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Hyponatremia review. Clinician's Brief

Article · January 2010

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Cristina Pérez Vera

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Consultant on Call INTERNAL MEDICINE

Cristina Perez Vera, DVM, &

Sally Bissett, BVSc, MVSc, Diplomate ACVIM,
North Carolina State University

Hyponatremia

PROFILE

Definition
Hyponatremia is defined as a plasma sodium (Na+) concentration < 140 mEq/L in dogs
and 150 mEq/L in cats.1 Because plasma Na+ concentration is the main determinant of
plasma osmolality (Posm), hyponatremia usually reflects hypoosmolality. Since the kid-
neys are highly efficient in excreting water, hypoosmolality almost always implies a
defect in renal water excretion and excess of water in the body due to one of the
following mechanisms:
● Impaired diluting ability in the loop of Henle and distal tubule (volume depletion,
renal failure, diuretics)
● Increased collecting-tubule permeability due to the presence of antidiuretic hormone
(ADH) (effective circulating volume depletion, inappropriate ADH secretion, pain,
adrenal insufficiency, or hypothyroidism)

CONTINUES

ADH = antidiuretic hormone; Na+ = sodium; Posm = plasma osmolality

Consultant on Call / NAVC Clinician’s Brief / February 2010 ................................................................................................................................................................49

 Consultant on Call CONTINUED

KEY WORDS

Signalment Pathophysiology: Why is there too

Na+ concentration: Reflects the Hyponatremia is a common electrolyte disor- much water?
content of sodium relative to der occurring in a broad spectrum of patients, Body fluid balance depends largely on the
the volume of water in the from ones without clinical signs to the criti- interrelationship of salt and water. Although
body, not total sodium content. cally ill. effective circulating volume is largely con-
Therefore, hyponatremic trolled by sodium balance, maintaining osmo-
patients can have decreased, Causes lality depends on regulation of water balance
increased, or normal total The principal causes of hyponatremia are: (Table 1).
sodium content. ● Disorders associated with impaired renal ● Na+ balance: Several sensors in the body
Na+ content: Reflects the total water excretion (more common): detect changes in extracellular fluid vol-
amount of sodium in ◗ Volume depletion ume (which is largely determined by total
extracellular fluid and is • Extrarenal losses: Gastrointestinal dis- sodium content).
calculated by multiplying the orders (vomiting, diarrhea); third-space ● Water balance: Although extracellular fluid
concentration of sodium by the disorders (pancreatitis, peritonitis) and intracellular fluid have different com-
volume of extracellular fluid. • Renal losses: Diuretic therapy (thiazide), positions, they must maintain the same
Osmolality: Concentration of osmotic diuresis (glucose, mannitol), tonicity. The balance is sensed and con-
osmotically active particles in a advanced renal failure (decreased trolled by thirst and osmoregulation sys-
solution. glomerular filtration rate) tems. Osmoreceptors of the hypothalamus
• Plasma osmolality (Posm) is • Edematous states: Congestive heart fail- and neurohypophysis are sensitive to alter-
the main determinant of ure, liver disease, nephrotic syndrome ations in plasma osmolality and hydro-
water distribution in the body. ◗ ADH excess: static pressure; they respond to plasma
Because water can move • Inappropriate ADH secretion hypertonicity by increasing thirst and
freely across almost all cell (SIADH) ADH secretion. When the osmolality is
membranes, the osmolalities • Mineralocorticoid deficiency low, ADH secretion is suppressed and
of intracellular and • Hypothyroidism urine is diluted.
extracellular fluids are the ● Disorders associated with normal renal

