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

List:

· Intro

· Renal water handling

· Iso-osmolar reabsorption

· Countercurrent multiplication

· Urea recycling

· Countercurrent exchange

· ADH

Intro:

Numbers

· Renal blood flow 7,200L/day

· Glomerular filtration 180L/day

· Urine output 1-3L/day

Summary

· 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:

	Proportion	Mechanism
Proximal tubule	65%	· Osmosis · Gradient established by basolateral Na⁺K⁺ATPase
Thin descending limb of loop of Henle	10%	· 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	5-24.7%	· Osmosis · Dependent upon creation and preservation of hypertonic interstitium · Under control of ADH

Iso-osmolar absorption:

Location

· Proximal tubule >> other

Mechanism

· Basolateral Na⁺K⁺ATPase establishes solute gradients

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

· Water follows by osmosis

Autoregulation

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)

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

· 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)

Anti-diuretic hormone (ADH):

Source

· 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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