Water Homeostasis

Question 1

Osmolarity

Osmolality

Tonicity

Answer 1

• Osmolarity - mmol/L of solution
• Osmolality - mmol/kg of water (amount of solvent remains constant despite temp and pressure)
• Tonicity - just looks at conc of molecules that can cross semi-permeable membrane b/c these are the only ones that exert osmotic effect (effective in moving water)

Question 2

How does vasopressin/ADH work on principal cells in CD?

Answer 2

• V2 receptor - on principal cells basolateral membrane –> Gs –> inc cAMP –> act PKA –> more AQP2 channels on apical membrane (water reabsorption)
• Water then driven into interstitium by hypertonic gradient (also maintained by vasopressin - inc Na-K-2Cl in TAL and UTA1 in collecting duct for urea transport)

Question 3

How is water generally handled in ea segment of nephron?

Answer 3

• Proximal tubule - 65-80% reabsorbed
  
  • Transcellular (AQP1) and paracellular
  • Then driven into peritubular caps b/c inc hydrostatic p of interstitium
• Thin descending - 15% reabsorbed (AQP1)
• Thin ascending/TAL/distal tubule - NONE reabsorbed (lack AQP1)
• Collecting duct - depends on if vasopressin is present
  
  • If vasopressin … permeable to water (V2 mechanism above - AQP2)
  • If no vasopressin … impermeable to water

Question 4

What are the 3 contributions to the corticopapillary gradient?

Answer 4

1- countercurrent multiplication; ACTIVE

2- Urea cycle

3- countercurrent exchanger (vasa recta); PASSIVE

Question 5

How do you make hypertonic urine?

Answer 5

• Reabsorb a larger percent in proximal tubule
• Then normal proceedings thru loop
• ADH/vasopressin present in collecting ducts = permeable to water and urea = hypertonic urine
  
  • Urea contributes to high Osm of interstit (1200)
  • Water can now be reabsorbed –> hypertonic urine

Question 6

How do you make hypotonic urine?

Answer 6

• Reabsorb smaller percent in proximal tubule
• Then normal proceedings thru loop
• ADH/vasopressin not present in collecting ducts = not permeable to water or urea = hypotonic urine
  
  • Salt cont to be reabsorbed but water remains in tubules
  • No urea contribution to medullary interstit gradient (only 600)

Question 7

Electrolyte Free Water Clearance

Answer 7

-Amount of solute-free water excreted by kidney in 24 hr period

• CeH2O = V x [1- (Una - Uk)/ Pna]
  - V= urine vol in 24 hr
• If do not know V you can still predict CeH2O based on (Una - Uk)/ Pna
  - If (Una - Uk)/ Pna is >1 then CeH2O will be neg
  (water retention)
  - If (Una - Uk)/ Pna is = 1 then CeH20 is zero
  - If (Una - Uk)/ Pna is <1 then CeH2O will be pos
  (water excretion)

Question 8

5 Steps of Countercurrent Multiplication

Answer 8

• 1- starts as isotonic (Osm fluid in loop = Osm medullary inter = 300)
• 2- thin ascending and TAL push salt out (impermeable to water) –> medullary inter (400) more conc than tubule fluid (200)
• 3- water leaves thin descending until its fluid is at same Osm as medullary inter (both at 400)
• 4-as new tubular fluid flows into loop of Henle this new fluid is at a lower Osm –> causes hyperosmotic thin descending fluid to shift to ascending limbs
• 5- Now more solute leaves the thin ascending and TAL –> more hypertonic medullary interstit
• REPEAT until very hypertonic interstitium (1200)

Question 9

Urea Cycle

Answer 9

• 100% filtered
• 50% reabsorbed in prox tubule
  
  • Paracellularly first then passive b/c
  • Transcellularly later b/c as water is reabsorbed there is urea gradient
• Urea conc inc in thin descending - b/c water is being reabsorbed and urea secretion into tubule (UT-A2 urea transporters)
• Urea conc cont to in in thin ascending - b/c cont secretion
• No change in urea in TAL and distal tubule b/c impermeable to both water and urea
• Cortical CD / Outer Med CD - if vasopressin present then water permeable but not urea permeable so inc urea conc
• Inner Med CD - if vasopressin present then permeable to urea –> into interstit (this is the urea that is secreted earlier in nephron)

Question 10

Countercurrent Exchanger

Answer 10

• Vasa recta branches off efferent and follows same U shape as loop
• Low flow to medulla so SLOW flow
• Totally passive (unlike countercurrent multiplication)
• Vasa recta Osm inc as it descends BUT vasa recta Osm then dec as it ascends (this maintains high Osm interstitium)