3/10/24, 11:03 AM Manifestations of hyponatremia and hypernatremia in adults - UpToDate

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Manifestations of hyponatremia and hypernatremia in

adults
AUTHOR: Richard H Sterns, MD
SECTION EDITOR: Michael Emmett, MD
DEPUTY EDITOR: John P Forman, MD, MSc

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2024.

This topic last updated: Jan 23, 2024.

INTRODUCTION

Symptoms of hyponatremia or hypernatremia are primarily neurologic. They are related to

the severity and, in particular, the rapidity of the change in the serum sodium concentration
[1-3]. Patients with hyponatremia and hypernatremia may also have complaints related to
concurrent volume depletion and possible underlying neurologic diseases that predispose to
the electrolyte abnormality. These include a wide variety of neurologic disorders that can
lead sequentially to either the inappropriate secretion of antidiuretic hormone, water
retention, and hyponatremia, or to the lack of expression of thirst, which is normally the
major protective mechanism against the development of hypernatremia.

The cerebral adaptation and clinical manifestations of hyponatremia and hypernatremia will
be reviewed here. The etiology and treatment of hyponatremia and hypernatremia are
presented elsewhere:

● (See "Causes of hypotonic hyponatremia in adults".)

● (See "Overview of the treatment of hyponatremia in adults".)

● (See "Etiology and evaluation of hypernatremia in adults".)

● (See "Treatment of hypernatremia in adults".)

HYPONATREMIA
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The symptoms directly attributable to hyponatremia primarily occur with acute and marked
reductions in the serum sodium concentration and reflect neurologic dysfunction induced by
cerebral edema [1,2,4,5], and possibly adaptive responses of brain cells to osmotic swelling
[1]. In this setting, the associated fall in serum osmolality creates an osmolal gradient that
favors water movement into the cells, leading to brain edema.

The development of cerebral edema in hyponatremic patients is dependent upon the

transfer of water from plasma and cerebrospinal fluid into the brain. Insight into this process
is provided by studies in mice without the genes for aquaporin-4, a water channel expressed
at the interface between the brain and blood and between the brain and cerebrospinal fluid
[6]. Compared with wild-type mice, knockout mice exhibit considerably less brain edema,
morbidity, and mortality after the induction of acute hyponatremia, suggesting that
aquaporin-4 mediates a substantial portion of osmotic water transport into the brain.

Hyponatremia-induced cerebral edema occurs primarily with rapid reductions in the serum
sodium concentration, usually less than 24 hours [5], as most often occurs in postoperative
patients given large quantities of hypotonic fluid and in patients with self-induced water
intoxication due to primary polydipsia or exercise-associated hyponatremia. Hypoxic brain
injury also may contribute to the neurologic deficit if respiratory arrest has occurred [7]. (See
"Exercise-associated hyponatremia".)

Importance of hypoosmolality in symptom development — Hyponatremia is almost

always associated with hypoosmolality, and it is the fall in plasma osmolality that promotes
the movement of water into the cells and the possible development of cerebral edema. The
contribution of hyponatremia itself to the neurologic manifestations is uncertain. This is an
important issue, since there are a variety of settings in which hyponatremia is associated
with a normal or high measured serum osmolality. These disorders are discussed in detail
separately. (See "Causes of hypotonic hyponatremia in adults".)

Summarized briefly:

● In pseudohyponatremia, both the serum osmolality and the concentration of sodium

in plasma water are normal, and patients are asymptomatic. Such patients have either
hyperproteinemia or hyperlipidemia, which reduce the fraction of the plasma that is
water from the normal value of 93 percent (the remaining 7 percent is due to proteins
and lipids with a small contribution from dissolved solutes) to a lower value that can be
less than 80 percent. In such settings, the physiologically important sodium
concentration per liter of plasma water is normal, although the sodium concentration
per liter of plasma is reduced. The plasma osmolality is normal because osmometers
measure the activity of solutes in plasma water.

