Hyponatremia

Definition
Hyponatremia is a plasma sodium concentration of <135 mmol/L


Epidemiology
Most common electrolyte disorder seen in general hospital population
Predominant age: All ages
Male = Female
2.5% of hospitalized patients

Risk Factors
Genetics

• Polymorphisms have been demonstrated.
• Mutations have beem associated with nephrogenic syndrome of inapproapriate antidiuresis (NSIAD).

Pathophysiology and Aetiology

Types	Urine Na	Pathophysiology	Aetiology
Hypovolemic hyponatremia	Extrarenal loss of sodium (urine Na <30 mmol/L)	Decrease in total body water and greater decrease in total body sodium; decreased extracellular fluid volume; orthostatic hypotension and other changes consistent with hypovolemia are present.	GI loss: Vomiting, diarrhea Third spacing: Peritonitis, pancreatitis, burns, rhabdomyolysis Skin loss: Burns, sweating, cystic fibrosis Heat-related illnesses
Euvolemic hyponatremia	urine Na >30 mmol/L	Increase in total body water with normal total body sodium; extracellular fluid volume is minimally to moderately increased but with no edema.	HypothyroidismnHypopituitarism or other cause of glucocorticoid deficiency Medications (e.g., carbamazepine, clofibrate, cyclosporine, levetiracetam, opiates, oxcarbazepine, phenothiazines, tricyclic antidepressants, vincristine) Primary polydipsia Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Iatrogenic (e.g., excess hypotonic IV fluids)
Hypervolemic hyponatremia	urine Na <30 mmol/L, except chronic renal failure	Increase in total body sodium and greater increase in total body water; extracellular fluid increased markedly; edema present	Nephrotic syndrome Cirrhosis Congestive heart failure (CHF) Chronic renal failure
Redistributive hyponatremia		Shift of water from intracellular compartment to extracellular compartment with resulting dilution of sodium; total body water and total body sodium unchanged; occurs with hyperglycemia	Hyperglycemia Mannitol infusion Hypertriglyceridemia
Pseudohyponatremia		Dilution of aqueous phase by excessive proteins, glucose, or lipids; total body water and total body sodium unchanged	hypertriglyceridemia or multiple myeloma

Low sodium creates an osmotic gradient between plasma and cells, and fluid shifts into cells, causing edema and increased intracranial pressure (ICP).

Presentations
Symptoms related to the rate of fall in serum sodium and the degree of hyponatremia
Usually asymptomatic, Nausea, vomiting, malaise, Headache, lethargy, restlessness, disorientation
can cause seizure, coma, and respiratory arrest and may be fatal
Weakness, muscle cramps, anorexia, hiccups, depressed deep tendon reflexes, hypothermia, positive Babinski responses, cranial nerve palsies, orthostatic hypotension
Skin turgor, jugular venous pressure, heart rate, orthostatic BP

Investigation
Serum sodium <135 mmol/L
Plasma osmolality
Urine sodium and osmolality
Renal function, Liver function, Thyroid function
Serum glucose, lipids
CT scan of head if pituitary problem suspected or if SIADH from CNS problem suspected
CXR to rule out pulmonary pathology if SIADH diagnosed

Result

Plasma osmolality low Blood urea nitrogen (BUN):creatinine ratio >20:1 Urine sodium >20 mEq/L (>20 mmol/L): Renal loss Urine sodium <10 mEq/L (<10 mmol/L): Extrarenal loss Serum potassium >5.0 mEq/L (>5 mmol/L): Consider mineralocorticoid deficiency	Hypovolemic hyponatremia
Plasma osmolality low BUN:creatinine ratio <20:1 Urine sodium >20 mEq/L (>20 mmol/L) Thyroid-stimulating hormone (TSH) test to rule out hypothyroidism 1-h cosyntropin-stimulation test to rule out adrenal insufficiency	Euvolemic 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	Hypervolemic hyponatremia
Plasma osmolality normal or high Glucose or mannitol levels elevated	Redistributive hyponatremia
Plasma osmolality normal Triglyceride, glucose, or protein levels elevated	Pseudohyponatremia

Treatment
Treatment tailored to clinical situation:

Asymptomatic, euvolemic	fluid restriction plus addressing the underlying cause.
hyponatremic /symptomatic	increase the serum Na by 0.6–2.0 mEq/L each hour, not to exceed 8 mEq/24 h.
Euvolemic or hypervolemic	tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations.
Caution!	Rapid correction of severe symptomatic hyponatremia has been associated with central pontine myelinolysis, a neurologic disorder that induces loss of myelin and supportive structures in pons and occasionally in other areas of the brain. This results in irreversible injury. Symptoms are apparent 2–6 days after injury and include seizure, coma, spastic paraparesis, dysarthria, and dysphagia.
hypertonic saline (3% NaCl)	has only a slight evidence base; consider consulting with specialist before undertaking this treatment
Chronic hyponatremia owing to SIADH	Demeclocycline (inhibits ADH action at the collecting duct) if fluid restriction alone is not effective: Contraindication: Can cause nephrotoxicity in patients with liver disease In doses of 600–1,200 mg/d, drug produces a nephrogenic diabetes insipidus. Significant possible interactions: Oral anticoagulants, oral contraceptives, penicillin
General measures	Inpatient treatment mandatory if acute hyponatremia or symptomatic; acute (developing over <48 h) hyponatremia carries the risk of cerebral edema. Inpatient treatment is advised if asymptomatic and serum sodium <125 mEq/dL. Assess all medications patient is taking. Institute seizure precautions.

Complications

• Occult tumor may present with SIADH.
• Hypervolemia if saline used
• Central pontine myelinolysis (see above)
• Hyponatremia is cause in 30% new-onset seizures in ICU.

Prognosis

• In hospitalized patients, hypnatremia is associated with 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 liver cirrhosis and in patients waiting for liver transplant