HYPONATREMIA

BY:
DR. SAMMON K TAREEN
 DEFINITION

• Hyponatremia is defined as a plasma Na+ concentration

<135mEq/L ( 135 mmol/L)

• Common in upto 22% of hospitalised patients

 SUBCLASSIFICATION

Mild 130-134 mEq/L

Moderate 124-129 mEq/L

Severe Below 125 mEq/L

ETIOLOGY
 A. ISOTONIC HYPONATREMIA

• Pseudohyponatremia
• Serum osmolality normal ( 280-295 mOsm/kg )
• Laboratory artifact that can cause Na+ concentration to underestimated in the
setting of an abnormally elevated percentage of serum, that is solid rather than
liquid, such as with hyperlipidemia or hyperproteinemia

• Treatment :
Pseudohyponatremia from hypertriglyceridemia or hyperproteinemia requires no
therapy directed toward the hyponatremia except confirmation with the clinical
laboratory
 B. HYPERTONIC HYPONATREMIA

• Translocational hyponatremia
• Occurs when a large amount of a substance that cannot easily cross the cell
membrane is added to the ECF
• This change in tonicity pulls the water into the ECF and dilutes the Na+ concentration
• Serum osmolality High ( >295 mOsm/kg )
• Eg., Hyperglycemia and iatrogenic Mannitol

• Not a disorder of Na+ and water, rather it is water redistributing in response to

change in tonicity
• Hypertonic hyponatremia from Hyperglycemia: experts advocate a single correction
factor, serum Na+ decreases by 1.6mEq/L for every 100 mg/dL rise in plasma glucose
• some recommend factors as high as 2.4 mEq/L per 100 mg/dL
 Treatment :

• Translocational hyponatremia from glucose or mannitol can be

managed; with hyperglycemia treatment or mannitol discontinuation
• Rapid reduction in serum osmolality associated with correction of
substantial hyperglycemia may cause cerebral edema and many
authors recommend that this potential complication be considered
when selecting fluids for treatment of severe hyperglycemia
 C. HYPOTONIC HYPONATREMIA

• indicates that water intake exceeds the excretional capacity of the kidney.
• Due to either appropriate or inappropriate ADH secretion
• the pituitary gland secretes ADH when the osmolality increases or there is
substantially low effective arterial blood volume
• promotes water reabsorption in the distal nephron, thus minimizing urinary water
losses

• Clinically, volume status is a useful way to categorize hypotonic hyponatremia

1. Hypovolemic hypotonic hyponatremia
2. Euvolemic hypotonic hyponatremia
3. Hypervolemic hypotonic hyponatremia
• Treatment : Mild to moderate hypotonic hyponatremia is generally treated
according to the presumed etiology
• Regardless of etiology, experts generally recommend correction rates for chronic
hypotonic hyponatremia of 4–6 mEq/L/24 h and no more than 6–8 mEq/L/24 h
• Slow correction in chronic hyponatremia is intended to avoid rapid shifts that may
lead to osmotic demyelination syndrome
• Acute hyponatremia, for example postoperative hyponatremia, can be corrected
quickly.
• Symptomatic and severe hypotonic hyponatremia are discussed separately below
 1. HYPOVOLEMIC

• renal or extrarenal volume loss

• Total body sodium and body water are decreased
• to maintain intravascular volume, the pituitary increases ADH secretion, causing
free water retention from the hypotonic fluid replacement.
• In short, losses of water and salt are replaced, at least in part, by water alone
• Urine Na+ be a clue as to whether volume losses are more likely renal (UNa
greater than 20 mEq/L) OR extrarenal (UNa below 10 mEq/L), though urinary
sodium excretion also depends on sodium and fluid intake
• Renal causes : Diuretics, nephropathies, mineralocorticoid deficiency, cerebral
salt wasting syndrome
• Extrarenal : GI losses, skin losses and third spacing
• Treatment :

