Urine concentration and dilution Flashcards
What is osmolality?
The measure of how CONCENTRATED a solution is
How is osmolality calculated?
Osmolality = [X] x n
n = the number of particles that substance X dissociates into in solution
What are the units of osmolality?
mOsmol/kgH2O
What is counter-current multiplication?
Regulation of the concentration of urine (increase concentration)
What parts of the nephron are important in counter current multiplication?
Loop of Henle
Collecting duct
Which type of nephron is important in the concentration of urine?
What % of the nephrons in the kidney do these make up?
Juxtamedullary nephrons
15% of the nephrons in the kidney
What are the ONLY animals that are able to concentrate urine?
Why?
Mammals and birds
As these are the only species to have a loop of Henle
What is important about the loop of Henle that allows the concentration of urine?
The actual LOOPING shape
Where does water leave the nephron?
Where does it move from/to?
From the tubular fluid of the THIN DESCENDING limb
Into the inner/outer medulla
Where does water NOT move across in the LOH?
The ASCENDING limb (thick or thin)
When does the movement of water from the tubular fluid into the inner/outer medulla happen?
Only occurs in the presence AVP (arginine vasopressin)
Where do Na+ and Cl- leave the loop of Henle?
Why is this important?
Leaves from the THIN and THICK ascending limb
Important in setting up the process of counter current multiplication:
- Allows the regulated water reabsorption from the collecting duct (in the presence of AVP)
What is ‘reabsorption’ in the kidney?
Movement of water from the thin descending limb of the LOH and the collecting duct
INTO the medullar (inner/outer cortex)
What is the osmolality in the cortex?
Around 290 mOsmol
What happens to the osmolality in the INTERSTITIAL FLUID as go deeper into the medulla?
What does this cause? Why?
Increases
Driving force for water to leave from the tubular fluid - from high –> low osmotic gradient
(HIGH osmolality, LOW osomolarity)
What does the osmolality of the tubular start as?
How does it change?
Why?
Starts at 290 mOsmol
At the tip - 1400 mOsmol
At the top of the ascending limb - 90 mOsmol
Decreases due to water moving OUT (leaving behind a more concentrated solution)
Increases as go up the ascending limb - Na+ and Cl- move OUT
What was the hypothesis that was designed before we knew how urine was concentrated?
Thought that:
- Solute leaves the ascending limb and enters the descending limb
- Causing an osmolality decrease in the ascending limb and an osmolality increase in the ascending limb
- Fluid moves constant through the tubule and its actually the solute that moves
What is the vertical gradient in the loop of henle?
Fluid in at 290 mOsmol
Increase to 1400 mOsmol
Decrease to 90 mOsmol
What is the trasnverse gradient in the loop of henle?
Osmolality in the ascending limb is LOWER than in the descending limb
What provides the driving force for the water to be reabsorbed from the descending limb?
Why is this a continuous process?
CONTINOUS process:
The solute that leaves the ascending limb and goes into the interstitial fluid
Causes the osmolality of the interstitial fluid (medulla) to increase and the osmolarity to decrease
Driving force for water movement
Continuous as:
- The the movement of water from the TDL and the collecting duct then promotes Na+ and Cl- loss from the AL
What happens when vasopressin is present is present?
Have high levels of aqua porins in the membrane - water leaves from the collecting duct
When does the urine become concentrated?
- Larger the loss of Na+ and Cl- from the AL to the interstitial fluid
- Bigger the osmotic gradient
- More water leaves (from DL and collecting duct)
- More concentrated urine
What does vasopressin regulate?
Aqua porin2 and water handling in the COLLECTING DUCT
Describe the permeability of thin descending limb to NaCl
Essentially impermeable but there is a very small NaCl leak from the interstitial fluid –> thin descending limb
How does water leave the thin descending limb?
Through CONSTITUATIVELY open aquaporin1 channel
What happens with AQP1 KO?
Problems concentrating urine
How do NaCl and urea leave the thin ascending limb?
Passively
Why are the transport systems in the thin ascending limb not very well understood?
Unable to access the segment in order to study it
What are the channels present on the basolateral membrane of the TAL?
What do these channels do?
- CLCK and Barttin
- Na/K ATPase
These channels:
- Set the negative membrane potential
- Set the low intracellular Na+
- Provide the driving force for NKCC2
What is NKCC2?
Protein channel found in the apical membrane of the TAL
Transports Na, K and 2 Cl
Where does the Na+ that travels through NKCC2 in the apical membrane go to?
Out through the Na/K ATPase
Where does the Cl- that travels through the NKCC2 channel go to?
Out through CLCK
Where does the K+ that travels through the NKCC2 channel go to?
Recycled out through ROMK channel in the apical membrane
What is needed for NKCC2 to work?
ALL 4 proteins to bind:
1 x Na
1 x K
2 x Cl
What happens if ROMK is blocked in the apical membrane of the TAL?
