where salt goes, water (also) follows

by Adam George











  • Hyponatremia refers to a low blood sodium (Na) concentration. Specifically, it can be classified as a serum sodium level <135 mmol/L, although usually patients with sodium levels >125 mmol/L are asymptomatic.
  • Sodium concentration is dependent not only on sodium levels but also on water levels in vivo. Water in the body exists either intracellularly or extracellularly, with approximately 13 of the body’s water being intracellular and 23 being extracellular.
    • Intracellular fluid is simply fluid within the cell, whereas extracellular fluid comprises fluid in blood vessels, lymphatic vessels, and the interstitial space.
  • Ordinarily both the intracellular and extracellular compartments have equivalent solute concentrations (osmolarity) enabling free movement of water between both spaces. However, they exhibit contrasting solute compositions. Intracellularly, the prevailing anions are phosphate and negatively charged proteins, and the most common cations are potassium and magnesium. Extracellularly, the prevalent anion is chloride, and the most common cation is sodium. It is sodium though that determines the balance of osmolarity. Sodium is continually in flux between both compartments and minute fluctuations in sodium concentration shift the balance of osmolarity, precipitating the movement of water. Fundamentally, water follows the migration of sodium.
  • In hyponatremia, a low extracellular sodium concentration (thus a low blood sodium concentration) can materialise either via the loss of more sodium than water, or the acquisition of more water than sodium. In both instances the result is the same – the extracellular sodium concentration is decreased.
  • Water volume status is the key determinant in classification of hyponatremia. Depending on the water volume status hyponatremia can be separated into three categories:
    • Hypervolaemic hyponatremia
    • Hypovolaemic hyponatremia
    • Euvolaemic hyponatremia


  • Hypervolaemic hyponatremia occurs when there is an immense increase in total body water without a commensurate increase in total body sodium. Commonly this develops in situations of fluid overload such as nephrotic syndrome, cirrhosis, or heart failure where fluid moves from blood vessels into the interstitial space, precipitating oedema. Despite an overload of water, because there is less fluid in the blood vessels, the effective circulating volume is lower. The body attempts to compensate via the release of anti-diuretic hormone (ADH) to retain water, and stimulation of the renin-angiotensin-aldosterone system (RAAS) to increase aldosterone secretion and preserve sodium. However, this rise in sodium induces further ADH release, causing hyponatremia.
  • Hypovolaemic hyponatremia develops when there is a slight decrease in total body water accompanied by a considerable decrease in total body sodium. Catalysts include:
    • Diuretic use: is one of the most common causes of severe hypovolaemic hyponatremia. Thiazide diuretics (and loop diuretics to a lesser extent) are primarily responsible for diuretic-induced hyponatremia, generating urinary sodium excretion.
    • Situations leading to loss of gastrointestinal contents: (eg: diarrhoea and/or vomiting) expel sodium within the chyme before the body has a chance to reabsorb it, giving rise to hypovolaemic hyponatremia.
    • Cerebral salt wasting (CSW): is a rare but important potential cause of hyponatremia, especially in the context of central nervous system (CNS) disease and subarachnoid haemorrhage in particular. The pathophysiology of CSW is a point of conjecture, however, excess secretion of natriuretic peptides and the loss of sympathetic renal stimulation have been implicated. The end result is extracellular volume depletion due to a tubular defect in sodium transport, increased urine production, and elevated urinary sodium excretion.
    • Other causes: comprise mineralocorticoid deficiency (Addison’s disease), renal failure with polyuria, general bleeding/haemorrhage, or the recovery phase of acute tubular necrosis (ATN).
  • Euvolaemic hyponatremia: is somewhat of a misnomer, materialising when total body sodium is within normal limits but there is actually an increase in total body water. It is considered “euvolemic” since water does not move into the interstitial space and there is no oedema, thus no clinical signs of hypervolaemia. Causes include:
    • Syndrome of inappropriate secretion of Anti diuretic hormone (SIADH): accounts for the highest proportion of euvolemic hyponatremia cases. SIADH leads to enhanced ADH or receptor activation via a variety of mechanisms, facilitating increased renal water retention and consequent euvolaemic hyponatremia.
    • Exercise-associated hyponatremia (EAH): is another consequential generator of euvolaemic hyponatremia, whereby ingestion of water in excess of fluid losses – associated with persistent ADH secretion in some cases – within 24 hours of strenuous exercise provokes euvolaemic hyponatremia.
    • Primary polydipsia: is characterised by compulsive water intake. It mostly develops in psychiatric illnesses (eg: schizophrenia, obsessive compulsive disorder), or due to lesions in the hypothalamic thirst centre. Primary polydipsia generates highly dilute urine, eventually begetting hyponatremia.
    • Low dietary solute intake: in beer drinkers (beer potomania) or other malnourished patients with low protein/high water intake diets there is a notable decline in water excretion capacity regardless of ADH suppression. In beer potomania, the carbohydrate load stifles endogenous protein disassembly and urea excretion. This results in daily solute excretion of <250mmol, and hyponatremia if daily fluid intake exceeds 4 L/day.
    • Other causes: include acute or chronic renal failure, glucocorticoid deficiency (adrenal insufficiency), severe hypothyroidism, and excessive infusion of hypotonic (eg: 0.45% NaCl) or sodium-free isotonic IV fluids.
  • Pseudohyponatremia: is a laboratory abnormality that should also be considered in conditions where blood protein levels are markedly elevated (eg: multiple myeloma), or where blood glucose is raised significantly (eg: DKA). These cases may engender a laboratory artifact of erroneously low serum sodium concentration.