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● With moderate to advanced kidney function impairment or with ethanol

intoxication, hyponatremic patients may have a higher osmolality than that predicted
by their sodium concentration due to the contribution of urea or ethanol in the
extracellular fluid. However, urea and ethanol are ineffective osmoles since they can
freely cross cell membranes and therefore do not obligate water movement out of the
cells. Thus, the effective serum osmolality (measured osmolality minus the contribution
of urea or ethanol) in such patients is low. As a result, hyponatremic patients with
kidney failure or ethanol intoxication are as likely to develop symptoms at a given
serum sodium concentration as patients without these conditions. (See "Causes of
hypotonic hyponatremia in adults".)

● In patients with uncontrolled diabetes, the serum osmolality is typically elevated. In

contrast to urea, glucose is an effective osmole since it does not freely enter cells. The
increase in effective serum osmolality pulls water out of the cells and lowers the serum
sodium by dilution, an effect that may be at least partially reversed by the free water
loss resulting from the associated glucosuria-induced osmotic diuresis. The neurologic
symptoms in these patients are not generated by the hyponatremia since the effective
plasma osmolality is usually increased rather than reduced. (See "Diabetic ketoacidosis
and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and
diagnosis", section on 'Serum sodium' and "Diabetic ketoacidosis and hyperosmolar
hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on
'Neurologic symptoms'.)

● Isosmotic (or near isosmotic) non-sodium containing, nonconductive irrigation

solutions containing glycine, mannitol, or sorbitol may be used during transurethral
resection of the prostate or bladder, during hysteroscopy, or laparoscopic surgery. Only
a small quantity of this solution is usually absorbed systemically. However, large
amounts of the irrigant are occasionally infused by accident into veins or body cavities.
Severe hyponatremia due to dilution can result (serum sodium less than 110 mEq/L).
Severe neurologic symptoms can occur, but the cause varies, depending upon the
irrigant used. Absorption of sorbitol irrigants eventually results in hypotonic
hyponatremia as the sorbitol is metabolized. Most glycine irrigants are hypo-osmolar,
and absorption of large volumes of the irrigant results in a modest degree of hypotonic
hyponatremia; however, in addition to hyponatremia, glycine toxicity and the
accumulation of ammonia, serine, and/or glyoxylate from the metabolism of glycine
may contribute to neurologic manifestations. (See "Hyponatremia following
transurethral resection, hysteroscopy, or other procedures involving electrolyte-free
irrigation", section on 'Pathogenesis of neurologic symptoms'.)

Clinical manifestations of acute hyponatremia — The severity of symptoms in patients

with acute hyponatremia generally reflects the severity of cerebral overhydration, which is

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related to the degree of hyponatremia [2]. The major clinical manifestations of acute
hyponatremia include [1,2,7-11]:

● Nausea and malaise, which are the earliest findings, may be seen when the serum
sodium concentration falls below 125 to 130 mEq/L.

● Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest
can occur if the serum sodium concentration falls below 115 to 120 mEq/L.
Noncardiogenic pulmonary edema has also been described.

Acute hyponatremic encephalopathy may be reversible, but permanent neurologic damage

or death can occur, particularly in premenopausal females [7,10]. Overly rapid correction also
may be deleterious, particularly in patients with chronic hyponatremia. (See 'Susceptibility of
premenopausal females' below and 'Osmotic demyelination' below.)

Osmolytes and cerebral adaptation to hyponatremia — The degree of cerebral edema

and therefore the severity of neurologic symptoms are much less with chronic hyponatremia
[2,12,13]. This protective response, which begins on the first day and is complete within
several days, occurs in two major steps.

● The initial cerebral edema raises the interstitial hydraulic pressure, creating a gradient
for extracellular fluid movement out of the brain into the cerebrospinal fluid [14].

● The brain cells then lose solutes, leading to the osmotic movement of water out of the
cells and a decrease in brain swelling [4,5,12,14-18]. Brain cell potassium is lost rapidly
through normally quiescent cation channels in the cell membrane that are activated by
cell swelling. Subsequently, organic solutes (called organic osmolytes) are lost via
swelling-activated membrane channels that also transport chloride and other anions
[4,15]. Substantial depletion of brain organic osmolytes occurs within 24 hours, and
additional losses occur over two to three days owing to downregulation of the synthesis
and uptake of these solutes [4,5].

