2008A15 Describe how the kidney establishes the medullary concentrating gradient.

Description

·   Ascending concentration gradient from superficial to deep medulla

·   Max osmolality ~1200mOsm

Purpose

·   Allows selective reabsorption of water in medullary collecting ducts (ADH -> aquaporin-2)

Aetiology

·   Established by countercurrent multiplication (CCM) 50% and urea recycling 50%

·   Maintained by countercurrent exchange (CCE) in vasa recta

·   Only relevant to juxtamedullary nephrons

Step 1

·   Thick ascending limb is permeable to solute, not water

·   Filtered solute reabsorbed by 2° active transport (~25% filtered Na⁺/Cl^-/K⁺)

·   Passage via apical Na⁺K⁺2Cl^- symporter

·   Basolateral Na⁺K⁺ATPase creates Na⁺ gradient

·   Effects: ↓urine osmolality, ↑interstitial osmolality to a level above normal

Step 2

·   Thin descending limb is permeable to H₂O, not solute

·   Filtered H₂O reabsorbed by osmosis (eventually 10% of that filtered)

·   Effects: ↑urine osmolality, ↓interstial osmolality but not back to starting level

Steps 3+

·   Process is repeated hence amplified

Urea handling

·   Freely filtered

·   50% reabsorbed by proximal tubule

·   Same 50% secreted into thin descending loop of Henle

·   Same 50% reabsorbed in medullary collecting ducts via ureaporins (if ADH present)

Mechanism

·   Repeat transit between thin descending loop of Henle and medullary collecting duct

o Antegrade via the urine

o Retrograde via the interstitium

·   Multiple passages of each molecule before excretion -> ↑interstitial osmolality
(as if several cars cycling a round-a-bout)

Principle

·   Unidirectional rapid blood supply would cause dilution of interstitium by osmosis -i.e. elsewhere

·   Bidirectional slow flow minimizes dilution – i.e. vasa recta

Mechanism

·   Vasa recta exist alongside juxtamedullary nephrons

·   Descending limb: water lost, solute gained

·   Ascending limb: water gained, solute lost

·   Hence minimal change to interstitium

·   (Note also some reabsorption into lymphatics)

Problem

·   Slow flow

·   Low oxygen supply

·   High oxygen extraction ratio (medulla 0.8 cf. cortex 0.2)

·   Vulnerable to ischaemia