Water balance

Question 1

What is meant by osmolarity

Answer 1

measure of the solute concentration in a solution (osmoles/liter; 1 Osmole = 1 mole of dissolved solutes per liter); depends on the number of dissolved solutes present. The greater the number of dissolved particles, the greater the osmolarity

Question 2

What does the kidney need to do

Answer 2

Maintain plasma osmolarity under lots of different conditions
Some- high conc urine
Others- low conc urine

Question 3

Describe the flow of water

Answer 3

Water flows across a semi permeable membrane from a region of low osmolarity to a region of high osmolarity

Question 4

What is the consequence of a permeable system

Answer 4

Increase salt reabsorption- water will also move to balance it- thus increasing volume of the ECF

Question 5

Describe the inter-relation between salt and water regulation

Answer 5

Increasing salt increases water reabsorption, which increases plasma volume and maintains osmolarity
§ Water balance is used to regulate plasma osmolarity.
§ Salt levels are used to determine the ECF volume.

Question 6

What is the major salt

Answer 6

Na+- most prevalent solute in plasma and ECF

Question 7

On average, what do we consume daily

Answer 7

On an average day we consume 20-25% more water and salt than we need to replace that lost.
o Must get rid of excess volume – or become hypertensive and oedematous.
o Must get rid of excess water – or cells will swell in the body (dilute salt in body).

Question 8

Why is it important to get rid of the excesses

Answer 8

Must get rid of any excess water
To keep osmolarity up

Must get rid of any excess salt
To stop osmolarity going too high

If you don’t get rid of excess water you will dilute your body salt and the cells will expand, if you don’t get rid of excess salt the cells will shrink.

Question 9

Describe the osmolarity that we should maintain the plasma at

Answer 9

o Plasma osmolarity = 285-295mosmol.L-1 (greatest proportion is ~140mmol.L-1 Na).

Question 10

What are the most abundant components and solute of the plasma and ECF

Answer 10

Water: most abundant component of the plasma and ECF
Sodium: most prevalent solute in the plasma and ECF

Question 11

What is the key difference in terms of the movement of water and salt

Answer 11

Water can move freely, but salt cannot- therefore we balance salt.

Question 12

Describe the proportions of water found in different compartments of the body

Answer 12

In the body, 25L (65%) is found intracellularly and 15L (35%) is found extracellularly (e.g. plasma and interstitial).

Question 13

What compensates for a low IC cl- conc

Answer 13

A high IC HPO42-

Question 14

Describe some other relative concs of ions

Answer 14

HCO3- lower in cells than ECF or plasma

Ca2+ higher in cells

Question 15

Describe how we get rid of water

Answer 15

· Sweat – 450ml.days-1 – UNCONTROLLABLE (variable: fever, climate, activity)

· Faeces – 100ml.days-1 – UNCONTROLLABLE (Diahhroea up to 20L/day with cholera)

· Respiration – 350ml.days-1 – activity- UNCONTROLLABLE.

· Urine - ~1500ml.days-1 – CONTROLLABLE (variable).

Question 16

Where is water reabsorbed

Answer 16

All along the nephron except for the ascending limb

Question 17

Summarise the reabsorption of water

Answer 17

§ Even though 180L.days-1 is filtered, only 1-2L.days-1 is produced as urine. 
§ ~60-70% reabsorbed at PCT. 
§ ~30% reabsorbed at LoH. 
§ ~20% reabsorbed at DCT. 
§ ~1-10% reabsorbed at collecting duct. 

Regulation occurs at the collecting duct

Question 18

What is maximum urine osmotic concentration proportional to

Answer 18

Relative medullary area
Longer descending limb= more concentrated urine- important in animals that need to reabsorb more water
Also depends on activity of the transport system too- not just the length.

Question 19

How can you concentrate urine above normal plasma osmolarity?

Answer 19

Produce a region of ‘hyperosmolar’ interstitial fluid

Question 20

What is essential to remember about the movement of water

Answer 20

We cannot pump it, therefore we must create a gradient for it to move to produce urine that is more concentrated than the plasma.

Question 21

Outline how this gradient is established

Answer 21

Use schematic too!
Initially no gradient
Salt pumped out of ascending limb- decreasing osmolarity in the ascending limb (increasing it in I.F)
Descending limb detects this- water moves out to equilibrate- increasing osmolarity in the descending limb
More fluid comes in - osmolarities move around i.e high osmolarity of descending limb enters ascending limb
Same happens again
Only this time water at bottom of descending limb has a higher osmolarity and water leaving ascending limb has a lower osmolarity
Ascending limb capable of generating a 200 mosmol/L difference between it and the I.F (i.e loses 100 to increase the I.F by 100

Question 22

Can this movement generate the full 1200mosmol/L gradient

Answer 22

No

Question 23

How do we get to this 1200mosmol/L gradient

Answer 23

§ Concentration of the urea in the tube becomes higher as it goes up the ascending limb of the LoH and back down in the collecting duct as more and more water is removed (while the membrane is IMPERMEABLE to urea).
§ This means when it gets to the inner medulla CD, the membrane becomes permeable and urea passes down it’s concentration gradient into the bottom of the descending limb
Urea then follows this path until max osmolarity of urine- 1200momol/L is reached.

