Describe the half-Life of ADH?
~10 mins
So it can be rapidly adjusted based on H2O need
What does ADH do?
It determines the water solubility of the collecting duct, more ADH = more water resorped = More concentrated urine
What controls ADH?
Osmoreceptors
ECF volume
Pain/emotion/stress/exercise/nicotine/morphine/traumatic surgery all increase ADH
- Alcohol suppresses ADH
Where are osmoreceptors found?
Anterior Hypothalamus
How do osmoreceptors work?
They use stretch sensitive ion channels to detect movement of water in and out the cell
They trigger more ADH release when water moves out of them and they shrink
What does it mean to say osmolarity receptors are a “high gain” system?
only a 2.5% increase in osmolarity will increase ADH 10x
How do tonicity/osmolarity affect osmoreceptors?
Tonicity is the relevant one.
Only molecules that can’t cross the cell membrane (and therefore can’t equalize) will affect the movement of water. E.g. Na+ but not urea
What effect does ECF volume have on ADH?
More ECF volume decreases ADH and vice versa
What detects ECF volume?
Low P receptors in Atria & Great Veins (aka volume receptors)
High P receptors in carotid & aortic arch baroreceptors
How do Low P receptors in atria/great veins work?
They have a base tonic inhibitory effect on ADH secreting neurons via the vagal nerve.
When ECF volume decreases, they fire less and more ADH is released so more fluid is retained)
(Important in hemorrhage)
How does ADH increase Water reabsorption from the collecting ducT?
Acts on a an ADH receptor
- -> Activates a cAMP 2* messenger
- -> Causes storage vesicles to express aquaporin-2 water pores on the luminal surface of the cell membrane
These increase water permeability
What causes water to move out the collecting duct?
Once ADH makes the duct cells permeable to water it travels out thanks ot the high medullary interstitial osmolarity created by the loop of henle (from there into the blood)
So it gets more concentrated the further down the collecting duct as the interstitial osmolarity increases as it goes
What is the role of urea in water conservation during anti-diuresis?
ADH makes the collecting permeable to urea
When water leaves it concentrates urea so it then follows.
There it reinforces the interstitial gradient and reserves water (if it stayed in the tubule more water would need to be excreted with it)
What is Diabetes Insipidus?
A condition where ADH fails and you cant concentrate urine. Instead you excrete a large amount of hypotonic urine
What are the signs of DI?
Polyuria (>10L/day) and consequent Polydipsia
What are the types of DI?
Central DI:
- Disease of ADH synthesizing part of Hypothalamus e.g. tumour/meningitis/surgery
Peripheral DI:
- Desensitization of the Collecting duct to ADH
E.g. genetic defects in V2 (ADH) receptor or in the aquaporins
How do you treat DI?
Peripheral DI relies on thirst mechanism for you to survive. Its usually down to hypercalcaemia or hypokalemia and will resolve when the ion disorders does.
Central DI needs exogenous ADH
How much fluid passes through the bowmens capsule, proximal tubule, end of loop of henle adn end of collecting duct per day?
Bowmans capsule filters 190l/day (300mOsM)
End of proximal tubule sees 54L/day (the rest is reabsorped) (300mOsM)
End of Loop of henle sees 18L/day (rest is secreted into interstitium and taken up by vasa recta) (100mOsM)
End of collecting duct sees 1.5L/day of final urine (Avg) (50-1200mOsM depending on ADH)
