L3 - Urine Concentration and Dilution

Question 1

What is the units and equation of osmolarity?

Answer 1

Osmolality = [X] * n
Units = mOsmol/kgH2O

Question 2

What is the osmolality of 100 mM NaCl?

Answer 2

100 * 2 = 200 mOsmol/kgH2O

Question 3

What does counter current multiplication involve?

Answer 3

Involves loop of Henle and collecting ducts

Question 4

How many nephrons are juxtamedullary?

Answer 4

15% of nephrons in the kidney are juxtamedullary – especially important in concentrating urine

Question 5

How is water handled in the loop of Henle?

Answer 5

Reabsorbed via the thin descending limb
Water will only leave in the presence of vasopressin in the collecting duct
Ascending limb is water impermeable

Question 6

How is Na and Cl handled in the loop of Henle?

Answer 6

Reabsorbed via the thin and thick ascending limb

Critical for setting up the process of counter current multiplication

Question 7

How does interstitial fluid osmolality change during the loop of Henle?

Answer 7

Interstitial fluid (outside) osmolality rises down the descending limb

Question 8

How does the tubular fluid osmolality change during the loop of Henle?

Answer 8

Tubular fluid (inside) osmolality decreases up the ascending limb

Question 9

What is the transverse and vertical gradient hypothesis?

Answer 9

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

Question 10

Transverse and vertical gradient hypothesis method

Answer 10

1. NaCl moves out of ascending limb and they believed it moved into the descending limbs
2. Osmolality goes up in the descending limb
3. NaCl then moved into ascending limb by the flow in the tubular fluid
4. Continuous process creating high osmolality at bottom of loop
5. Descending limbs osmolality increases as water leaving
6. Ascending limbs osmolality decreases as NaCl leaving
   a. Creates driving force for reabsorption of water in the descending limb
7. Transverse gradient - not equal osmolality at same level in the ascending/descending limb
8. Tubular fluid is very dilute when it reaches the collecting duct
9. If vasopressin present, high NaCl in interstitial fluid drives water reabsorption
   a. High osmotic driving force
   b. More concentrated urine

Question 11

How does vasopressin regulate NaCl?

Answer 11

Regulates NaCl handling in the thick ascending limb

• Causes loss of more NaCl into interstitial fluid
• Higher osmotic driving force

Question 12

What is the thin descending limb permeable to?

Answer 12

Aquaporin 1 – water permeable

Leaves into interstitial fluid – water reabsorption

Question 13

What is the thin descending limb impermeable to?

Answer 13

NaCl and urea impermeable
Small leak of NaCl into ascending limb
Increases concentration of solutes for the ascending limb

Question 14

What is the thin ascending limb permeable to?

Answer 14

NaCl and urea permeable

Question 15

What is the thin ascending limb impermeable to?

Answer 15

Water impermeable

Question 16

What channels are found on the basolateral membrane of the thick ascending limb?

Answer 16

Na/K ATPase
K channel
Cl channel
Barttin channel

Question 17

What channels are found on the apical membrane of the thick ascending limb?

Answer 17

NKCC2

ROMK

Question 18

What is Bartters syndrome caused by?

Answer 18

Caused by mutations in NKCC2 found in the thick ascending limb
Genetic inheritance

Question 19

What are the symptoms of Bartters syndrome?

Answer 19

Salt wasting

Polyuria

Question 20

How is water reabsorbed in the cortical and outer medullary collecting ducts?

Answer 20

Water reabsorption by aquaporins

Due to the driving force created by the high NaCl concentration in interstitial fluid

Question 21

What is aquaporin2 regulated by?

Answer 21

Vasopressin causes the insertion of vesicles, containing AQP2, into membrane

Question 22

What is interstitial osmolality controlled by?

Answer 22

50% NaCl

50% Urea

Question 23

Role of urea in the early collecting duct?

Answer 23

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

Question 24

Role of urea in the inner medullary collecting ducts?

Answer 24

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

Question 25

How is urea transported in the inner medullary collecting duct?

Answer 25

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

Question 26

What is urine osmolality in the wildtype mice?

Answer 26

Urine osmolality - 2000

Question 27

What is urine osmolality in the UT-A1/A3 knockout mice?

Answer 27

Have lost ability to reabsorb urea in the colleting duct
Have lost half the driving force for water reabsorption
Urine osmolality – 1000

Question 28

Where does counter current exchange take place?

Answer 28

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

Question 29

What does counter current exchange ensure?

Answer 29

Ensures we have lots of NaCl and urea in the interstitial fluid

Question 30

Osmolality changes in the vasa recta?

Answer 30

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

Question 31

What is the UT-B channel?

Answer 31

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