Control of plasma osmolarity
Changes in extracellular fluid osmolality can have significant effects on cells with fluid shifts leading to cell swelling or cell shrinkage. If not controlled these changes may cause cell death. Control of osmolality takes precedence over control of body fluid volume.
Increased water ingestion decreases osmolality due to dilution. In dehydration water deficiency causes osmolality to increase. Osmoreceptors in the anterior hypothalamus are sensitive to small changes in osmolality as little as 1%. Osmoreceptors send action potentials to trigger anti-diuretic hormone (ADH) release in response to increased osmolality and stimulate thirst.
ADH binds to V2 receptors on renal principal cells increasing cyclic AMP (cAMP) causing aquaporin channels to incorporate into the apical membrane. This allows water to enter the principal cells.
ADH also binds to V1 receptors causing renal vasoconstriction.
Important values
Normal urine production is ~60ml/h.
Maximum ADH reduces urine production to a minimum of 400ml/day
Normal urine osmolality is 300-800 mosmol/kg H2O
Maximum urine osmolality is ~1400 mosmol/kg H2O
ADH is mainly metabolised in the liver and kidneys & is rapidly removed from the plasma, with plasma levels often falling 50% in as little as 10 minutes.
Increased water ingestion decreases osmolality due to dilution. In dehydration water deficiency causes osmolality to increase. Osmoreceptors in the anterior hypothalamus are sensitive to small changes in osmolality as little as 1%. Osmoreceptors send action potentials to trigger anti-diuretic hormone (ADH) release in response to increased osmolality and stimulate thirst.
Increased osmolality triggers anti-diuretic hormone (ADH) release.
ADH is synthesised in the hypothalamus and transported to the posterior pituitary where it is stored in secretory vesicles pending release.
ADH is synthesised in the hypothalamus and transported to the posterior pituitary where it is stored in secretory vesicles pending release.
ADH binds to V2 receptors on renal principal cells increasing cyclic AMP (cAMP) causing aquaporin channels to incorporate into the apical membrane. This allows water to enter the principal cells.
ADH also binds to V1 receptors causing renal vasoconstriction.
- Plasma osmolality is proportional to plasma ADH levels
- Urine osmolality is proportional to plasma ADH levels
Important values
Normal urine production is ~60ml/h.
Maximum ADH reduces urine production to a minimum of 400ml/day
Normal urine osmolality is 300-800 mosmol/kg H2O
Maximum urine osmolality is ~1400 mosmol/kg H2O
In the absence of ADH urine volume could reach ~25 litres per day with a minimum urine osmolality of ~60 mosmol/kg H2O. This is clinically relevant in diabetes insipidus (DI) where ADH is either deficient (cranial DI) or there is a defective response to ADH (nephrogenic DI)
ADH is mainly metabolised in the liver and kidneys & is rapidly removed from the plasma, with plasma levels often falling 50% in as little as 10 minutes.