Collecting duct principal cell: aquaporin-2 and antidiuretic hormone
Collecting duct · AQP2 V2/cAMP Vaptans Lithium
The only water permeability the nephron can regulate: vasopressin inserts aquaporin-2 into the apical membrane so that fluid arriving hypotonic from the distal tubule equilibrates first with the cortical (300) and then the medullary (up to 1200 mOsm/kg) interstitium, or is passed unchanged as dilute urine.
Traced from the start
- Glomerular filtration barrier
- Proximal tubule: Na+/H+ exchange and bicarbonate reclamation
- Thick ascending limb of Henle (NKCC2)
- Early distal convoluted tubule: thiazide-sensitive NaCl cotransporter
- Collecting duct principal cell: aquaporin-2 and antidiuretic hormone
Detail
- Reabsorbs
- Water: from almost none (urine ~50 mOsm/kg, up to ~20 L/day) to ~10-15% of the filtered load with maximal ADH (urine ~1200 mOsm/kg, ~0.5 L/day)
- Transporter
- AQP2 shuttled into the apical membrane from subapical vesicles; AQP3 and AQP4 basolateral and constitutive
- Hormone
- ADH (vasopressin) from the supraoptic and paraventricular nuclei via the posterior pituitary; V2 receptor, Gs, cAMP, PKA phosphorylates AQP2 for insertion; released when plasma osmolality exceeds ~280-285 mOsm/kg (a 1% change is sensed) or when blood volume or pressure falls by roughly 10% or more (less sensitive but more powerful)
- Release modifiers
- Inhibited by alcohol, ANP and hypo-osmolality; stimulated by pain, nausea, hypoglycaemia, angiotensin II and drugs (SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, MDMA)
- Diuretic
- Vaptans (tolvaptan, conivaptan): V2 antagonists producing 'aquaresis'; lithium and demeclocycline blunt AQP2 expression (drug-induced nephrogenic DI)
When it goes wrong
Central diabetes insipidus (pituitary surgery, head trauma, craniopharyngioma, infiltration)
Polyuria of dilute urine (under 300 mOsm/kg) with thirst; hypernatraemia if water intake fails; urine concentrates after desmopressin in the water-deprivation test
Nephrogenic diabetes insipidus (lithium, hypercalcaemia, hypokalaemia, X-linked V2 receptor or AQP2 mutations, relief of obstruction)
Same polyuria with no response to desmopressin; treat the cause, then thiazide plus amiloride (amiloride blocks lithium entry through ENaC)
SIADH (small-cell lung cancer, pneumonia, SSRIs, carbamazepine, head injury)
Euvolaemic hyponatraemia with inappropriately concentrated urine (over 100 mOsm/kg) and urine Na+ over 30 mmol/L; fluid restrict and correct no faster than 8-10 mmol/L per 24 h to avoid osmotic demyelination
Tolvaptan for hyponatraemia or ADPKD
Aquaresis with risk of over-rapid Na+ correction; hepatotoxicity with long-term use
Practise this structure
1 question in the bank tagged Antidiuretic Hormone.