Defined by a lower plasma sodium concentration of 136 mmol / L, hyponatremia are among the most frequent and electrolyte abnormalities, both in hospitals and in general practice. They are in good standing witness to a hypotonic plasma, biological expression of an intracellular hydration and consequence of a positive water balance. It is necessary to oppose acute hyponatremia, made in less than forty-eight hours to chronic hyponatremia, progressive installation. The first are rare but dreaded because sometimes responsible for cerebral edema and intracranial hypertension; many of them are iatrogenic and result from fluid intake or infusions prescribed in disregard of an underlying urine dilution disorder; their correction is urgent because there is a risk to life or serious neurological sequelae. The latter are much more common; they complicate or reveal a wide range of pathological conditions including accurate identification conditions the nature of symptomatic treatment; Here, the urgency is not in order, on the contrary, as their fast or overcorrection exposed to severe delayed neurological complication central pontine myelinolysis osmotic syndrome.

Hyponatremia - Sodium
Hyponatremia – Sodium


Serum sodium and plasma tone:

Plasma tonicity or effective plasma osmolality is determined solely by the vis-à-vis the particles of which the cell membrane is impermeable: mainly sodium salts, and glucose. Unlike the total plasma osmolality, it is not directly measurable, but we can approach its value MOPP (in mosm / kgH2O) = 2Na + glucose (mmol / L) or MOPP (in mosm / kgH2O) = Total plasma osmolality measured – urea (mmol / L), normally 285 ± 5 mOsm / kgH2O. Any change in the plasma tonicity instantly determines a transfer transmembrane water restores osmotic balance between the extracellular and intracellular segments.

Thus, hyponatremia is almost always witnessed a hypotonic plasma and biological expression of an intracellular hydration. Two exceptions:

– The pseudohyponatrémies, artifacts inherent in certain measurement methods: flame photometry, or more often today indirect potentiometry determines a sodium concentration of plasma volume.

If hyperprotidémie or major hypertriglyceridemia, the solid fraction of the plasma (normally 6-7% of the plasma volume) is increased. The concentration of sodium per liter of total plasma measured by these techniques is diminished but the concentration of sodium per liter of water and plasma in plasma osmolality are normal;

– The translocationnelles hyponatremia are the result of a transfer of water from the intracellular environment to the extracellular environment due to the accumulation in the plasma of an osmotically active particle. The most common situation is that hyperglycemia of diabetes.

There is in this case a plasma and intracellular dehydration Hyperosmolality (see Box 1 Diagnostic).

Pathophysiology of hypotonic hyponatremia:

It is “a history of water that do not always lack of salt.”

Serum sodium concentration is either the ratio of an amount of sodium in a fluid volume in a plasma sample. The respective values ​​of the numerator or denominator can be derived. It is therefore not confuse “hyponatremia” and “lack of salt” at risk of therapeutic nonsense. In reality, hyponatremia is compatible with a normal soda capital decreased or increased, respectively, and can occur in a normal extracellular volume context, dehydration or overhydration extracellular.

Whatever soda capital hypotonic hyponatremia with plasma is always against the consequence of a positive water balance.

Normal renal elimination capacity of the water is very high: in the absence of antidiuretic hormone, kidney develops a diluted urine of osmolality can be lowered up to 50 mosm / kgH2O. Under usual feeding conditions (intake of 600 to 800 milliosmoles per day), 12 to 15 liters, can be eliminated.

It is exceptional that hyponatremia is the result of an isolated increase in water intake. Generally, hyponatremia settles in a patient whose water intake is not restricted while the renal elimination capacity of water is compromised.This may be the result of a major reduction in glomerular filtration rate.

Much more often it is due to urine dilution disorder itself determined by the abnormal presence of antidiuretic hormone in the circulation. The persistence of antidiuretic hormone secretion despite a hypotonic plasma occurs in practice in three situations (Box 2):

– There is a non-osmotic stimuli of the antidiuretic hormone secretion: usually it is a hemodynamic stimulus (real or effective hypovolemia arterial hypovolemia). Another example is the postoperative nausea and statements;

– During certain endocrine disorders: adrenocortical insufficiency, hypothyroidism, hypopituitarism; in the absence of any stimulus or osmotic – not detectable osmotic and endocrinopathy: the definition of inappropriate secretion of antidiuretic hormone (SIADH).

Neurological symptoms and impact:

The majority of hyponatremia are asymptomatic, discovered systematic examination or biological monitoring of a pathology or treatment at risk.

