HYPO NATREMIA

CAUSES,DIAGNOSIS,AND MANAGEMENT
BY A H M E D A B D E L G E L I L , M D
DEFINITION

Hyponatremia is commonly defined as a serum sodium concentration

below 135 meq/L.This is usually accompanied by a proportional fall in
serum osmolality (to a level below 275 mosmol/kg)
hyponatremia results from the intake (either oral or intravenous) and
subsequent retention of water.A water load will, in normal individuals, be
rapidly excreted as the dilutional fall in serum osmolality suppresses the
release of antidiuretic hormone (ADH), also called vasopressin, thereby
allowing excretion of the excess water in a dilute urine,However,patients
who develop hyponatremia typically have an impairment in renal water
excretion, most often due to an inability to suppress ADH secretion. An
uncommon exception occurs in patients with primary polydipsia who can
become hyponatremic because they drink such large quantities of fluid that
they overwhelm the excretory capacity of the kidney even though ADH
 Incidence:
Most common electrolyte disorder seen in the general hospital population.
Geriatric Considerations:
The elderly have lower total body water, a decreased thirst mechanism, and
decreased urinary concentrating ability; their kidneys are less responsive to
antidiuretic hormone (ADH), and they show decreased renal mass, renal
blood flow, and glomerular filtration rate, making them at higher risk for
hyponatremia.
Low sodium creates an osmotic gradient between plasma and cells and fluid
shifts into cells, causing edema and increased intracranial pressure.
Physical Exam:
Volume status: Skin turgor, jugular venous pressure, heart rate, orthostatic BP
Exam for underlying illness: Signs of CHF, cirrhosis, hypothyroidism
WORK UP
Initial Tests (lab, imaging)
Comprehensive metabolic profile (BUN, creatinine (Cr), glucose,
electrolytes, liver function studies, etc.)
Thyroid-stimulating hormone (TSH)
Lipid panel
Serum osmolality
Urine sodium and osmolality
CT scan of head if pituitary problem suspected or if SIADH from CNS
problem suspected
Chest x-ray to rule out pulmonary pathology if SIADH diagnosed
WORK UP CONTINUED
Hypovolemic hyponatremia:
Plasma osmolality low
BUN:Cr ratio >20:1
If urine sodium >20 mEq/L (>20 mmol/L): Renal loss
If urine sodium <10 mEq/L (<10 mmol/L): Extrarenal loss
Serum potassium >5 mEq/L (>5 mmol/L): Consider mineralocorticoid
deficiency.
Euvolemic hyponatremia:
Plasma osmolality low
BUN:Cr ratio <20:1
Urine sodium >20 mEq/L (>20 mmol/L)
TSH test to rule out hypothyroidism
1-hour cosyntropin-stimulation test to rule out adrenal insufficiency
WORK OUT CONTINUED
Hypervolemic hyponatremia:
Plasma osmolality low
Urine sodium <10 mEq/L (<10 mmol/L) in nephrotic syndrome, CHF,
cirrhosis
Urine sodium >20 mEq/L (>20 mmol/L) in acute and chronic renal failure
Redistributive hyponatremia:
Plasma osmolality normal or high
Glucose or mannitol levels elevated
Pseudohyponatremia:
Plasma osmolality normal
Triglyceride, glucose, or protein levels elevated
ADMISSION CRITERIA

Admission is mandatory if the patient has acute hyponatremia or is

symptomatic; acute hyponatremia (developing over <48 hours) carries the
risk of cerebral edema.
Admission is advised if patient is asymptomatic and has a serum sodium
<125 mEq/dL.
ASSOCIATIONS
Associated Conditions:
Hypothyroidism
Hypopituitarism
Adrenocortical hormone deficiency
HIV patients
SIADH is associated with cancers, pneumonia, tuberculosis, encephalitis,
meningitis, head trauma, cerebrovascular accident, HIV infection.
Acute neurological patients, brain injury
Marathon runners in hot environments
CAUSES AND CLASSIFICATION

