Hyponatremia
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p272-273
2025-08-27
366
Hyponatremia, defined as plasma Na+ concentration <135 mmol/L, represents the most common alteration of body fluids and electrolyte balance. From a clinical point of view, hyponatremia is characterized by a broad spectrum of signs and symptoms, from subtle to severe, and is associated with increased mortality and morbidity.
Hyponatremia is characterized by water excess over sodium content in ECF, which may result from water accumulation or Na+ depletion.
Hyponatremia can be classified according to several criteria, such as Na+ concentration (mild, moderate, severe), the timing of onset (acute or chronic), the severity of symptoms (moderate or severe), and serum osmolality (hypotonic, iso tonic, and hypertonic) (Table 1).
Table1. Hyponatremia classification
Tonicity (or effective osmolality) is defined as the total osmolality capable of inducing the movement of water between compartments, and it is determined by all those solutes that cannot pass freely through cell membranes.
Hypotonic hyponatremia (or true hyponatremia), characterized by reduced plasma osmolality, is generally due to either a primitive water increase (and a secondary loss of Na+) or a primitive Na+ loss (and a secondary increase in water) and can be further classified into (Table 2):
Table2. Causes of hypotonic hyponatremia classified by volume
• Hypovolemic: This is characterized by ECF depletion due to a primitive Na+ loss (and a relative increase of water) that can be of renal or extrarenal origin. The contraction of ECF volume stimulates thirst and ADH secretion. Increased water intake and reduced renal excretion result in hyponatremia.
• Euvolemic: This is characterized by a modest ECF excess due to a primitive water increase and relative Na+ deficiency. The syndrome of inappropriate ADH secretion (SIADH) represents the most common cause of euvolemic hyponatremia.
• Hypervolemic: This is characterized by an ECF excess due to a primitive Na+ increase in Na+ less than the secondary water increase. It is usually associated with edema. This form is due to pathologies, such as liver cirrhosis, which are associated with a reduction in effective circulating arterial volume resulting in increased ADH levels and a sense of thirst. Chronic and acute renal failure with oliguria may be associated with hyponatremia if water intake exceeds its elimination capacity.
Isotonic hyponatremia (or pseudohyponatremia), characterized by normal plasma osmolality, results from the accumulation of large amounts of isotonic substances lacking Na+ that can freely cross membranes, such as urea, non- hypertonic mannitol, and ethanol, causing pseudohyponatremia (laboratory artifact).
Hypertonic hyponatremia, characterized by increased plasma osmolality, is the result of water transfer from cells to the extracellular compartment due to an excess of osmotic substances. It is usually due to hyperglycemia. In a patient with diabetes mellitus with poor metabolic control, glucose becomes an effective osmolyte capable of drawing water into the extracellular environment, resulting in hyponatremia; for each excess of 100 mg/dL in plasma glucose concentration, there is a 1.4 mmol/L reduction in plasma Na+ concentration. In addition, intravenous administration of mannitol is another cause of hypertonic hyponatremia.
The clinical manifestations of hyponatremia are related to the water osmotic displacement, which results in an increased ICF volume. Neurons are the most susceptible to this alteration due to the inability of the cranial box to expand. Consequently, the symptoms of hyponatremia are predominantly neurological (hyponatremic encephalopathy) and their severity depends on the absolute Na+ reduction in Na+ and the development rapidity. Mild forms are generally asymptomatic. Nausea and general malaise are the first symptoms of moderate forms. The symptoms of hyponatremia, especially when it is mild or moderate, are nonspecific and often lead to a failure to diagnose it, with consequent therapeutic delay (Table 3). Seizures occur at extremely low natremia values, with a high risk of permanent brain damage. The guidelines suggest a thresh old of 48 hours to distinguish acute from chronic hyponatremia because cerebral edema occurs more frequently when hyponatremia develops in less than 48 hours. Indeed, the brain needs about 48 hours to adapt to a hypotonic environment and, before adaptation, there is a high risk of edema. Adaptation involves the activation of compensatory mechanisms leading to the loss of Na+ and K+, followed by the loss of organic osmolytes, aimed at protecting cell volume through the displacement of water from ICF to ECF. However, once adaptation is complete, if Na+ concentration increases too rapidly, neurons may undergo further damage. One of the most serious complications associated with correcting hyponatremia is the demyelinating osmotic syndrome, characterized by the breakdown of the myelin sheath that insulates neurons.
Table1. Symptoms of hyponatremia
Diagnosis and Therapy
Hyponatremia represents the manifestation of numerous dis eases. Therefore, the diagnostic approach to a patient with hyponatremia is first based on history and objective examination that includes the assessment of the ECF status and circulating volume. Gathering the patient’s medical history may direct toward the cause of hyponatremia.
Clinical laboratory provides valuable information for the differential diagnosis of hyponatremia. In particular, the key tests include plasma and urinary osmolality, and urinary Na+ concentration (Fig. 1). In addition, blood glucose and hormonal patterns (including the hypothalamic–pituitary–thyroid and hypothalamic–pituitary adrenal axes) provides essential support for differential diagnosis.
Fig1. Diagnostic algorithm of hyponatremia. (Copyright EDISES 2021. Reproduced with permission)
Recently, an algorithm for the differential diagnosis of the causes of hyponatremia has been proposed and it is based on the determination of copeptin (Fig. 2).
Fig2. Algorithm for the differential diagnosis of hyponatremia based on copeptin. (Copyright EDISES 2021. Reproduced with permission)
SIADH is characterized by hypotonic hyponatremia with inappropriately concentrated urine (urinary osmolality >100 mOsm/kg). Patients usually are euvolemic and have a normal Na+ balance.
The aim of hyponatremia therapy is, to correct the plasma Na+ concentration and resolve the primary disease underlying altered Na+ concentration. In an asymptomatic patient with mild hyponatremia, therapy consists of treating the underlying pathologies, removing the causal factors, such as the use of diuretics, the use of drugs that can cause SIADH, as well as stress, pain, and anxiety, which can stimulate the secretion of ADH. In a symptomatic patient, therapy is based on the correction of hyponatremia through the administration of 0.9% isotonic saline solution or 3% or 5% hypertonic saline solution by slow drip.
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