 12 mEq/L, less than 10% of its extra-
cellular concentration.
 Serum Na concentration is a reflection of the amount of Na relative to the volume
of water in the body and not a reflection of total body Na content. Hypernatremic
patients may have decreased, increased, or normal total body Na content.
 Hypernatremia is more commonly associated with a decrease in the amount of
water in the body, hence a free water deficit, relative to the amount of Na. The
majority of the free water deficit comes from the intracellular fluid (ICF) compart-
ment. Alternatively, hypernatremia can be secondary to an increase in the
amount of Na relative to the volume of water in the body (ie, salt gain).
 Adjustments in water balance are mediated by changes in water reabsorption in the
collecting tubules of the kidney in response to vasopressin (antidiuretic hormone

The authors have nothing to disclose.

a
Emergency and Critical Care Service, Department of Veterinary Clinical Sciences, The Ohio
State University, 601 Vernon L. Tharp Street, Columbus, OH 43210, USA; b Department of Vet-
erinary Clinical Sciences, The Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH
43210, USA
* Corresponding author.
E-mail address: Guillaumin.2@osu.edu

Vet Clin Small Anim 47 (2017) 209–212

http://dx.doi.org/10.1016/j.cvsm.2016.10.002 vetsmall.theclinics.com
0195-5616/17/ª 2017 Elsevier Inc. All rights reserved.
210 Guillaumin & DiBartola

[ADH]) action and changes in water intake driven by the thirst mechanism. These
mechanisms maintain normal serum osmolality and serum Na concentration.
 Adjustments in Na balance maintain normal extracellular fluid (ECF) volume by
decreasing or increasing renal Na excretion. These adjustments include the ef-
fects of glomerulotubular balance, aldosterone, atrial natriuretic peptide, and
renal hemodynamic factors.
 Na and its attendant anions account for approximately 95% of the osmotically
active substances in the extracellular water. Hypernatremia is associated with
hyperosmolality.

REFERENCE RANGE AND DANGER VALUES

 Typical reference range: reference values range from 140 mEq/L to 150 mEq/L
for dogs and from 150 mEq/L to 160 mEq/L for cats. These values may vary
slightly among laboratories.
 Danger values: clinical signs of hypernatremia are more related to rapidity of
onset than to magnitude of change and associated hyperosmolality. Neurologic
signs may occur with Na concentrations greater than 170 mEq/L in dogs and
greater than 175 mEq/L in cats.

CAUSES OF HYPERNATREMIA

Hypernatremia is a common electrolyte disorder in critically ill and hospitalized pa-

tients.2 A large study investigating 16,691 dogs and 4211 cats during a 60-month
period showed that 5.7% of dogs and 8.0% of cats suffered from hypernatremia.2
The most frequent disease processes identified in dogs were neurologic (21.4%),
neoplastic (21.4%), and respiratory (19.6%). In cats, the most frequent disease pro-
cesses were urologic (55%), neurologic (25%), and hyperthyroidism (20%). In both
dogs and cats, many animals had greater than 1 concurrent disease process.
Pathophysiologic factors potentially contributing to the development of hypernatre-
mia were investigated.2 In dogs, gastrointestinal fluid loss was the most commonly
identified factor (39.3%), followed by central diabetes insipidus (23.2%), and fever
or hyperthermia (23.2%). In cats, the most common pathophysiologic factors poten-
tially contributing to the development of hypernatremia were chronic kidney disease
(30%) and nonoliguric acute kidney injury (25%), followed by gastrointestinal fluid
loss (25%). Many animals had greater than 1 pathophysiologic factor potentially lead-
ing to hypernatremia.
Hypernatremia was associated with a higher case fatality rate than having a normal
serum Na concentration or hyponatremia in both dogs and cats.
Serum Na concentration should be measured in patients at high risk of having or
developing hypernatremia. These include dogs and cats that are dehydrated or not
drinking water, those with abnormal mentation or behavior, those having seizures,
and those with polyuria, polydipsia, vomiting, and diarrhea.1
Hypernatremia is accompanied by hyperosmolarity and can be further categorized
by volume status (Table 1).
Hypernatremia most commonly is associated with water loss in excess of Na (most
common) or salt gain (typically associated with restriction of access to water). For
example, although diarrheal losses are isosmotic, the combined Na and K concentra-
tion of diarrhea fluid is lower than that of plasma (typically approximately 40–100
mEq/L of Na and K combined). Therefore, more free water is lost and the patient be-
comes hypernatremic, which is a common clinical scenario. The same applies for renal
losses. Loss of free water through osmotic diuresis or lack of ADH secretion or action
 A Quick Reference on Hypernatremia 211