two classification systems used for the etiology of hyponatremia with a low
serum osmolality: one stratifies patients according to whether circulating
antidiuretic hormone (ADH) levels are inappropriately elevated or
appropriately suppressed, and the other stratifies patients according to
volume status (hypovolemia, normovolemia, or hypervolemia)
A)According to serum ADH levelsUrinary excretion of a water load
requires the suppression of ADH release, which is mediated by the
reduction in serum osmolality. An inability to suppress ADH release is the
most common cause of hyponatremia:1-True volume depletion, which can
be due to gastrointestinal losses (eg, vomiting or diarrhea) or renal losses
(most often thiazide rather than loop diuretics).2-Decreased tissue
perfusion (also called effective arterial volume depletion) due to reduced
cardiac output in heart failure or to systemic vasodilation in cirrhosis.3-A
CAUSES AND CLASSIFICATION
CONTINUED
B)According to volume status:1-Hypovolemia due to gastrointestinal
losses (eg, vomiting or diarrhea) or renal losses (most often thiazide rather
than loop diuretics).2-Normovolemia, which is most often associated with
the SIADH but can also be seen with primary polydipsia and a low dietary
solute intake.3-Hypervolemia due to heart failure or cirrhosis
Serum osmolarity equation :Sosm (mmol/kg) = (2 x serum [Na]) +
(serum [glucose]/18) + (blood urea nitrogen/2.8)
The two most common causes of hyponatremia with a low serum osmolality
are effective arterial blood volume depletion and the syndrome of
inappropriate antidiuretic hormone (ADH) secretion, both of which are
associated with persistent ADH release.
CAUSES AND CLASSIFICATION
CONTINUED
Effective arterial blood volume depletion can occur by two mechanisms:
true volume depletion; and edematous patients with heart failure or
cirrhosis in whom tissue perfusion is reduced because of a low cardiac
output or arterial vasodilation, respectively. The reduction in tissue
perfusion is sensed by baroreceptors at three sites: in the carotid sinus and
aortic arch that regulate sympathetic activity and, with significant volume
depletion, the release of antidiuretic hormone; in the glomerular afferent
arterioles that regulate the activity of the renin-angiotensin system; and in
the atria and ventricles that regulate the release of natriuretic
peptides.decreased tissue perfusion is a potent stimulus to the secretion of
ADH.This response is mediated by baroreceptors in the carotid sinus, which
sense a reduction in pressure or stretch, and can overcome the inhibitory
effect of hyponatremia on ADH secretion. Thus, water retention and
 CAUSES AND CLASSIFICATION
CONTINUED
HYPONATREMIA WITH A HIGH Serum osmolarity :1-advanced renal
failure, the associated elevation in blood urea nitrogen can counteract the
fall in serum osmolality induced by hyponatremia. However, the effective
serum osmolality is reduced in proportion to the hyponatremia in this
setting since urea is an ineffective:Corrected Sosm = Measured Sosm -
(BUN 2.8).
2-marked hyperglycemia in patients with diabetic ketoacidosis or
hyperosmolar hyperglycemic state (also known as nonketotic
hyperglycemia).
CAUSES AND CLASSIFICATION
CONTINUED
Hyponatremia with normal serum osmolarity:1-Nonconductive irrigation
solutionsIsosmotic hyponatremia can be produced by the addition of an
isosmotic (or near isosmotic) but non-sodium-containing fluid to the
extracellular space. This problem primarily results from the absorption of
variable quantities of nonconductive glycine or sorbitol irrigation solutions
during transurethral resection of the prostate or bladder or during
hysteroscopy or laparoscopic surgery.These patients may develop marked
hyponatremia (below 110 meq/L) and neurologic symptoms.
2-Pseudohyponatremia which is associated with a normal serum
osmolality, refers to those disorders in which marked elevations in serum
lipids or proteins result in a reduction in the fraction of serum that is water
and an artificially low serum sodium concentration
EVALUATION AND MANAGEMENT

diagnosis of hyponatremia is based upon a combination of findings on

history, physical examination, appropriate laboratory tests, and, in selected
patients, assessing the response to volume expansion with isotonic saline.
The history and physical examination in hyponatremic patients should be
directed toward identification of findings that are typical of the particular
causes of hyponatremia and assessment of volume status .These include a
history of fluid loss with associated clinical findings, an edematous state
such as heart failure or cirrhosis, or a cause of the syndrome of
inappropriate antidiuretic hormone (ADH) secretion.
six laboratory tests: chemistry panel, serum osmolality, urine osmolality,
and urine sodium, potassium, and chloride concentrations.
hypokalemia and metabolic acidosis favor diarrhea or laxative abuse as the
EVALUATION AND MANAGEMENT

