Regulation of Osmolarity Flashcards
What is water regulation controlled by?
ADH (vasopressin) = arginine vasopressin (AVP)
Describe ADH
Polypeptide synthesised in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain
Posterior pituitary hormone
Half life around 10 mins
What is the primary control of ADH secretion?
Plasma osmolarity
What happens when OP of plasma increases?
The rate of discharge of ADH secretin neurons in SO and PVN is increased
So increased release of ADH from posterior pituitary
What are changes in neuronal discharge mediated by?
Osmoreceptors in anterior hypothalamus close to SO and PVN
Other receptors in lateral hypothalamus mediate thirst
What happens if there is an increase in osmolarity?
Increased H2O out of cell
Cell shrinks so stretch sensitive ion channel activated
Increased neural discharge
What happens if there is a decrease in osmolarity?
H2O enters cells
Cells swell
Decreased neuronal discharge
Decreased ADH secretion
What does change in volume of osmoreceptors do?
Changes in osmoreceptor discharge - stretch sensitive ion channels
What is normal plasma osmolarity?
280-290mOsm/kg H2O
Regulated very precisely
What is the plasma osmolarity control of ADH described as?
High gain - 2.5% increase in osmolarity can produce 10x increase in ADH
Very sensitive
Why does an increase in osmolarity that does not cause increase in tonicity is ineffective?
Solutes that can penetrate membranes move together with water and don’t produce osmotic drag or tonicity
Describe what an increase in urea causes to volume and ADH release
No change in volume, discharge or ADH release as urea is an ineffective osmole as no tonicity
What happens if increased osmolarity and NaCl?
Decreased volume
Increased discharge and ADH release
So water moves out
What does the amount of urine produced depend on?
Conc. of ADH
Amount of solute excreted
What does the ingestion of hypertonic solutions like seawater do?
Increase the solute load to be excreted which increases urine flow leading to dehydration as more H2O s required to excrete the solute load
What does urine osmolarity depend on?
Reabsorption in the collecting duct
What happens after vasopressin binds to the membrane receptor?
Receptor activates cAMP second messenger system
Cell inserts AQP2 water pores into apical membrane
Water is absorbed by osmosis into blood
How is there increased permeability of collecting ducts to H2O?
By incorporating H2O channels into luminal membrane - aquaporins
What happens to cortical CD if ADH is present?
H2O able to leave CD so cortical CD becomes equilibrated with cortical interstitium - 300mOsm/l
CD passes through hypertonic medullary interstitial gradient created at loop of Henle
What happens if there is maximum conc. of ADH?
Produces small volume of highly concentrated urine which contains less H2O than solute which compensates for water deficit
Adds pure H2O to ECF as reabsorbed by high oncotic pressure in vasa recta
What happens in the absence of ADH?
CD are impermeable to H2O so medullary interstitial gradient is ineffective in movement of H2O - large volume dilute urine is excreted
mOsm/l can fall to 30-50
What is the role of urea?
Plays role in production of concentrated urine
In presence of ADH, movement of H2O out of CD concentrates the urea in ducts
Is urea permeable in CD?
Relatively permeable - particularly towards medullary tips
As approached medullary tips - increasing tendency to move out down conc. gradient
What is permeability of late medullary CD enhanced by?
ADH
Describe urea during anti-diuresis
High levels of ADH - urea reabsorbed from CD into interstitium where acts to reinforce interstitial gradient in ascending loop of Henle
Why is urea retained in anti-diuresis?
Order to save water and reinforce medullary gradient in region of thin ascending limb of Loop of Henle
Uraemia occurs
What would happen if urea is not reabsorbed in the tubule?
It would exert osmotic effect to hold H2O in tubule and therefore reduce potential for rehydration
Why is reabsorption of urea possible at any level of ADH?
So that CD permeability of CD can be precisely graded to meet demands of body for H2O regulation
What is the ECF volume effect on ADH secretion?
Increase ECF volume - decrease ADH secretion
Decrease ECF volume - increase ADH secretion
What is the relationship between ECF volume and ADH secretion?
Inverse relationship between rate of ADH secretion and rate of discharge of stretch receptor afferents in low and high pressure areas of circulation
Where are low pressure receptors located?
L and R atria and great veins
Where are high pressure receptors located?
Carotid and aortic arch baroreceptors
What do moderate decreases in ECF volume primarily effect?
Atrial receptors
Decrease atrial receptor discharge so increase ADH release
Normally exert tonic inhibitory discharge of ADH secretion via vagus nerve
What receptors are involved if volume changes enough to affect MBP?
Carotid receptors which also contribute to ADH secretion
What happens to ADH release when going from lying down to standing up?
Increase ADH release
What are ADH secreting cells?
Neurons
They receive multiple inputs which they integrate to determine ADH conc.
What stimuli increase ADH?
Pain, emotion, stress, exercise, nicotine, and morphine
Also following traumatic surgery
What stimuli supresses ADH release?
Alcohol
What is central diabetes insipidus?
Hypothalamic areas synthesizing ADH become diseased due to tumours, meningitis or damaged in surgery
What is peripheral diabetes insipidus?
CD is insensitive to ADH
What are patient with DI characterised by?
Passage of large volumes of very dilute urine
>10l/day and they drink large volumes of water
What is the treatment for DI?
Central - ADH
Peripheral - Fix ion disorders (hypercalcaemia and hypokalaemia) as cant give ADH
What are the changes in volume of fluid along the nephron?
Bowman’s - 180l/day
End of proximal tubule - 54l/day
End of loop of Henle - 18l/day
End of CD - 1.5l/day
What are the changes in osmolarity along the nephron?
Bowman’s - 300mOsm
End of proximal tubule - 300
End of loop of Henle - 100
End of CD - 50-1200