The symptoms are not specific: nausea, vomiting, muscle cramps, especially neurological symptoms: headache, agitation or lethargy, vigilance disorders including coma, generalized seizures. Any neurological or psychiatric manifestation badly explained should always suggest the diagnosis.

The occurrence of these symptoms is determined by the speed of formation of hyponatremia.

Cerebral edema and intracranial hypertension they translate are indeed the prerogative of hyponatremia whose installation was fast, in less than 48 hours. The risk is that of an infratentorial engagement with compression of respiratory centers and anoxic cardiac arrest. The presence of neurological signs therefore requires urgent symptomatic treatment (see below). Chronic hyponatremia, even very deep, are usually asymptomatic. Their progressive installation is indeed compatible with the implementation of specific coping mechanisms of brain cells to plasma Hypotonicity: in this context, these cells have the particularity to decrease 36-48 hours their cell electrolyte content and organic osmolytes and avoid an increase in their volume. Unlike the acute forms, such hyponatremia should be corrected very gradually. Indeed, the reversibility of coping hypotonic to plasma is not immediate and rapid increase in plasma tonicity can cause brain cell dehydration. The risk is that of the delayed onset (2-7 days) of a rare syndrome osmotic demyelination typically combining pseudobulbar impairment and flaccid quadriplegia, cerebral myelinolysis expression of central pontine lesions usually visualized by magnetic resonance imaging.


The main causes of hyponatremia are classified in Boxes 1 and 2.

Box 1. Classification of Non pathophysiological hypotonic hyponatremia
Pseudohyponatrémies: normal plasma tone
Major Hypertryglycéridémies (milky serum)
Major Hyperprotidémies (myeloma, Waldenstrom)
Hyponatremia translocationnelles: plasma hypertonicity
Intravenous immunoglobulins

Box 2. pathophysiological classification hypotonic hyponatremia
to. Kidney removal capacity of normal water
Psychiatric Polydipsies
Potomania beer drinkers “Tea and toast diet”
b. Kidney removal capacity decreased water
Urine dilution ADH-dependent disorder:
α. Effective arterial hypovolemia: congestive heart failure, ascites oedemato-cirrhosis, nephrotic syndrome, other causes of hypoalbuminemia
β. True hypovolemia:
– Extra-renal sodium losses: diarrhea, vomiting, excessive sweating (marathon runners)

– Renal sodium loss: diuretics (thiazides ), salt-losing nephropathy, acute adrenal insufficiency
– Third Sector
γ. Normal blood volume:
– Endocrinopathy (adrenal insufficiency, hypothyroidism, hypopituitarism)
– SIADH: medicine, cancer, neurological disease, lung disease, SIADH “transitional” (postoperative period, nauseous or hyperalgesic states)

Here as elsewhere the history, physical examination and some simple laboratory tests used to easily reach the diagnosis in most cases. Emphasize the importance of taking a urine sample with determination of electrolytes and osmolality before undertaking any symptomatic treatment.

The general approach is shown schematically in Fig. 1 and can be summarized in three steps.

Evaluation of plasma tone:

Before any other action, it is necessary to ensure the plasma Hypotonicity diagnosis.

The pseudohyponatrémies are rare and easily recognized by an assay of the serum protein (this is hyperprotidémies above 90 or 100 g / L as in some monoclonal gammopathies) and lipids (major hypertriglyceridemia with milky serum).

The overall tone and plasma osmolality (estimated as osmolality – urea) are normal.

No specific treatment is required.

The translocationnelles hyponatremia are often the result of decompensated diabetes.

A rise of 1 g / L of blood glucose is responsible for a decrease of 1.5 to 2 mmol / L of serum sodium. The total plasma osmolality and tonicity are high. There is an intracellular dehydration. The treatment is that the metabolic disorder.Other causes are anecdotal mannitol infusions, use of irrigation solutions containing glycine in prostate resections transuréthrales, intravenous infusions of immunoglobulins.

Figure 1. Causes of Hyponatremia.
Figure 1. Causes of Hyponatremia.

Evaluation of the capacity of the renal urine dilution:

It is highly unusual that the renal response is appropriate to plasma hypotonicity: emitting a dilute urine with an osmolality below 100 mOsm / kgH2O (urine osmolality can be measured on sample or evaluated as (2Na + 2K + urea .) Hyponatremia can not be generated in this case by a considerable increase in water intake (see above), or by a combination of plentiful drinks and low osmolar contributions These contingencies are rare. polydipsies (10 to 15 liters day) encountered in some patients with psychiatric disease, potomanies malnourished beer drinkers, some so-called diets “tea and toast”.