same. water excretion: Signs

◗ Excessive water intake (primary Depending on the severity of hyponatremia,
• Normal plasma osmolality
polydipsia) patients may have no clinical signs or present
ranges from 290 to 310
◗ Reset osmostat syndrome with varying degrees of neurologic signs.
mOsm/kg in dogs and 290 to
◗ Rapid infusion of hypotonic fluids Cerebral edema and water intoxication occur
330 mOsm/kg in cats.
● Disorders associated with pseudohypona- as serum sodium concentration decreases, and
Posm = 2 × Na+ + glucose/18 +
tremia or translocational hyponatremia: the osmotic gradient that develops makes
BUN/2.8
◗ Hyperlipidemia water move into the brain. Typical neurologic
• The contributions of glucose ◗ Hyperproteinemia signs include the following:
and BUN to Posm are ◗ Hyperglycemia ● Lethargy
normally small, except in ● Irritability
diabetes mellitus and renal Risk Factors ● Nausea/vomiting
failure. Urea can freely cross There are currently no reports of risk factors ● Mental dullness or depression
cell membranes; its for hyponatremia in dogs and cats, but serum ● Stupor
contribution to Posm can be Na+ concentration should be measured in ● Seizures
excluded: small animals with: ● Coma
Effective Posm = ● Suspected hypoadrenocorticism
measured Posm – BUN/2.8 ● Vomiting and diarrhea Clinical signs related to the underlying cause
Tonicity: Osmotic pressure of a ● Diuretic use of the hyponatremia may also be present:
solution. It determines the ● Effusive disorders ● Tachycardia
ability of a solution to move ● Polyuria and polydipsia ● Hypotension
across a membrane. ● Abnormal mental status or behavior ● Prolonged capillary refill time
● Seizures ● Weakness
Na+ expressed as mEq/L; glucose
● Ascites
expressed as mg/dL; BUN expressed
as mg/dL ● Edema

50 ................................................................................................................................................................NAVC Clinician’s Brief / February 2010 / Consultant on Call

 Table 1. Regulation of Body Fluid Balance

Water Balance Na+ Balance (Volume Regulation)

Signal Plasma osmolality Effective circulating volume
Sensors Hypothalamic osmoreceptors • Baroreceptors of the aorta, carotid sinus, and
afferent glomerular arteriole
• Atrial distension
Effectors Antidiuretic hormone • Sympathetic nervous system
• Renin-angiotensin aldosterone system
• Atrial natriuretic peptide
• Antidiuretic hormone
• Pressure natriuresis
Response • Water excretion (via antidiuretic Na+ excretion
hormone)
• Water intake (via thirst)

ties on T2-weighted scans, which represent an

DIAGNOSIS increase in water density associated with
inflammation, gliosis, edema, or necrosis.
Definitive Diagnosis Central nervous system lesions may not
● Hyponatremia: Serum Na+ concentration always be visible on MRI early in the course
< 140 mEq/L in dogs or < 150 mEq/L in of neurologic disease.
cats.
● Neurologic signs are not usually seen unless Clinical Approach
Na+ concentrations are < 120 mEq/L in dogs If the cause of hyponatremia is not readily appar-
or < 130 mEq/L in cats. However, the devel- ent (also see Diagnostic Tree: Hyponatremia,
opment of neurologic signs is also related to page 55):
rapidity of onset of hyponatremia. In chronic ● Evaluate blood sample for lipemia and meas-
disorders, the signs are more subtle and non- ure plasma protein concentration to rule out ADH = antidiuretic hormone;
BUN = blood urea nitrogen:
specific because the brain has had enough pseudohyponatremia. Lipemia and hyperpro- MRI = magnetic resonance
time to adapt to plasma hypotonicity. teinemia underestimate Na+ concentration imaging; Na+ = sodium; SIADH
= syndrome of inappropriate
when flame photometry is used, but this does
antidiuretic hormone secretion
Laboratory Findings & Imaging not happen with ion-selective electrode tech-
● Laboratory data should ideally include plasma niques. Plasma osmolality is normal because
osmolality, Na+, potassium, chloride, bicarbon- lipids and proteins contribute little to plasma
ate, BUN, and glucose concentrations, and, osmolality.
where necessary, urine Na+ concentration and ● Measure glucose concentration to rule out
osmolality and venous or arterial pH (see translocational hyponatremia. The following
Clinical Approach). formula can be used to correct sodium in the
● MRI (after rapid correction of hyponatremia presence of hyperglycemia:
and myelinolysis):2,3 Extrapontine lesions are Corrected Na+ = Measured Na+ +
most common, especially lesions within the 1.6 [(Serum glucose - 100)/100]
thalamus. The lesions are described as nonen-
hancing, symmetrical increased signal intensi- CONTINUES