These processes are reversed with correction of the hyponatremia [4,5,18]. However, the
reuptake of brain solutes during correction occurs more slowly than the loss of brain solutes
during the onset of hyponatremia.

Organic osmolytes account for approximately one-third of the solute loss in chronic
hyponatremia ( figure 1) [17]. Reducing the intracellular content of these solutes has the
advantage of restoring cell volume without interfering with protein function. By comparison,
there would be a potentially deleterious effect on protein function if the volume adaptation
were mediated entirely by changes in the cell cation (potassium plus sodium) concentration.

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Studies in hyponatremic animals have shown that the major osmolytes lost from the brain
cells are the amino acids glutamine, glutamate, and taurine, and, to a lesser degree, the
carbohydrate myoinositol [5,16,17]. A study using proton NMR spectroscopy found a slightly
different pattern in humans with chronic hyponatremia; myoinositol and choline compounds
were the primary organic solutes lost, with a smaller change occurring in glutamine and
glutamate [18]. Myoinositol also appears to be the primary osmolyte taken up by the brain
as part of the protective response in patients with hypernatremia. (See 'Cerebral adaptation
to hypernatremia' below.)

Clinical manifestations of chronic hyponatremia — The cerebral adaptation permits

patients with chronic hyponatremia to appear to be asymptomatic despite a serum sodium
concentration below 120 mmol/L. When symptoms do occur in patients with serum sodium
concentrations at this level, they are relatively nonspecific [1,9,19-22]:

● Fatigue
● Nausea
● Dizziness
● Vomiting
● Gait disturbances
● Forgetfulness
● Confusion
● Lethargy
● Muscle cramps

Nausea and vomiting affect approximately one-third of patients with chronic hyponatremia
who have a serum sodium concentration <120 mmol/L [20-22]. Nausea and vomiting can be
ominous symptoms of life-threatening cerebral edema in patients with acute hyponatremia;
by contrast, in chronic hyponatremia, these symptoms are not associated with adverse
outcomes. Seizures and coma are uncommon and often reflect an acute exacerbation of the
hyponatremia. Symptomatic chronic hyponatremia is rarely, if ever, associated with cerebral
edema severe enough to cause herniation of the brain. In a series of 223 patients
hospitalized for symptomatic chronic hyponatremia due to thiazide diuretics, there was a 1
percent incidence of seizures and no cases of herniation [20]. (See "Diuretic-induced
hyponatremia".)

The older literature includes reports of brain damage in outpatients with thiazide-induced
hyponatremia [8]. However, at the time of the study, the consequences of overly rapid
correction were unknown. The reported patients were all treated with hypertonic saline,
increasing the serum sodium concentration by more than 25 mEq/L in 48 hours, a rate of
correction that is associated with osmotic demyelination. (See 'Osmotic demyelination'
below.)

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Subtle manifestations in mild to moderate chronic hyponatremia — Patients with

moderate chronic hyponatremia often appear asymptomatic but may have subtle neurologic
manifestations that can easily be missed. These manifestations may be consequences of the
brain's adaptations to hyponatremia that make survival possible [23]. The following
observations illustrate the range of findings:

● The SALT-1 and SALT-2 trials evaluated the efficacy of the oral vasopressin receptor
antagonist tolvaptan compared with placebo in patients with chronic hyponatremia;
none of the patients had clinically apparent neurologic symptoms at baseline and
almost all had a serum sodium concentration of 120 mEq/L or higher [24]. Gradually
raising the serum sodium with tolvaptan was associated with significant improvement
on the Mental Component of the Medical Outcomes Study Short-Form General Health
Survey at 30 days. This benefit was significant only in patients with a serum sodium
concentration between 120 and 129 mEq/L and was not seen with correction of mild
hyponatremia (130 to 134 mEq/L) or in the placebo group. (See "Overview of the
treatment of hyponatremia in adults", section on 'Vasopressin receptor antagonists'.)

● A case control study found that older adult patients (mean age 72 years) who presented
to an emergency department with falls were significantly more likely to have mild to
moderate hyponatremia (serum sodium concentration 120 to 130 mEq/L) than older
adult patients who did not experience falls [25]. Serial studies in the same patients
suggested improvement in gait when the serum sodium concentration was normal.

