Pathophysiology

• ADH enables the integration of aquaporins into the plasma membrane of collecting duct cells → reabsorption of free water

Either ↓ ADH (central DI) or defective renal ADH receptors (nephrogenic DI) → impaired ability of the kidneys to concentrate urine (hypotonic collecting ducts) → dilute urine (low urine osmolarity)

• Normal: 500–800 mOsmol/kg

• Partial DI (300–500 mOsmol/kg)

• Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)

• Loss of fluid with urine → increased extracellular fluid osmolarity → passage of fluid from the intracellular to the extracellular space → equalization of the osmolarities of the extracellular and intracellular fluid

• Due to the loss of fluid, the osmolarities of intracellular and extracellular compartments are now higher (hyperosmotic) than the initial values.

• The fluid volume is redistributed between the two compartments to equalize the osmolarities and remains lower than the initial values in each of them (volume contraction)

Note that in central DI, ADH levels are decresed, while in nephrogenic DI, they are normal or increased to compensate for the high urine output.