hyponatremia
HYPONATREMIA

Hyponatremia is serum sodium concentration <135 mEq/L due to failure of normal water excretion.

Most common causes are medication effects, fluid retention and syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Volume status should be assessed to help determine the underlying cause.

Commonly, patients with hyponatremia are asymptomatic and it is only an incidental finding.

 

Hyponatremia Diagnosis

Diagnosis

  • Volume status should be assessed to help determine the underlying cause
  • If hyperglycemia is present, the serum sodium concentration should be corrected for the effect of glucose to exclude hypertonic hyponatremia

Classification

Classification Based on Duration

Acute

  • Hyponatremia that has developed over a period of <48 hours or onset of <3 days
  • Usually results from parenteral fluid administration in postoperative patients and from self-induced water intoxication
  • The main pathologic consequence is the development of cerebral edema that may lead to raised intracranial pressure, cerebral herniation, hypoxia and even death

Chronic

  • Hyponatremia that has been present for ≥48 hours or the duration is unclear
  • Due to the presence of cerebral adaptive mechanisms, many patients exhibit no apparent ill effects despite severe biochemical hyponatremia
    • Initial adaptive mechanism is the loss of intracerebral fluid with depletion of sodium and potassium to prevent cerebral edema and gain of water

Classification Based on Severity/Degree of Hyponatremia

Mild

  • Serum sodium concentration of 130-135 mEq/L

Moderate

  • Serum sodium concentration of 120-129 mEq/L

Severe

  • Serum sodium concentration of <120 mEq/L; may occur at <125 mEq/L

Classification Based on Tonicity 

Hypotonic Hyponatremia 

  • Serum osmolality of <275 mOsm/kg H2O
  • Most common cause is impairment in urinary dilution mediated by vasopressin and patients may be hypovolemic, euvolemic or hypervolemic

Isotonic Hyponatremia 

  • Serum osmolality of 275-295 mOsm/kg H2O
  • Can be associated with pseudohyponatremia 

Hypertonic Hyponatremia 

  • Serum osmolality of >295 mOsm/kg H2O
  • A translocational hyponatremia most commonly seen in hyperglycemia

Classification Based on Extracellular Volume Status

Hypovolemic Hyponatremia

  • Decreased total body water with greater decrease in sodium level
  • Extracellular fluid losses can occur from kidney, gastrointestinal tract or the skin
  • Most common cause is thiazide diuretic therapy; other causes are Addison’s disease and cerebral salt wasting
  • Signs and symptoms associated with volume depletion:
    • Dry mucous membranes
    • Decreased skin turgor
    • Vomiting
    • Diarrhea
    • Tachycardia
    • Hypotension
    • Elevated blood urea nitrogen-to-creatinine ratio and uric acid level
  • Urinary sodium usually <20 mEq/L unless the kidney is the site of sodium loss

Euvolemic Hyponatremia

  • Increased total body water with normal sodium level
    • Accounts for the majority of hyponatremia cases
  • Most commonly caused by syndrome of inappropriate antidiuretic hormone (SIADH)
    • Other causes are hypothyroidism, primary polydipsia and glucocorticoid deficiency
  • Clinical signs depend on the underlying illness
  • Diagnostic lab findings:
    • Low serum uric acid levels
    • Normal blood urea nitrogen-to-creatinine ratio
    • Spot urinary sodium >20 mEq/L

Hypervolemic Hyponatremia

  • Increased total body water compared with sodium that occurs when kidneys cannot excrete water efficiently
  • Common causes include heart failure, liver cirrhosis and kidney injury
  • Clinical signs include:
    • Peripheral edema
    • Ascites
    • Raised jugular venous pressure
    • Pulmonary edema
    • Underlying illness
  • Useful diagnostic lab findings are elevated plasma levels of brain natriuretic peptide and spot urine of <20-30 mEq/L

History

  • Inquire from patient’s history possible causes of hyponatremia
  • History of cardiac, cancer, pulmonary, endocrine, gastrointestinal, neurologic and renal diseases
  • History of electrolyte-rich fluid loss (eg vomiting, diarrhea or diuretic therapy)
  • History of low protein intake and/or high fluid intake
  • Medications used (eg diuretics, Carbamazepine, selective serotonin reuptake inhibitors)
  • Alcohol and illicit drug use (eg beer, 3,4-methylenedioxymethamphetamine/”Ecstasy”)
  • For athletes, training regimens because high-endurance activities can cause hyponatremia
  • History of very recent surgery

Physical Examination

  • Signs of extracellular volume depletion eg decreased skin turgor, low jugular venous pressure, orthostatic or persistent hypotension indicating hypovolemia
  • Signs of peripheral edema and/or ascites that can be due to heart failure, cirrhosis or renal failure
  • Signs that are suggestive of adrenal insufficiency or hypothyroidism

Laboratory Tests

  • Complete metabolic panel
  • Urinary sodium and creatinine levels
    • Calculate for serum osmolality and fractional excretion of sodium
  • Serum glucose
  • Other tests to rule out other causes:
    • Thyroid-stimulating hormone
    • Urinary uric acid
    • Adrenocorticotropic hormone
    • Plasma cortisol
    • Brain natriuretic peptide

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

  • Diagnosis is based on the clinical euvolemic state with low serum sodium and osmolality, raised urine sodium and osmolality
  • Essential diagnostic criteria based on Bartter and Schwartz
    • Hyposmolality; plasma osmolality <275 mOsm/kg
    • Inappropriate urinary concentration (UOsm >100 mOsm/kg)
    • Clinically euvolemic patient
    • Elevated urinary sodium (>20-40 mEq/L), with normal salt and water intake
    • Hypothyroidism and glucocorticoid deficiency excluded particularly in patients with neurosurgical conditions
    • No recent use of diuretic agents
    • Absence of heart failure, cirrhosis or advanced kidney disease
  • Can occur due to medications, malignancy (eg small cell lung cancer), pulmonary disease or any disorder involving the central nervous system (eg subarachnoid hemorrhage)
    • Nonspecific but potent stimulus for vasopressin secretion
    • Frequent causes of SIADH in hospitalized patients are general anesthesia, nausea, pain, stress and a variety of drugs
  • Hyponatremia that resulted from antidiuretic hormone-induced retention of ingested or infused water
    • May result from increased release by the pituitary gland or from ectopic production
    • May also result from increased activity of the vasopressin in the collecting duct or from gain-of-function mutation in its type 2 receptor
  • Choice of therapy depends on several factors ie degree of hyponatremia, presence or absence of symptoms and urine osmolality
    • Fluid restriction of 800-1200 mL/24 hr is the mainstay of treatment
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