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

List:

· Summary of functions

· Diagramme of juxtamedullary nephron

· Reabsorption

· Countercurrent multiplication

· Urea recycling

· Countercurrent exchange

· Autoregulation of GFR

Summary of functions:

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

Diagramme of juxtamedullary nephron:

Reabsorption:

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⁺

Countercurrent multiplication:

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 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 crowding 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)

Autoregulation of glomerular filtration rate:

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