Table 1
Causes of hypernatremia categorized by volume status

Hypovolemia Normovolemia Hypervolemia

Renal losses (chronic kidney Hypodipsia (uncommon) Salt intoxication
disease and nonoliguric Diabetes insipidus (with  Iatrogenic
acute kidney injury) decreased water intake)  Sea water ingestion
Gastrointestinal losses  Central (neurogenic) Hypertonic saline infusion
(vomiting or diarrhea) diabetes insipidus Na bicarbonate infusion
Burns  Congenital nephrogenic Primary hyperaldosteronism
Osmotic diuresis diabetes insipidus Hyperadrenocorticism
 Diabetes mellitusa  Acquired nephrogenic dia
 Diabetic ketoacidosisa betes insipidus
 Hyperosmolar nonketotic Fever
syndromea Decreased access to water
 Mannitol infusion
 Postobstructive diuresis
a
Use corrected Na value (see Julien Guillaumin and Stephen P. DiBartola’s article, “A Quick
Reference on Hyponatremia,” in this issue for further discussion).

also is common. Usually, the body responds with ADH release and stimulation of the
thirst mechanism, and the hypernatremia and hyperosmolality are corrected. If a
neurologic disease, however, decreased access to free water or both are present,
then hypernatremia develops.

CLINICAL SIGNS OF HYPERNATREMIA

Most of the signs of hypernatremia arise from the central nervous system. The more
rapid the development of hypernatremia, the more severe the neurologic signs are
likely to be. Acute hypernatremia results in acute hyperosmolality of ECF and potential
shrinkage of brain cells. A rapid decrease in brain volume may cause rupture of cere-
bral vessels and focal hemorrhage. If hypernatremia develops slowly, the brain has
time to adapt to the hypertonic state and clinical signs are minimal or absent.
Anorexia, lethargy, vomiting, muscular weakness, behavioral changes, disorienta-
tion, ataxia, seizures, coma, and death have been identified in dogs and cats with
hypernatremia and hypertonicity. Because hypernatremia develops primarily with
decreased ICF, signs of ECF loss (ie, isotonic dehydration) and hypovolemia may
be minimal.
For example, consider a normal (ie, serum Na concentration, 145 mEq/L) 10-kg dog
that experiences a free water loss of 500 mL secondary to diabetes insipidus and lacks
access to drinking water to compensate. This dog’s total body water is 60%, or 6 L,
divided between ICF (67% or 4 L) and ECF (33% or 2 L). ECF volume is divided be-
tween interstitial fluid volume (75% of ECF or 1.5 L) and intravascular fluid volume
(25% of ECF or 0.5 L). The 500 mL of free water loss comes from ICF (67% of
500 mL or 335 mL) and ECF (33% of 500 mL or 165 mL). Within the ECF, the loss
of 165 mL comes from interstitial fluid (75% of the loss or 124 mL) and intravascular
fluid (25% of the loss or 41 mL). The loss of 124 mL from the ECF corresponds to
1.2% dehydration, which is undetectable clinically. The loss of 41 mL of free water
from the intravascular compartment (80 mL/kg or 800 mL for this dog) represents a
loss of approximately 5% of the blood volume, which also is undetectable clinically.
In the meantime, the new serum Na concentration caused by a loss of 500 mL can
be calculated. In this case, the ECF loses one-third of the volume, or 167 mL, and the
212 Guillaumin & DiBartola

ICF loses two-thirds of it, or 333 mL. The initial amount of solute (considering an initial
osmolality of 300 mOsm/kg), however, is the same but merely concentrated in a
smaller compartment. The initial amount of solute is 600 mOsm (300 mOsm/L 
2 L) in the ECF and 1200 mOsm (300 mOsm/L  4 L) in the ICF. Considering the
ECF, those 600 mOsm are now concentrated in 1833 mL (2000–167 mL), increasing
the osmolality to 327 mOsm/kg, and thus a serum Na concentration of 163 mEq/L,
assuming both serum urea nitroben and glucose are normal.3

CLINICAL APPROACH TO HYPERNATREMIA

History is important to consider in animals with hypernatremia. Burns, postobstructive

diuresis, and infusion of salt-containing fluids should be evident from the history. Other
potential causes of free water loss also should be considered carefully. Finally, the
owners should be carefully asked about any mentation changes, signs of neurologic
disease, and the animal’s access to water. The presence or absence of polyuria
and polydipsia also is important.
Diabetes insipidus usually is diagnosed based on urinalysis (ie, marked hyposthenu-
ria), which can include evaluation of urine electrolytes and urine osmolarity, followed
by routine diagnostic evaluation and response to treatment, which are not covered
in this article. Evaluation of serum biochemistry results facilitate the diagnosis of dia-
betes mellitus or hyperadrenocorticism.

REFERENCES

1. de Morais HA, DiBartola SP. Hypernatremia: a quick reference. Vet Clin North Am
Small Anim Pract 2008;38:485–9, ix.
2. Ueda Y, Hopper K, Epstein SE. Incidence, severity and prognosis associated with
hypernatremia in dogs and cats. J Vet Intern Med 2015;29:794–800.
3. DiBartola SP. Fluid, electrolyte, and acid-base disorders in small animal practice.
St Louis (MO): Saunders/Elsevier; 2012. p. 45–79.