Osmoregulation Flashcards
Where is osmolality detected?
Within the AV3V where the BBB is incomplete.
Where do the neurons of AV3V project to and what do they detect?
Neurons project to supraoptic and paraventricular nuclei of the hypothalamus.
How will the nuclei respond to an increased osmolality in the blood?
Neurons respond to an increased osmolality by increasing ADH release form the posterior pituitary.
Where is ADH/vasopressin sythesised?
In the cell bodies of the neurons of the hypothalamus as a prehormone which is cleaved as it descends to the pituitary via axons.
What products result from prehormone cleaving to produce ADH?
ADH and other peptides
Where does ADH act systemically?
Travels in circulation to V2 receptors on the basolateral membrane of the CCT.
What are V2 receptors? What is there function when activated?
GsPCR that use the AC pathway to activate PKA for phosporylation and exocytosis of vesicles containing AQP2 on to the apical membrane of CCT for increased water reabsorption.
What is the structure of an AQP and how does it allow water to pass?
Multisubunit oligomer that is arranged into a tetramer of identical units, on which has a glycon attached. Water passes through its pour.
Where are the different AQPs located?
AQP1 - PT and DL
AQP2 - Apical of CCT and MCD
AQP3 - Across basolateral
Why is oxytocin released alongside ADH? Where does oxytocin act?
To increase thirst.
AV3V neurons projecting to the median preoptic area stimulate thirst through oxytocin release which acts as an agonist on V1 and V2 receptors.
What effect does the combination of ADH and oxytocin produce?
Decreased output and increased input
Why is osmoregulation response activated frequently in humans?
Due to binge drinking rather than drinking small continuous infusions.
What is the concentration of ADH proportional to?
Rate of secretion of water in the kidney.
In what fashion is ADH released?
Tonic release that is slow and graded
What will MAX ADH cause?
HIGH osmolality, low volume urine
1400mOsm , 300ml.day
What will no ADH cause?
LOW osmolality, high volume urine
60-90mOsm , 25L.day
What is a normal daily urine output?
1.8L.day
Why does sea water cause dehydration?
It has a high osmolality of 2000mOsm. To removed a solution of this osmolality at a max of 1400mOsm, it would require 1.4L of water to be excreted. (2000/1400)
What is the max osmolality of urine that the kidney can produce?
1400mOsm per Litre (finite range of water excretion) - Any substance above this osmolality will cause dehydration
What is the max. renal osmolality of a neonate? Why does this put them at risk?
500mOsm - If a formula feed exceeds this it will draw more water into the renal tubules and cause dehydration.
What are the most dominant osmolytes of the circulation?
Na and Cl
Why do proteins, fats and carbohydrates that are consumed in large amounts have less of an effect on osmolality than the two dominant osmolytes?
The substances are broken down into products that are used for other functions or are less water soluble.
What are carbohydrates broken down into? What are they used for?
Simple sugars - transported into cells.
Glucose is oxidised to CO2 and H2O.
What are proteins broken down into? What are they used for?
AA - rapidly taken up into cells
N2 is removed as urea which has a HIGH FLUX but low contribution to osmolality.
Why is K not an effective osmolyte?
Cells are relatively more permeable to K, creating an intracellular K reservoir.
K is cleared more rapidly than Na so has a HIGH FLUX but low effect on osmolality due to its high clearance.
What is a hyperosmolar hyperglycaemic state?
In DM, glucose can become high enough to contribute to osmolality if >320mOsm. The hyperosmolality stimulates thirst to prevent dehydration but excess intake will cause hyponatraemia.
What are the effects of hyponatraemia?
Affects mental status, seizures, neurology, increased blood viscosity and clotting risk.
What are the side effects of delivering ADH intranasally?
Nasal necrosis as a result of V1 mediated vasoconstrction, limiting the blood supply to the nasal tissue.
What ADH analogue is used to treat high osmolality?
Desmopressin
What is the bodies main priority?
Body will correct BP / Volume changes before correcting osmolality.
What contributes to correcting a volume change?
Increased osmolality = increased ADH = Increased thirst = Increased volume
What is the issue with correcting osmolality in regards to volume?
Solute content changes will disturb volume to regulate the concentrations.
