Concentrating and diluting urine

Question 1

Accomplishing urinary concentration

Answer 1

• Urine can be as concentrated as 1200mOsm or as dilute as 50mOsm
• This is done by osmolality gradient established by Na reabsorption in LOH and urea recycling along the nephron
• Couple this w/ the AQP profile and there can be great variability in H2O reabsorption
• All of this is regulated by ADH
• Important to realize that the LOH and CDs share a ISF, so changing the osmolality in the ISF by altering Na reabsorption in LOH will affect H2O reabsorption in the CD

Question 2

Hypertonic NaCl reabsorption by TAL

Answer 2

• This is the diluting segment, since Na is pumped out of TAL into the ISF but this segment is impermeable to H2O (and urea)
• Therefore the fluid in the tubule after the TAL will be dilute since Na has been removed from it
• At the same time as the luminal fluid is diluted, the ISF is concentrated
• TAL uses NKCC to do this, thus there are many apical K channels to allow for K recycling
• ADH increases NKCC and thus increases the gradient

Question 3

Formation of dilute urine (absence of ADH)

Answer 3

• W/o ADH H2O and urea permeability in distal nephron (DT, CCD, IMCD are low due to retraction of AQP2 and UT1 from the apical membrane
• These regions can continue to reabsorb Na w/o H2O to further dilute the urine
• Even though there is an osmotic gradient favoring water reabsorption, no reabsorption occurs if the cells aren’t permeable to water
• Cannot extract all of the salt from the urine (need to excrete some salt to excrete water)

Question 4

Formation of concentrated urine (presence of ADH)

Answer 4

• ADH increases water and urea permeability in distal nephron (up regulates AQP2 and UT1)
• Normally the distal neprhon is not permeable to these two
• But when upregulated by ADH, the increased permeability for H2O allows the osmotic gradient of the ISF around the distal nephron to pull water back out of the lumen and into the blood
• Urea recycling helps this, because reabsorbing urea form the IMCD will increase the ISF osmolality and help pull water from the distal nephron (urea is recycled to LOH)

Question 5

Urea recycling

Answer 5

• When ADH is stimulated and H2O/urea permeability in distal nephron are increased, H2O is allowed to leave the lumen more proximal than urea (H2O can leave after TAL, urea not until IMCD)
• As the H2O leaves the luminal fluids [urea] increases, so that once the fluid reaches the IMCD there is a large gradient favoring reabsorption of urea
• Urea enters the ISF and then is secreted into the thin ascending (mostly) and descending limbs of LOH, as well as some being carried away by vasa recta (all down the concentration gradient)

Question 6

Various permeabilities of LOH

Answer 6

• In descending limb there is progressive increase in [NaCl] since there is reabsorption of H2O via AQP1 into the surrounding hypertonic ISF, low permeability to NaCl (concentrating segment)
• A little bit of urea secretion
• In thin ascending limb: there is passive NaCl reabsorption and secretion of urea all the time
• In TAL: active reabsorption of NaCl w/o water reabsorption or urea secretion (diluting segment)
• The LOH (specifically the descending and TAL) maintains the osm gradient within the nephron that goes from 285 (cortex)-> 1200 (papilla)

Question 7

Role of vasa recta 1

Answer 7

• Slow flow and loop arrangement allow equilibration of ISF and blood and prevents medullary osmotic gradient washout
• Increasing flow rate dissipates the medullary gradient (reduces ISF osm), and decreasing the rate limits O2 delivery and thus active transport

Question 8

Role of vasa recta 2

Answer 8

• In descending loops of vasa recta there is efflux of water (high ISF osm) and influx of solute (reabsorbing salt)
• In the ascending vasa recta there is influx of water as the distal tubule begins to reabsorb water and the ISF gradient falls
• Simultaneously there is a decrease in solute reabsorption into the vasa recta in the ascending regions
• Net effect: more control over vasa recta osmolality

Question 9

Cell survival in hypertonic ECF

Answer 9

• IMCD cells are in a unique environment where ECF and ICF osmolalities are both high
• They have proteins that can increase expression of osmolytes (like sorbitol) to prevent shrinkage of the cell in the hypertonic environment
• The cells also have transporters that can bring in other osmotically active molecules to help hold onto the water so the cells do not shrink in the hypertonic ECF
• The transporters and sorbitol are synthesized in response to hypertonicity of the ECF

Question 10

Estimating urinary concentration and diluting ability

Answer 10

• Urine is isoosmotic when Uosm is equal to Posm
• If urine is dilute, plasma becomes more concentrated (Uosms ability to concentrate urine and dilute ECF)
• CH2O: clearance of free water, reciprocal to Cosm (ability of kidney to dilute urine and concentrate ECF)
• Cosm = (Uosm x V)/Posm
• CH2O = V - Cosm (positive if urine is dilute, negative if its concentrated)

Question 11

Summary

Answer 11

• Increased Posm leads to increased ADH release and thus increase in H2O reabsorption
• There is excretion of small amount of concentrated urine, and return of free water to plasma leading to decrease in Posm
• When Posm is low there is reduced ADH release, leading to decreased H2O reabsorption and excretion of large amounts of dilute urine
• This is excreting lots of free water thus Posm goes up