Control of water balance

Question 1

Osmolarity definition

Answer 1

Measure of the solute concentration in a solution that depends upon the number of dissolved solutes
present, i.e. the greater the number of dissolved particles, the greater the osmolarity.

Question 2

Plasma osmolarity

Greatest proportion

Answer 2

Plasma osmolarity = 285-295mosmol.L-1 (H2O= most abundant)

greatest proportion is ~140mmol.L-1 Na= most abundant solute

Question 3

Methods of getting rid of water

Answer 3

Sweat (450ml/day) – Uncontrollable (variable).
Faeces (100ml/days) – Uncontrollable
Respiration (350ml/day) – Uncontrollable
Urine (1500ml/day)= controllable (variable).

Question 4

What is H2O regulation for?

What is salt regulation for?

Answer 4

Regulation of plasma osmolarity

Determine ECF volume

Question 5

Counter current flow explain

Proportion of Na+ contribution?

Answer 5

1. Each flow pumps sodium out in the thick ascending limb of the LoH= creates hyper-osmotic extracellular environment.
2. Each flow will contribute to this more and more.
3. The ascending limb is impermeable to water. Water= drawn out in thin descending limb of LoH while
   this limb is impermeable to salts.

The sodium pumped out only creates 600mosmol.L-1
of the total 1200mosmol.L-1 osmolarity of the interstitial fluid. (other part= UREA)

Question 6

Na+ variation in different fluids

Answer 6

Low in intracellular fluid
High in ECF (IF)
High in plasma

Question 7

K+ variation in different fluids

Answer 7

High in intracellular fluid
Low in ECF (IF)
Low in plasma

Question 8

Protein variation in different fluids

Answer 8

High in intracellular fluid
Low in ECF
High in plasma

Question 9

Cl- variation in different fluids

Compensation ion?

Answer 9

Low in tracellular fluid
High in ECF (IF)
High in plasma

HPO4- (high where Cl- isn’t)

Question 10

Plasma osmolarity

Greatest proportion

Answer 10

Plasma osmolarity = 285-295mosmol.L-1 (H2O= most abundant)

greatest proportion is ~140mmol.L-1 Na= most abundant solute

Question 11

Urea role
Importance?
Change in urea concentration?

Answer 11

Up ascending loop, water doesn’t move out but Na+ moves out, so by distal convoluted tubule there wouldn’t be a gradient if urea wasn’t there

1. Concentration of urea in  tube = higher as it goes up ascending limb of LoH + back down in the
collecting duct (impermeable to urea at these points) as more and more water is removed 
2. When it gets to the inner medulla collecting duct,
membrane becomes permeable and urea passes down it’s concentration gradient back into bottom of loop through interstitium

Question 12

Urea transporters
Deficiency of each one=?
In humans?

Answer 12

UT-A1, UT-A3 – Inner medullary collecting duct.
Deficiency= decrease urea in inner medulla, decrease ability to concentrate urine, increased water intake, no ability to reduce urine output if water restricted for 24h

UT-A2 – Thin descending limb.
Deficiency=Only observable if on low protein diet, low blood pressure

UT-B1 – Descending vasa recta.
Deficiency=Increased urine production, decreased urine concentrating ability, weight loss

Question 13

Vasa recta adaptations
As it descends?
As it ascends?

Answer 13

Fully permeable to both water and solutes.

As it descends, blood loses water + concentration of
solute rises.

As it ascends, the opposite occurs so the gradient isn’t removed.

However, still carries away EXCESS to maintain the
equilibrium.

Question 14

High ADH leads to?

Answer 14

Maximal water reabsorption = urine becomes
concentrated = has a high osmolarity = less hypotonic urine leaving the LoH + more hypertonic urine entering the LoH.

Increased plasma osmolarity → increased thirst & increased ADH release (osmoreceptors) → More ADH release → increased collecting duct water
permeability → decreased urine flow rate.

Question 15

Where is the only place that water isn’t absorbed?

Answer 15

Ascending loop of Henle

Question 16

Urea role
Importance?
Change in urea concentration?

Answer 16

Up ascending loop, water doesn’t move out but Na+ moves out, so by distal convoluted tubule there wouldn’t be a gradient if urea wasn’t there

1. Concentration of urea in  tube = higher as it goes up ascending limb of LoH + back down in the
collecting duct (impermeable to water at these points) as more and more water is removed 
2. When it gets to the inner medulla collecting duct,
membrane becomes permeable and urea passes down it’s concentration gradient back into vasa recta through interstitium

Question 17

Urea transporters

Answer 17

UT-A1, UT-A3 – Inner medullary collecting duct.
UT-A2 – Thin descending limb.
UT-B1 – Descending vasa recta.

Question 18

Vasa recta adaptations
As it descends?
As it ascends?

Answer 18

Fully permeable to both water and solutes.

As it descends, blood loses water + concentration of
solute rises.

As it ascends, the opposite occurs so the gradient isn’t removed.

However, still carries away EXCESS to maintain the
equilibrium.

Question 19

Vasopressin binds to?
Actions?
Triggers?
Inhibited by?

Answer 19

Principal cells in collecting ducts

1. Insertions of Aquaporin2 (AQA2) molecules into the luminal membrane.
2. Stimulates urea transport from IMCD into thin ascending LoH and interstitial tissue by increasing localisation of UT-A1 and UT-A3 in the CCD.

Osmolarity rise above 300mosmol.L-1 – osmoreceptors regulated.
Marked fall in blood volume/pressure – baroreceptor regulate

Ethanol INHIBITS ADH release = dehydration.

Question 20

Low ADH leads to?

Answer 20

Minimal water reabsorption= urine remains diluted= low osmolarity= more hypotonic urine entering+ leaving LoH

Decreased plasma osmolarity → Less ADH release (osmoreceptors) → reduction in collecting duct permeability to water → Increased urine flow rate.

Question 21

High ADH leads to?

Answer 21

Maximal water reabsorption = urine becomes
concentrated = has a high osmolarity = less hypotonic urine leaving the LoH + more hypertonic urine entering the LoH.

Increased plasma osmolarity → increased thirst & increased ADH release (osmoreceptors) → More ADH release → increased collecting duct water
permeability → decreased urine flow rate.

Question 22

Disorder of water balance
Caused by?
Leads to?

Answer 22

Diabetes insipidus

No/ insufficient production of ADH
No detection of ADH (mutant ADH receptor)
No response to ADH signal (mutant aquaporin)

Excretion of large amounts of watery urine
Thirst

Question 23

SAQ:

4 components that allow generation of hyperosmolar environment

Answer 23

Counter current mechanism
Descending loop impermeable to salt but permeable to water
Ascending loop impermeable to water but permeable to salt: Na+/K+ ATPase activity of ascending loop but not descending loop
Urea permeability of bottom of loop+ collecting duct

Question 24

SAQ

Why is the hyperosmolar environment required for water retention?

Answer 24

Water is reabsorbed by osmosis so need to generate a hyperosmolar environment compared to fluid in collecting duct
Fluid starts with an osmolarity approaching that of plasma+ contains solutes that need to be excreted. Removal of water= increased osmolarity= need to maintain osmotic gradient that allows this to happen as fluid passes along latter part of nephron

Question 25

SAQ | How does ADH increase water retention?

Answer 25

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

Question 26

SAQ | What is the importance of urea permeability in the CCD in response to ADH?

Answer 26

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

Question 27

SAQ | Identify 2 triggers of ADH secretion?

Answer 27

Hyperosmolarity identified by osmoreceptors | Low blood pressure identified by baroreceptors