Lecture 5: How do we concentration urine Flashcards
What kind of environment is the renal medulla?
Dry hyperosmotic
What must happen to the last portion of the tubule?
It has to go back through the hyperosmotic environment in the renal medulla which we have created
What happens if no AQP are present in the collecting duct?
no water will be reabsorbed.
if no water is reabsorbed how much of GFR can be lost?
up to ~15%
1L/h of H2O in urine
What if there are AQP?
Water will move out of the collecting duct via AQP into the hypertonic environment if there are aquaporins in the tube’s epithelial cells
Describe the process if antidiuretic hormone (vasopressin) is released
Ultimately water is reabsorbed.
- Osmoreceptors in hypothalamus detect lower body fluids than normal
- ADH released from posterior pituitary
- ADH binds to V2 receptor in collecting duct
- AQP are inserted in lumenal side
- Max: reduce water loss from 1L/h ->15mL/h
What do long descending thin limbs (of the loop of henle) have, ONLY in the outer medulla?
aquaporins.
short descending thin limbs have no detectable AQP
What do short descending thin limbs have?
lots of chloride channels
what channels/transporters etc do the thick ascending limb of the loop of henle have?
Na2ClK pump, Na K ATPase
Cl channel, K channel
ROMK (renal outer medullary potassium channel)
What does ROMK do?
it recirculates potassium
What does Furosemide do?
it blocks the 2Cl- from entering the thick ascending limb
What happens to the remaining K and surplus Cl left from the proximal tubule?
they are reabsorbed, through the two Cl- and K+ channels
What is the maximum achieveable gradient across the thick ascending limb known as ?
the single effect
What is this maximum achieveable gradient across the TAL?
Tubular lumen has osmolarity of 290mosm/L
the Basolateral ECF has an osmolarity of 310mosmol/L
there is a 20mosmol/L gradient from tubular lumen to ECF
Describe the short loops and the countercurrent multiplier they have
- No aquaporins
- NaCl pumped out of thck ascending limb -> ECF -> thin descending limb
- filtrate with higher NaCl concentration moves down the thin descneding limb
What does optimum exchange require?
slow flow in order to achieve near equilibrium
Why would a decrease in medullary blood flow be required?
E.g. in volume depletion, to improve the efficiency of the countercurrent exchange by allowing more time for blood in the ascending vasa recta to achieve osmotic equilibration.
Where might an increase in medullary blood flow be required?
e.g. in osmotic diuresis, a decrreased urine concentrating ability and it will impair the efficiency of countercurrent exchange.
Why is there no active mechanism in the Thick ascending limb of the long loops?
they do not extend into the outer medulla
What is the current best guess of mechanism of concentration in the outer medulla?
the passive hypothesis
How much of the total loops do the long loops of henle make up?
~15%
The long loops which extend into inner medulla are
not the same as the short loops
What happens in the thin descending limb to concentrate the urine?
AQP are in the apical and basolateral membranes
ECF gradient is created by the thick ascending limb and short loops
Net water absorption occurs
The filtrate volume is reduced. This causes a reduced flow to the outer medulla which increases the filtrate
What happens if antidiuresis is present?
Dehydration will activate antidiuresis.
ADH inserts AQP2 channels in collecting duct
Urea concentration in collecting duct will rise due to water being reabsorbed
But there will also be some Urea channels open. Urea reabsorbed with the water ONLY IN THE INNER MEDULLA
What causes NaCl to leave the thin descending limb and the thin ascending limb?
The reabsorption of water and urea dilutes the ECF sodium concentration
This gradient is facilitaed by the ClCK1
The total inner medulla osmolarity will rise due to the urea and Sodium
This osmolarity will be 1200mosmol/L cosisting of 50% urea and 50% NaCl
What happens to the urea?
it goes round and round
How much of tubular fluid is left at the end of the loop of henle?
~15% of glomerular filtrate
What is the osmolarity at the end of the loop of Henle?
It is less than ECF, ~100mosmol/L
What is the concentration at the hairpin bend of the loop?
4x that of anywhere else.
~1200mosmol/L
Why is Urea surprisingly critical?
At the hairpin end during antidiuresis, the osmolaltiy of 1200-1400mosmol is ~ 50% NaCl and 50% Urea
Patients on low protein diets have a low urea production and therefore a low concentration ability
Urea can be restored rapidly by giving intravenous urea
