L3 - Urine Concentration and Dilution Flashcards
What is the units and equation of osmolarity?
Osmolality = [X] * n Units = mOsmol/kgH2O
What is the osmolality of 100 mM NaCl?
100 * 2 = 200 mOsmol/kgH2O
What does counter current multiplication involve?
Involves loop of Henle and collecting ducts
How many nephrons are juxtamedullary?
15% of nephrons in the kidney are juxtamedullary – especially important in concentrating urine
How is water handled in the loop of Henle?
Reabsorbed via the thin descending limb
Water will only leave in the presence of vasopressin in the collecting duct
Ascending limb is water impermeable
How is Na and Cl handled in the loop of Henle?
Reabsorbed via the thin and thick ascending limb
Critical for setting up the process of counter current multiplication
How does interstitial fluid osmolality change during the loop of Henle?
Interstitial fluid (outside) osmolality rises down the descending limb
How does the tubular fluid osmolality change during the loop of Henle?
Tubular fluid (inside) osmolality decreases up the ascending limb
What is the transverse and vertical gradient hypothesis?
NaCl moves out of ascending limb and they believed it moved into the descending limb
Created high osmolarity at the bottom of the loop
Created a transverse gradient across the loop
Transverse and vertical gradient hypothesis method
- NaCl moves out of ascending limb and they believed it moved into the descending limbs
- Osmolality goes up in the descending limb
- NaCl then moved into ascending limb by the flow in the tubular fluid
- Continuous process creating high osmolality at bottom of loop
- Descending limbs osmolality increases as water leaving
- Ascending limbs osmolality decreases as NaCl leaving
a. Creates driving force for reabsorption of water in the descending limb - Transverse gradient - not equal osmolality at same level in the ascending/descending limb
- Tubular fluid is very dilute when it reaches the collecting duct
- If vasopressin present, high NaCl in interstitial fluid drives water reabsorption
a. High osmotic driving force
b. More concentrated urine
How does vasopressin regulate NaCl?
Regulates NaCl handling in the thick ascending limb
- Causes loss of more NaCl into interstitial fluid
- Higher osmotic driving force
What is the thin descending limb permeable to?
Aquaporin 1 – water permeable
Leaves into interstitial fluid – water reabsorption
What is the thin descending limb impermeable to?
NaCl and urea impermeable
Small leak of NaCl into ascending limb
Increases concentration of solutes for the ascending limb
What is the thin ascending limb permeable to?
NaCl and urea permeable
What is the thin ascending limb impermeable to?
Water impermeable
What channels are found on the basolateral membrane of the thick ascending limb?
Na/K ATPase
K channel
Cl channel
Barttin channel
What channels are found on the apical membrane of the thick ascending limb?
NKCC2
ROMK
What is Bartters syndrome caused by?
Caused by mutations in NKCC2 found in the thick ascending limb
Genetic inheritance
What are the symptoms of Bartters syndrome?
Salt wasting
Polyuria
How is water reabsorbed in the cortical and outer medullary collecting ducts?
Water reabsorption by aquaporins
Due to the driving force created by the high NaCl concentration in interstitial fluid
What is aquaporin2 regulated by?
Vasopressin causes the insertion of vesicles, containing AQP2, into membrane
What is interstitial osmolality controlled by?
50% NaCl
50% Urea
Role of urea in the early collecting duct?
In early collecting duct – low urea permeability
- However is permeable to water in the presence of vasopressin
Concentration of urea in tubular fluid increases going down the collecting duct
Role of urea in the inner medullary collecting ducts?
In inner medullary collecting duct - in the presence of vasopressin there is urea permeability
- Concentration of urea in tubular fluid high so it leaves into interstitial fluid
- Provides a driving force for water reabsorption
A small amount of urea leaks back into thin ascending and descending limb
How is urea transported in the inner medullary collecting duct?
Basolateral membrane is on the interstitial fluid side
This transport is driven by the fact that the early collecting duct is urea impermeable
Urea only transported if urea channels are present
- Apical side – UT-A1
- Basolateral – UT-A3
What is urine osmolality in the wildtype mice?
Urine osmolality - 2000
What is urine osmolality in the UT-A1/A3 knockout mice?
Have lost ability to reabsorb urea in the colleting duct
Have lost half the driving force for water reabsorption
Urine osmolality – 1000
Where does counter current exchange take place?
Takes place in vasa recta
- Blood supply to the kidney that also dip down into medulla and then back out to the cortex
- This prevents wash out
What does counter current exchange ensure?
Ensures we have lots of NaCl and urea in the interstitial fluid
Osmolality changes in the vasa recta?
Osmolality starts at 290 then increases to 1400 in the medulla and back to 290 once out the medulla
- Concentration gradient for water to leave and solutes to enter – descending limb
- Concentration gradient for water to enter and solutes to leave – ascending limb
What is the UT-B channel?
Urea transporter on RBCs
RBCs take in some of the urea from the plasma
However in the ascending limbs urea moves back into the interstitial fluid