A Uosm less than 100 mosmol/kg indicates appropriate suppression of ADH

may be due to primary polydipsia.
The urine sodium concentration is used to help distinguish between
effective volume depletion and other causes of hyponatremia in which
normovolemia is present. The urine sodium should be less than 25 meq/L
with hypovolemia unless there is salt wasting due, for example, to diuretic
therapy. By comparison, the urine sodium is generally above 40 meq/L in
the SIADH.
The urine chloride rather than the urine sodium is used to identify volume
depletion in patients with metabolic alkalosis due to gastric fluid losses.
hypovolemic hyponatremic patients who have metabolic alkalosis caused
by vomiting, the urine sodium concentration may be greater than 25 meq/L,
EVALUATION AND MANAGEMENT
initial therapy in patients with hyponatremia depends upon the duration of
the hyponatremia, the severity of the hyponatremia, and whether or not
patients are symptomatic.
Acute or hyperacute hyponatremia If it is known, or if it can be presumed,
that the hyponatremia developed within the previous 24 hours, it is called
"acute." If the hyponatremia developed over just a few hours due to a
marked increase in water intake (self-induced water intoxication, as may be
seen in marathon runners, psychotic patients, and users of ecstasy), it is
called "hyperacute.
hronic hyponatremia If it is known that the hyponatremia has been
present for more than 48 hours, or if the duration is unknown (such as in
patients who develop hyponatremia at home), it is called "chronic." If the
hyponatremia is known to have developed within the previous 24 to 48
hours, it is called "subacute.
EVALUATION AND MANAGEMENT

Mild hyponatremia is usually defined as a serum sodium concentration

between 130 and 135 meq/L; moderate hyponatremia is often defined as a
serum sodium concentration between 121 and 129 meq/L.Severe
hyponatremia can be defined as a serum sodium of 120 meq/L or less.
Absent symptoms Patients with hyponatremia are frequently
asymptomatic, particularly if the hyponatremia is chronic and of mild or
moderate severity (ie, serum sodium >120 meq/L). However, such patients
may have subclinical impairments in mentation and gait.Mild to moderate
symptoms Mild to moderate symptoms of hyponatremia are relatively
nonspecific and include headache, nausea, vomiting, fatigue, gait
disturbances, and confusion. In patients with chronic hyponatremia (ie, >48
hours duration), these findings are not associated with impending
herniation; however, in patients with more acute hyponatremia, such
EVALUATION AND MANAGEMENT
Severe symptoms include seizures, obtundation, coma, and respiratory
arrest.
Patients with acute or hyperacute hyponatremia, most patients with severe
hyponatremia, and many symptomatic patients with moderate
hyponatremia should be treated in the hospital. In contrast, patients with
mild hyponatremia and asymptomatic patients with moderate
hyponatremia usually do not require hospitalization.
Emergent therapy :the following hyponatremic patients, with hypertonic
saline to raise the serum sodium to goal as soon as possible (over several
hours), rather than using other therapies:1-Patients with severe symptoms
due to hyponatremia, such as seizures or obtundation.2-Patients with acute
hyponatremia who have symptoms due to hyponatremia, even if such
symptoms are mild.3-Patients with hyperacute hyponatremia due to self-
induced water intoxication, even if there are no symptoms at the time of
initial evaluation.4-Symptomatic patients who have either acute
postoperative hyponatremia or hyponatremia associated with intracranial
EVALUATION AND MANAGEMENT
.Nonemergent therapy Other hyponatremic patients do not require
emergent therapy, although we usually treat the following patient
subgroups initially in the hospital rather than in the ambulatory setting:1-
Asymptomatic patients with acute or subacute hyponatremia. In such
patients, we suggest initial treatment with hypertonic saline rather than
other therapies to raise the serum sodium.2-Patients with severe
hyponatremia (ie, serum sodium 120 meq/L) who have either absent or
mild to moderate symptoms.Initial treatment with hypertonic saline rather
than other therapies to raise the serum sodium.3-Patients with moderate
hyponatremia who have mild to moderate symptoms. In such patients,
initial therapy depends in large part upon the underlying etiology.
In all hyponatremic patients, therapy should also be directed at the
underlying disease (eg, saline infusion in hypovolemic patients,
glucocorticoids in patients with adrenal insufficiency)
EVALUATION AND MANAGEMENT
.In hyponatremic patients who are treated to increase the serum sodium, we
recommend that the serum sodium initially be increased by 4 to 6 meq/L
during the first 24 hours and by less than 9 meq/L over any given 24-hour
period. This rate of correction can be repeated until the sodium is normal or
near normal. In patients who require emergent therapy, the goal of a 4 to 6
meq/L increase should be achieved quickly, over six hours or less; thereafter,
the serum sodium can be maintained at a constant level for the remainder of
the 24-hour period to avoid overly rapid correction. In patients who require
nonemergent therapy, this goal can be achieved slowly.
.Patients receiving emergent therapy should have their serum sodium
measured every two hours to ensure that it has increased at the desired rate.
Other patients who are treated for chronic hyponatremia in the hospital
