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