Mild/moderate hyponatremia (serum Na 120-135 mmol/L, no cerebral symptoms)

Mild/moderate symptoms of hyponatremia usually develop slowly, with an onset > 48 hours, and are frequently non-specific. Patients with mild/moderate hyponatremia can also present as asymptomatic. Mild/moderate symptoms include:

    • Headache/dizziness
    • Forgetfulness
    • Nausea
    • Vomiting
    • Fatigue/lethargy
    • Muscle weakness
    • Gait disturbances

Severe symptomatic hyponatremia (serum Na < 120 mmol/L or cerebral symptoms)

Severe symptoms of hyponatremia usually develop acutely, with an onset < 48 hours. Severity generally correlates with the extent of cerebral oedema. Severe symptoms include:

    • Seizures
    • Respiratory failure
    • Coma, confusion
    • Ataxia
    • Non-specific symptoms: headache, nausea, vomiting, lethargy

Investigations – recommended if Na < 130mmol/L


    • Serum and urine osmolality
    • EUC
    • TFTs
    • BSL (if hyperglycaemia present)
    • Lithium levels (if appropriate – hypernatremia reduces excretion and increases toxicity risk)
    • Random serum cortisol levels or ACTH stimulation test – if adrenal suppression considered (eg: recent steroid use)
    • Consider blood gas if patient is sick


    • Urinary Na
    • Urine osmolality


  • Hypervolaemic hyponatremia: when sodium and water depletion is definitive, may respond to IV NaCl 0.9% with K+ supplementation if required. Any drugs suspected as a cause of hypovolaemic hyponatraemia should be halted prior to initiation of IV treatment.
  • Hypovolaemic hyponatremia: where oedema is implicated due to heart, liver, or renal failure may respond to fluid restriction. A loop diuretic may be prescribed if the intravascular volume can be maintained.
  • Euvolaemic hyponatremia: involves the consideration of three key factors:
    • Presence of CNS symptoms (headache, drowsiness, seizure, unconsciousness)
    • Severity
    • Rate of development

In acute symptomatic hyponatremia, treatment is typically IV NaCl 3%. In

chronic/slowly developing hyponatremia, initial management may be via

fluid restriction.

Mild/moderate hyponatremia (serum Na 120-135 mmol/L, no cerebral symptoms)

      • May be treated with fluid restriction (eg restrict to 500 mL to 1 litre per 24 hours, or 500 mL less than daily urine output), monitoring of serum electrolytes, creatinine and urine output daily or twice daily.

Severe symptomatic hyponatremia (serum Na < 120 mmol/L or cerebral symptoms)

  • May be treated with IV sodium chloride 3% (513 mmol/L). The initial target serum sodium concentration should not be higher than 120 mmol/L.
  • NB: Rapidly correcting hyponatraemia may produce central pontine myelinolysis, a permanent central nervous system injury due to osmotic demyelination. In cases of chronic hyponatraemia (>48 hours) this is of particular importance.
  • Prevention of osmotic demyelination is best managed by increasing serum sodium concentration by no more than
    • 0.5mmol/L per hour
    • 10 mmol/L in the first 24 hours
    • 18 mmol/L in the first 48 hours
  • If there is a risk of overcorrection, target increases should be lower, however. Namely, 4-8 mmol/L daily.

Additional considerations

  • Faster initial correction may be considered in instances of:
    • Seizures or coma
    • Self-induced acute water intoxication
    • Known hyponatraemia for < 48 hours
    • Intracranial pathology or increased intracranial pressure.
  • In these cases, serum sodium concentration should be raised by 4-6 mmol/L. prevent neurological damage secondary to brain herniation, swelling and cerebral ischaemia. Treatment is: NaCl 3% 100 mL IV over 10 minutes. Repeat as needed up to a maximum of 3 infusions.


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