Consultant on Call / NAVC Clinician’s Brief / February 2010 ................................................................................................................................................................51

 Consultant on Call CONTINUED

● Measure or calculate Posm, other electrolytes, ● Volume-depleted patients require inpatient

and urea concentrations with or without pH: management with IV fluids.
◗ Posm < 290 mOsm/kg confirms hypoosmo- ● Normovolemic or edematous patients may be
lality. However, increased BUN may cause able to be managed as outpatients.
FIND MORE plasma osmolality to be normal or high
while the effective osmolality is reduced. Medical
A case study ◗ Metabolic alkalosis and hypokalemia sug- ● Two basic goals of therapy for hyponatremia:
addressing
treatment for
gest vomiting or diuretic use. ◗ Treat underlying cause
hyponatremia ◗ Metabolic acidosis and hyperkalemia sug- ◗ Increase plasma Na+ concentration at a safe
in a dog with gest Addison’s disease or gastrointestinal rate
lethargy, disease (eg, trichuriasis) when renal func- ● In general, hyponatremia is corrected by giv-
vomiting, and
diarrhea can
tion is normal. ing Na+ to patients who have extracellular
be viewed at ● Measure urine osmolality (Uosm) to determine fluid volume depletion and by restricting
whether water excretion is normal or impaired. sodium in patients who are hyponatremic but
cliniciansbrief.com The normal response to hyponatremia is to normovolemic or edematous (eg, sodium-
>>Go to Journal suppress ADH secretion, resulting in maxi- retaining states, such as congestive heart fail-
Extras on our mally dilute urine (< 100 mOsm/kg or urine ure, cirrhosis, and nephrotic syndrome).
homepage.
specific gravity < 1.003).
◗ Hyponatremia with Posm and Uosm Rate of Correction
< 100 mOsm/kg (ADH suppression) ● Ideally, the rate of correction should be similar
suggests primary polydipsia. to that at which hyponatremia developed. For
● Measure urine Na+ concentration (Una) to example, acute (< 24–48 hours’ duration)
differentiate volume depletion and SIADH hyponatremia with clinical signs should be
when urine osmolality is high. treated aggressively to reverse cerebral edema.
◗ Una should be < 20 mEq/L with hypovolemia. However, most patients develop hyponatremia
◗ Una should be > 20 mEq/L with Addison’s over 2 or more days (chronic hyponatremia), a
disease, diuretic therapy, or SIADH. While situation in which the brain has had time to
SIADH is a common cause of hypona- adapt to hypoosmolarity. Under these circum-
tremia in humans, it is rarely described in stances a conservative approach of no more
veterinary patients. than 0.5 mEq/L per hour or 10 mEq/L per
● Perform a fecal examination to rule out gas- day of sodium replacement is generally recom-
trointestinal parasitism.4 mended to avoid rapid correction of
● Consider an ACTH stimulation test to rule sodium.1,2,6
out Addison’s disease. Hypoadrenocorticism ● Rapid correction of chronic hyponatremia
leads to urinary loss of sodium chloride, vol- (generally > 15 mEq Na/L per day) can lead
ume depletion, and ADH release. As many as to a neurologic disorder called demyelinating
81% of dogs with hypoadrenocorticism are encephalopathy, or myelinolysis. The mecha-
hyponatremic at presentation.5 nism is not clear, but brain cells adapted to
● Consider measurement of T4 and/or TSH. hyponatremia may be at particular risk. Clini-
Myxedema coma due to hypothyroidism may cal signs typically develop 3 to 4 days after
cause hyponatremia in people and dogs, possi- correction of hyponatremia and are character-
bly because of ADH release secondary to ized by paraparesis or tetraparesis, dysphagia,
decreased cardiac output and decreased coma, and seizures.1–3
glomerular filtration rate (rare).6,7 ● In correcting severe hyponatremia, formulas
may be helpful, but serum Na+ concentrations
TREATMENT should be measured frequently (eg, every 3–6
hours) and therapy adjusted accordingly.
Inpatient or Outpatient ● Conventional crystalloid solutions are gener-
● Patients with neurologic signs or severe ally recommended for correcting hypovolemic
hyponatremia should be treated in an inten- hyponatremic patients. Table 2 provides the
sive care unit.
52 ................................................................................................................................................................NAVC Clinician’s Brief / February 2010 / Consultant on Call
 Table 2. Na+ Content & Main Composition of Various Crystalloid Fluids

