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

List:

· Intro

· Diagramme of juxtamedullary nephron

· Creation

· Maintenance

Intro:

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

Juxtamedullary nephron: 15% total

Countercurrent multiplication:

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 recycling:

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)

Countercurrent exchange:

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