● In a case series of 23 older adults with moderate hyponatremia, correction of

hyponatremia (usually with urea) improved performance on tests of reaction time and
gait; the potential effect was significant among patients older than 65 years but not
among younger individuals [26].

● In a randomized crossover trial of 14 older adults with moderate hyponatremia (median

serum sodium 131 mEq/L), a rise in serum sodium concentration during treatment with
a sodium-glucose cotransporter 2 (SGLT2) inhibitor improved scoring on a
neurocognitive test (Montreal Cognitive Assessment) [27].

Mild to moderate hyponatremia may contribute to fractures in older adult patients [28,29]. In
addition to a higher risk of falls, patients with hyponatremia are more likely to have
osteoporosis than patients without hyponatremia [29]. The higher prevalence of
osteoporosis may be due at least in part to loss of bone sodium. (See "Osteoporotic fracture
risk assessment", section on 'Possible risk factors'.)

Hyponatremia, even if mild, is associated with increased mortality in both hospitalized and
ambulatory patients [30-35]. The reasons for this association have not been identified, but
they could reflect some of the adaptations of several organ systems to hyponatremia that

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allow them to function at low serum sodium concentrations [23]. Mortality risk in
hospitalized patients with hyponatremia is increased across virtually all clinical subgroups
and persists after hospital discharge, regardless of the underlying disease [35]. A meta-
analysis of 15 studies encompassing 13,816 hyponatremic patients found that an
improvement in the serum sodium concentration was associated with a decreased mortality
rate [36]. This finding likely resulted from simultaneous improvements in underlying
comorbidities, rather than a cause-effect relationship between serum sodium and mortality.

However, the association between serum sodium concentration and mortality in hospitalized
patients is nonlinear. Several studies have found that mortality risk increases as serum
sodium decreases to approximately 125 mEq/L; below 120 mEq/L, patients have lower rather
than higher mortality risk [37-39]. The explanation for this paradox may be that extremely
low serum sodium concentrations are most commonly drug induced, whereas mild to
moderate hyponatremia is more likely to be associated with a life-threatening underlying
disease (malignancy, oliguric kidney failure, heart failure, or hepatic cirrhosis) [37-39].
Similarly, drug-induced hyponatremia tends to resolve spontaneously when the drug is
discontinued, while hyponatremia associated with a severe underlying disease tends to
persist [38,39].

Hyponatremia, even if mild, is also associated with increased morbidity in hospitalized

patients. As an example, in the American College of Surgeons National Surgical Quality
Improvement Program (ACS NSQIP) database, the 75,423 patients with preoperative
hyponatremia (sodium level of <135 mEq/L) compared with 888,840 patients with
normonatremia had significantly higher perioperative 30-day mortality (5.2 versus 1.3
percent), major coronary events (1.8 versus 0.7 percent), wound infection (7.4 versus 4.6
percent), and pneumonia (3.7 versus 1.5 percent) [33].

Susceptibility of premenopausal females — Premenopausal females and young children

with acute postoperative hyponatremia may progress rapidly from minimal symptoms
(headache and nausea) to respiratory arrest [7,40]. Cerebral edema and herniation have
been found at autopsy, leading some authors to suggest a possible hormonally-mediated
decrease in the degree of osmotic adaptation [7,41]. The observation that prepubertal
children are at equal risk of symptomatic hyponatremia is compatible with the importance of
sex hormones in conferring susceptibility to adult females [42]. Other factors may play a role,
such as the size of the brain in relationship to the capacity of the cranial vault, and a more
rapid onset of hyponatremia because of smaller body size with less muscle to "buffer" the
excess water.

Osmotic demyelination — The adaptation that returns the brain volume toward normal in
chronic hyponatremia protects against the development of cerebral edema but also creates a
potential problem when the serum sodium is therapeutically or spontaneously corrected. In

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this setting, an overly rapid increase in the serum sodium concentration can lead to an
osmotic demyelination syndrome (also called central pontine myelinolysis, although
demyelination is often more diffuse and does not necessarily involve the pons). These
changes can lead to potentially severe neurologic symptoms that are usually delayed for two
to six days after correction and may be irreversible. Thus, patients with symptomatic
hyponatremia may initially demonstrate neurologic improvement with correction of the
serum sodium but then show late deterioration. This complication of treatment may be
reversed by relowering of the serum sodium ( figure 2). These issues are discussed in
detail elsewhere. (See "Osmotic demyelination syndrome (ODS) and overly rapid correction
of hyponatremia", section on 'Patients who have exceeded correction limits (rescue strategy)'
and "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia",
section on 'Pathogenesis of ODS'.)