Question 24

Describe the roles of the different urea transporters

Answer 24

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

Question 25

What happens if we knock out UT-A1 or A3

Answer 25

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

Question 26

What would happen if we knocked out UT-A2

Answer 26

Very mild phenotype only observable on a low protein diet

Not making much urea on a low protein diet- less concentrating ability

Question 27

What would happen if we knock out UT-B

Answer 27

Increased urine production
Reduced urine concentrating ability
Weight loss

Question 28

What mutations have been observed in humans

Answer 28

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 29

Summarise what causes concentration of the urine

Answer 29

LoH creates an osmolarity gradient in the medullary interstitium
Collecting duct transverses medulla: urine concentrated by osmotic removal when duct wall made permeable to ADH

Question 30

Why doesn’t medullary blood flow eliminate countercurrent gradient?

Answer 30

Blood flow in the vasa recta is another counter-current

Permeable to water and solutes.
Water diffuses out of descending limb and solutes diffuse into descending limb.
In the ascending limb the reverse happens.
Thus oxygen and nutrients are delivered without loss of Gradient.
HOWEVER, the vasa recta DOES carry away the EXCESS to maintain the equilibrium.

Question 31

What is vasopressin

Answer 31

Derived from a single transcript that also encodes neurophysin II and copeptin

Peptide hormone
(9 amino acids)

Synthesised (transcribed and processed) in the hypothalamus
Packaged into granules

Secreted from the posterior pituitary (neurohypophysis)

Question 32

What does vasopressin bind to

Answer 32

Binds to specific receptors (V2) on basolateral membrane of principal cells in the collecting ducts

Question 33

Describe the actions of vasopressin to decrease plasma osmolarity

Answer 33

Causes insertion of water channels (aquaporins) into the cells membranes, hence increasing water permeability (predominantly AQP2 into the luminal membrane).

Also stimulates urea transport from IMCD into thin ascending limb of loop of Henle and interstitial tissue by increasing the membrane localisation of UTA1 and UTA3 in the CCD

Question 34

What triggers ADH release

Answer 34

-Plasma osmolarity is normally 285 - 295mosmol/L;

• ADH release regulated by osmoreceptors in the hypothalamus (if osmolarity rises above 300mOs = triggers release)
• Also stimulated by a marked fall in blood volume or pressure (monitered via baroreceptors or stretch receptors)

Question 35

What inhibits ADH release

Answer 35

-Ethanol inhibits ADH release, which leads to dehydration as urine volume increases

Question 36

Describe what happens in response to a decreased plasma osmolarity

Answer 36

Decrease detected by hypothalamic osmoreceptors
Decrease ADH release
Collecting duct water permeability decreases
Increased urine flow rate
Increased fluid loss will tend to raise plasma osmolarity

Question 37

What is the result of water diuresis (low ADH)

Answer 37

Result:
A large 
volume
of dilute 
urine 

Solute reabsorption without water reabsorption can lower urine osmolarity to 50 mosmol/l

Question 38

What happens in dehydration

Answer 38

Increased plasma osmolarity
Hypothalamic osmoreceptors detect this and stimulate thirst and ADH release
This increases collecting duct water permeability
Decreasing urine flow rate

 Decreased fluid loss will tend to lower plasma osmolarity
Increased water intake will tend to lower plasma osmolarity

Question 39

What is the result of maximal diuresis (high ADH)

Answer 39

Result:
A small 
volume
of 
concentrated 
urine 

Osmotic equilibration (with water) in cortex & medulla leads to high urine osmolarity

Question 40

How is plasma osmolarity kept within a normal range

Answer 40

-Feedback control via ADH keeps plasma osmolarity in a normal range (and determines urine output and water balance)

Question 41

What are the disorders of water balance and what can it lead to

Answer 41

§ No/insufficient ADH – Central DI.
§ No detection of ADH – Nephrogenic DI (mutant ADH receptor)
§ No response to ADH signal (mutant aquaporin)
o Gives polyuria.
Excretion of large amounts of watery urine (as much as 30 litres each day)

Unremitting thirst

Diabetes Insipidus