Fluid Na+ Cl K Ca Mg Dextrose (%) Buffer Osmolality

7.5% NaCl 1283 1283 - - - - - 2567
0.9% NaCl 154 154 - - - - - 308
Normosol-R (hospira.com) 140 98 5 - 3 - 27 acetate 294
23 gluconate
Lactated Ringer’s solution 130 109 4 3 - - 28 lactate 272
2.5% dextrose in 0.45% NaCl 77 77 - - - 2.5 - 280
0.45% NaCl 77 - - - - - 155
Normosol-M (hospira.com) 40 40 13 - 3 5 16 acetate 364
Dextrose 5% (D5W) - - - - - 5 - 253
Ions & buffers are expressed as mEq/L; osmolality is expressed as mOsmol/L
Ca = calcium; Cl = chloride; k = potassium; Mg = magnesium; Na+ = sodium

main composition of several crystalloid fluids. at cliniciansbrief.com). Therapy is then

● The degree to which a given fluid will adjusted on the basis of serial serum Na+
increase serum Na+ can be estimated by using concentrations.
the following formula (infusate Na+ = Na+
concentration of the corrective fluid): IN GENERAL
∆ Serum Na+ =
Infusate Na+ – Serum Na+/TBW + 1 Relative Cost
● The amount of sodium required (sodium The cost of investigating and treating hypona-
deficit) can also be estimated by using the tremia depends on the cause and severity. If the Cost Key
following formula: patient has no clinical signs and underlying dis-
$ = < $100
∆ Na+ deficit = TBW × (desired Na+ – actual Na+) ease is treatable, the treatment may be relatively
$$ = $100–$250
● Unfortunately, the above formulas are only inexpensive ($$–$$$$). However, if the patient is
$$$ = $250–$500
estimates and do not account for the effect of showing neurologic signs, has severe hypona-
$$$$ = $500–$1000
concurrent potassium administration (which tremia, or needs intensive care because of the
will increase serum Na+ because of extracellu- underlying disease process, the cost will be much $$$$$ = > $1000
lar movement), the effect volume replacement higher ($$$$$).
has on ADH secretion, or ongoing fluid
losses. Prognosis & Course
● In general, for most patients with chronic Outcome depends on the cause of hyponatremia
hyponatremia and hypovolemia, the initial and the presence of neurologic signs. Many
fluid type and volume administered are based patients without clinical signs have an excellent
on the severity of hyponatremia, degree of prognosis, whereas patients with acute severe
volume depletion, estimated ongoing losses, hyponatremia that display neurologic signs
and maintenance fluids; the goal is a Na+ cor- (either before or during treatment) will have a
rection rate less than 0.5 mEq/kg per hour. At prognosis from good to guarded.
our institution, this usually results in the con-
current administration of maintenance (hypo- See Aids & Resources, back page, for references
tonic) and replacement (relatively isotonic) and suggested reading.
crystalloid solutions (Case Study available

ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; BUN = blood urea nitrogen; Na+ = sodium; Posm = plasma
osmolality; SIADH = syndrome of inappropriate antidiuretic hormone secretion; T4 = thyroxine; TBW = total body weight;
TSH = thyroid-stimulating hormone; Una = urine concentration; Uosm = urine osmolality

Consultant on Call / NAVC Clinician’s Brief / February 2010 ................................................................................................................................................................53

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