Control of water balance

Question 1

what is osmolarity and what does this depend on?

Answer 1

Measure of the solute concentration in a solution, depends on the number of dissolved solutes present. The greater the number of dissolved particles, the greater the osmolarity

Question 2

what determines the ECF volume?

Answer 2

Salt concentration (because water follows salt)

Question 3

What is the most abundant component of the plasma and ECF, and what is the most prevalent solute in the plasma and ECF?

Answer 3

Water: most abundant component of the plasma and ECF

Sodium: most prevalent solute in the plasma and ECF

Question 4

What are the normal ranges for plasma osmolarity and urine osmolarity?

Answer 4

Plasma - 285-295 mosmol/L

Urine - 50-1200 mosmol/L

Question 5

What would happen if we didn’t get rid of the excess volume, excess water and excess salt?

Answer 5

Excess Volume - oedema + increase in blood pressure
Excess Water - cells swell
Excess Salt - cells shrink

Question 6

What is the main fluid compartment?

Answer 6

Intracellular - 65%

Question 7

What are the different routes of getting rid of water? How much is removed via each of these methods?

Answer 7

Skin/sweat: variable but uncontrollable- 450 mL/day
Faeces: uncontrollable
- 100 ml/day
Respiration: uncontrollable
- 350 ml/day
URINE: : variable and controllable - 1500 ml/day - CONTROLLABLE and variable

Question 8

Which part of the nephron is impermeable to water?

Answer 8

Ascending limb of the loop of Henle

Question 9

Describe how much water is reabsorbed in each of the different parts of the nephron.

Answer 9

70% in the PCT
10% in the loop of Henle
Amount reabsorbed in the collecting duct varies

Question 10

what is the relationship between Renal relative medullary area and maximal urine osmolic concentration?

Answer 10

Linear relationship

Question 11

What needs to be created for water to be drawn out of the tubules and into the interstitium?

Answer 11

Hyperosmolar Region

Question 12

Describe the osmolarity gradient in the interstitium.

Answer 12

Lowest concentration (around the same as plasma) in the cortex
Highest concentration in the inner medulla

Question 13

What is the approximate gradient between the ascending loop of Henle and the interstitium?

Answer 13

200 mosmol/L

Question 14

What else accounts for the hyperosmolarity of the interstitial space?

Answer 14

UREA

Question 15

Which parts of the nephron are permeable to urea? How does this set up a circulation of urea?

Answer 15

The bottom part of the collecting duct (inner medullary collecting duct)
The bottom of the descending limb of the loop of Henle
The upper part of the collecting duct is permeable to water so the urea gets concentrated as it passes down the collecting duct. The urea moves out into interstitial space (down the concentration gradient) and then it passes into the loop of Henle and recirculates.

Question 16

Where are the urea transporters: A1, A2, A3 and B1 found?

Answer 16

UT-A1 - tubular side of the collecting duct cells
UT-A2 - thin descending limb of the loop of Henle
UT-A3 - basolateral membrane of collecting duct cells
UT-B1 - vasa recta

Question 17

How important are the Urea transporters?

Answer 17

UT-A1/3 KO:

• Reduced urea in the inner medulla
• Severe reduction in ability to concentrate urine
• Increased water intake by 20%
• No ability to reduce urine output if water restricted for 24h

UT-A2 KO
-Very mild phenotype only observable on a low protein diet

UT-B KO
Increased urine production
Reduced urine concentrating ability
Weight loss

Question 18

what type of mutations occur in humans?

Answer 18

• Point mutations in UT-A2 have been observed: Reduced blood pressure
• Loss of function mutations in UT-B are observed: Reduction in urine concentrating ability

Question 19

Now that a hyperosmolar region has been created, what regulates the amount of water that is drawn out by this region?

Answer 19

ADH - changes the number of aquaporin 2 on the apical membrane of the collecting duct cells thus regulating water reabsorption

Question 20

How do you prevent the vasa recta from washing out the countercurrent gradient?

Answer 20

The vasa recta passes along the same path as the loop of Henle so as it moves down towards the bottom of the loop of Henle it loses water and gains salt as it.
As it goes back up it gains water and loses salt as it travels down the osmolarity gradient meaning that it doesn’t change the countercurrent gradient.
This way it can deliver oxygen and nutrients without disrupting the countercurrent gradient.

Question 21

What cells do ADH bind to?

Answer 21

Principal cells in the collecting duct

Question 22

Which transport channels does ADH stimulate? Include one transport channel that does not transport water.

Answer 22

Aquaporin 2 - more move to the apical surface and increase water reabsorption
UT-A1 and UT-A3 - stimulates urea transport through the inner medullary collecting duct into the thin ascending limb of the loop of Henle

Question 23

State factors that affect ADH release.

Answer 23

Increase in plasma osmolarity

Ethanol inhibits ADH release - leads to an increase in urine volume and dehydration

Question 24

State three issues that can cause problems with water balance. Which disease involves these three issues and what are the symptoms?

Answer 24

Absent ADH
No detection of ADH
No response to the ADH signal (due to problem with aquaporin 2)
Diabetes Insipidus - polyuria and polydipsia

Question 25

what is vasopressin?

Answer 25

-Vasopressin (ADH; antidiuretic hormone)
-Peptide hormone
(9 amino acids)
-Derived from a single transcript that also encodes neurophysin II and copeptin
-Synthesised (transcribed and processed) in the hypothalamus
Packaged into granules
-Secreted from the posterior pituitary (neurohypophysis)
-In response to increased osmolarity or reduced volume
-Binds to specific receptors (V2) on basolateral membrane of principal cells in the collecting ducts

Question 26

Identify 4 components that allow the generation of this hyperosmolar environment:

Answer 26

1. Counter current mechanism
2. Descending loop impermeable to salt but permeable to water
3. Ascending loop impermeable to water but permeable to salt
   - Na+/K+ ATPase activity of the ascending loop but not descending loop
4. Urea permeability of the bottom of the loop and the collecting duct

Question 27

why is the hyperosmolar environment required for water retention?

Answer 27

1. water is reabsorbed by osmosis so need to generate a hyperosmolar environment compared to the fluid in the collecting duct
2. This fluid starts with an osmolarity approaching that of plasma and contains solutes that need to be excreted. Removal of water would increase the osmolarity so need to maintain an osmotic gradient that allow this to happen as the fluid passes along the the latter part of the diaphragm.

Question 28

how does ADH increase water retention?

Answer 28

Causes the principal cells to relocalise transporters (AQP2, UTA1, and UTA3) to the apical and basolateral membranes, so increases the permeability of the cells to water and urea

Question 29

what is the importance of urea permeability in the CCD in response to ADH?

Answer 29

Increased urea permeability causes urea to move down its concentration gradient into the interstitium and increase the interstitial osmolarity. Consequently more water can be reabsorbed.

Question 30

Identify 2 triggers of ADH secretion?

Answer 30

Hyperosmolarity identified by osmoreceptors.

Low blood pressure, identified by baroreceptors