2020B04 Describe the physiological mechanisms by which the renal collecting duct is able to produce both dilute and concentrated urine.



·        Intro

·        Renal water handling

·        Iso-osmolar reabsorption

·        Countercurrent multiplication

·        Urea recycling

·        Countercurrent exchange

·        ADH




·  Renal blood flow 7,200L/day

·  Glomerular filtration 180L/day

·  Urine output 1-3L/day


·  Iso-osmolar absorption of the majority (cortical nephrons)

·  Variable concentration of the remainder (juxtamedullary nephrons)

o Tonicity gradient created by countercurrent multiplication and urea recycling

o Tonicity gradient maintained by countercurrent exchange

o Variable water reabsorption [ADH]


Renal water handling:




Proximal tubule


·  Osmosis

·  Gradient established by basolateral Na+K+ATPase

Thin descending limb of loop of Henle


·  Osmosis

·  Gradient established by Na+K+ATPase in thick ascending limb

Thick ascending limb of loop of Henle



Distal convoluted tubule



Connecting tubule



Collecting ducts


·  Osmosis

·  Dependent upon creation and preservation of hypertonic interstitium

·  Under control of ADH


Iso-osmolar absorption:


·   Proximal tubule >> other


·   Basolateral Na+K+ATPase establishes solute gradients

·   Na+ reabsorption is paired with multiple osmolytes (K+, Cl-, HCO3-, glucose, amino acids)

·   Water follows by osmosis


i.e. glomerulotubular balance:

·   Fixed proportion (not amount) of glomerular filtrate is reabsorbed by the proximal tubule

·   Prevents overwhelming of loop of Henle and distal nephron

·   ? due to ↑glucose and amino acid filtration -> ↑reabsorption paired with Na+

·   ? due to changes in oncotic pressure in the lateral intercellular space and peritubular capillaries


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)


·   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:


·   Unidirectional rapid blood supply would cause dilution of interstitium by osmosis

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


·   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)


Anti-diuretic hormone (ADH):


·   Produced by supra-optic and paraventricular nuclei of the hypothalamus

·   Released by posterior pituitary

Release stimuli

·   Osmolality (sensitive to 2%)

·   ↓Blood volume (sensitive to 10% but overrides osmolality)

·   ↓mAP

·   Angiotensin 2

·   Stress response e.g. surgery

·   Many drugs

Renal effects

·   Insertion of aquaporin 2 into apical membrane of collecting duct -> ↑H2O reabsorption hence urine concentration

·   Insertion of ureaporin into apical membrane of medullary collecting duct -> ↑urea recycling -> ↑interstitial osmolality -> ↑capacity for H2O reabsorption

·   (Also ↑Na+ reabsorption in thick ascending loop of Henle)



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