Renal response is almost always inappropriate hypotonic to plasma: There is a urine dilution disorder defined by a higher urine osmolality of 100 mosm / kgH2O.

Determining the pathophysiologic mechanism responsible for the renal elimination capacity of water:

If ESRD exception is the abnormal presence of antidiuretic hormone in the circulation is at issue. This may be due to a non-osmotic stimuli (true or effective hypovolaemia, primarily), a endocrinopathy or SIADH.

In practice, it is the assessment of extracellular volume which directs the diagnosis.

Increased extracellular volume:

These are straightforward inflation situations hydrosodée but where blood volume is seen as diminished by arterial baroreceptors. There is talk of effective arterial hypovolemia, non-osmotic stimuli of the antidiuretic hormone secretion.

The diagnosis is easy rule: congestive heart failure, edematous states of hypoalbuminémies whatever the cause, especially in the nephrotic syndrome and decompensated cirrhosis.


All sodées loss, renal, gastrointestinal, skin, and the presence of a third sector (burns, obstruction, pancreatitis) may be involved: volume, perceived by arterial baroreceptors, stimulates antidiuretic hormone secretion. Hyponatremia is not the direct result of sodées losses are usually hypotonic or isotonic: she moved in patients who continue to drink while their dilution capacity of the urine is altered by antidiuretic hormone.

Diagnosis is based on history and physical examination: notion of taking diuretics or digestive disorders, highlighting of orthostatic hypotension, a skin fold flat peripheral veins, invisibility of the external jugular vein in position half sitting.

This can be difficult if modest deficit soda, obese, elderly, when the physical exam is not contributory. The following laboratory tests then have a very good value orientation.

Uric acid:

She precociously elevated in patients with hypovolemia, whatever the cause. However, it is lowered, often below 150 mmol / L in the syndrome of inappropriate secretion of antidiuretic hormone.

Other components of the blood electrolytes: potassium and bicarbonatémie

The euvolémiques hyponatremia are perfectly isolated. In contrast, hypovolemic hyponatremia is often associated with other electrolytes abnormalities: metabolic alkalosis with hypokalemia if vomiting or taking diuretics; metabolic acidosis and hypokalemia if electrolytic diarrhea; metabolic acidosis and hyperkalemia in acute adrenal insufficiency.

The diagnosis of acute adrenal insufficiency should be considered quasi-systematic manner in view of the potential severity, even in the absence of frank acidosis or hyperkalemia. It is easy to confirm by an assay of cortisol and a test synacthen. Doubt imposes a hydrocortisone emergency treatment without waiting for the results of the assays.

Urinary electrolytes on sample:

Natriuresis is appropriate to hypovolemia, less than 20 mmol / L, when the losses are extrarenal sodées or formerly renal (diuretic interrupted for more than 24 hours). Recent vomiting is one exception: the urine is rich in sodium bicarbonate and low sodium chloride. The urinary sodium can exceed 30 mmol / L, but the urinary chlorine is indosable.

Natriuresis is inappropriate to hypovolemia, exceeding 30 mmol / L when sodées losses of renal origin (current diuretic action, osmotic diuresis, acute adrenal insufficiency, renal disease with salt loss).

Natriuresis reflects dietary intake, usually greater than 30 mmol / L, in the euvolémiques hyponatremias syndromes of inappropriate secretion of antidiuretic hormone or endocrinopathies.

In ambiguous situations, not exceptional, changes in serum sodium after soda refill dispositive. In this case, only the hypovolemic hyponatremia is correct.

Normal extracellular volume:

It is hyponatremia complicating certain endocrinopathies and those of inappropriate secretion of antidiuretic hormone syndromes.

Their clinical presentation is near and some authors include endocrinopathies among the causes of SIADH.


It is the chronic adrenocortical insufficiency, hypothyroidism and hypopituitarism. Their diagnosis is based on the test synacthen the TSH, thyroid hormones and dosing of gonadotropins.