HYPERNATREMIA

Hypernatremia is basically a mirror image of hyponatremia [1,2,4,5,43]. A rise in the serum

sodium concentration and osmolality causes water movement out of the brain.

Manifestations of acute hypernatremia — With acute hypernatremia (eg, after the

inadvertent infusion of hypertonic saline into a uterine vein during therapeutic abortion, or
the ingestion of large amounts of salt) the rapid decrease in brain volume can cause rupture
of the cerebral veins, leading to focal intracerebral and subarachnoid hemorrhages and
possibly irreversible neurologic damage [1,2,4,44]. Acute hypernatremia can also result in
demyelinating brain lesions similar to those associated with overly rapid correction of
chronic hyponatremia [45-50]. (See 'Osmotic demyelination' above.)

The clinical manifestations of acute hypernatremia begin with lethargy, weakness, and
irritability, and can progress to twitching, seizures, and coma. Severe symptoms usually
require an acute elevation in the serum sodium concentration to above 158 mEq/L. Values
above 180 mEq/L are associated with a high mortality rate, particularly in adults [51].

Cerebral adaptation to hypernatremia — Beginning on the first day, the initial reduction in
brain volume is largely reversed due both to water movement from the cerebrospinal fluid
into the brain (thereby increasing the interstitial volume) [5,52] and to the uptake of solutes
by the cells (thereby pulling water into the cells and restoring the cell volume) [5,53,54]. The
latter response involves an initial uptake of sodium and potassium salts, followed by the later
accumulation of osmolytes, which in animals consists primarily of myoinositol, the amino
acids glutamine, glutamate, and taurine [53-56]. Myoinositol and taurine are taken up from
the extracellular fluid via an increase in the number of sodium-myoinositol and sodium-
taurine cotransporters in the cell membrane [54-56]; the source of glutamine and glutamate
(uptake from the extracellular fluid or production within the cells) is unknown. The net effect
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is that these osmolytes, which do not interfere with protein function [18], account for
approximately 35 percent of the new cell solute [54].

A report of an infant with an initial serum sodium concentration of 195 mEq/L confirmed the
general applicability of these observations to humans [57]. The patient was first studied
using proton NMR spectroscopy on day four when the serum sodium concentration had
fallen to 156 mEq/L. At this time, there was a 17 mosmol/kg increase in brain osmolyte
concentration, due primarily to the accumulation of myoinositol. The excess brain osmolyte
concentration fell to 6 mosmol/kg on day 7 and was normal by day 36.

Manifestations of chronic hypernatremia — As in hyponatremia, the cerebral adaptation

in hypernatremia has two important clinical consequences:

● Chronic hypernatremia, which is defined as hypernatremia that has been present for
more than a day, is much less likely to induce neurologic symptoms. Assessment of
symptoms attributable to hypernatremia is often difficult because most affected adults
have underlying neurologic disease. The latter is required to diminish the protective
thirst mechanism that normally prevents the development of hypernatremia, even in
patients with arginine vasopressin disorders (formerly called diabetes insipidus). (See
"Etiology and evaluation of hypernatremia in adults".)

Like hyponatremia, hypernatremia, even if mild, is associated with increased morbidity

and mortality. A cohort study using the American College of Surgeons National Surgical
Quality Improvement Program (ACS NSQIP) compared 20,029 patients with
preoperative hypernatremia (>144 mmol/L) to 888,840 patients with a normal baseline
serum sodium (135 to 144 mmol/L) [58]. Preoperative hypernatremia was associated
with increased perioperative 30-day mortality (5.2 versus 1.3 percent), perioperative
major coronary events (1.6 versus 0.7 percent), pneumonia (3.4 versus 1.5 percent), and
venous thromboembolism (1.8 versus 0.9 percent).

