2011A11 Describe the functions of the loop of Henle, including the physiological mechanisms involved.

Reabsorption

·   Water and solute

·   Less important than proximal tubule

Urine concentration

·   More important for juxtamedullary nephrons

·   Hypertonic interstitium allows selective water reabsorption under control of ADH

o Created by countercurrent multiplication (50%) and urea recycling (50%)

o Maintained by countercurrent exchange in vasa recta

Autoregulation of GFR

·   Adjust afferent arteriolar tone depending upon distal tubule flow rate

·   Chemical: tubuloglomerular feedback

·   Hormonal: renin-angiotensin

Thin descending limb

·   Solute-impermeable

·   Water reabsorbed by osmosis

Thick ascending limb

·   Secondary active solute transport

·   Apical Na⁺K⁺2Cl^- symporter

·   Basolateral NaKATPase

·   ~25% of filtered Na⁺, Cl^-, K⁺

Step 1

·   Thick ascending limb is permeable to solute, not water

·   Filtered solute reabsorbed by 2° active transport

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

·   Gradient created by basolateral Na⁺K⁺ATPase

·   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 crowding 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)

Chemical

i.e. tubuloglomerular feedback

·   ↓n(NaCl) delivered to macula densa in distal convoluted tubule

·   ↓Cell stretch

·   ↓ATP release via stretch-activated channel hence ↓adenosine

·   Dilatation of afferent arteriole -> ↓resistance to flow -> ↑renal blood flow and GFR

Hormonal

i.e. renin-angiotensin system

·   ↓n(NaCl) delivered to macula densa in distal convoluted tubule

·   ↓Cell stretch -> a ) ↓PGE₂ release b) ↓adenosine (as above)

·   ↑Renin release from juxtaglomerular cell -> ↑Angiotensin 2

·   Generalised vasoconstriction -> ↑mAP -> ↑RBF and GFR

·   Efferent > afferent arteriolar vasoconstriction -> GFP ± GFR

·   ↑Na⁺/H₂O reabsorption from proximal tubule -> ↑ECF volume -> ↑mAP -> ↑RBF and GFR