• Hypovolemic hyponatremic patients require adequate fluid resuscitation,

usually with isotonic fluid, to suppress the hypovolemic stimulus for ADH release
• Diuretics should be withheld in hypovolemic patients and the underlying etiology
of volume depletion addressed
 2. HYPERVOLEMIC

• occurs - cirrhosis, heart failure, nephrotic syndrome, and advanced kidney

disease
• in cirrhosis and heart failure, effective arterial blood volume is decreased due to
peripheral vasodilation or decreased cardiac output
• Increased ADH secretion, secondary to low effective arterial blood volume,
results in water retention
• Note the pathophysiologic similarity to hypovolemic hyponatremia: The body
sacrifices osmolality in an attempt to restore effective arterial blood volume
• Treatment :

• Hypotonic hypervolemic hyponatremic patients generally require loop

diuretics to correct increased total body water and sodium; patients with
hypotonic hypervolemic hyponatremia and severe acute or chronic kidney injury
generally require dialysis
• V2 receptor antagonists (such as tolvaptan) may be helpful for severe
hypervolemic hyponatremia from heart failure but are contraindicated in
cirrhosis.
• V2 receptor antagonists can only be safely initiated in the hospital, with careful
attention to urinary output and serum sodium to avoid rapid overcorrection
 3. EUVOLEMIC

• Diseases in this category are often divided into those with a high urine osmolality and those
with a low urine osmolality
• A : Uosm >100 mOsm/kg usually >300 mOsm/kg
• SIADH
• Hypothyroidism
• Glucocorticoid deficiency

• B : Uosm <100 mOsm/kg

• Psychogenic polydipsia
• Low solute diet

• C : Variable Uosm
• Reset osmostat
A : UOSM >100 MOSM/KG USUALLY >300
MOSM/KG
 SIADH

• common cause of euvolemic hypotonic hyponatremia, particularly among hospitalized

patients
• ADH is generally secreted in response to hyperosmolality or very low effective arterial
blood volume, but many conditions and medications can lead to ADH secretion in the
absence of these physiologic stimuli (ie, ADH secretion is inappropriate)
• In SIADH, there is a nonphysiologic ADH secretion, which means that water is
inappropriately retained leading to relatively concentrated urine (urine osmolality is usually
greater than 300 mOsm/kg).
• Urinary solute handling remains preserved; thus, urine sodium is generally not low (UNa
greater than 20 mEq/L), although it will depend on dietary ingestion of sodium
• Conditions associated with SIADH include CNS disorders, pulmonary disorders, and
malignancies
• Some common symptoms, such as pain and nausea, stimulate ADH release

• SIADH is a clinical diagnosis. Classically, it is characterized by

1. Hypotonic hyponatremia
2. absence of heart, kidney, or liver disease
3. normal thyroid and adrenal function
4. urine sodium usually over 20 mEq/L
European guidelines for the treatment of syndrome of inappropriate antidiuresis include the
following recommendations for management of moderate or profound hyponatremia  [29] :
1. Restrict fluid intake as first-line treatment
2. Second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day of urea or a
combination of low-dose loop diuretics and oral sodium chloride
3. Use of lithium, demeclocycline, or vasopressin receptor antagonists is not recommended

• Patients with symptomatic or severe hyponatremia (or both) generally require hospitalization
for careful monitoring of fluid balance and weight, treatment, and frequent sodium checks.
• Inciting medications should be discontinued if possible
• In acute symptomatic hyponatremia and chronic hyponatremia with severe symptoms (such as
seizure), patients can be given 100 mLof 3% hypertonic saline infused over 10 minutes (repeated
twice as necessary) aiming to immediately reverse symptoms
• Generally, the 24-hour correction goal rate of 4–6 mEq/L(for chronic hyponatremia) is still
recommended, so after a brief period of rapid correction, no further correction may be needed
until the next day.
• Chronic hyponatremic patients, at high risk for demyelination, who are corrected too rapidly, are
candidates for treatment with a combination of desmopressin (DDAVP) and intravenous dextrose 5% to
re-lower the serum sodium in consultation with nephrology