In infants, correction of chronic hypernatremia must occur slowly to prevent rapid fluid
movement into the brain and cerebral edema, changes that can lead to seizures and
coma [59]. Although the brain cells can rapidly lose potassium and sodium in response
to cell swelling, the loss of accumulated osmolytes and the water they obligate occurs
more slowly [5,54]. The loss of myoinositol, for example, requires both a reduction in
the synthesis of new sodium-inositol cotransporters [55] and the activation of a specific
inositol efflux mechanism in the cell membrane [60]. The delayed clearance of
osmolytes from the cell can predispose to cerebral edema if the serum sodium
concentration is lowered too rapidly. As a result, the rate of correction in young children
with hypernatremia should be less than 10 to 12 mEq/L per day [61,62].

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Rapid correction of hypernatremia has not been shown to have adverse consequences
in adults [63-65], and fear of cerebral edema from overly rapid correction of
hypernatremia, which has only been reported in infants, should not deter vigorous
rehydration of adults with acute hypernatremia who are at risk of developing osmotic
demyelination or brain hemorrhage from untreated hypernatremia. Unlike
hyponatremia, there is little risk of inadvertent overcorrection in adults with
hypernatremia; such patients are often undertreated, and more rapid correction may
be beneficial [1,66,67]. As an example, in a retrospective study of 4265 adults with
serum sodium concentrations ≥155 mEq/L (most had chronic hypernatremia), patients
corrected by >0.5 mEq/L per hour had decreased 30-day mortality compared with those
corrected more slowly [65]. Although it is difficult to exclude confounding by
comorbidities, there was no evidence of harm from more rapid correction. These
findings support vigorous rehydration of adults with hypernatremia regardless of the
duration of the disturbance. (See "Treatment of hypernatremia in adults", section on
'Choosing a rate of correction'.)

SENSING OF CHANGES IN PLASMA OSMOLALITY

Although the mechanisms of protective solute loss in hyponatremia and solute uptake in
hypernatremia have been largely defined, the mechanisms by which the alterations in
plasma osmolality are sensed by the cells (particularly brain cells) and then lead to the
physiologically appropriate changes in solute content are not well understood. There is
preliminary evidence that hyperosmolality, perhaps via stress on the cytoskeleton as the cell
volume falls, activates a specific protein kinase [68]. This kinase, via protein phosphorylation,
may then lead to activation of transporters, such as the sodium-inositol cotransporter, that
promote solute uptake into the cells.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Hyponatremia" and
"Society guideline links: Fluid and electrolyte disorders in adults".)

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Here are the patient education articles that are relevant to this topic. We encourage you to
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● Basics topics (see "Patient education: Hyponatremia (The Basics)")

SUMMARY

Symptoms associated with hyponatremia or hypernatremia are primarily neurologic and

related to the severity and rapidity of the change in the serum sodium concentration. Such
symptoms must be distinguished from those of concurrent volume depletion and possible
underlying neurologic diseases that may predispose to the electrolyte abnormality. (See
'Introduction' above.)

● Hyponatremia: Clinical manifestations

• Symptoms directly attributable to hyponatremia reflect neurologic dysfunction

induced by cerebral edema. Cerebral edema is due to a decrease in serum
osmolality which causes water movement into cells.

• Clinical manifestations of acute hyponatremia reflect the severity of cerebral

overhydration. Nausea and malaise are the earliest findings, and may be seen at a
serum sodium concentration below 125 to 130 mEq/L. Headache, lethargy,
obtundation and eventually seizures, coma, and respiratory arrest may occur if the
serum sodium concentration falls below 115 to 120 mEq/L. Hyponatremic
encephalopathy may be reversible or permanent. Premenopausal females appear to
be at greater risk for severe hyponatremic symptoms and for residual neurologic
injury. (See 'Clinical manifestations of acute hyponatremia' above and 'Susceptibility
of premenopausal females' above.)

• Because of the cerebral adaptation, neurologic symptoms are much less severe with
chronic hyponatremia. Patients with chronic hyponatremia may appear to be
asymptomatic despite a serum sodium concentration that is persistently below 120
mEq/L. Symptoms that do occur include fatigue, nausea, dizziness, gait
disturbances, forgetfulness, confusion, lethargy, and muscle cramps. Seizures and
coma are uncommon and often reflect an acute exacerbation of the hyponatremia.