should have their serum sodium measured often enough to ensure an
appropriate rate of correction and to allow the clinician to react quickly to
impending overly rapid correction (eg, every four hours). The urine output
EVALUATION AND MANAGEMENT
Goal of emergent therapy The goal of emergent therapy is to rapidly
increase the serum sodium by 4 to 6 meq/L over a period of several hours.
However, the increase in serum sodium should not exceed 8 meq/L in any
given 24-hour period. Raising the serum sodium by 4 to 6 meq/L should
generally alleviate symptoms and prevent herniation. Goal of nonemergent
therapy The goal of nonemergent therapy is to slowly raise the serum
sodium and alleviate symptoms. In general, raising the serum sodium by 4 to
6 meq/L should improve a patient's symptoms. The increase in serum sodium
should not exceed 8 meq/L in any given 24-hour period. The long-term goal is
to slowly bring the serum sodium to the normal or near-normal range.
Most cases of osmotic demyelination syndrome have occurred in patients
with severe hyponatremia whose serum sodium concentration was raised
by more than 10 to 12 meq/L within 24 hours or more than 18 meq/L within
48 hours. Patients at highest risk for osmotic demyelination are those with
serum sodium concentrations of 105 meq/L and those with hypokalemia,
alcoholism, malnutrition, and liver disease.
EVALUATION AND MANAGEMENT
Risk of herniation:Fatal herniation is the most dreaded complication of
hyponatremia. Herniation has been reported almost exclusively in the
following settings:Women and children with acute postoperative
hyponatremia,Patients with hyperacute hyponatremia caused by massive
water ingestion associated with psychosis, marathon running, or use of the
recreational drug, ecstasy,Hyponatremic patients with intracranial
pathology.
Risk of seizure: Convulsions are more likely to occur in patients with an
underlying seizure disorder and in patients who are withdrawing from
alcohol. Active seizures associated with hyponatremia can be treated
successfully with a 4 to 6 meq/L increase in the serum sodium
concentration.Seizures are common in patients with a rapid onset of
hyponatremia, and they are relatively uncommon in patients with chronic
hyponatremia, even those with very low serum sodium concentrations.
When hypertonic saline is not requiredWe do not typically use
EVALUATION AND MANAGEMENT
Fluid restriction in most patients:Fluid restriction to below the level of
urine output is indicated for the treatment of symptomatic or severe
hyponatremia in edematous states (such as heart failure and cirrhosis),
SIADH, and advanced renal impairment. Restriction to 50 to 60 percent of
daily fluid requirements may be required to achieve the goal of inducing
negative water balance .In general, fluid intake should be less than 800
mL/day.Fluid restriction is also warranted in hyponatremic patients with
primary polydipsia in whom increased fluid intake is the primary problem.
Loop diuretics when the urine cation concentration is
highConcurrent use of a loop diuretic may be beneficial in patients with
SIADH who have a urine to serum cation ratio greater than 1. By inhibiting
sodium chloride reabsorption in the thick ascending limb of the loop of
Henle, furosemide interferes with the countercurrent mechanism and
induces a state of ADH resistance, resulting in the excretion of a less-
concentrated urine and increased water loss. Oral salt tablets in
patients with SIADHPatients with syndrome of inappropriate
EVALUATION AND MANAGEMENT
Isotonic saline in true volume depletionIn states of true volume
depletion (eg, diarrhea, vomiting, diuretic therapy), the administered
sodium and water will initially be retained. In this setting, isotonic saline
corrects the hyponatremia by two mechanisms:It slowly raises the serum
sodium by approximately 1 meq/L for every liter of fluid infused since
isotonic saline has a higher sodium concentration (154 meq/L) than the
hyponatremic plasma.By correcting the hypovolemia, it removes the
stimulus to ADH release, thereby allowing the excess water to be excreted
in a dilute urine. At this time, the serum sodium concentration may return
rapidly toward normal; in some patients, overly rapid correction of
hyponatremia can lead to the severe neurologic disorder, osmotic
demyelination
isotonic saline in hypovolemic patientsIsotonic saline has a limited
role in the management of hyponatremia. It is primarily used to correct
hyponatremia in patients with minimal or no symptoms and serum sodium
concentrations of >120 meq/L who are at low risk of complications from
EVALUATION AND MANAGEMENT

Do not use isotonic saline in edematous patientsor in SIADH

PROGNOSIS
In hospitalized patients, hyponatremia is associated with an elevated risk of
adverse clinical outcomes and higher mortality.
Recently, in community-dwelling, middle-aged, and elderly adults, mild
hyponatremia has been shown to be an independent predictor of death.
Associated with poor prognosis in patients with acute pulmonary embolism
Associated with poor prognosis in patients with liver cirrhosis and those
waiting for liver transplant; it is associated with significant postop risk and
short-term graft loss.
COMPLICATIONS
Occult tumor may present with SIADH.
Hypervolemia if saline used
Osmotic demyelination (central pontine and extrapontine irreversible
myelinolysis) (6).
Hyponatremia is the cause in 30% new-onset seizures in intensive care
settings.
Chronic hyponatremia is associated with increased odds of osteoporosis.
THANK YOU