Primary Function of Antidiuretic Hormone (ADH) Secretion
Antidiuretic hormone (ADH) primarily increases water reabsorption in the kidney by stimulating vasopressin V2 receptors, thereby reducing urine production and helping maintain water balance in the body. 1
Mechanism of Action
ADH (also known as arginine vasopressin or AVP) works through several key mechanisms:
Renal water conservation: ADH binds to V2 receptors on the collecting duct cells in the kidney, triggering a cascade of events 1:
- Activation of G proteins
- Stimulation of adenylyl cyclase
- Production of cyclic AMP (cAMP)
- Activation of protein kinase A (PKA)
- Exocytotic insertion of aquaporin-2 (AQP2) water channels from intracellular vesicles into the apical membrane 2
Aquaporin regulation: The insertion of AQP2 water channels allows water to be reabsorbed from the collecting duct into the cell, while constitutively expressed AQP3 and AQP4 in the basolateral membrane allow water to exit into the hypertonic interstitium 2
Urine concentration: This process leads to increased water reabsorption, decreased urine volume, and increased urine osmolality 1
Physiological Effects
When ADH is secreted, it produces several important physiological effects:
Reduced urine output: Can decrease adult urine output to as little as 500 mL per day when secreted in excess 3
Increased plasma osmolality: By retaining water, ADH helps maintain normal plasma osmolality 4
Water homeostasis: Without ADH influence (as in diabetes insipidus), a person would need to ingest 5-15 L of water daily to match urinary losses 3
Regulation of uromodulin: ADH administration reduces uromodulin secretion and its protein levels in the kidney, though it can acutely cause a burst of urinary release 5
Clinical Relevance
The function of ADH is particularly important in several clinical contexts:
Diabetes insipidus: A condition characterized by ADH deficiency or kidney resistance to ADH, resulting in excessive urine production and thirst 5
SIADH (Syndrome of Inappropriate ADH secretion): Excessive ADH secretion leads to water retention, hyponatremia, and potential neurological symptoms 4
Heart failure: The renin-angiotensin-aldosterone system with ADH is activated in heart failure, leading to increased sodium and water reabsorption, perpetuating congestion 5
Hyponatremia management: Understanding ADH function is crucial for managing hyponatremia, which can be classified as mild (126-135 mmol/L), moderate (120-125 mmol/L), or severe (<120 mmol/L) 5
Regulation of ADH Secretion
ADH secretion is regulated by:
- Plasma osmolarity: Primary regulator - increased osmolarity stimulates ADH release 6
- Blood volume: Decreased effective circulating volume stimulates ADH release 5
- Stress: Acts as a non-osmotic stimulus for ADH secretion 6
- Medications: Certain drugs can affect ADH secretion or action, including antidepressants, antipsychotics, and some antibiotics 7
Understanding ADH's function is essential for managing fluid balance disorders, particularly in critically ill patients where water imbalance is common and can be potentially lethal if not properly addressed 3.