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(See 'Osmolytes and cerebral adaptation to hyponatremia' above and 'Clinical

manifestations of chronic hyponatremia' above.)

• Neurologic manifestations resulting from chronic hyponatremia, including gait

disturbance and attention deficits, may result in increased falls among older adult
patients. Even mild hyponatremia is associated with increased mortality, although
the hyponatremia may just be a marker for more severe underlying disease. (See
'Subtle manifestations in mild to moderate chronic hyponatremia' above.)

• An overly rapid increase in the serum sodium concentration can lead to osmotic
demyelination syndrome (also called central pontine myelinolysis) resulting in
severe and potentially irreversible neurologic symptoms. (See 'Osmotic
demyelination' above and "Osmotic demyelination syndrome (ODS) and overly rapid
correction of hyponatremia", section on 'Pathogenesis of ODS'.)

● Hypernatremia: Clinical manifestations

• Hypernatremia causes water movement out of the brain resulting in a decrease in

brain volume that, if acute, can cause focal intracerebral and subarachnoid
hemorrhages, demyelinating brain lesions, and irreversible neurologic damage. (See
'Manifestations of acute hypernatremia' above.)

• Hypernatremic patients who become symptomatic present with lethargy, weakness,

and irritability, and may develop twitching, seizures, and coma. Severe symptoms
usually require an acute elevation in the serum sodium concentration to above 158
mEq/L. Values above 180 mEq/L are associated with a high mortality rate,
particularly in adults. (See 'Manifestations of acute hypernatremia' above.)

• Because of the cerebral adaptation, chronic hypernatremia is less likely to induce

neurologic symptoms. The correction of chronic hypernatremia must occur slowly to
prevent rapid fluid movement into the brain and cerebral edema. The rate of
correction in asymptomatic patients should not exceed 12 mEq/L per day, which
represents an average of 0.5 mEq/L per hour. (See 'Cerebral adaptation to
hypernatremia' above and "Treatment of hypernatremia in adults", section on
'Choosing a rate of correction'.)

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Topic 2287 Version 21.0

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GRAPHICS

Cerebral osmotic adaptation to severe hyponatremia

Changes in brain water, sodium-plus-potassium (Na + K) content, and three organic solutes – inositol,
glutamine, and taurine – two and seven days after the onset of severe hyponatremia (plasma sodium
concentration of less than 110 meq/L). The numbers at the bottom represent the baseline values. The
return of brain water toward normal at day 7 is due to loss of sodium, potassium, and the organic
solutes (called osmolytes). Although the absolute osmolyte loss is less than that of sodium plus
potassium, the fractional loss is much greater – 36 of 60 or 60 percent versus 60 of 670 or less than 10
percent. Preferential osmolyte loss has the added advantage of not interfering with protein function
within the cells.

Data from Verbalis, JG, Gullans, SR, Brain Res 1991; 567:274.

Graphic 71152 Version 3.0

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Delayed appearance of osmotic demyelination and relowering of the serum

sodium

Neurologic symptoms of osmotic demyelination syndrome (ODS) typically occur 2 to 6 days after
correction of the hyponatremia. In this patient, severe hyponatremia was corrected too quickly (23
mEq/L in 48 hours), and coma developed 2 days later. The serum sodium was quickly relowered and
then slowly corrected. Neurologic symptoms improved, which may have been due to relowering of the
serum sodium or may have represented spontaneous resolution.

sNa: serum sodium.

Reproduced with permission from: Oya S, Tsutsumi K, Ueki K, Kirino T. Reinduction of hyponatremia to treat central pontine
myelinolysis. Neurology 2001; 57:1931. Copyright © 2001 Lippincott Williams & Wilkins.

Graphic 76131 Version 16.0

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Contributor Disclosures
Richard H Sterns, MD No relevant financial relationship(s) with ineligible companies to
disclose. Michael Emmett, MD No relevant financial relationship(s) with ineligible companies to
disclose. John P Forman, MD, MSc No relevant financial relationship(s) with ineligible companies to
disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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