Water balance Flashcards
What is meant by osmolarity
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
What does the kidney need to do
Maintain plasma osmolarity under lots of different conditions
Some- high conc urine
Others- low conc urine
Describe the flow of water
Water flows across a semi permeable membrane from a region of low osmolarity to a region of high osmolarity
What is the consequence of a permeable system
Increase salt reabsorption- water will also move to balance it- thus increasing volume of the ECF
Describe the inter-relation between salt and water regulation
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.
What is the major salt
Na+- most prevalent solute in plasma and ECF
On average, what do we consume daily
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).
Why is it important to get rid of the excesses
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.
Describe the osmolarity that we should maintain the plasma at
o Plasma osmolarity = 285-295mosmol.L-1 (greatest proportion is ~140mmol.L-1 Na).
What are the most abundant components and solute of the plasma and ECF
Water: most abundant component of the plasma and ECF
Sodium: most prevalent solute in the plasma and ECF
What is the key difference in terms of the movement of water and salt
Water can move freely, but salt cannot- therefore we balance salt.
Describe the proportions of water found in different compartments of the body
In the body, 25L (65%) is found intracellularly and 15L (35%) is found extracellularly (e.g. plasma and interstitial).
What compensates for a low IC cl- conc
A high IC HPO42-
Describe some other relative concs of ions
HCO3- lower in cells than ECF or plasma
Ca2+ higher in cells
Describe how we get rid of water
· 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).
Where is water reabsorbed
All along the nephron except for the ascending limb
Summarise the reabsorption of water
§ 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
What is maximum urine osmotic concentration proportional to
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.
How can you concentrate urine above normal plasma osmolarity?
Produce a region of ‘hyperosmolar’ interstitial fluid
What is essential to remember about the movement of water
We cannot pump it, therefore we must create a gradient for it to move to produce urine that is more concentrated than the plasma.
Outline how this gradient is established
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
Can this movement generate the full 1200mosmol/L gradient
No
How do we get to this 1200mosmol/L gradient
§ 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.
Describe the roles of the different urea transporters
o UT-A1, UT-A3 – Inner medullary collecting duct.
o UT-A2 – Thin descending limb.
o UT-B1 – Descending vasa recta.
What happens if we knock out UT-A1 or A3
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
What would happen if we knocked out UT-A2
Very mild phenotype only observable on a low protein diet
Not making much urea on a low protein diet- less concentrating ability
What would happen if we knock out UT-B
Increased urine production
Reduced urine concentrating ability
Weight loss
What mutations have been observed in humans
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
Summarise what causes concentration of the urine
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
Why doesn’t medullary blood flow eliminate countercurrent gradient?
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.
What is vasopressin
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)
What does vasopressin bind to
Binds to specific receptors (V2) on basolateral membrane of principal cells in the collecting ducts
Describe the actions of vasopressin to decrease plasma osmolarity
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
What triggers ADH release
-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)
What inhibits ADH release
-Ethanol inhibits ADH release, which leads to dehydration as urine volume increases
Describe what happens in response to a decreased plasma osmolarity
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
What is the result of water diuresis (low ADH)
Result: A large volume of dilute urine
Solute reabsorption without water reabsorption can lower urine osmolarity to 50 mosmol/l
What happens in dehydration
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
What is the result of maximal diuresis (high ADH)
Result: A small volume of concentrated urine
Osmotic equilibration (with water) in cortex & medulla leads to high urine osmolarity
How is plasma osmolarity kept within a normal range
-Feedback control via ADH keeps plasma osmolarity in a normal range (and determines urine output and water balance)
What are the disorders of water balance and what can it lead to
§ 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