NKCC2 no longer works
What can lead to Bartter’s syndrome?
INHERITED mutations in: NKCC2, ROMK or Barttin
What are 2 symptoms of Bartter’s syndrome?
Why?
1) SALT WASTING
- Can’t reabsorb NaCl as cannot pass through NKCC2
- Increased loss of NaCl in urine
2) POLYURIA (increased urine flow rate)
- Less NaCl in the interstitial fluid
- Less of a driving force for water out of the collecting duct through AQPs
What is the key cell in the collecting duct?
What is this cell involved in?
Principle cell
Involved in water reabsorption (water through these cells from the inside to the tubule, to the medulla)
What MUST be present for water reabsorption?
AVP and AQP2 in the apical membrane of the proximal cell
What channels does water move through in the principle cell?
Apical membrane:
- AQP2
Bastolateral membrane:
- AQP3
- AQP4
What does vasopressin activate?
AQP2 BUT NOT AQP3 or APQ4
What happens in the PRESENCE of vasopressin?
1) Activation of the AVP receptor
2) Insertion of vesicles containing AQP2 into the apical membrane
What is the ‘shuttling hypothesis’?
When vasopressin levels DROP, vesicles shuttle OUT of the membrane, taking APQ2 with them
What does problems with APQ2/vasopressin lead to?
Diabetes insipidus
Where does 50% of the interstitial osmolality that drives water reabsorption come from?
50% from NaCl transport out of the ascending limb
50% from transport of urea
What happens to the concentration of urea in the collecting duct?
Why?
Increases
- Early part of the collecting duct is permeable to water (in the presence of AVP) but NOT urea
- Water moves out, therefore concentrating the urea in the tubular fluid
- In the later part of the CD - urea concentration in the tubular fluid decrease as the CD is now permeable to urea
- Urea OUT from the CD into the interstitial fluid
What are the 2 driving forces for water reabsorption?
NaCl and Urea
What happens to some urea when it is present in the interstitial fluid?
Some leaks back into the thin descending limb and some into the thin ascending limb
But, this is very small and is recycled - becomes concentrated and transported out again
Where are the urea transporters present?
In the INNER MEDULLARY COLLECTING DUCT
What are the urea transporters?
UT-A1 (apical membrane)
UT-A3 (basolateral membrane)
What is the driving force for urea across the inner medullary cell?
High concentration of urea at the apical membrane, low concentration at the basolateral membrane
Why does urea not move out in the early collecting duct?
No UT present
What happens in UT-A1/UT-A3 double KO mice?
- Lose ability to absorb urea in the inner medullary collecting duct
- Urea excreted in the urine
What impact does the UT-A1/UT-A3 double KO have on osmolality?
What does this cause?
- Osmolality is HALF in the KO compared to the WT due to minimal urea in the IF (but Na and Cl - 50% of driving force)
- Lose half the driving force for water reabsorption in the collecting duct
- Less concentrated urine
What is the difference between WT and UT-A1/UT-A3 double KO in water deprived environments?
In WT - urine concentration goes up (more water reabsorbed)
In KO - no change in urine concentration/osmolality
What is the vasa recta?
Where do they travel?
Specialise blood supply to the kidney, which leads on from the efferent arteriole
Dip down into the medulla and then back up into the cortex
Where does counter-current exchange occur?
In the vasa recta
What is the function of the ‘dipping’ of the vasa recta?
What would happen if it was just a conventional blood supply?
Prevent wash out of the interstitial fluid
If conventional blood supply:
- Much of the NaCl will go into the blood supply and be carried AWAY from the interstitial fluid
What happens to the osmolality of the interstitial fluid (outside of the vasa recta) as you go deep into the medulla
What does this cause?
Osmolality INCREASES
- Osmotic gradient for water to LEAVE the vasa recta and solutes to go INTO the vasa recta
If water LEAVES the vasa recta and solutes to goes INTO the vasa recta (from the interstitial fluid) why are the solutes of the interstitial fluid not carried away in the blood?
Because the plasma moves through the vasa recta and then the vessel travels upwards (past the point where water has entered and ions have just left)
So:
- Driving force for water IN and solutes OUT of the vasa recta, back into the interstitial fluid
What is UTB?
A urea transporter in RBC
What happens to the solutes when they get transported into the plasma of the vasa recta, when it dips DOWN into the medulla?
Urea gets transported into the RBC
What is the efflux pathway of urea back into the interstitial fluid in the ascending limb?
Urea lost from the RBC through UTB
What happens in patients that are lacking UTB?
Why?
Can’t concentrate their urine:
- Urea trapped inside the RBC (from the interstitial fluid) and carried away in the plasma in the vasa recta
- Lower driving force for water reabsorption
- Excretion of a dilute urine at higher volumes
