Description

• Most common cause of hyponatremia occurring in up to 15–30% of hospitalized patients (and significantly increases patient mortality in some studies)
• A water balance problem more than one of sodium (Na) balance
• Normal regulation of water balance:
  • Antidiuretic hormone (ADH):
    • Integral controller of water balance
    • Increases water permeability of the collecting tubules, resulting in free water reabsorption
    • Synthesized by hypothalamus but secreted by posterior pituitary gland
  • Water deprivation (increased plasma osmolality) stimulates secretion as sensed by:
    • Osmoreceptors/atrial stretch receptors
    • Carotid baroreceptors
    • Aortic arch/pulmonary veins
• Hyponatremia:
  • Mild: Serum sodium <135 mEq/L
  • Moderate: Serum sodium <130 mEq/L
  • Severe: Serum sodium <125 mEq/L
  • Excess extracellular water relative to Na
  • Depletional hyponatremia:
    • Sodium depletion can be caused by diet, GI losses, diuretic use, and renal or adrenal disease
    • Often accompanied by extracellular fluid volume depletion
    • Hyponatremia associated with clinical signs of hypovolemia
    • Increased Hct, BUN, Cr
    • Urinary sodium excretion <20 mEq/L
  • Dilutional hyponatremia:
    • Increased extracellular water in the presence of normal or increased total body sodium
    • Can be caused by increased fluid intake (oral, IV), drugs, or medical conditions
    • Euvolemia with edema
    • Normal or decreased Hct, BUN, Cr
    • Urinary sodium excretion >20 mEq/L
    • Inappropriate ADH secretion is a form of dilutional hyponatremia
• Definition of SIADH:
  • ADH secretion in the absence of hyperosmolality or hypovolemia leading to inappropriate elevation of arginine vasopressin (AVP) causing stimulation of aquaporins, and reabsorption of water from renal tubules
• Criteria for definition:
  • Essential features:
    • Plasma osmolality of <270 mOsm/kg
    • Evidence of inappropriate urinary concentration (UOsm >100 mOsm/kg of water)
    • Clinical euvolemia (no evidence of volume overload or depletion)
    • Elevated plasma Na (>30 mmol/L) with normal salt intake
    • Absence of concomitant hypoadrenalism, hypothyroidism, or renal dysfunction
    • No recent diuretic use
  • Supplemental features:
    • Plasma uric acid <4 mg/dL
    • BUN <10 mg/dL
    • FENa >1%
    • Failure to correct hyponatremia after an infusion of normal saline (NS) 0.9%
    • Abnormal water load test (inability to excrete ≥90% of a 20 mL/kg water load in 4 hr)

Etiology

• ADH-producing tumors
• Cancer (small-cell lung, pancreatic, prostate)
• Pituitary tumors
• Thymoma
• Lymphoma

• Infections (pneumonia/TB/lung abscess)
• Mechanical dysfunction (COPD/PPV)

• Mass lesions (tumor/abscess/subdural hematoma)
• Inflammation (meningitis/encephalitis)
• Demyelination (multiple sclerosis/Guillain–Barré)
• Subarachnoid hemorrhage
• Traumatic brain injury
• Acute psychosis
• CVA

• Stimulators of AVP release (nicotine, TCAs, phenothiazines)
• Altering renal function (DDAVP, oxytocin, vasopressin, prostaglandin synthesis inhibitors – NSAIDs)
• ACE inhibitors and thiazides, especially in combination
• Chlorpropamide
• Vincristine
• Anticonvulsants (carbamazepine, oxcarbazepine)
• Antidepressants (Trazadone, Mirtazapine, Venlafaxine, SSRIs)
• Antipsychotics (with higher risk associated with first generation drugs)
• Ecstasy (MDMA)

• Endurance exercise
• General anesthesia
• Pain
• Stress

• Often multifactorial
• Hereditary
• HIV/AIDS
• Idiopathic

• Symptoms can mimic underlying psychiatric conditions
• Many psychiatric conditions (i.e., schizophrenic polydipsia, compulsive drinking behaviors, anorexia-related water loading) and medications precipitating SIADH (see Medications under Etiology)

• Seen in patients with cerebral tumors or subarachnoid hemorrhage and in neurosurgical patients
• Etiology unclear
• Represents appropriate water resorption in the face of salt wasting (urine Na >30–40 mmol/L)
• Fluid restriction can help differentiate the 2:
  • In SIADH: Hypouricemia will correct
  • In CSWS: Hypouricemia will persist
• Treatment of CSWS may differ from that of SIADH:
  • Infusion of NS
  • May benefit from fludrocortisones therapy