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  • Uncontrolled free water losses lead to severe hypernatremia and significant dehydration


  • Normal plasma osmolality: 275 to 295 mOsm/L

  • Controlled via thirst and arginine vasopressin

  • Arginine vasopressin (AVP): Produced in supraoptic and paraventricular nuclei of hypothalamus, released in posterior pituitary

    • Vasopressin receptors

      • V1: liver, vasculature – contributes to vasoconstriction, hepatic gluconeogenesis

      • V2: kidney – functions to increase renal tubule water permeability

    • AVP mechanism

      • Binds V2 in renal collecting ducts: increases permeability via aquaporin-2 channels – allows diffusion of water from tubules to plasma

      • Release regulated by osmoreceptors near anterior hypothalamus

      • Nonosmotic factors affecting AVP release: volume depletion, hypotension, pain, nausea, medications

      • Desmopressin (DDAVP) – lacks smooth muscle contraction effects; more specific for V2 receptor


  • Central DI: defect in secretion or synthesis of vasopressin → decreased free water reabsorption in renal collecting tubules

    • Genetic

    • Injury/damage to pituitary gland and/or hypothalamus

      • Post–hypothalamic-pituitary surgery; may be transient (permanent if transection of pituitary stalk)

      • Central nervous system (CNS) infections

      • CNS tumors (e.g., craniopharyngioma)

      • Traumatic brain injury

      • Hypoxic ischemic injury

      • Brain death

  • Nephrogenic DI: impaired ability to concentrate urine

    • Genetic

    • Drugs: lithium, amphotericin B, rifampin

    • Neoplasm

    • Sickle cell

    • Metabolic derangements

    • Obstructive uropathy


  • Hallmarks:

    • Polyuria and polydipsia

    • Urine specific gravity <1.005

    • Urine output (UOP) >4 mL/kg/hr

    • Serum Na >145 mEq/L

    • Serum osmolality >285 mOsm/L

    • Urine osmolality <100 to 200 mOsm/L

  • Serum sodium and osmolality depend on hydration status


  • Thirst, polyuria, dilute urine, hypovolemia, tachycardia, poor perfusion, shock

  • CNS abnormalities – lethargy, irritability, seizure, coma

  • Hyperosmolar state – risk of venous sinus thrombosis


  • Fluid resuscitation to reverse hypovolemic shock if necessary

  • Then hypotonic fluid to replace urine losses in addition to maintenance requirements

  • Avoid hyperglycemia if giving large volumes of dextrose-containing fluids – risk of osmotic diuresis worsening dehydration

  • If vasopressin sensitive (central DI), initiation of vasopressin administration

  • Avoid rapid correction of hypernatremia – correct over 48 to 72 hours to avoid cerebral edema


  • Relative hypersthenuria (increased urine osmolality) and hyponatremia


  • Pituitary hypersecretion of vasopressin → excess of water in extracellular and intracellular compartments → renin/aldosterone activity reduced → increased natriuresis due to expansion of extracellular volume

  • Causes of SIADH

    • CNS: brain injury, tumors, infections

    • Adrenal insufficiency

    • Drugs: vincristine, cyclophosphamide, carbamazepine, barbiturates

    • Malignancy

    • Hypothyroidism

    • Guillan-Barre

    • Infant botulism

    • Pulmonary diseases: tuberculosis, cystic fibrosis

    • Positive end-expiratory pressure (PEEP)


  • Hypotonic hyponatremia

  • Serum sodium <125 mEq/L

  • Serum osmolality <260 mOsm/L

  • Urine sodium >18 mEq/L

  • Inappropriate urine concentration at some level of serum hypo-osmolality

  • Elevated urinary sodium excretion with normal salt and water intake

  • Signs of hypovolemia or ...

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