Diagnosis of SIADH:

It is a diagnosis of exclusion. The dosage expensive antidiuretic hormone, imprecise and especially non-discriminating, is irrelevant. The diagnostic criteria are those proposed during the first description of Bartter and Schwartz: hyponatremia with hypotonic dilution inappropriate urine (urine osmolality> 100 mOsm / kgH2O), normal blood volume (natriuresis> 30 mmol / L normosodé plan) functions kidney, heart and liver normal and lack of endocrinopathy. The diagnosis of SIADH always requires a rigorous etiological investigation. There are four groups of causes (Box 3).

Box 3. Causes of drug and toxic SIADH
Analogues of ADH
Drugs stimulating the secretion of ADH
Antidepressants, antipsychotics
Drugs potentiate renal effects of ADH
Drugs acting by an uncertain mechanism
Inhibitors of serotonin reuptake

Drug causes:

They are very common. The list of potentially responsible drugs is growing every year. We must insist on psychotropic drugs known prescribing frequency, including inhibitors of serotonin reuptake (Box 3).

SIADH paraneoplastic:

It is essentially lung anaplastic small cell carcinoma, and cancers of the head and neck. Other associations are anecdotal.

Nervous system disorders:

All diffuse diseases of the central nervous system may be involved. The mechanism is probably the interruption tonic inhibitory circuits of the antidiuretic hormone secretion.

Non-cancerous lung diseases:

Foremost among which we find tuberculosis, pneumonia in general and advanced chronic obstructive lung disease.

After this survey, a significant proportion of SIADH remains unexplained, especially in the elderly.


The guidance takes into account three factors: the presence of symptoms, speed of installation and the state of the extracellular volume.

Acute symptomatic hyponatremia:

Severity necessary to remember that prevention is almost always possible. It begins with the identification of key risk situations: post-operative period, use of certain drugs (oxytocin, vasopressin, cyclophosphamide), intense exercise (marathon) weeks of a thiazide diuretic therapy in the elderly. All these situations are characterized by a marked reduction in the capacity of the renal urine dilution. It is essential to avoid the mistake of encouraging taking plenty of fluids without associated electrolyte intake or intravenous prescription hypotonic solutions (glucose-free electrolyte).

These hyponatremia are therapeutic emergency requiring care in intensive care. It uses a combination of hypertonic saline and loop diuretics (furosemide) intravenously. For example 1 to 2 mL / kg / hr of 3% saline and 40 mg IV furosemide during the first hours. The aim is an initial increase in serum sodium levels of the order of 1 to 2 mmol / L / h to 125-130 mmol / L.

Symptomatic hyponatremia of uncertain duration:

The risk of central pontine myelinolysis osmotic which expose too rapid correction and / or excessive hyponatremia should be taken into account here. An initial correction of the order of 1 mmol / L / h until no neurological signs is recommended. A 10% rise in serum sodium is usually sufficient. Subsequently, the correction rate should not exceed 0.5 mmol / L / h and 8 mmol / L in 24 hours and the simple fluid restriction is sufficient. Caution is especially fitting in the elderly, alcoholics, malnourished, and in case of associated hypokalemia, circumstances in which the risk of secondary osmotic myelinolysis seems higher.

Chronic asymptomatic hyponatremia:

Symptomatic treatment depends on the state of the extracellular volume. Here there is no urgency to their correction should be less than 8 mmol / L during the first 24 hours.

Hyponatremia with true hypovolemia (soda balance negative):

Soda refill, per os or intravenously (normal saline) corrects hypovolemia and thus makes clear the non-osmotic stimuli of the antidiuretic hormone secretion.

The kidney can then develop a dilute urine and correct hyponatremia.

Hyponatremia with hypovolemia effective and increased total blood extracellular volume (positive balance soda):

These hyponatremia often reflect the progress of the underlying organ failure (severe heart or liver failure) and control can be difficult. Symptomatic treatment is based on loop diuretics on sodium diet and fluid restriction.

The results of the first clinical trials with antagonists of vasopressin V2 receptors are promising.

Hyponatremia euvolémiques:

Their symptomatic treatment based on fluid restriction and maintaining osmolar intake (sodium intake) normal. A restriction of less than one liter per day is difficult to enforce outpatient. The combination of furosemide in two or three daily doses (the loop diuretics help eliminate hypotonic urine and thus increase the elimination of free water) and a diet rich in osmoles (in practice: 200 mmol / day of Na) often allows to control the situation. Was exceptionally use demeclocycline, antidiuretic hormone antagonist, because of its toxicity. The new V2 receptor specific antagonists of the antidiuretic hormone are under development in this indication.