Dilute and Concentrated Urine Formation
Dilute Urine (ADH low/absent)
- Trigger ➜ over-hydration, plasma osmolarity ↓
- Thick ascending limb (TAL)
• Impermeable to water; NKCC pumps Na\^+, K\^+, 2 Cl\^- out
• Tubular fluid osmolarity falls to ≈ 150 mOsm vs IF 300 - Descending limb
• Impermeable to salts, permeable to water
• Water exits → tubular fluid concentrates until iso-osmotic with IF - Late distal convoluted tubule (DCT) & collecting duct (CD)
• Principal cells lack aquaporins → water cannot follow Na\^+
• Na\^+ actively reabsorbed; tubular fluid osmolarity drops (≈ 100→50 mOsm)
• Few urea transporters only near papillary end; limited urea recycling - Result ➜ large volume, hypo-osmotic urine; blood volume ↓
Concentrated Urine (ADH high)
- Trigger ➜ dehydration, plasma osmolarity ↑
- Common loop actions remain (salt pump in TAL, water equilibration in descending limb)
- ADH effects on late DCT & CD
• Inserts aquaporin-2 → water reabsorption ↑ dramatically
• Up-regulates urea transporters along CD - Consequences
• Water exit concentrates tubular urea
• Steeper urea gradient drives urea out of CD into medulla → enters thin limbs → recycles
• Urea + NaCl maintain steep medullary gradient (up to ≈ 1200 mOsm) - Result ➜ small volume, hyper-osmotic urine; plasma osmolarity ↓
Segment Functions (key points)
- TAL: “Pump” – sets gradient via active NaCl transport, no water flow
- Descending limb: “Equilibrate” – passive water loss to match IF
- Collecting duct: variable water & urea handling; ADH-regulated
- Vasa recta: counter-current exchanger preserves medullary gradient
Urea Recycling Essentials
- ADH ↑ CD urea transporters → more urea enters medulla
- Urea diffuses into thin limbs, returns to TAL/DCT, re-enters CD
- Reinforces medullary osmotic gradient; critical for maximal urine concentration
Diuretics (clinical tie-in)
- Caffeine ➜ inhibits Na\^+ reabsorption in DCT/CD → water retained in lumen
- Loop diuretics (e.g., Lasix) ➜ block NKCC in TAL → medullary gradient ↓ → water loss ↑
- Alcohol ➜ suppresses ADH release → CD water permeability ↓ → diuresis