2017A13 Describe how the large daily volume of glomerular filtrate is altered by the kidney
to form a relatively low volume of 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

How it’s done

·  Large volume of iso-osmolar absorption, by both cortical and juxtamedullary nephrons

·  Effective concentration of the remainder, mainly by juxtamedullary nephrons

o Hyperosmotic interstitium created by countercurrent multiplication and urea recycling

o Hyperosmotic interstitium maintained by countercurrent exchange

o Selective water reabsorption under control of 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 -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)

 

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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