• In severe chronic euvolemic hypotonic hyponatremia that is symptomatic or not responsive to fluid
restriction, but without seizure or other immediately life-threatening symptoms, the clinician can
deliver 3% hypertonic saline at a slow rate, adjusting in real time, to achieve a correction rate of 4–6
mEq/L/24 h. This approach is generally used for SIADH, since the other etiologies of hypovolemic and
euvolemic hypotonic hyponatremia are usually responsive to treatments directed at the underlying
etiology

• Acute hypernatremia can be corrected more quickly because there is much less concern for osmotic
demyelination syndrome

• Hypertonic saline is generally avoided in hypervolemic hyponatremia in the absence of critical

symptomatic hyponatremia out of concern for worsening volume overload
 The most recent United States hyponatremia treatment guidelines from 2013 recommend that :
• 3% hypertonic saline be given at an initial rate of 0.5–2 mL/kg/h without further calculation of an
infusion rate
• There should then be frequent monitoring of serum sodium to avoid overcorrection, which is less
likely to occur if the initial rate of infusion is with the lower end of the recommended range
• Regardless of the strategy used, close monitoring of serum sodium (initially every 1–2 hours) and
urine output is strongly recommended with titration of the 3% hypertonic saline infusion rate to
achieve the goal correction rate
• A high urinary output may be the first sign that ADH secretion has stopped and the patient is at
even higher risk of overcorrection
• Some experts add DDAVP to reduce the risk of overcorrection
• Nephrology consultation is indicated for all patients with severe hyponatremia, since there are
several approaches to treatment, minimal data to support therapy, and a high risk of overcorrection
• Vaptans impair ADH action by inhibiting the vasopressin type-2 ( V2 )- receptors in the collecting
duct, thereby inducing water diuresis. V2 receptors antagonist can also be considered when Na=
levels below 125 mEq/L or milder hyponatremia that is symptomatic and resistant to fluid restriction
 HORMONAL ABNORMALITIES

• Severe hypothyroidism and glucocorticoid insufficiency can cause hyponatremia

that cannot be differentiated from SIADH by urine or serum electrolytes alone.
These disorders can generally be identified by testing hormone levels.
B : UOSM <100 MOSM/KG
 PSYCHOGENIC POLYDIPSIA AND LOW SOLUTE DIET

• Marked free water intake relative to solute intake produces hyponatremia

• Among euvolemic people who have normal serum osmolality, solute and water
excretion approximate solute and water intake.
• The maximal urine dilution in healthy adults is about 50 mOsm/kg. Because even
maximally dilute urine has an obligate solute concentration, there is a maximal amount
of water a healthy person can drink before becoming hyponatremic, even if ADH is
appropriately suppressed. This maximal amount of water depends on the solute intake
(the more solute that is taken in, the more water that can be ingested and excreted
successfully).
• In psychogenic polydipsia, patients generally ingest a normal amount of solute and
have normal kidney function. However, when water intake exceeds 10–15 L/day, even
normally functioning kidneys with a normal amount of solute to excrete begin to retain
water because the kidney cannot excrete pure free water
• Patients with low solute intake or those who cannot dilute their urine
osmolality to 50 mOsm/kg become hyponatremic with less water intake. With a
low solute diet (sometimes called “beer potomania” or “tea and toast diet”), a
patient’s daily water intake may be less than 10 L. However, the maximal amount
of free water these patients can ingest before becoming hyponatremic is lower
because the kidney cannot excrete water that is devoid of solute

• Patients with significant chronic kidney disease (CKD) may not be able to dilute
their urine to 50 mOsm/kg. Rather, their maximally dilute urine may be as high as
100-250 mOsm/kg even if ADH is maximally suppressed. Therefore, a relatively
modest increase in water intake or decrease in solute intake can result in
hyponatremia when there is impaired ability to dilute urine
• Treatment:

• Psychogenic polydipsia can correct quickly with water restriction alone; if hyponatremia is
moderate to severe
• patients need close monitoring during treatment to avoid overcorrection
• It is imperative to monitor serum sodium carefully (every 2–8 hours depending on the severity
of the hyponatremia) as well as hourly urinary output.
• High urinary output strongly suggests that serum sodium will rise rapidly unless oral intake is
also relatively high
• If there is concern for overcorrection, a stat serum sodium should be checked and the fluid
restriction should be temporarily liberalized or lifted entirely
• In the case of clinician uncertainty, overcorrection, or severe hyponatremia thought
secondary to psychogenic polydipsia, subspecialist consultation should be obtained
• low solute diet can be treated with increased oral solute intake as well as fluid restriction with
monitoring for overcorrection, except with severe hyponatremia when more aggressive
therapies with close monitoring would be indicated.
C. VARIABLE OSM
 RESET OSMOSTAT

• rare cause of hyponatremia characterized by appropriate ADH regulation

in response to water deprivation and fluid challenges.
• Patients with reset osmostat regulate serum sodium and serum osmolality
around a lower set point, concentrating or diluting urine in response to
hyperosmolality and hypoosmolality.
• The mild hypoosmolality of pregnancy is a form of reset osmostat
 .
OTHER CAUSES

• Use of 3,4-methylenedioxymethamphetamine (MDMA, also known

as Ecstasy) can lead to hyponatremia and severe neurologic symptoms, including
seizures, cerebral edema, and brainstem herniation
• MDMA and its metabolites increase ADH release from the hypothalamus
• Primary polydipsia may contribute to hyponatremia since MDMA users typically
increase fluid intake while intoxicated
CLINICAL FINDINGS
 SYMPTOMS & SIGNS

• Whether hypotonic hyponatremia is symptomatic depends on its severity and acuity.

The
symptoms of hypotonicity are mainly neurologic and relate to brain edema
• Chronic hyponatremia can be severe yet remarkably asymptomatic because the brain
has adapted by decreasing its tonicity over weeks to months
• Acute disease that has developed over hours to days can be severely symptomatic with
relatively modest hyponatremia
• Mild hyponatremia (sodium concentrations of 130–135 mEq/L) is usually asymptomatic,
though it has been linked to gait disturbances, falls, and fractures.
• As the sodium concentration drops , mild symptoms of nausea and malaise progress to
headache, lethargy, and disorientation.
• The most serious symptoms are seizure and, very rarely, coma, brainstem
herniation, and death
• Evaluation starts with a careful history for new medications and changes in fluid and
solute intake (polydipsia, anorexia, intravenous fluid rates and composition) and
• fluid output (vomiting, diarrhea, ostomy output, polyuria, oliguria, insensible losses)
• The physical examination should help categorize the patient’s volume status into
hypovolemia, euvolemia, or hypervolemia
 LABORATORY FINDINGS

• Laboratory assessment should include serum electrolytes, creatinine, and osmolality as

well as urine sodium, potassium, and osmolality.
• Additional tests of thyroid and adrenal function will occasionally be necessary.
• In clinical practice, ADH levels are not measured.
• Urine osmolality should be checked not only at the time of diagnosis, but maybe useful if
checked serially throughout the therapy.
• Measurement of blood glucose levels
• Elevated BUN and creatinine indicate renal dysfunction as a potential cause of
hyponatremia, whereas hyperkalemia may suggest adrenal insufficiency or
hypoaldosteronism
 COMPLICATIONS

• Overly rapid correction of hypotonic hyponatremia, particularly severe chronic

hypotonic hyponatremia, can cause cerebral osmotic demyelination syndrome
• Osmotic demyelination syndrome symptoms generally present several days after
the rapid sodium correction
• While a variety of neurologic symptoms can occur, the classic presentation altered
mental status, quadriparesis, and pseudobulbar symptoms that develop within a
few days of rapid sodium correction
• Risk factors for osmotic demyelination syndrome include serum sodium less than
120 mEq/L, malnourishment, and liver disease
• Symptoms may be reversible or permanent
• Diagnosis can be confirmed with MRI, though MRI findings may occasionally be
delayed so a normal MRI in the acute setting does not entirely exclude osmotic
demyelination syndrome.
THANK YOU