Describe the counter-current mechanism of urine concentration. Explain the role of the loop of Henle, vasa recta and ADH.

Introduction

Components of the Counter-current System

• Only the juxtamedullary nephrons (15%), with their long loops, take part

Counter-current Multiplier — Mechanism

The single effect

• Thick ascending limb actively pumps NaCl out (NKCC2) but is impermeable to water
• This creates a gradient of 200 mOsm at any horizontal level — the "single effect"

Ascending limb pumps NaCl into interstitium (water stays) → Interstitium becomes hypertonic → Water leaves the descending limb (which is water permeable) → Descending limb fluid becomes hypertonic → This fluid flows round into the ascending limb → Single effect is multiplied along the length of the loop → Gradient 300 → 1200 mOsm from cortex to papilla

• The counter-current (hairpin) flow is what multiplies a small horizontal gradient into a large vertical one
• The longer the loop, the greater the concentrating ability — desert rodents have very long loops

The Medullary Osmotic Gradient

• Composition of the gradient — roughly half NaCl and half urea

Dilution of Urine

Water excess → ADH suppressed → Thick ascending limb continues to pump NaCl out → Collecting duct remains impermeable to water → Dilute fluid passes through unchanged → Urine osmolality 50 mOsm/kg

• Maximum urine flow in water diuresis — about 16–20 mL/min
• Note that dilution is the passive default; concentration requires ADH

Role of Urea

• Urea contributes about 40–50% of the medullary hypertonicity
• ADH increases urea permeability of the inner medullary collecting duct (UT-A1 transporter)
• Urea recycling — urea diffuses into the interstitium, re-enters the thin loop, and returns to the collecting duct
• This is why a protein-deficient diet impairs urinary concentrating ability

Counter-current Exchanger — Vasa Recta

• Hairpin capillaries running parallel to the loops of Henle
• Freely permeable to water and solutes — act as passive exchangers

Descending vasa recta → water out, solute in → Blood becomes hypertonic at the tip → Ascending vasa recta → water in, solute out → Solute is retained in the medulla; the gradient is preserved

• Blood flow through the vasa recta is very low (1–2% of renal blood flow) and sluggish — further limiting washout
• ↑ Medullary blood flow (as with vasodilators) washes out the gradient → impaired concentration

Role of ADH

• ADH acts on V2 receptors → cAMP → insertion of aquaporin-2 into the apical membrane
• Obligatory urine volume = 500 mL/day — the minimum needed to excrete the daily solute load of 600 mOsm at maximum concentration

Free Water Clearance

Applied Aspects

• Diabetes insipidus

– Central — ↓ ADH secretion; responds to desmopressin

– Nephrogenic — tubules unresponsive (lithium, hypercalcaemia, aquaporin-2 defect); does not respond to ADH

• SIADH — excess ADH → water retention → dilutional hyponatraemia with concentrated urine
• Loop diuretics abolish the medullary gradient by blocking NKCC2 → the kidney can neither concentrate nor dilute
• Osmotic diuresis (as in uncontrolled diabetes) — unabsorbed glucose holds water in the tubule → polyuria